Arpi.unipi.it



Sj?gren’s SyndromePilar Brito-Zerón1,2,3, Chiara Baldini4, Hendrika Bootsma5, Simon J. Bowman6, Roland Johnson7, Xavier Mariette8,9, Kathy Sylvis10, Elke Theander11, Athanasios Tzioufas12 and Manuel Ramos-Casals2,3,13.1Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain.2Sj?gren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain.3Department of Autoimmune Diseases, ICMiD, Hospital Clínic, C/Villarroel, 170, 08036, Barcelona, Spain.4Rheumatology Unit, University of Pisa, Pisa, Italy. 5Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands.6Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.7Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.8Université Paris Sud, INSERM, Paris, France.9Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – H?pitaux de Paris, H?pitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Paris, France.10Oklahoma Sj?gren’s syndrome Center of Research Translation, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.11Department of Rheumatology, Malm? University Hospital, Lund University, Lund, Sweden. 12Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece.13Department of Medicine, University of Barcelona, Barcelona, Spain.Correspondence to: M.R-C. mramos@clinic.ub.esCompeting interestsThe authors declare no competing interests.AcknowledgementsNothing to acknowledge.Author contributionsIntroduction (P.B-Z.); Epidemiology (M.R-C.); Mechanisms/pathophysiology (A.T., K.S and R.J.); Diagnosis, screening and prevention (C.B. and P.B-Z.); Management (E.T., H.B. and X.M.); Quality of life (S.B.); Outlook (M.R-C.); Overview of Primer (M R-C.) AbstractSj?gren's syndrome (SjS) is a systemic autoimmune disease with a specific predilection for involving the exocrine glands. The clinical consequence is dryness of the mucosal surfaces, principally in the mouth and eyes. The disease overwhelmingly affects middle-aged women, but may also affect children, men and the elderly. The clinical spectrum of SjS extends from dryness of the main mucosal surfaces to systemic involvement and includes a large number of manifestations. Therapeutic approaches include both topical and systemic medications. SjS may be a serious disease with excess mortality, mainly related to systemic involvement and haematological cancer. Knowledge of SjS has progressed substantially, but the five features defined in the early years (sicca features, systemic involvement, lymphocytic infiltration, Ro/La autoantibodies, and increased risk of lymphoma) still essential characterize the disease. [H1] IntroductionSj?gren’s syndrome (SjS) is a systemic autoimmune disease with a specific predilection for causing inflammation of the exocrine glands. The clinical consequence is dryness of the mucosal surfaces, principally in the mouth and eyesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1756-1833", "PMID" : "22700787", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3-Almirall", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ (Clinical research ed.)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "e3821", "title" : "Primary Sjogren syndrome.", "type" : "article-journal", "volume" : "344" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1. Patients affected by isolated sicca symptoms were first reported at the end of the 19th century (Figure 1); these symptoms were integrated into a “sicca syndrome” by Gougerot in 1925, but the first to suggest they could be attributed to a systemic disease was the Swedish ophthalmologic, Henrik Sj?gren (1899-1986), who, in 1933, established that the disease spectrum extended beyond glandular involvement. Subsequent studies in the mid-20th century confirmed the association of sicca syndrome with other rheumatic and autoimmune diseases and with an unusually-high frequency of hematological malignancies. The autoimmune etiopathogenesic basis of SjS was confirmed in the 1960s, and the presence of autoantibodies (Ro/SS-A and La/SS-B) and organ-specific lymphocytic infiltration (focal lymphocytic sialadenitis) become central for the pathobiology and diagnosis of the disease. Since then, knowledge of SjS has progressed substantially, but the five features defined in the early years (sicca features, systemic involvement, lymphocytic infiltration, autoantibodies, and increased risk of lymphoma) still essential characterize the disease. In this Primer, we describe the epidemiology and etiopathogenic mechanisms of Sj?gren’s syndrome, the whole clinical picture including both glandular and systemic manifestations, approaches to diagnosis and treatment, quality of life and we end by presenting an outlook for potential future advances on the knowledge of the disease. [H2] EpidemiologyThe frequency of SjS varies widely according to the study design (higher frequencies in studies without a population-based design) and the classification criteria used (Table 1) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4065/76.6.593", "ISSN" : "0025-6196", "PMID" : "11393497", "abstract" : "OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sj\u00f6gren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients.\n\nPATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk.\n\nRESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia.\n\nCONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.", "author" : [ { "dropping-particle" : "", "family" : "Pillemer", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "E L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "L T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "P B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melton", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Fallon", "given" : "W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mayo Clinic proceedings", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001", "6" ] ] }, "page" : "593-9", "title" : "Incidence of physician-diagnosed primary Sj\u00f6gren syndrome in residents of Olmsted County, Minnesota.", "type" : "article-journal", "volume" : "76" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.2003.014027", "ISSN" : "0003-4967", "PMID" : "15194588", "abstract" : "OBJECTIVE: To determine the annual incidence of primary Sj\u00f6gren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.", "author" : [ { "dropping-particle" : "", "family" : "Plesivcnik Novljan", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rozman", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hocevar", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "874-876", "title" : "Incidence of primary Sjogren's syndrome in Slovenia.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/rheumatology/kei107", "ISSN" : "14620324", "PMID" : "16332955", "abstract" : "OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sj\u00f6gren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.", "author" : [ { "dropping-particle" : "", "family" : "Alamanos", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Voulgari", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venetsanopoulou", "given" : "a. I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siozos", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "a. a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "187-191", "title" : "Epidemiology of primary Sj??gren's syndrome in north-west Greece, 1982-2003", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3899/jrheum.100883", "ISSN" : "0315-162X", "PMID" : "21239759", "abstract" : "To estimate the incidence and mortality of treated primary Sj\u00f6gren's syndrome (pSS) by sex and age group in Taiwan.", "author" : [ { "dropping-particle" : "", "family" : "Weng", "given" : "Meng-Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Yu-Tung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ming-Fei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Tsung-Hsueh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "706-708", "title" : "Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: a population-based study.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/acr.21820", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22899470", "abstract" : "OBJECTIVE: The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population-based database.\\n\\nMETHODS: We used the longitudinal health insurance database (comprising 1,000,000 beneficiaries) of the Taiwan National Health Insurance from 2000 to 2008 and the National Death Registry of Taiwan from 2000 to 2008.\\n\\nRESULTS: The overall prevalence of major ARDs was 101.3 (95% confidence interval [95% CI] 27.5-107.9) per 100,000 populations; the prevalence was 165.1 (95% CI 44.8-177.1) in women and 40.1 (95% CI 10.9-46.1) in men. The prevalences of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis, vasculitis, and Beh\u00e7et's disease were 52.4 (95% CI 14.2-57.2), 37.0 (95% CI 10.0-41.0), 16.0 (95% CI 4.3-18.7), 3.8 (95% CI 1.0-5.3), 2.9 (95% CI 0.8-4.2), 5.7 (95% CI 1.6-7.4), and 1.4 (95% CI 0.4-2.3) per 100,000 persons, respectively. Between 2001 and 2008, the incidence rates (per 100,000 person-years) for these diseases were 17.3, 8.4, 10.6, 1.5, 1.5, 1.2, and 0.8, respectively. The incident cases with ARDs had a higher risk of mortality, with the standardized mortality ratio (SMR) ranging from 1.3 to 3.7.\\n\\nCONCLUSION: In 2000, the prevalence of major ARDs was 1.4-52.4 per 100,000 persons in Taiwan. Between 2000 and 2008, the incidence rates of various ARDs were 0.8-17.3 per 100,000 person-years. The prevalence and incidence of RA were the highest, followed by SLE and Sj\u00f6gren's syndrome, and those of Beh\u00e7et's disease were the lowest. Patients with different types of ARDs had higher mortality and SMR than those of the general population.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "See", "given" : "Lai-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang-Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I-Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Meng-Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "244-50", "title" : "Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.semarthrit.2013.06.001", "ISBN" : "0049-0172", "ISSN" : "00490172", "PMID" : "23916348", "abstract" : "Objectives: The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. Methods: A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. Results: Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sj\u00f6gren's syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Beh\u00e7et disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sj\u00f6gren's syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). Conclusions: ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sj\u00f6gren's syndrome and SLE, while the incidence of Beh\u00e7et disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases. \u00a9 2013 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "See", "given" : "Lai Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I. Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiou", "given" : "Meng Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "381-386", "title" : "Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1136/bmjopen-2013-003569", "ISSN" : "2044-6055", "PMID" : "24282246", "abstract" : "OBJECTIVE: A very few studies describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). METHODS: A population-based incidence cohort of patients diagnosed with pSS in 1976-2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. RESULTS: 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18-44 years: 2.1/100 000 vs \u226575 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (\u00b13%) at 1 year after diagnosis of pSS and increased to 20% (\u00b14%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). CONCLUSIONS: pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.", "author" : [ { "dropping-particle" : "", "family" : "Nannini", "given" : "Carlotta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jebakumar", "given" : "Adlene J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crowson", "given" : "Cynthia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryu", "given" : "Jay H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "Eric L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-7", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "e003569", "title" : "Primary Sjogren's syndrome 1976-2005 and associated interstitial lung disease: a population-based study of incidence and mortality.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.3109/03009742.2014.931457 [doi]", "ISBN" : "0300-9742", "ISSN" : "1502-7732; 0300-9742", "PMID" : "25222653", "abstract" : "Objectives: To define the incidence rate of primary Sjogren's syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. Method: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. Results: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3-4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89-0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. Conclusions: The incidence rate of pSS is 3.1 (95% CI 2.3-4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.", "author" : [ { "dropping-particle" : "", "family" : "Kvarnstrom", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ottosson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordmark", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahren-Herlenius", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-8", "title" : "Incident cases of primary Sjogren's syndrome during a 5-year period in Stockholm County: a descriptive study of the patients and their characteristics", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1186/1471-2474-11-98", "ISBN" : "1471-2474 (Electronic) 1471-2474 (Linking)", "ISSN" : "1471-2474", "PMID" : "20504294", "abstract" : "BACKGROUND: Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece.\\n\\nMETHODS: In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases.\\n\\nRESULTS: The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sj\u00f6gren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension.\\n\\nCONCLUSIONS: Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.", "author" : [ { "dropping-particle" : "", "family" : "Anagnostopoulos", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinzaras", "given" : "Elias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexiou", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papathanasiou", "given" : "Aphrodite a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davas", "given" : "Evangelos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koutroumpas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barouta", "given" : "Georgia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakkas", "given" : "Lazaros I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC musculoskeletal disorders", "id" : "ITEM-9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "98", "title" : "The prevalence of rheumatic diseases in central Greece: a population survey.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1111/j.1742-1241.2008.01749.x", "ISSN" : "1742-1241", "PMID" : "18422594", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.", "author" : [ { "dropping-particle" : "", "family" : "Birlik", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gurler", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sari", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birlik", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarioglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oktem", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Can", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayahan", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akkoc", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onen", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of clinical practice", "id" : "ITEM-10", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "954-61", "title" : "Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "ISBN" : "1395-3907 (Print) 1395-3907 (Linking)", "ISSN" : "1395-3907", "PMID" : "9253975", "abstract" : "PURPOSE: To investigate the presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome a sample of 504 persons aged 30-60 years from Copenhagen was studied. METHODS: The presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome was estimated according to both the Copenhagen set of criteria and the preliminary European criteria. RESULTS: Symptoms of dry eye and oral dryness were very common and with no significant correlation to age or sex. Keratoconjuncitivis sicca was most frequent in persons aged 50-59 years and was equally common in men and women. Primary Sj\u00f6gren's syndrome could only be diagnosed in one person according to the Copenhagen criteria (cut-off the Schirmer-1 test < or = 5 mm/5 min), and in three persons according to the preliminary European criteria. CONCLUSION: The frequency of keratoconjunctivitis sicca in persons aged 30-60 years in Copenhagen may be estimated to be 11% according to the Copenhagen criteria and 8% according to the preliminary European criteria. The frequency of primary Sj\u00f6gren's syndrome in persons aged 30-60 years in Copenhagen may be estimated to be between 0.2% and 0.8% according to the Copenhagen criteria and between 0.6% and 2.1% according to the preliminary European criteria.", "author" : [ { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta ophthalmologica Scandinavica", "id" : "ITEM-11", "issue" : "3", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "281-286", "title" : "Keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome in a Danish population aged 30-60 years.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "ISSN" : "0300-9742", "PMID" : "15124941", "abstract" : "To establish the prevalence among women of primary Sj\u00f6gren's syndrome (PSS) in Birmingham, UK.", "author" : [ { "dropping-particle" : "", "family" : "Bowman", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibrahim", "given" : "G H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamburger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ainsworth", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-12", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "39-43", "title" : "Estimating the prevalence among Caucasian women of primary Sj\u00f6gren's syndrome in two general practices in Birmingham, UK.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-13", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9370875", "abstract" : "OBJECTIVE: To define the prevalence of Sj\u00f6gren's syndrome (SS) through an epidemiological survey in a closed rural community. The classification of SS is based on the validated criteria reported by a multicentre study performed in Europe and supported by the Epidemiology Committee of the European Community (EEC-COMAC Epidemiology).\\n\\nMETHODS: The population under study consisted of 837 women aged 18 years or older, residing in the Astakos community of Aitoloakarnania, Greece. The study protocol was subdivided in two parts. In part I, an exhaustive epidemiological survey of these women was conducted in July and August of 1992. The validated questionnaire used in the survey assesses both ocular and oral involvement. In part II, 45 of the women reporting symptoms of both dry eye and dry mouth were approached for a full examination based on the validated set of classification criteria of SS. The full complement of the diagnostic tests was performed on 35 of these women. A subject is classified as a definite primary SS case if at least four of six items of the subject's test items are positive. If three of six items are positive the subject is classified as a probable primary SS case.\\n\\nRESULTS: The classification criteria for definite primary SS were satisfied by five women. This number corresponds to an estimated prevalence of 0.60% (exact 95% CI 0.19%, 1.39%). Probable primary SS was diagnosed for 25 women (prevalence = 2.99%).\\n\\nCONCLUSION: Because of the loss of follow up (10 of 45) and the use of slightly stricter criteria for inclusion of possible SS cases in part II of the study, we consider our estimate of the prevalence of SS to be conservative. This study concurring with other recent reports, suggests that SS is more prevalent than previously thought.", "author" : [ { "dropping-particle" : "", "family" : "Dafni", "given" : "U G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staikos", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skopouli", "given" : "F N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-13", "issue" : "9", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "521-5", "title" : "Prevalence of Sj\u00f6gren's syndrome in a closed rural community.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-14", "itemData" : { "DOI" : "10.1007/s12026-009-8153-2", "ISBN" : "0257-277X", "ISSN" : "0257277X", "PMID" : "20066507", "abstract" : "Epidemiologic studies of autoimmune diseases have not considered them in the aggregate. The objective was to estimate the prevalence of 30 autoimmune diseases separately and in aggregate according to ICD-10 classification. The lifetime prevalence of the entire population of 5,506,574 persons alive in Denmark on October 31, 2006, was estimated by linking records of all visitors to hospitals and specialty clinics via National Patient Registers from January 1, 1977 through October 31, 2006. The prevalences vary from 0.06/1,000 for Pemphigus to 8.94/1,000 for Type 1 diabetes. Nearly 4% of the population had one or more autoimmune disease. The general conclusion is that autoimmune diseases as an aggregate are common.", "author" : [ { "dropping-particle" : "", "family" : "Eaton", "given" : "William W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Marianne G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atlad\u00f3ttir", "given" : "Hj\u00f6rd\u00eds \u00d3sk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregory", "given" : "Patricia E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Noel R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mortensen", "given" : "Preben Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Immunologic Research", "id" : "ITEM-14", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "228-231", "title" : "The prevalence of 30 ICD-10 autoimmune diseases in Denmark", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-15", "itemData" : { "DOI" : "10.3109/03009742.2010.536164", "ISSN" : "1502-7732", "PMID" : "21231797", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (PSS) is a chronic autoimmune inflammatory disease characterized by exocrine gland inflammation producing clinical symptoms such as dryness of the mouth and eyes. The reported prevalence of PSS is variable, probably because of different classification criteria used and selection bias. The aim of this study was to determine the prevalence of PSS in a well-defined Norwegian Caucasian population using the revised American-European Consensus Group (AECG) criteria.\\n\\nMETHODS: Three hospitals and three private rheumatology practices provide all of the rheumatology services to the local population in Hordaland and Rogaland counties, which included 852 342 Caucasian inhabitants as of 1 January 2009. Patients on file fulfilling the new revised AECG criteria for PSS were included, and patients with incomplete data were invited to a screening visit.\\n\\nRESULTS: A total of 424 PSS patients were identified. Their mean age was 61.6 \u00b1 13.2 years; 28 (7%) were men and 396 (93%) were women. The point estimate for the proportion of PSS was 0.050% [95% confidence interval (CI) 0.048-0.052].\\n\\nCONCLUSION: The prevalence of PSS in this Norwegian population of Caucasians is lower than previously reported when less stringent criteria for identifying PSS were used, but is in line with more recent studies using the same criteria and methods as in this study.", "author" : [ { "dropping-particle" : "", "family" : "G\u00f8ransson", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haldorsen", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harboe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skarstein", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Time", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omdal", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-15", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "221-4", "title" : "The point prevalence of clinically relevant primary Sj\u00f6gren's syndrome in two Norwegian counties.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-16", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-16", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-17", "itemData" : { "DOI" : "10.1080/03009740600759704", "ISSN" : "0300-9742", "PMID" : "17062438", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sj\u00f6gren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey.\\n\\nMATERIALS AND METHOD: The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive.\\n\\nRESULTS: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria.\\n\\nCONCLUSION: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.", "author" : [ { "dropping-particle" : "", "family" : "Kabasakal", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turk", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oder", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durusoy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mete", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egrilmez", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akalin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-17", "issue" : "5", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "379-83", "title" : "The prevalence of Sj\u00f6gren's syndrome in adult women.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-18", "itemData" : { "DOI" : "10.1002/acr.22115", "ISSN" : "2151-4658", "PMID" : "23983119", "abstract" : "Purpose: To describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS) in a multi-racial/ethnic population. Methods: A cross-sectional study, with 5 case-retrieval sources, identified adults with pSS living in the Greater Paris area (population 1,172,482 adults) in 2007. Diagnoses were verified by the American-European Consensus Group (AECG) criteria and study-specific enlarged criteria based on the presence of \u22653/4 AECG items among subjective oral or ocular dryness, anti-SSA/SSB positivity and positive minor salivary-gland biopsy results. Prevalence estimates were standardized to those for the world population and 5-source capture-recapture analysis (CRA) was used. Racial/ethnic differences in pSS features were evaluated. Results: In all, 133 subjects met the AECG criteria and 203 the enlarged criteria. The 2007 prevalence of pSS was 1.02 per 10,000 adults (95% confidence interval 0.85-1.22) for AECG criteria and 1.52 per 10,000 adults (1.30-1.76) for enlarged criteria. CRA indicated completeness of case findings of ~90%. Compared to subjects with European background, those with non-European background had 2.1-2.3 times higher pSS prevalence and were younger (P < 0.0001) and more likely to have polyclonal hypergammaglobulinemia (P < 0.0001) and SSA/SSB-antibodies (P = 0.0005 and < 0.0001 for AECG and enlarged criteria, respectively). Conclusion: The figure of 1.02-1.52 per 10,000 adults we found and estimates from the few other population-based census surveys support that the prevalence of diagnosed pSS is between 1 and 10 per 10,000 (0.01-0.1%) of the general population. Non-European race/ethnicity may be associated with increased pSS risk and a distinct disease profile. \u00a9 2013 American College of Rheumatology.", "author" : [ { "dropping-particle" : "", "family" : "Maldini", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhote", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amoura", "given" : "Zahir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandt", "given" : "Michel", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delassus", "given" : "Jean-Luc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falgarone", "given" : "G\u00e9raldine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guillevin", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lhote", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanoelina", "given" : "Jacky", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacr\u00e9", "given" : "Karim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uzunhan", "given" : "Yurdagul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leroux", "given" : "Jean-Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahr", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-18", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Epidemiology of primary Sj\u00f6gren's syndrome in a French Multi-Racial/Ethnic area.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-19", "itemData" : { "ISSN" : "0047-1852", "PMID" : "8531339", "abstract" : "A nationwide epidemiological survey of Japanese Sj\u00f6gren's syndrome (SS) patients was conducted in 1994 by the Research Committee on Epidemiology of Intractable Diseases and the Research Committee of Autoimmune diseases, Ministry of Health and Welfare, Japan. The total number of patients treated for SS in 1993, in Japan, was estimated as 17,000 (95% confidence interval 15,000-20,000). The estimated crude prevalence rates were 1.9 and 25.6 per 100,000 population in males and females, respectively. The ratio of female to male patients was 13.7. The peak of age distribution was in their fifties. New research trends to explore the pathogenesis of SS are also discussed here.", "author" : [ { "dropping-particle" : "", "family" : "Miyasaka", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nihon rinsho. Japanese journal of clinical medicine", "id" : "ITEM-19", "issue" : "10", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "2367-70", "title" : "Epidemiology and pathogenesis of Sj\u00f6gren's syndrome", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-20", "itemData" : { "DOI" : "10.1371/journal.pone.0032487", "ISBN" : "1932-6203", "ISSN" : "1932-6203", "PMID" : "22396771", "abstract" : "BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases.\\n\\nMETHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals.\\n\\nRESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted.\\n\\nCONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.", "author" : [ { "dropping-particle" : "", "family" : "Sardu", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cocco", "given" : "Eleonora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mereu", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massa", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuccu", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marrosu", "given" : "Maria Giovanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Contu", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-20", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e32487", "title" : "Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-21", "itemData" : { "PMID" : "9825745", "abstract" : "OBJECTIVE: Using the European Community (EC) criteria for classification\\nVitali et al. Arthritis Rheum 1993;36:340 7, we report the prevalence\\nestimates of Sjogren's syndrome (SS) from a general population and\\npresent the first population data to assess the impact of the syndrome.\\nMETHODS: A cross-sectional population-based survey performed on 1000\\nadults, aged 18-75 yr, randomly selected from a population register.\\nResponders to the initial postal phase were invited for an interview.\\nThe five criteria measured at interview were: (1) the reporting of\\nsubjective oral symptoms lasting for > 3 months; (2) the reporting\\nof subjective ocular symptoms lasting for >3 months; (3) Schirmer-I\\ntest; (4) unstimulated salivary flow; (5) autoantibodies [Ro (SS-A),\\nLa (SS-B), rheumatoid factor (RF), antinuclear antibodies (ANA)].\\nSS was diagnosed if at least four of these five criteria were positive.\\nThe MOS Short-form 36 (SF-36), General Health Questionnaire (GHQ)\\nand the Health and Fatigue Questionnaire (HFQ) were completed by\\nsubjects after the interview, and scores were compared between those\\nwith and without a diagnosis of SS. RESULTS: A total of 341 subjects\\ncompleted both the postal questionnaire and home visit. A diagnosis\\nof SS could be given to 13 subjects. After adjusting for the presence\\nof possible bias due to non-response, our best estimate of the prevalence\\nof SS in the study population was 33 per 1000 subjects (95% CI 22\\n44). The prevalence of the disorder was higher in females (38; 95%\\nCI 27-52) and for those subjects aged > or = 55 yr (46; 95% CI 34-61).\\nThose subjects diagnosed positively were more impaired for each of\\nthe eight dimensions of the SF-36 than those without a diagnosis,\\nand also suffered from higher levels of depression and fatigue. CONCLUSIONS:\\nSS affects approximately 3-4% of adults and in the general population\\nappears to be associated with a clinically significant impairment\\nof a subject's health and well-being.", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajeer", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silman", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Br J Rheumatol", "id" : "ITEM-21", "issue" : "10", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "1069-1076", "title" : "Sj\ufffdgren's syndrome: a community-based study of prevalence and impact.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-22", "itemData" : { "DOI" : "10.1093/rheumatology/38.2.164", "ISSN" : "14602172", "abstract" : "Objective. The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia., Methods. A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results. Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions. The estimated prevalence of definite SS in Slovenia is 0.60%", "author" : [ { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Logar", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkovic", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-22", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "164-170", "title" : "Prevalence of Sjogren's syndrome in Slovenia", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-23", "itemData" : { "ISSN" : "0315-162X", "PMID" : "12858464", "abstract" : "OBJECTIVE:To assess the prevalence of rheumatic diseases in Greek urban, suburban, and rural adult general populations.METHODS:This cross-sectional population based epidemiological study of rheumatic diseases in Greece (the ESORDIG Study) was conducted on the total adult population of 2 urban, one suburban, and 4 rural communities (8547 subjects), as well as on 2100 out of 5686 randomly selected subjects in one suburban and one rural community. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Either established classification criteria or criteria set for the purposes of the study were used for diagnosis.RESULTS:A total of 8740 subjects participated in the study (response rate 82.1%). The overall age and sex adjusted prevalence (prevalence(asa)) of rheumatic diseases in the total target adult population was 26.9% (95% CI 26.2-27.6), being significantly higher among women (33.7%) than men (19.9%) (p &lt; 0.0005). Disease prevalence(asa) increased significantly with age (p &lt; 0.0005). The most common disease group was low back pain, with a prevalence(asa) of 11.0%, followed by symptomatic peripheral osteoarthritis (7.9%), neck pain (4.8%), miscellaneous rheumatic disorders (4.4%), soft tissue rheumatism disorders (4.3%), and inflammatory rheumatic disease (2.1%). Logistic regression analysis showed a significant positive association of female or male sex, age &gt;or= 50 years, high body mass index, low level of education, moderate or heavy alcohol consumption, and high socioeconomic level with particular diseases or disease groups.CONCLUSION:These findings indicate rheumatic diseases are very common in the general adult population of Greece; 26.9% of adults currently have active or chronic rheumatic disease in remission.", "author" : [ { "dropping-particle" : "", "family" : "Andrianakos", "given" : "Alexandros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trontzas", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christoyannis", "given" : "Fotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dantis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voudouris", "given" : "Costas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgountzos", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaziolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vafiadou", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelidou", "given" : "Kyriaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamitsos", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontelis", "given" : "Leonidas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krachtis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nikolia", "given" : "Zouboulio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaskani", "given" : "Evaggelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavaniotou", "given" : "Elpiniki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antoniades", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karanikolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontoyanni", "given" : "Anastasia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Study", "given" : "ESORDIG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Rheumatology", "id" : "ITEM-23", "issue" : "7", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "1589-1601", "title" : "Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-24", "itemData" : { "DOI" : "10.3109/14397595.2013.843765", "ISSN" : "1439-7609", "PMID" : "24252039", "abstract" : "Abstract Objective. To characterize the epidemiology of Sj\u00f6gren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan. Methods. The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments. Results. The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 \u00b1 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%). Conclusion. The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.", "author" : [ { "dropping-particle" : "", "family" : "Tsuboi", "given" : "Hiroto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asashima", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takai", "given" : "Chinatsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiwara", "given" : "Shinya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiya", "given" : "Chihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosawa", "given" : "Masahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirota", "given" : "Tomoya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawakami", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sano", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsubota", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Yoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takamura", "given" : "Etsuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Ichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inoue", "given" : "Hiroko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Seiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moriyama", "given" : "Masafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Tsutomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yoshiya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirata", "given" : "Shintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mimori", "given" : "Tsuneyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshifuji", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohta", "given" : "Akiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsumoto", "given" : "Isao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sumida", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-24", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "464-70", "title" : "Primary and secondary surveys on epidemiology of Sj\u00f6gren's syndrome in Japan.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-25", "itemData" : { "abstract" : "There has been no previous prevalence study about of Sjogren's syndrome (SS) in Brazil. The aim was to evaluate the SS prevalence in a general population in Vitoria, ES, Brazil. This was an epidemiological, observational, and cross-sectional study conducted on 1,205 randomized people, aged 18-65 years, who lived in Vitoria. The subjects were screened for xerostomia and xerofphthalmia through home interviews. Those with sicca symptoms were asked to report to a hospital for further medical evaluation, unstimulated salivary flow, Schirmer I test, blood analysis and minor labial salivary biopsy. Sicca symptoms were found in 18% (217 subjects) of the sample. Of the 217 subjects with sicca symptoms, 127 (58%) were available for examination. In this sample, 61.7% were female and 46.8% were under medication. Sicca syndrome was confirmed in 12% by at least one examination (salivary flow or Schirmer I). Two patients (0.17%) matched four criteria according to American-European Criteria (95% CI = 0.020-0.5983)", "author" : [ { "dropping-particle" : "", "family" : "Valim", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zandonade", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira", "given" : "a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito", "given" : "O H", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Serrano", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musso", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giovelli", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciconelli", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista Brasileira de Reumatologia", "id" : "ITEM-25", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "24-34", "title" : "Primary Sjogren's syndrome prevalence in a major metropolitan area in Brazil", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-26", "itemData" : { "ISSN" : "0315-162X", "PMID" : "7791159", "abstract" : "OBJECTIVE: To determine the prevalence rate of primary Sj\u00f6gren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sj\u00f6gren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sj\u00f6gren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sj\u00f6gren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "N Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Q P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "G X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "L L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Z X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "X C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-26", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "659-61", "title" : "Prevalence of primary Sj\u00f6gren's syndrome in China.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^2\u201327", "plainTextFormattedCitation" : "2\u201327", "previouslyFormattedCitation" : "^2\u201327" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2–27. More recent studies have shown less heterogeneous figures. The incidence of SjS ranges between 3 and 11 cases per 100,000 persons, while the prevalence ranges between 0.01 and 0.72% (Figure 2). Only one study has evaluated the influence of race/ethnicity on the disease expression: this was in the general population of the Greater Paris areaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.22115", "ISSN" : "2151-4658", "PMID" : "23983119", "abstract" : "Purpose: To describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS) in a multi-racial/ethnic population. Methods: A cross-sectional study, with 5 case-retrieval sources, identified adults with pSS living in the Greater Paris area (population 1,172,482 adults) in 2007. Diagnoses were verified by the American-European Consensus Group (AECG) criteria and study-specific enlarged criteria based on the presence of \u22653/4 AECG items among subjective oral or ocular dryness, anti-SSA/SSB positivity and positive minor salivary-gland biopsy results. Prevalence estimates were standardized to those for the world population and 5-source capture-recapture analysis (CRA) was used. Racial/ethnic differences in pSS features were evaluated. Results: In all, 133 subjects met the AECG criteria and 203 the enlarged criteria. The 2007 prevalence of pSS was 1.02 per 10,000 adults (95% confidence interval 0.85-1.22) for AECG criteria and 1.52 per 10,000 adults (1.30-1.76) for enlarged criteria. CRA indicated completeness of case findings of ~90%. Compared to subjects with European background, those with non-European background had 2.1-2.3 times higher pSS prevalence and were younger (P < 0.0001) and more likely to have polyclonal hypergammaglobulinemia (P < 0.0001) and SSA/SSB-antibodies (P = 0.0005 and < 0.0001 for AECG and enlarged criteria, respectively). Conclusion: The figure of 1.02-1.52 per 10,000 adults we found and estimates from the few other population-based census surveys support that the prevalence of diagnosed pSS is between 1 and 10 per 10,000 (0.01-0.1%) of the general population. Non-European race/ethnicity may be associated with increased pSS risk and a distinct disease profile. \u00a9 2013 American College of Rheumatology.", "author" : [ { "dropping-particle" : "", "family" : "Maldini", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhote", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amoura", "given" : "Zahir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandt", "given" : "Michel", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delassus", "given" : "Jean-Luc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falgarone", "given" : "G\u00e9raldine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guillevin", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lhote", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanoelina", "given" : "Jacky", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacr\u00e9", "given" : "Karim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uzunhan", "given" : "Yurdagul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leroux", "given" : "Jean-Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahr", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Epidemiology of primary Sj\u00f6gren's syndrome in a French Multi-Racial/Ethnic area.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "¹⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19 and found a significant 2-fold higher prevalence among subjects with a non-European background compared with those with a European background.SjS has a very specific epidemiological profile at presentation and this may aid an early diagnosis. The first epidemiological clue is that the disease is diagnosed overwhelmingly in women and, in fact, is the systemic autoimmune disease with the most unbalanced gender ratio; a recent Big Data study collected 13,056 women vs. only 1364 men (a nearly 10:1 female/male ratio)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2015.03.008", "ISBN" : "1568-9972", "ISSN" : "15689972", "PMID" : "25842074", "abstract" : "Systemic autoimmune diseases (SAD) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1,000 patients) of SAD reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SAD. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sj\u00f6gren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodefficiencies and Schonlein-Henoch disease), young people (SLE Beh\u00e7et disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SAD with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a \u201cbig data\u201d approach enabled hitherto unseen connections in SAD to emerge.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "Belchin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3-Almirall", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buss", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilla", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "John H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khamashta", "given" : "Munther a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shoenfeld", "given" : "Yehuda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity Reviews", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "670-679", "title" : "Google-driven search for big data in autoimmune geoepidemiology: Analysis of 394,827 patients with systemic autoimmune diseases", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁸", "plainTextFormattedCitation" : "28", "previouslyFormattedCitation" : "²⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28. The phenotypic expression of SjS in men includes severe ocular involvement and less-pronounced systemic and immunological involvement (Table 2)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajo.2015.06.004", "ISBN" : "0002-9394", "ISSN" : "1879-1891", "PMID" : "26093285", "abstract" : "PURPOSE: To report the ocular complications of primary Sj\u00f6gren's Syndrome (SS) in men.\\n\\nDESIGN: Retrospective cohort study.\\n\\nMETHODS: Setting: Tertiary-care SS center.\\n\\nPATIENT POPULATION: 163 consecutive primary Sj\u00f6gren's Syndrome patients evaluated between January 2007 and March 2013.\\n\\nMAIN OUTCOME MEASURE: Frequency of extraglandular ocular and systemic manifestations and serological results in men compared to women.\\n\\nRESULTS: 14 (9%) of the 163 primary Sj\u00f6gren's Syndrome patients were men. On initial presentation, men were a decade older (61 vs 50 years, p<0.01) and less likely than women to have a prior diagnosis of SS (43% vs 65%, p=0.09). A majority of men reported dry eye on presentation (92%), albeit less chronic compared to women (5.9 vs 10.8 years, p=0.07). Men were more likely to present with serious ocular complications than women (43% vs 11%, p=0.001). Extraglandular systemic complications of SS (i.e. vasculitis, interstitial nephritis) were also more common in men (64% vs 40%, p=0.07). Further, men were more likely to be negative for anti-SSA/Ro, anti-SSB/La, and antinuclear antibodies than women (36% men vs 11% women, p=0.01).\\n\\nCONCLUSION: Men with primary SS have a higher frequency of serious ocular and systemic manifestations. Although primary Sj\u00f6gren's Syndrome is typically considered a disease of middle-aged women, it may be underdiagnosed and consequentially more severe in men. Physicians should have a lower threshold to test for SS in men with dry eye.", "author" : [ { "dropping-particle" : "", "family" : "Mathews", "given" : "Priya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hessen", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grader-Beck", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birnbaum", "given" : "Julius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akpek", "given" : "Esen K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of ophthalmology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Ocular Complications of Primary Sj\u00f6gren's Syndrome in Men.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.54.9.748", "ISSN" : "0003-4967", "PMID" : "7495348", "abstract" : "To describe the clinical expression of primary Sj\u00f6gren's syndrome (SS) in men, focusing on extraglandular manifestations (EGM) and serological markers of disease.", "author" : [ { "dropping-particle" : "", "family" : "Anaya", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "G T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Souza", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "748-51", "title" : "Primary Sj\u00f6gren's syndrome in men.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9175937", "abstract" : "OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sj\u00f6gren's syndrome (SS) patients.\n\nPATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.\n\nRESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.\n\nCONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.", "author" : [ { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsiakou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Politi", "given" : "E N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siamopoulou-Mavridou", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "page" : "333-5", "title" : "Subgroups of primary Sj\u00f6gren's syndrome. Sj\u00f6gren's syndrome in male and paediatric Greek patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0315-162X", "PMID" : "10555894", "abstract" : "To examine the clinical and serologic characteristics of 14 men compared to 28 women with primary Sj\u00f6gren's syndrome (SS) and contrast these findings with studies evaluating sex differences in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Brennan", "given" : "M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-4", "issue" : "11", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "2373-6", "title" : "Sex differences in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0961-2033", "PMID" : "10713648", "abstract" : "To determine the clinical and immunological characteristics of primary Sj\u00f6gren's syndrome (SS) in men from a large series of unselected patients with this condition.", "author" : [ { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morl\u00e0", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mu\u00f1oz", "given" : "F J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Artigues", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lupus", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "61-4", "title" : "Primary Sj\u00f6gren's syndrome in men: clinical and immunological characteristics.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "PMID" : "15229956", "abstract" : "OBJECTIVE: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease. It can be primary (pSS) or secondary (sSS) and is observed 90% more in women than in men, mainly in the fourth and fifth decades of life. We investigated the prevalence of serological and clinical manifestations in male and female patients with primary SS. METHODS: We analyzed 521 female and 28 male patients with pSS between 1993 and 2001. All patients fulfilled > or = 4 of the 1993 European Community Study Group criteria. RESULTS: Men presented higher concentrations of IgA, rheumatoid factor, and antinuclear antibodies than women. A higher percentage of women than men reported fibromyalgia, thyroidal manifestations, and carpal tunnel syndrome. There were no statistical differences between the 2 groups in relation to the presence of Raynaud's phenomenon, arthritis, erosive osteoarthritis, liver disease, or other visceral manifestations. CONCLUSION: The pattern of SS in our cohort of patients reveals a difference between male and female patients, in contrast with earlier studies.", "author" : [ { "dropping-particle" : "", "family" : "Diaz-Lopez", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geli", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corominas", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malat", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Torner", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Llobet", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Serna", "given" : "A R", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laiz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vazquez", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-6", "issue" : "7", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1352-1355", "title" : "Are there clinical or serological differences between male and female patients with primary Sjogren's syndrome?", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "ISSN" : "0300-9742", "abstract" : "OBJECTIVE: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient., METHODS: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study., RESULTS: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04)., CONCLUSION: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.", "author" : [ { "dropping-particle" : "", "family" : "Gondran", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauchais", "given" : "Al", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lambert", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ly", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launay", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Queyrel", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benazahari", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liozon", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loustaud-Ratti", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jauberteau", "given" : "Mo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Py", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "300-305", "title" : "Primary Sjogren's syndrome in men.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "", "ISBN" : "0770-3198", "ISSN" : "1434-9949", "PMID" : "2008546267", "abstract" : "The aim of the study was to define main symptoms of clinical appearance and immunoserological profile of male patients with primary Sjogren's syndrome (pSS). Four hundred and ninety-two patients fulfilling the European-American Consensus Criteria for pSS were involved in this study. The mean age of the patients was 55.93 years (55.67 years in women and 56.18 years in men). The female-male ratio was 7:1 (432 and 60 patients, respectively). At the time of the diagnosis of pSS, glandular, extraglandular manifestations (EGMs), and immunoserological parameters were assessed. The major EGMs differ between genders. Arthritis was frequently presented as EGM in both genders, but the ratio was higher in men (68% vs. 42%). Various vasculitis symptoms and lymphadenopathy were more frequent in men than in women, in contrast to Raynaud's phenomenon or autoimmune thyroiditis. Anti-SS-A and anti-SS-B were the most frequent autoantibodies in both genders, although autoantibodies against anti-nuclear factor and extractable nuclear antigens also presented in some patients. In a few cases, there were other specific autoantibodies correlated with EGMs, such as double-stranded DNA, anti-neutrophilic-cytoplasmic antibody, cyclic-citrullinated peptide, anti-thyreoglobuline antibodies, and anti-thyreoid-peroxidase antibodies. Based upon our large cohort of patients with pSS, we conclude that, although the disease is more frequent in women usually about climax, it develops also in men with the predominant symptoms of vasculitis or arthritis besides keratoconjunctivitis sicca or xerostomy. Clinical Rheumatology 2008.", "author" : [ { "dropping-particle" : "", "family" : "Horvath", "given" : "I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szodoray", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeher", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Rheumatology", "id" : "ITEM-8", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1479-1483", "title" : "Primary Sjogren's syndrome in men: Clinical and immunological characteristic based on a large cohort of Hungarian patients", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1097/MD.0b013e318181e6af", "ISBN" : "0025-7974 (Print)\\r0025-7974 (Linking)", "ISSN" : "0025-7974", "PMID" : "18626304", "abstract" : "We conducted the current study to characterize the clinical presentation of primary Sj\u00f6gren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gil", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pino-Montes", "given" : "Javier", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvo-Alen", "given" : "Jaime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Alonso", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mic\u00f3", "given" : "Maria-Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beltr\u00e1n", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belenguer", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "Lucio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "210-219", "title" : "Primary Sj\u00f6gren syndrome in Spain: clinical and immunologic expression in 1010 patients.", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^29\u201337", "plainTextFormattedCitation" : "29\u201337", "previouslyFormattedCitation" : "^29\u201337" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29–37. The infrequency of SjS in men means other diseases should be searched for (HCV infection, IgG4-RD, sarcoidosis)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0025-7974", "PMID" : "11204499", "abstract" : "Hepatitis C virus (HCV) infection is emerging as an extremely common and insidiously progressive liver disease that is often associated with several extrahepatic manifestations. In 1992, a possible relationship between Sj\u00f6gren syndrome (SS) and patients with HCV infection was first postulated. Subsequently, several studies demonstrated that a \"true\" SS, with similar clinical and histologic features to those observed in primary SS, may occur in some patients with chronic HCV infection. We report the clinical and immunologic characteristics of 35 patients with chronic HCV infection and a well-documented diagnosis of SS. Compared with 60 patients with primary SS who tested negative for HCV antibodies, SS-HCV patients showed a higher mean age (65.9 yr versus 61.5 yr, p = 0.04), a lower prevalence of parotidomegaly (17% versus 47%, p = 0.004), and a higher prevalence of liver involvement (94% versus 3%, p < 0.001). Moreover, those patients with HCV-related SS showed a higher prevalence of anti-parietal cell gastric antibodies (31% versus 13%, p = 0.03), antimitochondrial antibodies (14% versus 2%, p = 0.02), cryoglobulinemia (60% versus 10%, p < 0.001), hypocomplementemia (60% versus 8%, p < 0.001), and a lower prevalence of anti-Ro/SS-A (17% versus 38%, p = 0.03). The \"true\" SS observed in some patients with HCV may be considered 1 of the extrahepatic manifestations of HCV, and we suggest that HCV infection can be considered as an exclusion criterion for the diagnosis of primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trejo", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "la Red", "given" : "G", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00e1nchez-Tapias", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clinical", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "1-8", "title" : "Hepatitis C virus infection mimicking primary Sj\u00f6gren syndrome. A clinical and immunologic description of 35 cases.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.2011.150367", "ISSN" : "1468-2060", "PMID" : "21646415", "author" : [ { "dropping-particle" : "", "family" : "Nocturne", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pavy", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazure", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taoufik", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miceli", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "2234-5", "title" : "IgG4 multiorgan lymphoproliferative syndrome as a differential diagnosis of primary Sjogren's syndrome in men?", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^38,39", "plainTextFormattedCitation" : "38,39", "previouslyFormattedCitation" : "^38,39" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38,39.The second epidemiological clue is that, although SjS occurs at all ages, it is mainly diagnosed between the fourth and sixth decades of life. SjS in children is rare, with only 201 cases under the age of 14 being reported since 1994 (Table 3)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9175937", "abstract" : "OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sj\u00f6gren's syndrome (SS) patients.\n\nPATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.\n\nRESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.\n\nCONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.", "author" : [ { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsiakou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Politi", "given" : "E N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siamopoulou-Mavridou", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "page" : "333-5", "title" : "Subgroups of primary Sj\u00f6gren's syndrome. Sj\u00f6gren's syndrome in male and paediatric Greek patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0008-4182", "PMID" : "7859177", "author" : [ { "dropping-particle" : "", "family" : "Rocha", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kavalec", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian journal of ophthalmology. Journal canadien d'ophtalmologie", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1994", "10" ] ] }, "page" : "234-7", "title" : "Sj\u00f6gren's syndrome in a child.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0315-162X VN - ", "abstract" : "To describe the clinical characteristics of juvenile Sj&#xF6;gren's syndrome (JSS) and report 5 new primary cases.", "author" : [ { "dropping-particle" : "", "family" : "Anaya", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "1152-1158", "title" : "Sj\u00f6gren's syndrome in childhood.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0022-3476", "PMID" : "8523198", "abstract" : "A 9-year-old girl had hemiparesis, and a diagnosis of primary Sj\u00f6gren syndrome was made. The neurologic dysfunction was multifocal, involving both the brain and spinal cord, and was recurrent; the findings mimicked multiple sclerosis. Corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial.", "author" : [ { "dropping-particle" : "", "family" : "Ohtsuka", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasegawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tatsuno", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takita", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arita", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okuyama", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of pediatrics", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "1995", "12" ] ] }, "page" : "961-3", "title" : "Central nervous system disease in a child with primary Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0960-7439", "PMID" : "9601239", "abstract" : "A 5-year-old boy of Pakistani parents first presented with rampant dental caries and later developed bilateral parotid gland enlargement accompanied by intermittent nocturnal fever, anorexia, lethargy and weight loss. Investigations revealed anaemia, hypergammaglobulinaemia, elevated non-specific indices of inflammation, a reduced Schirmer's test value, lymphocytic infiltration and some atrophy of the parotid gland. The parotid gland enlargement, low Schirmer's test value and salivary gland biopsy showing non-focal lymphocytic infiltration led to the diagnosis of primary Sjogren's syndrome. The present case report highlights the need for health professionals to be aware that Sjogren's syndrome is a possible, if rare, predisposing cause of rampant dental caries in children.", "author" : [ { "dropping-particle" : "", "family" : "Nathavitharana", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarlow", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bedi", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Southwood", "given" : "T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children", "id" : "ITEM-5", "issue" : "3", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "173-176", "title" : "Primary Sjogren's syndrome and rampant dental caries in a 5-year-old child.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "ISSN" : "0007-0963", "PMID" : "8555033", "abstract" : "We report four children with anti-Ro/SSA positive who presented with an annular erythema as a manifestation of Sj\u00f6gren's syndrome. One patient had an aseptic meningoencephalitis as well as cutaneous lesions. Children with annular erythema should be carefully followed for features of Sj\u00f6gren's syndrome, which is believed to be a rare condition in children.", "author" : [ { "dropping-particle" : "", "family" : "Miyagawa", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iida", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukumoto", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsunaga", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshioka", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shirai", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British journal of dermatology", "id" : "ITEM-6", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "page" : "779-82", "title" : "Anti-Ro/SSA-associated annular erythema in childhood.", "type" : "article-journal", "volume" : "133" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "ISSN" : "0392-856X", "abstract" : "OBJECTIVE: Ten new cases with primary Sjogren's syndrome (pSS) whose disease began before age 16 are described. Special attention is paid both to the follow-up and treatment of this condition., METHODS: Cases with juvenile pSS were retrospectively identified from our series of 180 pSS patients. Ocular, salivary, and extraglandular manifestations as well as a full laboratory evaluation including HLA-DR typing were retrieved., RESULTS: A disease prevalence of 5.5% (10 cases, 8 female and 2 male) was found in our series. The mean age at onset was 11.0 years, but the disease started at the age of 4 in 2 patients. At onset, parotid swelling was found in 6 cases and extraglandular manifestations in 3. Throughout the follow-up period (mean 48.6 months from the time of diagnosis), the clinical picture was similar to that of pSS in adults, but oral involvement was generally milder. Extraglandular manifestations were always present but never severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB antibodies) were found in all patients. Specifically, ANA and anti-SSA were always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and DR 52 were closely associated with the disease. Clinical outcome was difficult to predict; however, no serious complications have been observed so far. We obtained good results with low-dose steroids and/or hydroxychloroquine, especially with regard to the extraglandular manifestations and laboratory abnormalities., CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely resembles pSS in adults except for the extremely high prevalence of recurrent parotitis and immunological findings.", "author" : [ { "dropping-particle" : "", "family" : "Ostuni", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ianniello", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sfriso", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzola", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andretta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gambari", "given" : "P F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-7", "issue" : "6", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "689-693", "title" : "Juvenile onset of primary Sjogren's syndrome: report of 10 cases.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "ISBN" : "0374-5600 (Print)\\r0374-5600 (Linking)", "ISSN" : "0374-5600", "PMID" : "8942017", "abstract" : "A case of Sj\u00f6gren's syndrome with glomerulonephritis is presented. The patient was a 13 year old male with hematuria and proteinuria discovered by urine screening of school children. Evaluation showed no evidence of any associated connective tissue disease. Kidney biopsy was consistent with membranous glomerulonephritis. Sj\u00f6gren's syndrome with membranous glomerulonephritis is rare and the patient was the youngest case in the literature.", "author" : [ { "dropping-particle" : "", "family" : "Yoshida", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kume", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isome", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta paediatrica Japonica; Overseas edition", "id" : "ITEM-8", "issue" : "5", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "533-6", "title" : "Sj\u00f6gren's syndrome with membranous glomerulonephritis detected by urine screening of schoolchildren.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "ISSN" : "0340-6199", "PMID" : "8891560", "abstract" : "Sj\u00f6gren syndrome (SS) is a common disorder in adults and involves both glandular and extraglandular systems. We report here four cases of childhood SS complicated by chronic thyroiditis, interstitial nephritis or sweat gland inflammation. Additionally, in one of these cases, the central nervous system was involved. All of these complications are common in adult cases. CONCLUSION: Childhood SS is a systemic \"ductilitis\" or \"exocrinopathy\" with complications which are commonly observed in adult cases.", "author" : [ { "dropping-particle" : "", "family" : "Kobayashi", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furuta", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tame", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawamura", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kojima", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Endoh", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okano", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakiyama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pediatrics", "id" : "ITEM-9", "issue" : "10", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "890-4", "title" : "Complications of childhood Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "ISBN" : "0374-5600 (Print)", "abstract" : "An 8-year-old girl with hypergammaglobulinemia showed an abnormal 67gallium accumulation in the orbits and parotid glands. Although she did not have any subjective siccant complaints, reported typical histopathological and sialographic changes suggesting Sjogren's syndrome (SjS) were observed in the salivary glands. Gallium scintigram might be a valuable and non-invasive diagnostic tool in the diagnosis of children with SjS without sicca symptoms.", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onodera", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ito", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higuchi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monma", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waga", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Paediatr Jpn", "id" : "ITEM-10", "issue" : "6", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "621-623", "title" : "Subclinical Sjogren's syndrome: a significant 67gallium accumulation in the orbits and parotid glands", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "ISSN" : "0392-856X", "PMID" : "10410277", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (pSS) in childhood is a rare disease. Diagnostic criteria are available for adult patients only. In order to establish diagnostic criteria for juvenile pSS an analysis of 7 girls and one boy suffering from pSS with early onset is reported. Due to the rarity of the disease, data on patients with pSS reported in the literature are included in the proposal for modified diagnostic criteria.\n\nMETHODS: The diagnosis of pSS was established according to the criteria for adulthood pSS, duly modified, which include clinical symptoms and laboratory immunological evaluation.\n\nRESULTS: The average age of our patients at clinical onset was 13.5 years (range: 10-17 yrs.). Clinical signs included systemic (fever, fatigue) as well as local (parotitis, vulvovaginitis, conjunctivitis) symptoms. Paralysis due to hypokalemia linked to renal tubular acidosis and central nervous system (CNS) involvement was seen in one patient. Asymptomatic renal tubular acidosis was diagnosed in another 2 patients. Autoimmune hepatitis was present in 2 patients. All patients had laboratory abnormalities: hyperimmunoglobulinemia IgG, high titers of antinuclear antibodies (anti-SS-A and/or anti-SS-B) and elevated serum amylases. Sicca syndrome was never seen during childhood, although it developed later in 3 patients, after 7 to 10 years of follow-up.\n\nCONCLUSIONS: It has been stressed that the classical diagnostic criteria for adult Sj\u00f6gren's syndrome, especially sicca syndrome, are not applicable to a pediatric onset of the disease. On the other hand, the presence of typical laboratory abnormalities can allow the diagnosis of these patients in the early stages. Both laboratory and clinical symptoms typical for childhood are included in our proposal for diagnostic criteria applicable to juvenile pSS. Life-threatening conditions such as hypokalemic paralysis, CNS involvement and hepatitis may also occur in children. Sicca syndrome tends to develop much later in pediatric patients.", "author" : [ { "dropping-particle" : "", "family" : "Bart\u016fnkov\u00e1", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediv\u00e1", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vencovsk\u00fd", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tesar", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-11", "issue" : "3", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "381-6", "title" : "Primary Sj\u00f6gren's syndrome in children and adolescents: proposal for diagnostic criteria.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "ISSN" : "1079-2104", "PMID" : "10556760", "abstract" : "OBJECTIVE: The application of anamnestic data on siccative symptoms required for classifying adult Sj\u00f6gren's syndrome is limited in childhood. Instrumental test procedures are therefore necessary for objectively recording the oral and ophthalmologic manifestations of the disease. The aim of this study was to clarify the sialographic changes that occur in Sj\u00f6gren's syndrome in children.\n\nSTUDY DESIGN: A total of 23 sialograms were obtained with both conventional and digital subtraction techniques in 21 children with primary (10 girls and 1 boy) or secondary Sj\u00f6gren's syndrome (10 girls). The films were assessed by 3 physicians and submitted for a consensus analysis if necessary.\n\nRESULTS: The pathologic features observed in the children varied from a slightly narrowed ductal system to multiple peripheral ductal ectasias and completely destroyed parenchyma. Sialographic examinations demonstrate that, with progressing disease, regression of acinar dilatations and rarification of the ductal system occur.\n\nCONCLUSION: The results show that the spectrum of sialographically recordable lesions in Sj\u00f6gren's syndrome in children is greater than is described thus far in the literature.", "author" : [ { "dropping-particle" : "", "family" : "Stiller", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golder", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6ring", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kliem", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics", "id" : "ITEM-12", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "11" ] ] }, "page" : "620-7", "title" : "Diagnostic value of sialography with both the conventional and digital subtraction techniques in children with primary and secondary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-13", "itemData" : { "ISSN" : "0340-6199", "PMID" : "10968247", "abstract" : "Complications observed in adulthood Sj\u00f6gren syndrome also occur in the childhood disease and suggest that Sj\u00f6gren syndrome should be considered as a cause of neuropathy in children. Treatment with corticosteroid is a choice for such cases.", "author" : [ { "dropping-particle" : "", "family" : "Kumon", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satake", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mizumoto", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishikawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pediatrics", "id" : "ITEM-13", "issue" : "8", "issued" : { "date-parts" : [ [ "2000", "8" ] ] }, "page" : "630-1", "title" : "A case of sensory neuropathy associated with childhood Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "159" }, "uris" : [ "" ] }, { "id" : "ITEM-14", "itemData" : { "DOI" : "10.1177/088307380101600911", "ISSN" : "0883-0738", "abstract" : "We describe a case of pediatric Sjogren's syndrome with progressive neurologic involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal syndrome. After being stable with facial diplegia and swelling for 5 years, she acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic findings confirmed primary Sjogren's syndrome. She responded well to intravenous methylprednisolone, with subsequent clinical improvement and MRI resolution. This report reviews the pediatric literature and underscores the importance of considering Sjogren's syndrome in a child with unexplained facial weakness and in the differential diagnosis of pediatric stroke.", "author" : [ { "dropping-particle" : "", "family" : "Gottfried", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Hunter", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentieri", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "R S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of child neurology", "id" : "ITEM-14", "issue" : "9", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "683-685", "title" : "Central nervous system Sjogren's syndrome in a child: case report and review of the literature.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-15", "itemData" : { "DOI" : "10.1016/S1079-2104(03)00159-8", "ISSN" : "10792104", "PMID" : "12847443", "abstract" : "Sj??gren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition. The purpose of this study is to report a case of primary SS (PSS) in a 4-year-old Venezuelan girl and to review the pertinent literature. The patient presented with bilateral recurrent parotid enlargement, predominantly on the right side. She did not complain of dry mouth or eyes; however, decreased stimulated salivary flow rate and positive Schirmer and rose bengal tests were obtained. Sialography, sonograms, and a computed tomography scan of the parotid glands revealed pathologic changes consistent with SS. Anti-SS-A and anti-SS-B antibodies were present. Evaluation for antibodies against cytomegalovirus, Epstein-Barr virus, and HIV rendered negative results. Histopathologic examination of incisional biopsies of the right parotid and labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. Taken together, these findings are consistent with the diagnosis of juvenile PSS. The salient features of this rare disease are summarized on the basis of a comprehensive review of the epidemiologic, clinical, and serologic findings of the previously reported cases of PSS in children.", "author" : [ { "dropping-particle" : "", "family" : "Nikitakis", "given" : "Nikolaos G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lariccia", "given" : "Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papadimitriou", "given" : "John C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sauk", "given" : "John J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics", "id" : "ITEM-15", "issue" : "1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "42-47", "title" : "Primary Sjogren syndrome in childhood: Report of a case and review of the literature", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-16", "itemData" : { "ISBN" : "0315-162X (Print)\\n0315-162X (Linking)", "PMID" : "11327263", "abstract" : "OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific for adult Sjogren's syndrome (SS) in patients with juvenile onset SS. METHODS: Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11 cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha-fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis. In contrast, reactivity was found in only 2 of the 16 patients with SLE. The clinical features of the 15 patients with juvenile onset SS were very specific; only 4 patients complained of dryness, while 6 had abnormal excretion ability. Salivary gland enlargement was the most common clinical manifestation. Characteristic laboratory findings in juvenile onset SS included a higher prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid factor, as well as increased erythrocyte sedimentation rate and hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be the same as that of adult SS, although subjective symptoms of dryness are less frequent in juvenile cases. This discrepancy may indicate that SS is a slowly progressive disease with a long time span. The anti-alpha-fodrin antibody is likely to be a reliable diagnostic marker for juvenile SS.", "author" : [ { "dropping-particle" : "", "family" : "Maeno", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imanaka", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayashi", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyata", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-16", "issue" : "4", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "860-864", "title" : "Anti-alpha-fodrin antibodies in Sjogren's syndrome in children", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] }, { "id" : "ITEM-17", "itemData" : { "ISSN" : "0886-4470", "PMID" : "12431170", "abstract" : "OBJECTIVES: To describe our experience with primary and secondary Sj\u00f6gren syndrome (SS) in the pediatric population and to evaluate the effectiveness of parotid gland biopsy in the diagnosis of pediatric SS.\n\nDESIGN: Case series review of 6 pediatric patients evaluated during a 4-year period with varied head and neck manifestations of SS.\n\nSETTING: Tertiary care children's hospital.\n\nPATIENTS: Six children (4 boys and 2 girls) ranging in age from 6 to 12 years, who were diagnosed as having primary or secondary SS.\n\nINTERVENTION: Six minor salivary gland and 4 parotid gland biopsies for pathologic examination.\n\nMAIN OUTCOME MEASURES: Pathologic examination of salivary tissue consistent with SS.\n\nRESULTS: All 6 patients underwent minor salivary gland biopsy, 2 (33%) were consistent with SS, while the remaining 4 (67%) were nondiagnostic. The 4 patients with nondiagnostic minor salivary gland biopsy results went on to have parotid biopsies, of which all 4 had histologic findings consistent with SS. No complications were encountered.\n\nCONCLUSION: Parotid gland biopsy is an effective and safe means of obtaining salivary gland tissue for histologic evaluation of SS in the pediatric population.", "author" : [ { "dropping-particle" : "", "family" : "McGuirt", "given" : "William F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whang", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreland", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-17", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "11" ] ] }, "page" : "1279-81", "title" : "The role of parotid biopsy in the diagnosis of pediatric Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] }, { "id" : "ITEM-18", "itemData" : { "DOI" : "10.1007/s00431-003-1277-9", "ISSN" : "1432-1076", "PMID" : "12898241", "abstract" : "Primary Sj\u00f6gren syndrome (SS) is very rare in childhood. We collected a series of primary paediatric SS cases from different centres. A data collection form was prepared and sent to rheumatologists who were willing to participate. Data on 40 cases of primary SS with onset before the 16th birthday were collected. Almost all patients (35/40) were females, age at onset varied from 9.3 to 12.4 years (mean 10.7 years). Signs and symptoms at disease onset were mainly recurrent parotid swelling followed by sicca symptoms. Abnormal laboratory tests were found in the majority of cases. Regarding treatment, 22 patients were treated at some time with oral corticosteroids, seven with non-steroidal anti-inflammatory drugs, and five with hydroxychloroquine; two patients needed cyclosporine and one cyclophosphamide. Follow-up varied from 0 to 7.5 years from onset, without major complications in the majority of patients. CONCLUSION: recurrent parotid swelling is a common feature of primary Sj\u00f6gren syndrome in childhood and often occurs as a presenting feature. Sicca symptoms may be rarer.", "author" : [ { "dropping-particle" : "", "family" : "Cimaz", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadei", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartunkova", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediva", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falcini", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picco", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taglietti", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zulian", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cate", "given" : "R", "non-dropping-particle" : "Ten", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sztajnbok", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voulgari", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Pediatrics", "id" : "ITEM-18", "issue" : "10", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "661-665", "title" : "Primary Sj\u00f6gren syndrome in the paediatric age: a multicentre survey", "type" : "article-journal", "volume" : "162" }, "uris" : [ "" ] }, { "id" : "ITEM-19", "itemData" : { "ISBN" : "1110-4902 (Print)", "PMID" : "15724389", "abstract" : "Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P < 0.05). There was no statistically significant difference of levels of ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine screening of alpha fodrin antibodies is a valuable tool for the diagnosis of SS.", "author" : [ { "dropping-particle" : "", "family" : "Lawind", "given" : "M F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alyasky", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elwan", "given" : "N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mourad", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Bendary", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Egypt J Immunol", "id" : "ITEM-19", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "75-81", "title" : "Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-20", "itemData" : { "DOI" : "0315162X-32-1603 [pii]", "ISBN" : "0315-162X", "PMID" : "16078341", "abstract" : "Primary Sjogren's syndrome (pSS) is uncommonly recognized in childhood, and familial cases are rare. Pulmonary involvement in pediatric pSS is infrequently reported. In adults, asymptomatic pulmonary involvement is increasingly recognized, manifest by pulmonary function test abnormalities and changes on high resolution computerized tomographic scan. We describe a case of pSS in a 14-year-old Vietnamese-Canadian girt who presented with pulmonary symptoms, radiologic changes, and biopsy confirmation of lymphocytic interstitial pneumonia. Her dizygotic twin sister has primary SS without extraglandular manifestations. To our knowledge this is the first report of pediatric pSS with lymphocytic interstitial pneumonia and multiple pulmonary nodules on chest radiograph, We review the literature on pulmonary involvement and familial cases of pSS in childhood", "author" : [ { "dropping-particle" : "", "family" : "Houghton", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabral", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petty", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "L B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Rheumatology", "id" : "ITEM-20", "issue" : "8", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1603-1606", "title" : "Primary Sjogren's syndrome in dizygotic adolescent twins: One case with lymphocytic interstitial pneumonia", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-21", "itemData" : { "DOI" : "0315162X-32-2225 [pii]", "ISBN" : "0315-162X (Print)\\r0315-162X (Linking)", "PMID" : "16265707", "abstract" : "OBJECTIVE: To compare the proposed criteria for the diagnosis of primary Sjogren's syndrome (pSS) in childhood to the validated American-European Consensus Group (AECG) classification criteria for pSS in adults. METHODS: Charts of 7 children with pSS seen at British Columbia's Children's Hospital (BCCH) and data on 128 children identified through Medline in the English language literature between 1963 and 2003 were reviewed for pediatric and AECG criteria for pSS. The presence of > or = 4 criteria was required to satisfy the respective classification criteria. The expert clinical opinion of pediatric rheumatologists was considered the gold standard for diagnosis. RESULTS: A total of 24/62 (39%) cases satisfied the AECG criteria; 47/62 (76%) satisfied the proposed pediatric criteria. Inclusion of recurrent parotitis increased the sensitivity of the pediatric clinical criteria. From the cases, 78/133 (59%) satisfied the pediatric oral symptom criteria; only 6/78 (8%) had xerostomia in the absence of recurrent parotitis. There was no reported case of recurrent conjunctivitis in the absence of keratoconjunctivitis sicca. We found 101/130 (78%) cases had at least one positive autoantibody test result [antinuclear antibodies (ANA), rheumatoid factor (RF), SSA, SSB]; 78/123 (63%) had autoantibodies to SSA or SSB. CONCLUSION: The AECG adult criteria for pSS should not be applied to children as the sensitivity is unacceptably low. The inclusion of recurrent parotitis increases the sensitivity of the pediatric criteria, and recurrent parotitis should alert the clinician to the possibility of pSS. The inclusion of recurrent conjunctivitis did not improve the sensitivity over the AECG ocular criteria. The addition of ANA and RF to the AECG criteria did not change the number of patients satisfying the criteria for pediatric pSS.", "author" : [ { "dropping-particle" : "", "family" : "Houghton", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malleson", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabral", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petty", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-21", "issue" : "11", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2225-2232", "title" : "Primary Sjogren's syndrome in children and adolescents: are proposed diagnostic criteria applicable?", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-22", "itemData" : { "DOI" : "10.1093/rheumatology/kei175", "ISSN" : "1462-0324", "PMID" : "16352643", "author" : [ { "dropping-particle" : "", "family" : "Ohlsson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strike", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James-Ellison", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tizard", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Ramanan", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-22", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "2" ] ] }, "page" : "238-40", "title" : "Renal tubular acidosis, arthritis and autoantibodies: primary Sj\u00f6gren's syndrome in childhood.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-23", "itemData" : { "DOI" : "10.1007/s10067-005-0042-z", "ISSN" : "0770-3198", "PMID" : "16391885", "abstract" : "Tumor necrosis factor alpha (TNFalpha) blockade has recently been found to be ineffective in treating glandular and extraglandular manifestations of adult Sj\u00f6gren syndrome (SS), including arthralgia and arthritis. We report a girl who developed purpura, polyarthritis, uveitis, and severe dental caries in the first year of life and optic neuritis by age three. SS was diagnosed at 11 years of age, when severe hypokalemic renal tubular acidosis developed during infliximab treatment for arthritis. In contrast to her other disease manifestations, the arthritis responded remarkably well to TNFalpha blockade, suggesting that TNFalpha blockers may have a role in the treatment of arthritis with pediatric SS.", "author" : [ { "dropping-particle" : "", "family" : "Pessler", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monash", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rettig", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forbes", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreiger", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cron", "given" : "R Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical rheumatology", "id" : "ITEM-23", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "9" ] ] }, "page" : "746-8", "title" : "Sj\u00f6gren syndrome in a child: favorable response of the arthritis to TNFalpha blockade.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-24", "itemData" : { "abstract" : "Primary Sjogren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjogren syndrome antigen A, and anti-Sjogren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of PSS", "author" : [ { "dropping-particle" : "", "family" : "Civilibal", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canpolat", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yurt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurugoglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdamar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagci", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sever", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasapcopur", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caliskan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arisoy", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Pediatrics", "id" : "ITEM-24", "issue" : "8", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "738-742", "title" : "A child with primary Sjogren syndrome and a review of the literature", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-25", "itemData" : { "DOI" : "10.1007/s10165-010-0313-7", "ISBN" : "1439-7609 (Electronic)\\r1439-7595 (Linking)", "ISSN" : "1439-7609", "PMID" : "20517630", "abstract" : "The number of patients with juvenile-onset Sj\u00f6gren's syndrome (SS) has recently increased. However, there is no drug that is safe and effective for the xerostomia that occurs in patients of this age group. We evaluated the efficacy and safety of orally administered pilocarpine hydrochloride for juvenile-onset SS patients. Five female patients, aged from 9 to 16 years, received 5-10 mg/day for 4 weeks. On days 1 and 28, salivary production was measured by the Saxon test, and patients completed subjective self-evaluations of xerostomia symptoms and were asked about changes in water intake and overall improvement of dry mouth on day 28. After 4 weeks of pilocarpine administration, salivary production increased significantly in all patients, and overall status was assessed as \"improved\" in all patients. One patient had excessive sweating. No serious adverse events or laboratory examination abnormalities correlated with pilocarpine administration were found. In conclusion, the results of this study suggest that orally administered pilocarpine is safe and effective for treating xerostomia in juvenile-onset SS patients. This is the first report of the efficacy of pilocarpine for juvenile SS patients; further evaluations are needed to confirm our result.", "author" : [ { "dropping-particle" : "", "family" : "Tomiita", "given" : "Minako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "Syuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuwada", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nonaka", "given" : "Yukiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Kimiyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimojo", "given" : "Naoki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Yoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-25", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "486-90", "title" : "Efficacy and safety of orally administered pilocarpine hydrochloride for patients with juvenile-onset Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-26", "itemData" : { "DOI" : "10.1007/s00467-009-1358-8", "ISSN" : "1432-198X", "PMID" : "19902265", "author" : [ { "dropping-particle" : "", "family" : "Jung", "given" : "Seong Kwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyu Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yim", "given" : "Hyung Eun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoo", "given" : "Kee Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Young Sook", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joo Won", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Won", "given" : "Nam Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric nephrology (Berlin, Germany)", "id" : "ITEM-26", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "567-8", "title" : "Primary Sj\u00f6gren's syndrome with mesangial proliferative glomerulonephritis and IgA deposits in a child.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-27", "itemData" : { "ISSN" : "1980-5322", "PMID" : "22086534", "author" : [ { "dropping-particle" : "", "family" : "Longhi", "given" : "Barbara S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Appenzeller", "given" : "Simone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centeville", "given" : "Maraisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gusm\u00e3o", "given" : "Reinaldo J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marini", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinics (S\u00e3o Paulo, Brazil)", "id" : "ITEM-27", "issue" : "11", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "1991-3", "title" : "Primary Sj\u00f6gren's syndrome in children: is a family approach indicated?", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-28", "itemData" : { "ISSN" : "0392-856X", "PMID" : "24847722", "abstract" : "Primary Sj\u00f6gren's syndrome (pSS) is a systemic autoimmune disease uncommon in children, clinically characterized by recurrent parotitis at the onset, which is a common disorder in childhood, most of them of infectious origin. Juvenile pSS diagnosis is based on clinical symptoms and presence of autoantibodies, after exclusion of infectious or lymphoproliferative diseases. However, salivary gland ultrasound (SGU) shows typical features of pSS that can add useful information for the diagnosis of this disorder. We describe three patients who presented with recurrent parotitis in which characteristic autoantibodies and typical SGU pattern allow us to make the diagnosis of juvenile pSS. We suggest that in children with recurrent parotitis SGU and autoantibodies should be routinely performed.", "author" : [ { "dropping-particle" : "", "family" : "Nieto-Gonz\u00e1lez", "given" : "Juan Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monteagudo", "given" : "Indalecio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bello", "given" : "Natalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Estupi\u00f1an", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naredo", "given" : "Esperanza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carre\u00f1o", "given" : "Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-28", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Salivary gland ultrasound in children: a useful tool in the diagnosis of juvenile Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-29", "itemData" : { "DOI" : "10.3899/jrheum.131511", "ISSN" : "0315-162X", "PMID" : "24786923", "abstract" : "OBJECTIVE: To determine an appropriate focus score cutoff for childhood Sj\u00f6gren syndrome (SS).\\n\\nMETHODS: Labial salivary gland tissue from specimens from children with SS and age-matched controls was retrospectively identified and reviewed by a blinded oral pathologist.\\n\\nRESULTS: The presence of any focal sialadenitis (focus score > 0 foci/4 mm(2)) was common among childhood SS samples but present in only 1 of 8 control samples.\\n\\nCONCLUSION: The presence of any focal lymphocytic sialadenitis in minor labial salivary gland tissue is suggestive of childhood SS and should be included in future childhood SS-specific diagnostic or classification criteria.", "author" : [ { "dropping-particle" : "", "family" : "Yokogawa", "given" : "Naoto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieberman", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alawi", "given" : "Faizan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bout-Tabaku", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guttenberg", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherry", "given" : "David D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vivino", "given" : "Frederick B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-29", "issue" : "6", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1178-82", "title" : "Comparison of labial minor salivary gland biopsies from childhood Sj\u00f6gren syndrome and age-matched controls.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{31,40\u201367}", "plainTextFormattedCitation" : "31,40\u201367", "previouslyFormattedCitation" : "^{31,40\u201367}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,40–67; the female gender gap in children is less evident (F:M ratio 5:1), the predominant feature at presentation is parotid enlargement (not sicca symptoms) and anti-Ro/SS-A (and not ANA) is the most-frequently reported autoantibody, although salivary gland biopsy is as useful in children as in adultsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1942-5473", "PMID" : "23211922", "abstract" : "Juvenile Sj\u00f6gren's syndrome is a rare condition that affects children and adolescents with distinctive clinical features. Parotid swelling usually precedes regular oral and ocular symptoms, while typical serological findings may be absent. Hence, diagnosing juvenile Sj\u00f6gren's syndrome may be challenging to the attending pediatric dentist, and long-term management without proper diagnosis may be jeopardized. The purpose of this report was to detail the features of an adolescent with primary Sj\u00f6gren's syndrome diagnosed 12 years after the onset of the disease. An updated literature review highlighted the unusual aspects of the pediatric form of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Souza", "given" : "Thayse Rodrigues", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "Igor Henrique Morais", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carvalho", "given" : "Alessandra Tavares", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gomes", "given" : "Valder Barbosa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duarte", "given" : "Angela Pinto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Le\u00e3o", "given" : "Jair Carneiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gueiros", "given" : "Luiz Alcino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric dentistry", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "427-30", "title" : "Juvenile sj\u00f6gren syndrome: distinctive age, unique findings.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁸", "plainTextFormattedCitation" : "68", "previouslyFormattedCitation" : "⁶⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }68. In contrast, parotid involvement and anti-Ro/SS-A antibodies have been reported less frequently in patients aged > 70 years, who also have a higher frequency of pulmonary involvementADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MD.0b013e318181e6af", "ISBN" : "0025-7974 (Print)\\r0025-7974 (Linking)", "ISSN" : "0025-7974", "PMID" : "18626304", "abstract" : "We conducted the current study to characterize the clinical presentation of primary Sj\u00f6gren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gil", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pino-Montes", "given" : "Javier", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvo-Alen", "given" : "Jaime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Alonso", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mic\u00f3", "given" : "Maria-Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beltr\u00e1n", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belenguer", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "Lucio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "210-219", "title" : "Primary Sj\u00f6gren syndrome in Spain: clinical and immunologic expression in 1010 patients.", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37.An overlap between systemic autoimmune diseases is frequent in daily practice (Table 4); in patients with SjS, the most-frequently diagnosed additional diseases are systemic lupus erythematosus (14-18%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.090804", "ISBN" : "0315-162X", "ISSN" : "0315-162X", "PMID" : "20360189", "abstract" : "The subset of patients with SLE and SS has a distinct clinical and laboratory phenotype, with a higher frequency of older white women with photosensitivity, oral ulcers, Raynaud's phenomenon, anti-Ro antibodies, and anti-La antibodies and a lower frequency of renal disease, anti-dsDNA antibodies, and anti-RNP antibodies.", "author" : [ { "dropping-particle" : "", "family" : "Baer", "given" : "A N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maynard", "given" : "J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaikh", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magder", "given" : "L S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petri", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1143-1149", "title" : "Secondary Sjogren's syndrome in systemic lupus erythematosus defines a distinct disease subset", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/RHU.0b013e31823ecbdf", "ISSN" : "1536-7355", "PMID" : "22157271", "abstract" : "This study aimed to compare the difference of the clinical and laboratory features of the patients between the combined systemic lupus erythematosus (SLE) and Sj\u00f6gren syndrome (SLE-SS) and SLE only.", "author" : [ { "dropping-particle" : "", "family" : "Yao", "given" : "Qingping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altman", "given" : "Roy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xiaofeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "28-32", "title" : "Systemic lupus erythematosus with Sj\u00f6gren syndrome compared to systemic lupus erythematosus alone: a meta-analysis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^69,70", "plainTextFormattedCitation" : "69,70", "previouslyFormattedCitation" : "^69,70" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }69,70, rheumatoid arthritis (7-17%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1462-0324", "PMID" : "10888704", "abstract" : "OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives.\n\nMETHODS: The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease-modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work.\n\nRESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0).\n\nCONCLUSIONS: Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.", "author" : [ { "dropping-particle" : "", "family" : "Young", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dixey", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emery", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallivan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gough", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prouse", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winfield", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2000", "6" ] ] }, "page" : "603-11", "title" : "How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0003-4967 (Print) 0003-4967 (Linking)", "ISSN" : "0003-4967", "PMID" : "12922967", "abstract" : "OBJECTIVES: To characterise RA in a sample of Spanish patients by estimating mean clinical activity, functional ability, and radiological damage, and current and cumulative prevalence of extra-articular manifestations. METHODS: Cross sectional analysis of a cohort of patients with RA randomly selected from the clinical databases of 34 centres. Standard definitions and measurements were used, and radiographs read centrally. Estimates and confidence intervals were adjusted to sampling. RESULTS: Data were available for 788 patients. Extra-articular RA was present in 285 (36.2%) patients. Cumulative prevalence and 95% confidence intervals of extra-articular manifestations were estimated: nodules 24.5% (21.5 to 27.5), Sj\u00f6gren's syndrome 17.0% (14.4 to 19.6), atlantoaxial subluxation 12.1% (9.8 to 14.4), carpal tunnel syndrome 10.7% (7.8 to 13.6), interstitial lung disease 3.7% (2.4 to 5.0), serositis 2.5% (1.4 to 3.5), eye disease 2.5% (1. to 3.9), vasculitis 1.3% (0.5 to 2.1), amyloidosis 0.6% (0.1 to 1.2), and Felty's syndrome 0.3% (<0.6). Mean (SD) activity/progression indexes were: DAS28-3 3.4 (1.2), HAQ 1.6 (0.4), Larsen score 54.7 (26.4). Less than 5% of the patients were in remission. 205 (72%) patients were receiving disease modifying antirheumatic drugs (DMARDs). CONCLUSION: Spanish patients with RA ever seen by a rheumatologist have, on average, a moderate degree of activity, despite widespread use of DMARDs. Measures of the degree of progression do not show a benign disease. The proportion of extra-articular manifestations in Spanish patients with RA is similar to that found in other Mediterranean populations, and lower than that reported in Anglo Saxon countries.", "author" : [ { "dropping-particle" : "", "family" : "Carmona", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Alvaro", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balsa", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angel Belmonte", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tena", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanmart\u00ed", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "897-900", "title" : "Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^71,72", "plainTextFormattedCitation" : "71,72", "previouslyFormattedCitation" : "^71,72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71,72 and systemic sclerosis (12%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.090815", "ISBN" : "0315-162X (Print) 0315-162X (Linking)", "ISSN" : "0315-162X", "PMID" : "20110522", "abstract" : "To assess the prevalence and potential associations with the systemic sclerosis (SSc) phenotype of additional autoimmune diseases (AID).", "author" : [ { "dropping-particle" : "", "family" : "Avouac", "given" : "J\u00e9r\u00f4me", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Air\u00f2", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dieude", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caramaschi", "given" : "Paola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiev", "given" : "Kiet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diot", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappelli", "given" : "Susanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Granel", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vacca", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wipff", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahan", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matucci-Cerinic", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allanore", "given" : "Yannick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "608-14", "title" : "Associated autoimmune diseases in systemic sclerosis define a subset of patients with milder disease: results from 2 large cohorts of European Caucasian patients.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷³", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "⁷³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73.[H1]Mechanisms/pathophysiology? ?????????When the genesis of SjS is discussed, it is considered that multiple environmental factors affecting an individual with a genetic susceptibility can lead to SjS. Abnormal responses of both T and B cells against autoantigens expressed by the epithelium of the exocrine glands (Ro and La molecules) induces the synthesis of cytokines and chemokines, leading to a chronic inflammatory damage of the exocrine glands and the final loss of their physiological functions. SjS-epithelia drive and regulate local autoimmune responses by actively mediating the accumulation, activation and differentiation of immune cells. Immune cells and inflammatory microenvironment further activate epithelial cells or regulate their survival, thus, creating a vicious cycle of epithelial/immune cell interaction that perpetuates the autoimmune responses observed in SjS.???????????????????????????????????????????????????????????[H2] Environmental factors Viral infections are considered one of the key etiologic factors involved in SjS, since the salivary gland tissue is a site of latent viral infections. The list of viruses is large and includes Epstein-Barr virus (EBV), which etiopathogenic role has been studied in patients with SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0002-9440 (Print)", "abstract" : "The association of Epstein Barr virus (EBV) with Sjogren's syndrome (SS) is still in dispute. This study is aimed to investigate the existence of EBV genomes and their products in salivary glands of SS. Salivary gland samples were surgically obtained from Chinese patients. EBV DNA was detected in three of seven cases by dot blot hybridization and in four of seven cases by in situ hybridization. The EBV-encoded small RNA-1 (EBER1) was detected in two of seven cases by in situ hybridization. The immunohistochemical staining of EBV proteins showed that the EBV latent membrane protein-1 was detected in four of seven cases and that BZLF1, BALF2, and gp350/220 proteins associating with virus production were not expressed. In eight controls, no positive signal was observed by these methods. DNA in situ hybridization identified ERV on both epithelial cells and lymphocytes. On the other hand, EBER1-positive signals were exclusively localized on lymphocytes. These results indicate that two forms of EBV infection may exist in salivary glands of SS. One is EBER1-positive latency in lymphocytes, the other is EBER1-negative latency in epithelial cells. Frequent EBV detection in salivary glands of SS suggests that EBV plays a role in the genesis of SS.", "author" : [ { "dropping-particle" : "", "family" : "Wen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimizu", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshiyama", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mizugaki", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shinozaki", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takada", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Pathol", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "1511-1517", "title" : "Association of Epstein-Barr virus (EBV) with Sjogren's syndrome: differential EBV expression between epithelial cells and lymphocytes in salivary glands", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁴", "plainTextFormattedCitation" : "74", "previouslyFormattedCitation" : "⁷⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74 .A higher prevalence of serum human herpesvirus-6 (HHV-6) specific antibodies has also been detected in patients with SjS than in normal individuals (36% versus 10%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0166-0934", "PMID" : "3053745", "abstract" : "Serologic studies were done to estimate the antibody prevalence against human herpesvirus 6 (HHV-6) in patients with malignant lymphomas, Sj\u00f6gren's syndrome and sarcoidosis. Serologic studies showed IgG antibody titers against HHV-6 in up to 41% of patients with sarcoidosis, 50-70% with malignant lymphomas and in 36% with Sj\u00f6gren's syndrome. In situ hybridization on lymph node biopsies was positive for HHV-6 genome in 1 out of 5 sarcoidosis lymph nodes.", "author" : [ { "dropping-particle" : "", "family" : "Biberfeld", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petr\u00e9n", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eklund", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindemalm", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barkhem", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ekman", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ablashi", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salahuddin", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of virological methods", "id" : "ITEM-1", "issue" : "1-4", "issued" : { "date-parts" : [ [ "1988", "9" ] ] }, "page" : "49-59", "title" : "Human herpesvirus-6 (HHV-6, HBLV) in sarcoidosis and lymphoproliferative disorders.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁵", "plainTextFormattedCitation" : "75", "previouslyFormattedCitation" : "⁷⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }75. However, other studies could not confirm this findingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0004-3591", "PMID" : "2173608", "author" : [ { "dropping-particle" : "", "family" : "Baboonian", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venables", "given" : "P J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maini", "given" : "R N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kangro", "given" : "H O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Osman", "given" : "H K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1990", "11" ] ] }, "page" : "1749-50", "title" : "Antibodies to human herpesvirus-6 in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0315-162X", "PMID" : "10493697", "author" : [ { "dropping-particle" : "", "family" : "Iakimtchouk", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Myrmel", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "1999", "9" ] ] }, "page" : "2065-6", "title" : "Serological screening for hepatitis B and C and human herpesvirus 6 in Norwegian patients with primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^76,77", "plainTextFormattedCitation" : "76,77", "previouslyFormattedCitation" : "^76,77" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }76,77. More recently, immune responses (IgG) to EBV have been demonstratedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2014.02.008", "ISSN" : "10959157", "PMID" : "24637076", "abstract" : "Sj\u00f6gren's syndrome (SS) is an autoimmune disease characterized primarily by lymphocytic infiltration of the exocrine glands, and autoantibody production. Multiple environmental factors affecting an individual with a genetic susceptibility may trigger the development of SS. Herein, we aimed to evaluate links between the different pebbles in the mosaic of SS. Demographic, clinical data and blood samples were gathered from 82 consecutive patients with SS, and 139 healthy controls. Samples were analyzed for infectious serology and auto-antibodies as well as for relevant genetic mutations (TAP genes) and cytokines levels. An immune response (IgG) against Epstein-Barr virus (EBV) early antigen (EA) was positively associated with SS (OR 4; 95% CI: 1.82-8.83, p=0.001) while a protective effect of IgG anti-cytomegalovirus (CMV) was observed (OR 0.3; 95%CI: 0.16-0.74, p=0.009). Anti-Ro/SSA, anti-LA/SSB, anti-nuclear, anti-gliadin, anti-TTG-IgG and anti-RNP antibodies were statistically more prevalent among SS patients than controls. Notably, the presence of anti-Ro/SSA and anti La/SSB correlated with anti-EBVEA IgG (OR 3.1; 95%CI: 1.08-8.74) and (OR 3.9; 95%CI: 1.37-10.96) respectively. Autoantibodies, cytokines and several genetic markers correlated with clinical manifestation of SS. Our data suggest that infectious agents may play both a causative and protective role in the pathogenesis of SS. Moreover certain autoantibodies, cytokines and specific TAP alleles correlate with clinical manifestations of SS, and may enable better prediction and/or directed therapy once confirmed in future studies. \u00a9 2014 Elsevier Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Kivity", "given" : "Shaye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arango", "given" : "Maria Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehrenfeld", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tehori", "given" : "Omer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shoenfeld", "given" : "Yehuda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anaya", "given" : "Juan Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agmon-Levin", "given" : "Nancy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Autoimmunity", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "17-22", "title" : "Infection and autoimmunity in Sjogren's syndrome: A clinical study and comprehensive review", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁸", "plainTextFormattedCitation" : "78", "previouslyFormattedCitation" : "⁷⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }78. Difficulties in analyzing the possible role of viral infection in relation to development of SjS is in particular hampered by the high prevalence of both herpesviruses (EBV and HHV-6) in the healthy population. Retroviruses are known to infect cells of the immune system and cause abnormalities in immune regulation. High serum titers of anti-human T lymphotropic virus type I (HTLV-I) antibodies and a high prevalence of salivary IgA-class anti-HTLV-I antibodies in patients with SjS were reported endemically in JapanADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(94)90630-0", "ISBN" : "0140-6736 (Print)", "ISSN" : "01406736", "PMID" : "7934493", "abstract" : "There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sj\u00f6gren's syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sj\u00f6gren's syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sj\u00f6gren's syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sj\u00f6gren's syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sj\u00f6gren's syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sj\u00f6gren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sj\u00f6gren's syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sj\u00f6gren's syndrome in endemic areas.", "author" : [ { "dropping-particle" : "", "family" : "Terada", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katamine", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eguchi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moriuchi", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kita", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimada", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamashita", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwata", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagataki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "8930", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "1116-1119", "title" : "Prevalence of serum and salivary antibodies to HTLV-1 in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "344" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁹", "plainTextFormattedCitation" : "79", "previouslyFormattedCitation" : "⁷⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }79. Recently, it has been shown that HTLV-1 is thought to infect salivary gland epithelial cells directlyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.39009", "ISSN" : "2326-5205", "PMID" : "25545344", "abstract" : "Objective: To explore whether Human T-cell leukemia virus type I (HTLV-I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of Sj\u00f6gren's syndrome (SS). Methods: We determined the inflammation-related molecules profiles after the co-culture of SGECs with HTLV-I, producing the CD4+ T-cell line HCT-5 or Jurkat by antibody dot-blot array, immunofluorescence (IF) and ELISA. The apoptosis-related molecules profile was determined by antibody dot-blot array and IF. We investigated the presence of HTLV-I-related molecules by IF and in situ PCR. The apoptosis of SGECs was evaluated by TUNEL staining. Results: 7.8 \u00b1 1.3 % of the SGECs were positive for HTLV-I-related proteins after 96-h co-culture with HCT-5 cells. Nuclear expression of NF-\u03baB p65 also became positive in 10% of the SGECs. The presence of HTLV-I proviral DNA in SGECs after co-culture with HCT-5 cells was detected by in situ PCR. A semiquantitative analysis by dot-blot antibody array in co-cultured supernatant with HCT-5 showed time-dependent increases of cytokines and chemokines including sICAM-1, RANTES, and interferon \u03b3-induced protein 10 kDa (IP-10/CXCL10), confirmed by IF and ELISA. The expressions of pro-apoptotic molecules (e.g., cytochrome C and Fas) and anti-apoptotic molecules [e.g., Bcl-2, Heme oxygenase-2 (HO-2) and HSP-27] were increased in the SGECs co-cultured with HCT-5, showing that apoptosis of SGECs was not detected after co-culture with HCT-5 or Jurkat. Conclusion: HTLV-I is thought to infect SGECs and alter their cellular functions. These changes may induce the niche of SS and contribute to the development of SS found in anti-HTLV-I antibody-positive subjects. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Hideki Nakamura, Yoshiko Takahashi, Tomomi Yamamoto-Fukuda, Yoshiro Horai, Yoshikazu Nakashima, Kazuhiko Arima, Tatsufumi Nakamura", "given" : "Takehiko Koji and Atsushi Kawakami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & Rheumatology", "id" : "ITEM-1", "issue" : "December", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Direct infection of primary salivary gland epithelial cells by HTLV-I that induces the niche of the salivary glands of Sj\u00f6gren's syndrome patients", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁰", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "⁸⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80. A higher frequency of chronic hepatitis C virus (HCV) infection has been reportedin patients with primary SjS from Mediterranean countries (14%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9135219", "abstract" : "OBJECTIVES: To determine the prevalence and clinical significance of hepatitis C virus (HCV) infection in a large cohort of patients with \"primary' Sj\u00f6gren's syndrome (SS). METHODS: 90 consecutive patients (83 female and seven male) were included, with a mean age of 62 years (range 31-80) who prospectively visited our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Serum from all patients was tested for antibodies to HCV by third generation enzyme linked immunoassay and positivity was confirmed by polymerase chain reaction. RESULTS: Antibodies to HCV were present in 13 (14%) patients with 'primary' SS. When compared with patients without HCV infection, patients with HCV infection presented a higher prevalence of hepatic involvement, (100% v 8%, p < 0.05). Transcutaneous liver biopsy was performed in five patients with HCV infection, and specimens obtained showed in all cases a chronic active hepatitis with varying degrees of portal inflammation. CONCLUSION: HCV infection is frequent in patients with \"primary' SS and liver involvement is presented in all these patients. The possible pathogenic role of HCV infection in these patients is still unclear.", "author" : [ { "dropping-particle" : "", "family" : "Garc\u00eda-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mu\u00f1oz", "given" : "F J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miret", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Espinosa", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "173-5", "title" : "Hepatitis C virus infection in 'primary' Sj\u00f6gren's syndrome: prevalence and clinical significance in a series of 90 patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸¹", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "⁸¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81 (82), and Haddad et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0140-6736", "abstract" : "Viral infection has often been suggested as a possible cause of Sjogren's syndrome or chronic lymphocytic sialadenitis, and Epstein-Barr virus has been found in the salivary glands of patients with this condition. After we had noted Sjogren's syndrome in several patients infected with hepatitis C virus (HCV), a virus also excreted in saliva, we set up a prospective study to investigate the association of chronic lymphocytic sialadenitis, with or without symptoms, to chronic HCV liver disease. The histological appearances of labial salivary glands in patients with proven HCV hepatitis or cirrhosis were compared with those in dead controls. Histological changes characteristic of Sjogren's syndrome were significantly more common in HCV-infected patients (16 of 28, 57%) compared with controls (1 of 20, 5%). Focal lymphocytic sialadenitis characteristic of Sjogren's syndrome (though only 10 patients had xerostomia and none complained of xerophthalmia) appears to be common in patients with chronic HCV liver disease; if this association is confirmed, identification of the underlying mechanism may improve our understanding of both disorders.", "author" : [ { "dropping-particle" : "", "family" : "Haddad", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deny", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munz-Gotheil", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ambrosini", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trinchet", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pateron", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mal", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callard", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beaugrand", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "321-323", "title" : "Lymphocytic sialadenitis of Sjogren's syndrome associated with chronic hepatitis C virus liver disease.", "type" : "article-journal", "volume" : "339" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸²", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "⁸²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82 reported a higher frequency of focal lymphocytic sialadenitis in the salivary gland biopsy of patients with chronic HCV infection in comparison with non-HCV infected controls (57% vs 5%) Lymphotropic viruses have been related with the development of autoimmune diseases. Some antigenic epitopes on the 48 KD La/SS-B protein have molecular similarities to some viral domains of the EBV, HHV-6 and HIV-IADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0300-9475", "PMID" : "8560190", "abstract" : "The aim of this study was to investigate the epitope recognition pattern of La(SS-B) autoantibodies in sera from patients with Sj\u00f6gren's syndrome (SS) and systemic lupus erythematosus (SLE) using overlapping synthetic decapeptides on solid phase. Eighty different decapeptides with five amino acids overlap from the human La(SS-B) autoantigen were synthesized on cellulose paper using F-moc chemistry. Tests were performed with 14 SS and six SLE sera. The results showed that the immune response to the La(SS-B) oligopeptides was restricted and unique for each individual with no particular pattern typical for each of the two diseases, apart from the fact that SLE sera gave positive reaction with fewer peptides. Regions within the N- and C-termini harboured most of the positive sequences. The authors specifically addressed the possibility of a viral aetiology for disease development or autoantibody generation. In this context the most frequently recognized linear epitopes on the La(SS-B) autoantigen showed sequence similarities with proteins from a range of ubiquitous human viruses, in particular from the herpes virus group. The La(SS-B) autoantibodies may thus be generated through molecular mimicry.", "author" : [ { "dropping-particle" : "", "family" : "Haaheim", "given" : "L R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "A K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kvakestad", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Normann", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of immunology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1996", "1" ] ] }, "page" : "115-21", "title" : "Serum antibodies from patients with primary Sj\u00f6gren's syndrome and systemic lupus erythematosus recognize multiple epitopes on the La(SS-B) autoantigen resembling viral protein sequences.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸³", "plainTextFormattedCitation" : "83", "previouslyFormattedCitation" : "⁸³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }83. The potential exposure of La/SS-B homologous sequences on the cellular surface induced by viral infections after translocation of self-determinants could promote the induction of autoantibodies. A recent study has found HCV infection in 13 % of a large series of Spanish patients with SjS, and the HCV-driven autoimmune response was characterized by an abnormal predominance of anti-La among anti-Ro antibodies in comparison with patients without HCV infectionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s13075-015-0766-3", "ISSN" : "1478-6362", "PMID" : "26370711", "abstract" : "INTRODUCTION: We conducted a study to analyze how infection by hepatitis C virus (HCV) may influence the immunological serum pattern of patients with Sj\u00f6gren syndrome (SS).\n\nMETHODS: Since 1994, we have tested serum HCV-IgG antibodies in 783 patients with SS diagnosed according to the 1993 European classification criteria. The immunological profile at diagnosis was compared according to the presence or absence of HCV.\n\nRESULTS: Of the 783 patients with SS, 105 (13.4 %) tested positive for HCV-IgG antibodies (88 females, 17 males, mean age at SS diagnosis: 62.9 years). Multivariate analysis showed that patients with SS-HCV had a higher mean age and a higher frequency of low C3/C4 levels, cryoglobulins, and hematological neoplasia compared with patients without HCV. The frequency of anti-La antibodies compared with anti-Ro antibodies was higher in patients with SS-HCV (17 % vs. 15 %) and lower in patients without HCV infection (30 % vs. 43 %). The frequency of concomitant detection of the three main cryoglobulin-related markers (cryoglobulins, rheumatoid factor activity, and C4 consumption) was threefold higher in patients with SS-HCV compared with patients without HCV. SS-HCV patients with genotype 1b showed the highest frequencies of immunological abnormalities related to cryoglobulins and the lowest frequencies of anti-Ro/La antibodies.\n\nCONCLUSIONS: We found HCV infection in 13 % of a large series of Spanish patients with SS. The HCV-driven autoimmune response was characterized by a lower frequency of anti-Ro/La antibodies, an abnormal predominance of anti-La among anti-Ro antibodies, and a higher frequency of cryoglobulinemic-related immunological markers in comparison with patients without HCV infection. This immunological pattern may contribute to the poor outcomes found in patients with SS-HCV.", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gheitasi", "given" : "Hoda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bov\u00e9", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Londo\u00f1o", "given" : "Mar\u00eda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00e1nchez-Tapias", "given" : "Jose-Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caballero", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "Belchin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forns", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Kaveri", "given" : "Srini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "250", "title" : "How hepatitis C virus modifies the immunological profile of Sj\u00f6gren syndrome: analysis of 783 patients.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁴", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "⁸⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84.With our growing understanding of the genetic complexity and the central role of type 1 IFN in systemic autoimmunityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.39204", "ISSN" : "2326-5205", "PMID" : "25988820", "abstract" : "OBJECTIVE: Sj\u00f6gren's syndrome (SS) is an autoimmune disease that targets the salivary and lacrimal glands. While all patients demonstrate inflammatory infiltration and abnormal secretory function in the target tissues, the disease features, pathology, and clinical course can vary. Activation of distinct inflammatory pathways may drive disease heterogeneity. The purpose of this study was to investigate whether activation of the interferon (IFN) pathway correlates with key phenotypic features.\n\nMETHODS: Clinical data and 1 labial salivary gland (stored frozen) were obtained from each of 82 participants (53 patients with primary SS and 29 control subjects) in the Sj\u00f6gren's International Collaborative Clinical Alliance (SICCA) registry. Salivary gland lysates were immunoblotted with markers of type I or type II IFN, and patterns of IFN activity were determined by hierarchical clustering. Correlations between SS phenotypic features and IFN activity in the salivary gland were performed.\n\nRESULTS: A total of 58% of the SS participants had high IFN activity and differed significantly from those with low IFN activity (higher prevalence of abnormal findings on sialometry, leukopenia, hyperglobulinemia, high-titer antinuclear antibody, anti-SSA, and high focus score on labial salivary gland [LSG] biopsy). Three distinct patterns of IFN were evident: type I-predominant, type II-predominant, and type I/II mixed IFN. These groups were clinically indistinguishable except for the LSG focus score, which was highest in those with type II-predominant IFN.\n\nCONCLUSION: The SS phenotype includes distinct molecular subtypes, which are segregated by the magnitude and pattern of IFN responses. Associations between IFN pathways and disease activity suggest that IFNs are relevant therapeutic targets in SS. Patients with distinct patterns of high IFN activity are clinically similar, demonstrating that IFN-targeting therapies must be selected according to the specific pathway(s) that is active in vivo in the individual patient.", "author" : [ { "dropping-particle" : "", "family" : "Hall", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Ami A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "Lindsey A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "Caroline H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosen", "given" : "Antony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casciola-Rosen", "given" : "Livia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "2437-46", "title" : "Molecular Subsetting of Interferon Pathways in Sj\u00f6gren's Syndrome.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁵", "plainTextFormattedCitation" : "85", "previouslyFormattedCitation" : "⁸⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85, the emphasis is now rather on how infectious agents may trigger autoimmunity through interaction with pattern recognition receptors (PRRs) such as toll-like receptors (TLR). This concept is also highly relevant to the emerging importance of gene-environment interaction in systemic autoimmunity, as TLR signalling involves many of the factors with genetic association in systemic autoimmunity. However, it has to be realized that an infectious agent may trigger an autoimmune reaction long before the disease is manifested, since autoantibodies are present for up to decades before diagnosis of SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2013.278448", "ISSN" : "0098-7484", "PMID" : "24193084", "abstract" : "The article discusses a study on autoantibodies present before symptom onset in patients with Sj\u00f6gren syndrome. The study found that there was no statistically significant difference in the time between a positive test result and a symptom onset between autoantibodies. It also noted that most cases produced autoantibodies many years before clinical onset of Sj\u00f6gren syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Jama", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1854", "title" : "Autoantibodies Present Before Symptom Onset in Primary Sj\u00f6gren Syndrome", "type" : "article-journal", "volume" : "310" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.39214", "ISSN" : "2326-5205", "PMID" : "26109563", "abstract" : "OBJECTIVE: Autoantibodies are highly characteristic of primary Sj\u00f6gren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets.\n\nMETHODS: A nested case-control design linking data from the Malm\u00f6 primary SS registry and 3 Swedish healthcare biobanks was applied. In all, 175 serum samples obtained from 117 individuals before diagnosis of primary SS and 1 serum sample from each of 117 matched controls were analyzed for antinuclear antibodies (ANAs), rheumatoid factor (RF), and antibodies against Ro 60/SSA, Ro 52/SSA, and La/SSB.\n\nRESULTS: Considering all patients with primary SS who were autoantibody positive after diagnosis, at least one autoantibody specificity was detected in 81% up to 20 years (median 4.3-5.1 years) before diagnosis. Those found most often were ANAs, followed by RF, anti-Ro 60/SSA, anti-Ro 52/SSA, and anti-La/SSB. Anti-Ro/SSA and anti-La/SSB antibodies were strongly associated with the risk of developing primary SS, especially early-onset disease and a severe disease course. When Bayesian prior prevalence estimates for primary SS were included in the calculation, prediagnostic anti-Ro 60/SSA and anti-Ro 52/SSA had the highest positive predictive values (25% and 100%, respectively).\n\nCONCLUSION: Our findings indicate that autoantibodies are present for up to 18-20 years before the diagnosis of primary SS, but we cannot exclude even earlier seropositivity, since for most patients, the earliest sample analyzed was positive. In families with multiple cases of autoimmune disease, autoantibody profiling, along with assessment of genetic risk, enables identification of susceptible individuals in a predisease state.", "author" : [ { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6str\u00f6m", "given" : "Bitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brokstad", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henriksson", "given" : "Gunnel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "2427-36", "title" : "Prediction of Sj\u00f6gren's Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^86,87", "plainTextFormattedCitation" : "86,87", "previouslyFormattedCitation" : "^86,87" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86,87. Among other possible relevant environmental factors, smoking has emerged as a risk factor for systemic lupus erythematosus, SjS and myositisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2010.142109", "ISBN" : "0003-4967", "ISSN" : "1468-2060", "PMID" : "21097657", "abstract" : "Prevention of disease can in principle be accomplished by identification of environmental and/or lifestyle risk and protective factors followed by public health measures (such as for smoking and lung cancer), or by modification of the individual's reactions to disease-inducing factors (such as in vaccinations against microbes). This review discusses both options based on emerging understanding of aetiologies in inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The major current opportunity for public health-based prevention lies in avoiding smoking. In RA, recent studies have calculated that, in Sweden (a country characterised by a low frequency of smoking), 20% of all RA cases and 33% of all cases of ACPA-positive RA would not have occurred in a smoke-free society. Smoking is also a major risk factor for SLE but no population attribution is yet available. New avenues for individualised and biology-based prevention are provided by the demonstration that several autoimmune rheumatic diseases are preceded by emergence of subclinical autoimmunity followed by laboratory-based signs of inflammation and finally overt disease. Examples of this process are provided from studies of autoimmunity to citrullinated proteins (in RA), to dsDNA (in SLE in general) and to Ro52 epitopes (in the case of neonatal heart block). The recognition of this sequence of events provides opportunities to intervene specifically and potentially curatively before onset of full-blown disease. Such prevention can be accomplished by modification of inciting antigens (environment), by modification of immunity (more or less specific immunomodulation) or by modification of specific gene functions. In all cases, prevention will be different in different subsets of disease and differ at different time points of disease development. Thus, the road map towards prevention of autoimmune rheumatic diseases includes increased understanding of how genes, environment and immunity interact.", "author" : [ { "dropping-particle" : "", "family" : "Klareskog", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregersen", "given" : "Peter K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huizinga", "given" : "Tom W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "2062-6", "title" : "Prevention of autoimmune rheumatic disease: state of the art and future perspectives.", "type" : "article-journal", "volume" : "69" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁸", "plainTextFormattedCitation" : "88", "previouslyFormattedCitation" : "⁸⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }88. In primary SjS, some studies have reported a lower frequency of smokersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/joim.12346", "ISSN" : "1365-2796 (Electronic)", "PMID" : "25582881", "abstract" : "OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjogren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of 1343 pSS patients. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events were compared between a subgroup of 788 female pSS patients aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in pSS patients. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Bartoloni", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schillaci", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quartuccio", "given" : "Luca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priori", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carubbi", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bini", "given" : "Vittorio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alunno", "given" : "Alessia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Vita", "given" : "Salvatore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giacomelli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of internal medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Cardiovascular disease risk burden in primary Sjogren's syndrome: results of a population-based multicentre cohort study.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1177/0961203310367504", "ISSN" : "1477-0962", "PMID" : "20581017", "abstract" : "We evaluated the prevalence and clinical significance of cardiovascular risk factors in a large series of patients with primary Sj\u00f6gren's syndrome (SS), focusing on the possible association with clinical and immunological SS features, the therapies administered, and the impact on cardiovascular disease. The study cohort included 312 patients fulfilling the 2002 classification criteria for primary SS, consecutively evaluated and followed in our department between 1984 and 2009. The control group consisted of 312 age- and sex-matched patients without systemic autoimmune diseases followed during the study period in a primary care centre. In comparison with the age- and sex-matched control group, patients with primary SS showed a higher frequency of diabetes mellitus (27% versus 13%, p < 0.001) and hypertriglyceridaemia (22% versus 15%, p = 0.023), and a lower frequency of hypertension (30% versus 46%, p < 0.001) and smoking (19% versus 31%, p < 0.001). The adjusted, multivariate analysis showed that SS patients with at least three cardiovascular risk factors had a higher mean age at SS diagnosis (p < 0.001), a higher frequency of liver involvement (p = 0.01) and central nervous system involvement (p = 0.001), higher mean levels of C-reactive protein (CRP, p = 0.001), a lower percentage of circulating gamma globulins (p = 0.001), and had received corticosteroids more frequently (p = 0.003) in comparison with patients without cardiovascular risk factors. Patients who had received corticosteroids showed a higher frequency of hypertension (37% versus 25%, p = 0.032), diabetes mellitus (37% versus 21%, p = 0.002), and hypertriglyceridaemia (33% versus 15%, p < 0.001). Patients with primary SS showed a twofold higher prevalence of diabetes mellitus and a 1.5-fold higher prevalence of hypertriglyceridaemia in comparison with primary care patients. Corticosteroid use was closely associated with cardiovascular risk factors. These results suggest that cardiovascular risk factors should be taken into account in the management of patients with primary SS and show the importance of recognizing and controlling both traditional and SS-related modifiable risk factors.", "author" : [ { "dropping-particle" : "", "family" : "P\u00e9rez-De-Lis", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diez-Cascon", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Lagares", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortiz", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez-Alvarez", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coca", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lupus", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "941-8", "title" : "Cardiovascular risk factors in primary Sj\u00f6gren's syndrome: a case-control study in 624 patients.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^89,90", "plainTextFormattedCitation" : "89,90", "previouslyFormattedCitation" : "^89,90" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89,90, while other studies have linked cigarette smoking with a higher frequency of ANAADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10165-011-0446-3", "ISBN" : "1439-7595", "ISSN" : "1439-7609", "PMID" : "21445716", "abstract" : "Smoking is well known to contribute to the pathogenesis and severity of some systemic autoimmune rheumatic diseases and especially to the production of certain autoantibodies. Primary Sj\u00f6gren's syndrome (pSS) is an autoimmune disease, affecting primarily the exocrine glands. It may also cause extraglandular involvement in some cases. In this study, we aimed to determine the frequency of smoking habits in our cohort of pSS patients and to investigate whether the frequencies of autoantibody positivity and extraglandular involvement were significantly different between patients with and without smoking. In this cross-sectional study, 207 patients with pSS (F/M 203/4), fulfilling the United States-European Consensus Criteria, and 602 healthy controls (F/M 534/68) were included. Patients and controls were classified into five groups: never smokers, current smokers, former smokers; ever smokers, and passive smokers. The \u03c7(2) and Kruskal-Wallis tests were used for statistical analysis; a p value of less than 0.05 was accepted as statistically significant. While the frequency of current smokers was significantly lower in the pSS group compared with the healthy controls (11.6 vs 22.3%), the frequencies of former smokers (30.4 vs 11.8%), ever smokers (42.0 vs 34.1%), and passive smokers (47.3 vs 37.5%) were significantly higher in the pSS group compared with the healthy controls. In pSS patients, only antinuclear antibody (ANA) positivity was significantly associated with smoking habits, while there was no significant association with other autoantibodies or with the presence of extraglandular involvement. We found that in pSS patients smoking was significantly associated only with ANA positivity. Unlike the deleterious effects of smoking upon disease severity and anti-cyclic citrullinated protein (CCP) antibody production in rheumatoid arthritis, we could not find any association of smoking with extraglandular involvement and/or anti-Ro/anti-La antibody positivity in pSS. These results are indeed in line with the limited number of previous studies reported in the literature. Further studies with higher numbers of pSS patients are required to confirm the seemingly negative association of smoking with pSS.", "author" : [ { "dropping-particle" : "", "family" : "Karabulut", "given" : "Gonca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "Gul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inal", "given" : "Vedat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalfa", "given" : "Melike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yargucu", "given" : "Figen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keser", "given" : "Gokhan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmungil", "given" : "Hakan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gokmen", "given" : "Nihal Mete", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kocanaogullari", "given" : "Hayriye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aksu", "given" : "Kenan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mod Rheumatol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "602-7", "title" : "Cigarette smoking in primary Sj\u00f6gren's syndrome: positive association only with ANA positivity.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹¹", "plainTextFormattedCitation" : "91", "previouslyFormattedCitation" : "⁹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }91 and with a lower frequency of focal lymphocytic sialadenitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "10627428", "abstract" : "OBJECTIVES: Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sj\u00f6gren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sj\u00f6gren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG.\n\nMETHODS: All living patients with primary Sj\u00f6gren's syndrome or stomatitis sicca only, who were still in contact with the Sj\u00f6gren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm(2) glandular tissue) into those being normal (focus score </= 1) or abnormal (focus score > 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and >/= 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely.\n\nRESULTS: The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score </= 1) was decreased in all three age groups (10-45: odds ratio 0.27, 95%CI 0.11 to 0.71; 46-60: odds ratio 0.22, 95%CI 0. 08 to 0.59; and >/= 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoke\u2026", "author" : [ { "dropping-particle" : "", "family" : "Manthorpe", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benoni", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirtava", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsson", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liedholm", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyhagen", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabery", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "54-60", "title" : "Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sj\u00f6gren's syndrome?", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹²", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "⁹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92.[H2] Genetic factors Genetic susceptibility to SjS is complex. Familial clustering studies show that about 35% of SjS patients have relatives with SjS or a related autoimmune disease such as SLE or rheumatoid arthritis (RA)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4819", "PMID" : "6437309", "abstract" : "The relationships of human leukocyte antigen (HLA) and heavy chain immunoglobulin (Gm) haplotypes to disease and autoantibody expression were examined in six large kindreds, each having one or more members with primary Sj\u00f6gren's syndrome. Various other autoimmune diseases and autoantibodies occurred among the 117 relatives in these families. The HLA and Gm haplotypes did not necessarily segregate persons into those with Sj\u00f6gren's syndrome, other autoimmune disorders, or serologic abnormalities, but HLA alleles DR3 and DR2 occurred in significant excess in relatives with Sj\u00f6gren's syndrome, irrespective of HLA haplotype. Segregation analysis suggested a Mendelian dominant genetic defect common to the many autoimmune diseases and serologic reactions that was not linked to HLA or Gm. A significant effect of female sex was also documented. These studies suggest that Sj\u00f6gren's syndrome results from the interaction of several HLA-linked and non-HLA-linked genes.", "author" : [ { "dropping-particle" : "", "family" : "Reveille", "given" : "J D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Provost", "given" : "T T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bias", "given" : "W B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of internal medicine", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1984" ] ] }, "page" : "748-56", "title" : "Primary Sj\u00f6gren's syndrome and other autoimmune diseases in families. Prevalence and immunogenetic studies in six kindreds.", "type" : "article-journal", "volume" : "101" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹³", "plainTextFormattedCitation" : "93", "previouslyFormattedCitation" : "⁹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }93. SjS is expected to be similarly complex to SLE and RA, each of which have over 100 established genetic associations to date. However, the genetic architecture of SjS remains remarkably unexplored. Early genetic association studies in SjS were limited to testing candidate gene studies and were substantially underpowered. More recent studies have used genome-wide association study (GWAS) designs that test for association with large numbers of single nucleotide polymorphisms (SNPs) mapped throughout the genome. To account for multiple testing in GWAS approaches, standard thresholds to declare a true positive association have been set at strong “genome wide” associations when p< 5x108, and as suggestive when 5x108<p< 5x104. Surpassing genome wide significance thresholds and demonstrating replication in independent cohorts are both considered essential for claiming a genetic association is “established”. Discovery of robust associations to establish SjS risk variants is critical for building a complete picture of the genetic architecture for this complex disease. In 2013, the first large-scale genetic studies in SjS using genome wide association study (GWAS) approaches were publishedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2792", "ISBN" : "1546-1718; 1061-4036", "ISSN" : "1546-1718", "PMID" : "24097067", "abstract" : "Sj\u00f6gren's syndrome is a common autoimmune disease (affecting \u223c0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sj\u00f6gren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 \u00d7 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 \u00d7 10(-19)), STAT4 (Pmeta = 6.80 \u00d7 10(-15)), IL12A (Pmeta = 1.17 \u00d7 10(-10)), FAM167A-BLK (Pmeta = 4.97 \u00d7 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 \u00d7 10(-8)) and TNIP1 (Pmeta = 3.30 \u00d7 10(-8)). We also observed suggestive associations (Pmeta < 5 \u00d7 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sj\u00f6gren's syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Lessard", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "He", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adrianto", "given" : "Indra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ice", "given" : "John a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen", "given" : "Astrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundahl", "given" : "Kiely M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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So far, genetic studies of Sj\u00f6gren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sj\u00f6gren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 \u00d7 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sj\u00f6gren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). 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"previouslyFormattedCitation" : "^94,95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94,95. Very strong association spanning the human leukocyte antigens (HLA) Class I, III, and II regions has been established, with multiple effects observed for HLA-DR and DQ lociADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2792", "ISBN" : "1546-1718; 1061-4036", "ISSN" : "1546-1718", "PMID" : "24097067", "abstract" : "Sj\u00f6gren's syndrome is a common autoimmune disease (affecting \u223c0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sj\u00f6gren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 \u00d7 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 \u00d7 10(-19)), STAT4 (Pmeta = 6.80 \u00d7 10(-15)), IL12A (Pmeta = 1.17 \u00d7 10(-10)), FAM167A-BLK (Pmeta = 4.97 \u00d7 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 \u00d7 10(-8)) and TNIP1 (Pmeta = 3.30 \u00d7 10(-8)). We also observed suggestive associations (Pmeta < 5 \u00d7 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sj\u00f6gren's syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Lessard", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "He", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adrianto", "given" : "Indra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ice", "given" : "John a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen", "given" : "Astrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundahl", "given" : "Kiely M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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So far, genetic studies of Sj\u00f6gren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sj\u00f6gren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 \u00d7 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sj\u00f6gren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Yongzhe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Kunlin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Fei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Juanjuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ziyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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"12905478", "abstract" : "OBJECTIVE: To reevaluate, in a large series of patients with Sj\u00f6gren's syndrome (SS) recruited from 2 French centers, the question of whether HLA is associated with SS itself or with a pattern of secretion of autoantibodies.\\n\\nMETHODS: One hundred forty-nine white patients fulfilling the American-European Consensus Group criteria for SS were divided into 3 subgroups, according to their anti-Ro/SSA and anti-La/SSB status, as follows: group 1 (n = 53), no antibody; group 2 (n = 46), anti-SSA only; group 3 (n = 50), both anti-SSA and anti-SSB. Patients were compared with 222 unrelated healthy subjects representative of the white population in France.\\n\\nRESULTS: Comparisons between the 149 SS patients and 222 controls confirmed the association of SS with DRB1*03 (the frequency was 25% in patients versus 10% in controls) and DQB1*02 (32% versus 22%). The association between HLA and SS was restricted to patients with anti-SSA and/or anti-SSB; no association with HLA was observed in patients in group 1 (no antibody). The frequency of HLA-DRB1*15 was highest in group 2 (24%), compared with 11% in group 1 and 11% in controls, whereas the frequency of HLA-DRB1*03 was highest in group 3 (44%), compared with 12% in group 1, 19% in group 2, and 10% in controls. Group 2 and group 3 had more clinical and biologic markers of activity than did group 1 but were not clinically different. HLA alleles were not associated with clinical features of the disease, and were associated with only some biologic features: rheumatoid factor positivity, increased serum IgG, and thrombocytopenia were associated with HLA-DRB1*03, and neutropenia was associated with DQB1*01.\\n\\nCONCLUSION: HLA class II markers confer genetic susceptibility to Sj\u00f6gren's syndrome. The association between HLA and SS is restricted to patients with anti-SSA and/or anti-SSB antibodies; HLA is not associated with SS in patients without these autoantibodies. The absence of a difference in disease severity between groups 2 and 3, as well as the restricted association of HLA-DRB1*03 in group 3, strongly suggest that HLA alleles predispose to autoantibody secretion, without being associated with clinical outcome. HLA class II phenotype might support epitope spreading: HLA-DR15 favors anti-SSA synthesis, whereas HLA-DR3 is associated with both anti-SSA and anti-SSB production.", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busson", "given" : "Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loiseau", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen-Solal", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lepage", "given" : "Virginia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Dominique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "2240-5", "title" : "In primary Sj\u00f6gren's syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^94\u201396", "plainTextFormattedCitation" : "94\u201396", "previouslyFormattedCitation" : "^94\u201396" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94–96. HLA class II alleles are associated with autoantibody production in SjS but not with other clinical featuresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.11103", "ISSN" : "0004-3591", "PMID" : "12905478", "abstract" : "OBJECTIVE: To reevaluate, in a large series of patients with Sj\u00f6gren's syndrome (SS) recruited from 2 French centers, the question of whether HLA is associated with SS itself or with a pattern of secretion of autoantibodies.\\n\\nMETHODS: One hundred forty-nine white patients fulfilling the American-European Consensus Group criteria for SS were divided into 3 subgroups, according to their anti-Ro/SSA and anti-La/SSB status, as follows: group 1 (n = 53), no antibody; group 2 (n = 46), anti-SSA only; group 3 (n = 50), both anti-SSA and anti-SSB. Patients were compared with 222 unrelated healthy subjects representative of the white population in France.\\n\\nRESULTS: Comparisons between the 149 SS patients and 222 controls confirmed the association of SS with DRB1*03 (the frequency was 25% in patients versus 10% in controls) and DQB1*02 (32% versus 22%). The association between HLA and SS was restricted to patients with anti-SSA and/or anti-SSB; no association with HLA was observed in patients in group 1 (no antibody). The frequency of HLA-DRB1*15 was highest in group 2 (24%), compared with 11% in group 1 and 11% in controls, whereas the frequency of HLA-DRB1*03 was highest in group 3 (44%), compared with 12% in group 1, 19% in group 2, and 10% in controls. Group 2 and group 3 had more clinical and biologic markers of activity than did group 1 but were not clinically different. HLA alleles were not associated with clinical features of the disease, and were associated with only some biologic features: rheumatoid factor positivity, increased serum IgG, and thrombocytopenia were associated with HLA-DRB1*03, and neutropenia was associated with DQB1*01.\\n\\nCONCLUSION: HLA class II markers confer genetic susceptibility to Sj\u00f6gren's syndrome. The association between HLA and SS is restricted to patients with anti-SSA and/or anti-SSB antibodies; HLA is not associated with SS in patients without these autoantibodies. The absence of a difference in disease severity between groups 2 and 3, as well as the restricted association of HLA-DRB1*03 in group 3, strongly suggest that HLA alleles predispose to autoantibody secretion, without being associated with clinical outcome. HLA class II phenotype might support epitope spreading: HLA-DR15 favors anti-SSA synthesis, whereas HLA-DR3 is associated with both anti-SSA and anti-SSB production.", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busson", "given" : "Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loiseau", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen-Solal", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lepage", "given" : "Virginia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charron", "given" : "Dominique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "2240-5", "title" : "In primary Sj\u00f6gren's syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁶", "plainTextFormattedCitation" : "96", "previouslyFormattedCitation" : "⁹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }96. By integrating transcriptional data measuring gene expression levels with genetic data, associations defined as expression quantitative trait loci, or eQTLs, have been found with five HLA Class I and II loci (A, C, DRB6, DPB1, and DQA1). These results suggest the intriguing possibility that not only could HLA risk alleles affect peptide binding and antigen presentation, but perhaps also influence expression levels of both Class I and Class II molecules. Seven non-HLA loci that surpass the genome-wide significance threshold have been reported that are important in a wide variety of innate and adaptive immune processes. Specific immune pathways implicated by these genetic associations that are clearly important contributors to SjS include Type 1 and Type 2 Interferon (IFN) signaling and responses (IRF5, IL12A, STAT4), NFkB signaling (TNIP1, TNFAIP3), lymphocyte trafficking (CXCR5), and activation and differentiation of antibody-producing cells (BLK). Very little is known about how these SjS-associated variants change normal biological activity to cause disease. However, eQTLs were also identified for the IL12A, BLK, and TNIP1 genetic effects suggesting that the associated variants act to influence expression levels of the transcripts produced at these lociADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2792", "ISBN" : "1546-1718; 1061-4036", "ISSN" : "1546-1718", "PMID" : "24097067", "abstract" : "Sj\u00f6gren's syndrome is a common autoimmune disease (affecting \u223c0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sj\u00f6gren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 \u00d7 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 \u00d7 10(-19)), STAT4 (Pmeta = 6.80 \u00d7 10(-15)), IL12A (Pmeta = 1.17 \u00d7 10(-10)), FAM167A-BLK (Pmeta = 4.97 \u00d7 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 \u00d7 10(-8)) and TNIP1 (Pmeta = 3.30 \u00d7 10(-8)). We also observed suggestive associations (Pmeta < 5 \u00d7 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. 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In addition, the precise immune cell subsets in which these variants cause pathogenic effects are unclear. Expression of BLK is relatively limited to B cells, but expression of all the other associated genes all have been shown in multiple subtypes such as natural killr cells, monocytes, dendritic cells, and T and B cells. Understanding these genetic effects and the consequences of risk variants in function of the immune system will be important for determining causal disease mechanisms in this complex disease. [H2] Autoimmune epithelitisIn 1994, Professor Harry Moutsopoulos, suggested the term “autoimmune epithelitis” as the etiologic name of primary SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1006/clin.1994.1123", "ISBN" : "0090-1229 (Print)\\r0090-1229", "ISSN" : "00901229", "PMID" : "8050187", "abstract" : "Sj\u00f6gren's syndrome (SS), the ideal model to study autoimmunity and lymphoid malignancy, is a common chronic disease which in the last 30 years has been studied extensively on clinical and pathophysiological grounds. Clinical studies regarding kidney disease in SS patients have shown that the predominate lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one-fourth of SS patients suffer from subclinical, interstitial lung disease. Reevaluation, however, of the pulmonary disease, using functional, radiologic (including CT-scan), and histopathologic studies, revealed that the lesion starts peribronehially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the majority of extraglandular manifestations of SS are due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the protooncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients, by in situ hybridization, revealed that the mRNA of the proinflammatory cytokines IL-1 and IL-6 also comes from the epithelial cells. Finally, proviral DNA is incorporated in the DNA of epithelial cells. On the basis of these clinical and basic observations, we suggest that the major suffering cell in SS patients is the epithelium and thus we propose this descriptive term \"autoimmune epithelitis\" instead of \"Sj\u00f6gren's syndrome.\"", "author" : [ { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Immunology and Immunopathology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "162-165", "title" : "Sj\u00f6c;gren's Syndrome: Autoimmune Epithelitis", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁷", "plainTextFormattedCitation" : "97", "previouslyFormattedCitation" : "⁹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }97, based in both the clinical picture of the disease and pathologic observations. He observed that SjS-related exocrinopathy and parenchymal organ involvement are associated with the development of lymphocytic infiltrates around or invading epithelial structures, suggesting that epithelium is the “inflamed” tissue in SjS. Hence, he formed the radical for the era theory that epithelia are not just innocent bystanders “suffering” from infiltrating cells, but central regulators of autoimmune responses acting as “atypical” antigen-presenting cells (Figure 3). To date, numerous studies from different groups, which analyze the affected salivary glands (SG), non-neoplastic SG epithelial cells (SGEC) and experimental models proved that epithelia are indeed able to orchestrate the innate and acquired immune responses in SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1006/clin.1994.1123", "ISBN" : "0090-1229 (Print)\\r0090-1229", "ISSN" : "00901229", "PMID" : "8050187", "abstract" : "Sj\u00f6gren's syndrome (SS), the ideal model to study autoimmunity and lymphoid malignancy, is a common chronic disease which in the last 30 years has been studied extensively on clinical and pathophysiological grounds. Clinical studies regarding kidney disease in SS patients have shown that the predominate lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one-fourth of SS patients suffer from subclinical, interstitial lung disease. Reevaluation, however, of the pulmonary disease, using functional, radiologic (including CT-scan), and histopathologic studies, revealed that the lesion starts peribronehially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the majority of extraglandular manifestations of SS are due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the protooncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients, by in situ hybridization, revealed that the mRNA of the proinflammatory cytokines IL-1 and IL-6 also comes from the epithelial cells. Finally, proviral DNA is incorporated in the DNA of epithelial cells. On the basis of these clinical and basic observations, we suggest that the major suffering cell in SS patients is the epithelium and thus we propose this descriptive term \"autoimmune epithelitis\" instead of \"Sj\u00f6gren's syndrome.\"", "author" : [ { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Immunology and Immunopathology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "162-165", "title" : "Sj\u00f6c;gren's Syndrome: Autoimmune Epithelitis", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. 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Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. 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SGEC have been shown to express constitutively plethora of immune-competent molecules implicated in lymphoid-cell recruitment, homing, activation, differentiation and proliferation, as well as immune-cell expansion and organizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. 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These include MHC class-I and class-II, B7 and CD40 costimulatory, adhesion and Fas/Fas-ligand apoptosis-related molecules, proinflammatory cytokines and cytokines involved in lymphoid-cell differentiation, as well as a plethora of T-cell-attracting and germinal-center forming chemokinesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. Herein, the known aspects of SS pathogenesis, as well as unmet issues are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "4-8", "title" : "Pathogenesis of Sj\u00f6gren's syndrome: what we know and what we should learn.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2010.06.011", "ISSN" : "1095-9157", "PMID" : "20685080", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. This fact strongly indicates the operation of intrinsic activation mechanisms in the epithelia of SS patients and further supports the active participation of these cells in the pathogenesis of the disorder.", "author" : [ { "dropping-particle" : "", "family" : "Manoussakis", "given" : "Menelaos N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "219-24", "title" : "The role of intrinsic epithelial activation in the pathogenesis of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^98,99", "plainTextFormattedCitation" : "98,99", "previouslyFormattedCitation" : "^98,99" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98,99. The constitutive epithelial expression of these molecules is further upregulated by immune-cell derived cytokines that are aberrant in tissue lesions, suggesting perplexed interactions between SGEC and immune-cells. Indeed, SGEC have been shown in-vitro to activate CD4+-T cells and mediate their differentiation to follicular-helper T-cells, which in turn enhance B-cell survivalADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. Herein, the known aspects of SS pathogenesis, as well as unmet issues are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "4-8", "title" : "Pathogenesis of Sj\u00f6gren's syndrome: what we know and what we should learn.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2010.06.011", "ISSN" : "1095-9157", "PMID" : "20685080", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. This fact strongly indicates the operation of intrinsic activation mechanisms in the epithelia of SS patients and further supports the active participation of these cells in the pathogenesis of the disorder.", "author" : [ { "dropping-particle" : "", "family" : "Manoussakis", "given" : "Menelaos N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "219-24", "title" : "The role of intrinsic epithelial activation in the pathogenesis of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^98,99", "plainTextFormattedCitation" : "98,99" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98,99, whereas they also directly interact with B-cells and promote their differentiation towards phenotypes similar to those observed in SG lesionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Morva A, Kapsogeorgou EK, Konsta OD, Moutsopoulos HM", "given" : "Tzioufas AG.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "12th International Symposium on Sj\u00f6gren's Syndrome (Kyoto, Japan, 2013).", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Salivary Gland Epithelial Cells (SGECs) promote the differentiation of B cells", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁰", "plainTextFormattedCitation" : "100", "previouslyFormattedCitation" : "¹⁰⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }100. SGEC can also sense innate immunity signals through TLR signaling that leads to the upregulation of the above-mentioned immune-competent molecules, thus linking innate and adaptive immune responsesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. Herein, the known aspects of SS pathogenesis, as well as unmet issues are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "4-8", "title" : "Pathogenesis of Sj\u00f6gren's syndrome: what we know and what we should learn.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2010.06.011", "ISSN" : "1095-9157", "PMID" : "20685080", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. This fact strongly indicates the operation of intrinsic activation mechanisms in the epithelia of SS patients and further supports the active participation of these cells in the pathogenesis of the disorder.", "author" : [ { "dropping-particle" : "", "family" : "Manoussakis", "given" : "Menelaos N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "219-24", "title" : "The role of intrinsic epithelial activation in the pathogenesis of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^98,99", "plainTextFormattedCitation" : "98,99", "previouslyFormattedCitation" : "^98,99" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98,99. Furthermore, TLR3 signaling leads to significant SG hypofunction, SGEC apoptosis and upregulation of Ro/SSA and La/SSB autoantigens in SGEC, suggesting that it might also be implicated in autoantigen presentationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. Herein, the known aspects of SS pathogenesis, as well as unmet issues are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "4-8", "title" : "Pathogenesis of Sj\u00f6gren's syndrome: what we know and what we should learn.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2010.06.011", "ISSN" : "1095-9157", "PMID" : "20685080", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. This fact strongly indicates the operation of intrinsic activation mechanisms in the epithelia of SS patients and further supports the active participation of these cells in the pathogenesis of the disorder.", "author" : [ { "dropping-particle" : "", "family" : "Manoussakis", "given" : "Menelaos N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "219-24", "title" : "The role of intrinsic epithelial activation in the pathogenesis of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/j.1601-0825.2011.01839.x", "ISSN" : "1601-0825", "PMID" : "21815968", "abstract" : "OBJECTIVE: Sj\u00f6gren's syndrome is a chronic autoimmune disorder characterized by progressive lymphocytic infiltration within the salivary and lacrimal glands. This study was undertaken to investigate the effects of innate immunity activation on sialoadenitis in a mouse strain genetically susceptible for development of SS-like disease.\n\nMETHODS: Female New Zealand Black X New Zealand White F1 mice were repeatedly treated with toll-like 3 receptor agonist poly(I:C). Submandibular glands were investigated at different time points for sialoadenitis by immunohistochemistry and for gene expression of different chemokines by quantitative PCR. Submandibular gland-infiltrating cells were characterized by flow cytometry.\n\nRESULTS: Poly(I:C) treatment significantly upregulated the expression of multiple chemokines within the submandibular glands. The severity and incidence of sialoadenitis was considerably higher in poly(I:C)-treated mice. There was a preponderance of dendritic cells and NK cells in the initial inflammatory cell infiltrates, and these were followed by CD4+ T cells.\n\nCONCLUSIONS: Our data clearly demonstrate that systemic activation of innate immunity accelerates sialoadenitis in a mouse model for SS-like disease. These findings suggest that chronic activation of innate immunity can influence certain features of SS.", "author" : [ { "dropping-particle" : "", "family" : "Nandula", "given" : "S-R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scindia", "given" : "Y M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dey", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagavant", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshmukh", "given" : "U S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral diseases", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2011", "11" ] ] }, "page" : "801-7", "title" : "Activation of innate immunity accelerates sialoadenitis in a mouse model for Sj\u00f6gren's syndrome-like disease.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1111/cei.12432", "ISSN" : "1365-2249", "PMID" : "25098814", "abstract" : "Up-regulated expression of Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2) and lupus LA protein/Sj\u00f6gren's syndrome antigen B (La/SSB) autoantigens has been described in the salivary gland epithelial cells (SGEC) of patients with Sj\u00f6gren's syndrome (SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional Toll-like receptor (TLR)-3, whereas Ro52/TRIM21 negatively regulates TLR-3-mediated inflammation. Herein, we investigated the effect of TLR-3-signalling on the expression of Ro52/TRIM21, as well as Ro60/TROVE2 and La/SSB autoantigens, by SGECs. The effect of TLR-3 or TLR-4 stimulation on autoantigen expression was evaluated by polyI:C or lipopolysaccharide (LPS) treatment, respectively, of SGEC lines (10 from SS patients, 12 from non-SS controls) or HeLa cells, followed by analysis of mRNA and protein expression. PolyI:C, but not LPS, resulted in a two-step induction of Ro52/TRIM21 mRNA expression by SGECs, a 12-fold increment at 6 h followed by a 2.5-fold increment at 24-48 h, whereas it induced a late two-fold up-regulation of Ro60/TROVE2 and La/SSB mRNAs at 48 h. Although protein expression levels were not affected significantly, the late up-regulation of Ro52/TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout the nucleus. These late phenomena were mediated significantly by interferon (IFN)-\u03b2 production, as attested by cognate secretion and specific inhibition experiments and associated with IFN regulatory factor (IRF)3 degradation. TLR-3-signalling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells. TLR-3 signalling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their over-expression in inflamed tissues and possibly in their exposure to the immune system.", "author" : [ { "dropping-particle" : "", "family" : "Kyriakidis", "given" : "N C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gourzi", "given" : "V C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konsta", "given" : "O D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baltatzis", "given" : "G E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental immunology", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "12" ] ] }, "page" : "548-60", "title" : "Toll-like receptor 3 stimulation promotes Ro52/TRIM21 synthesis and nuclear redistribution in salivary gland epithelial cells, partially via type I interferon pathway.", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{98,99,101,102}", "plainTextFormattedCitation" : "98,99,101,102", "previouslyFormattedCitation" : "^{98,99,101,102}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98,99,101,102 . Finally, SGEC possibly mediate the exposure and presentation of intracellular proteins to the immune system by the release of autoantigen-containing vesicles, including exosomes from healthy and apoptotic blebs from dying SGECADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. Herein, the known aspects of SS pathogenesis, as well as unmet issues are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "4-8", "title" : "Pathogenesis of Sj\u00f6gren's syndrome: what we know and what we should learn.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2010.06.011", "ISSN" : "1095-9157", "PMID" : "20685080", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. This fact strongly indicates the operation of intrinsic activation mechanisms in the epithelia of SS patients and further supports the active participation of these cells in the pathogenesis of the disorder.", "author" : [ { "dropping-particle" : "", "family" : "Manoussakis", "given" : "Menelaos N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "219-24", "title" : "The role of intrinsic epithelial activation in the pathogenesis of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^98,99", "plainTextFormattedCitation" : "98,99", "previouslyFormattedCitation" : "^98,99" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98,99. The significance of epithelial apoptosis in SjS pathogenesis is further supported by an experimental mouse model, in which silencing of IκB-ζ expression in lacrimal epithelial cells led to increased epithelial apoptosis within the lacrimal glands and development of a SjS-like inflammatory lesion, associated with high titers of serum anti-Ro/SSA and anti-La/SSB antibodies, which was reversed by caspase inhibitors, eventually blocking apoptosisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.immuni.2012.11.016", "ISSN" : "1097-4180", "PMID" : "23453632", "abstract" : "Sj\u00f6gren's syndrome (SS) is an autoimmune disease characterized by exocrinopathy that leads to dry eye and mouth. Although lymphocyte infiltration into exocrine glands and the generation of autoantibodies have been reported in SS, its pathogenic mechanism remains elusive. Here, we show that mice lacking the transcriptional regulator I\u03baB-\u03b6 developed SS-like inflammation characterized by lymphocyte-infiltrated dacryoadenitis and SS-associated autoantibodies. In particular, epithelial cells, but not hematopoietic cells, lacking I\u03baB-\u03b6 were essential for the development of inflammation. I\u03baB-\u03b6-deficient epithelial cells in the lacrimal glands exhibited enhanced apoptosis even in the absence of lymphocytes. Administration of caspase inhibitors ameliorated the inflammation, indicating the critical role of caspase-mediated apoptosis. Furthermore, epithelial cell-specific STAT3-deficient mice developed SS-like inflammation with impaired I\u03baB-\u03b6 expression in the lacrimal glands. Thus, this study reveals a pathogenic mechanism of SS in which dysfunction of epithelial cells caused by disruption of STAT3-mediated I\u03baB-\u03b6 induction elicits the activation of self-reactive lymphocytes.", "author" : [ { "dropping-particle" : "", "family" : "Okuma", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoshino", "given" : "Katsuaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohba", "given" : "Tomoyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukushi", "given" : "Sawako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aiba", "given" : "Setsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akira", "given" : "Shizuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ono", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaisho", "given" : "Tsuneyasu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muta", "given" : "Tatsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Immunity", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3", "21" ] ] }, "page" : "450-60", "title" : "Enhanced apoptosis by disruption of the STAT3-I\u03baB-\u03b6 signaling pathway in epithelial cells induces Sj\u00f6gren's syndrome-like autoimmune disease.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰³", "plainTextFormattedCitation" : "103", "previouslyFormattedCitation" : "¹⁰³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }103. The significantly higher and stable for several months of culture constitutive expression of the majority of the immune-active molecules in SGEC lines obtained from SjS-patients compared to sicca-controls, along with the in-situ evidence indicating the proto-oncogene c-myc expression and the redistribution of Ro/SSA and La/SSB autoantigens in the cytoplasm of SjS epithelia, suggest that intrinsic activation processes operate in the epithelial cells of SjS patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2010.06.011", "ISSN" : "1095-9157", "PMID" : "20685080", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. The application of long-term cultured non-neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit investigation of the role of these cells in the pathophysiology of SS. These studies have revealed the inherent capacity of SGEC to induce and promote chronic inflammatory reactions, as corroborated by the constitutive or inducible expression of various molecules implicated in innate and acquired immune responses. Furthermore, significantly increased constitutive expression of several molecules has been observed in SGEC lines derived from SS patients, as compared to those obtained from disease control patients. This fact strongly indicates the operation of intrinsic activation mechanisms in the epithelia of SS patients and further supports the active participation of these cells in the pathogenesis of the disorder.", "author" : [ { "dropping-particle" : "", "family" : "Manoussakis", "given" : "Menelaos N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "219-24", "title" : "The role of intrinsic epithelial activation in the pathogenesis of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁹", "plainTextFormattedCitation" : "99", "previouslyFormattedCitation" : "⁹⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }99. The offending factor(s) of the epithelial activation are not known. Epigenetic changes or latent viral infections, which have for long been suspected to participate in SjS pathogenesis, may be causally implicated in the epithelial activation of SjS patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.002", "ISSN" : "1095-9157", "PMID" : "22326205", "abstract" : "Sj\u00f6gren's syndrome (SS) or autoimmune epithelitis is a prototype autoimmune disorder with unique features: a broad clinical spectrum that extends from local exocrinopathy to systemic disease and lymphoma development, and an easy access to the inflamed tissues (minor salivary glands; MSG), which enables the investigators to study the autoimmune processes. The autoimmune lesion consists of lymphocytic infiltrates that develop around the ducts and vary in severity and composition. T cells (mainly CD4(+)) are the dominant lymphocytes in mild MSG lesions, whereas B cells in severe ones. Th1 cytokines predominate in SS infiltrates, albeit Th2 and Th17 responses have been also reported. Notably, increased infiltration by IL-18(+) cells has been associated with parotid gland enlargement and C4-hypocomplementemia, which are adverse prognostic factors for lymphoma development. Even though SS pathogenesis has not been fully revealed, several aspects have been delineated. Among them, the key role of MSG epithelia in the initiation and perpetuation of local autoimmune responses is well-established and involves the capacity of epithelial cells to mediate the recruitment, homing, activation, proliferation and differentiation of immunocytes. In addition, genetic features, including certain HLA phenotypes and polymorphisms in genes encoding cytokines or factors implicated in cytokine signaling, environmental (such as viruses) and hormonal factors are thought to participate in disease pathogenesis. Herein, the known aspects of SS pathogenesis, as well as unmet issues are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "4-8", "title" : "Pathogenesis of Sj\u00f6gren's syndrome: what we know and what we should learn.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁸", "plainTextFormattedCitation" : "98", "previouslyFormattedCitation" : "⁹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98. Indeed, histopathological studies revealed that glandular epithelia express molecules indicative of both type-I (IFNβ) and type-II interferon signature, whereas immune cells of type-II interferons (IFNγ)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/cei.12432", "ISSN" : "1365-2249", "PMID" : "25098814", "abstract" : "Up-regulated expression of Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2) and lupus LA protein/Sj\u00f6gren's syndrome antigen B (La/SSB) autoantigens has been described in the salivary gland epithelial cells (SGEC) of patients with Sj\u00f6gren's syndrome (SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional Toll-like receptor (TLR)-3, whereas Ro52/TRIM21 negatively regulates TLR-3-mediated inflammation. Herein, we investigated the effect of TLR-3-signalling on the expression of Ro52/TRIM21, as well as Ro60/TROVE2 and La/SSB autoantigens, by SGECs. The effect of TLR-3 or TLR-4 stimulation on autoantigen expression was evaluated by polyI:C or lipopolysaccharide (LPS) treatment, respectively, of SGEC lines (10 from SS patients, 12 from non-SS controls) or HeLa cells, followed by analysis of mRNA and protein expression. PolyI:C, but not LPS, resulted in a two-step induction of Ro52/TRIM21 mRNA expression by SGECs, a 12-fold increment at 6 h followed by a 2.5-fold increment at 24-48 h, whereas it induced a late two-fold up-regulation of Ro60/TROVE2 and La/SSB mRNAs at 48 h. Although protein expression levels were not affected significantly, the late up-regulation of Ro52/TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout the nucleus. These late phenomena were mediated significantly by interferon (IFN)-\u03b2 production, as attested by cognate secretion and specific inhibition experiments and associated with IFN regulatory factor (IRF)3 degradation. TLR-3-signalling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells. TLR-3 signalling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their over-expression in inflamed tissues and possibly in their exposure to the immune system.", "author" : [ { "dropping-particle" : "", "family" : "Kyriakidis", "given" : "N C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gourzi", "given" : "V C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konsta", "given" : "O D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baltatzis", "given" : "G E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental immunology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "12" ] ] }, "page" : "548-60", "title" : "Toll-like receptor 3 stimulation promotes Ro52/TRIM21 synthesis and nuclear redistribution in salivary gland epithelial cells, partially via type I interferon pathway.", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1073/pnas.1209724109", "ISSN" : "1091-6490", "PMID" : "23045702", "abstract" : "Elucidating the molecular pathways active in pathologic tissues has important implications for defining disease subsets, selecting therapy, and monitoring disease activity. The development of therapeutics directed at IFN-\u03b1 or IFN-\u03b3 makes the discovery of probes that report precisely on the activity of different IFN pathways a high priority. We show that, although type I and II IFNs induce the expression of a largely overlapping group of molecules, precise probes of IFN-\u03b3 activity can be defined. Used in combination, these probes show prominent IFN-\u03b3 effects in Sj\u00f6gren syndrome (SS) tissues. In contrast, dermatomyositis muscle shows a dominant type I IFN pattern. Interestingly, heterogeneity of IFN signatures exists in patients with SS, with some patients demonstrating a predominant type I pattern. The biochemical patterns largely distinguish the target tissues in patients with SS from those with dermatomyositis and provide a relative weighting of the effects of distinct IFN pathways in specific biopsies. In SS, type I and II IFN effects are localized to the same epithelial cells, surrounded by inflammatory cells expressing IFN-\u03b3-induced proteins, suggesting reinforcing interactions. Precise probes of the different IFN pathways active in tissues of complex rheumatic diseases will be critical to classify disease, elucidate pathogenesis, and select therapy.", "author" : [ { "dropping-particle" : "", "family" : "Hall", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casciola-Rosen", "given" : "Livia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Alan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheadle", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosen", "given" : "Antony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences of the United States of America", "id" : "ITEM-2", "issue" : "43", "issued" : { "date-parts" : [ [ "2012", "10", "23" ] ] }, "page" : "17609-14", "title" : "Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases.", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^102,104", "plainTextFormattedCitation" : "102,104", "previouslyFormattedCitation" : "^102,104" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }102,104. The interferon signature in the SG lesions of SjS patients and the high constitutive TLR3 expression and responsiveness by SGEC further support the implication of viral infection in SjS pathogenesis. [H2] Lymphoma development Patients with SjS are at increased risk of developing lymphoma. Indeed, two of the disease’s main features – chronic antigen stimulation and high disease activity – may promote lymphomagenesis. For instance, a predictive risk factor for developing lymphoma in patients with SjS is the presence of germinal center (GC)-like structures (171) at mucosal sites. Interestingly, CXCL13, a chemokine attracting memory B cells within GC has been recently found to be increased in patients with SjS and lymphoma (177). Two recent studies have demonstrated that BAFF is more increased in patients with lymphoma than in those without (133,178). Polymorphisms of BAFF and BAFF-R genes have been found to be associated with lymphoma in SjS (179). Flt3-L is a cytokine related to the differentiation and proliferation of early B cell progenitors and has been found increased in patients with SjS and lymphoma (180). In patients with SjS, lymphomagenesis is a multiple step etiopathogenic process. The first step is the chronic stimulation of polyclonal B cells, especially of those with RF activity. This polyclonal B cell activation may be associated with an increased risk of oncogenic mutations and monoclonal selection. A dysfunction of any check-point of autoimmune B-cell activation could precipitate the development of a hematological malignancy as the last step of the process. It was recently found that functional germinal mutations in theTNFAIP3/A20 gene, a gene controlling NF-kB activation, were associated with SjS-related lymphomas (181).[H1] Diagnosis, screening and prevention[H2] Overview of clinical expression SjS is a chronic slowly progressing autoimmune disease, with a clinical expression characterized by an extreme variability, with the disease ranging from (a.) an organ-specific autoimmune exocrinopathy to (b.) a systemic autoimmune disease, up to (c.) a lymphoproliferative condition. The vast majority of patients with SjS present decreased lachrymal and salivary secretion resulting in the typical ocular and oral dryness. Systemic manifestations are seen in approximately 50-60% of patients. Cutaneous, respiratory, renal, hepatic, neurological and vascular involvements can occur resulting from either a peri-epithelial focal lymphocytic infiltration of the affected tissue or from the immune complex deposition, indirect sign of an ongoing B-cells hyperactivityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2009.11.004", "ISSN" : "1873-0183", "PMID" : "19903539", "abstract" : "Sjogren's syndrome (SS) is a slowly progressing autoimmune disease, affecting predominantly middle-aged women, with a female to male ratio reaching 9:1. It is characterized by lymphocytic infiltration of the exocrine glands, mainly the lacrimal and salivary glands, resulting in reduced secretory functions and oral and ocular dryness. The syndrome can present alone as primary SS (pSS) or in the context of underlying connective tissue disease as secondary SS (sSS). While the pathogenesis of the disease remains elusive, environmental, genetic and hormonal contributors seem to be involved. Over the last years, compelling evidence has suggested a pivotal role of the epithelium in orchestrating the immune response in the histopathological lesion of Sjogren's syndrome and the term \"autoimmune epithelitis\" has been proposed as an etiological term. Although the clinical manifestations of pSS patients are mainly those of an autoimmune exocrinopathy, almost half of patients develop extraglandular disease, which may be manifested either by epithelial lymphocytic invasion of lung, liver, or kidney (resulting in interstitial nephritis) or by skin vasculitis, peripheral neuropathy, glomerulonephritis, and low C4 levels. The latter reflect immune-complex mediated disease and confer increased risk for lymphoma development.", "author" : [ { "dropping-particle" : "", "family" : "Mavragani", "given" : "Clio P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity reviews", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "A305-10", "title" : "The geoepidemiology of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁵", "plainTextFormattedCitation" : "105", "previouslyFormattedCitation" : "¹⁰⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }105. The former systemic manifestations are generally characterized by a benign course whereas the latter are more severe and have been widely associated to an increased risk for lymphoma developmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0049-0172(00)80016-5", "ISBN" : "0049-0172", "ISSN" : "0049-0172", "PMID" : "10805354", "abstract" : "OBJECTIVES: To study the clinical and laboratory profile evolution, as well as morbidity and mortality impact, of primary Sj\u00f6gren's syndrome (pSS), in a large cohort of patients followed-up longitudinally. METHODS: We studied the evolution of the clinical picture and laboratory profile of pSS, the incidence and predictors for systemic sequelae, and the impact of pSS on overall survival in a prospective cohort study of 261 patients with pSS. Analyses included calculation of incidence rates, Cox proportional hazards predictive models, and estimation of standardized mortality ratios (SMRs) compared with the general Greek population, adjusting for age and sex. RESULTS: Glandular manifestations of the syndrome were typically present at the time of diagnosis. Systemic manifestations such as arthritis, Raynaud's phenomenon, purpura, interstitial nephritis, and liver involvement, as well as the serological profile, also did not change substantially during subsequent follow-up. Incidence rates for peripheral neuropathy, glomerulonephritis, and lymphoproliferative disorders were 3.3, 6.6, and 12.2 per 1,000 person-years, respectively. Glomerulonephritis and lymphoma tended to co-exist in the same patients (relative risk, 34.0; P < .0001). The development of lymphoproliferative disorders was associated with low levels of C4 complement (relative risk, 7.5; P = .0016), the presence of mixed monoclonal cryoglobulins (relative risk, 7.9; P = .0012), and purpura (relative risk, 3.9; P = .037). Low levels of C4 was the strongest predictor for mortality after adjusting for age (relative risk, 6.5; P =.0041). Patients with pSS had an SMR of 2.07 (95% CI, 1.03 to 3.71). However, when patients with adverse predictors were excluded, the mortality rate was identical to that of the general population (SMR 1.02). CONCLUSIONS: The initial presentation of pSS determines subsequent outcome. Purpura, decreased C4 complement levels, and mixed monoclonal cryoglobulinemia are adverse prognostic factors. The overall mortality of patients with pSS compared with the general population is increased only in patients with adverse predictors.", "author" : [ { "dropping-particle" : "", "family" : "Skopouli", "given" : "F N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dafni", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ioannidis", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in arthritis and rheumatism", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "296-304", "title" : "Clinical evolution, and morbidity and mortality of primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁶", "plainTextFormattedCitation" : "106", "previouslyFormattedCitation" : "¹⁰⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }106. Severe clinical manifestations have been described in the 15-20% of SjS patients, whereas the prevalence of lymphoma has been estimated around 5%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket427", "ISSN" : "1462-0324", "PMID" : "24369420", "abstract" : "OBJECTIVE: The aims of this study were to describe the clinical presentation of primary SS (pSS) in a large cohort of patients by assessing the prevalence of the patient subgroups at high risk for severe extraglandular manifestations and to explore the influence of the patients' serological profile on disease severity and on immunosuppressive drug utilization.\n\nMETHODS: Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent serological markers for glandular and extraglandular disease manifestations were identified by logistic regression.\n\nRESULTS: The cohort included 1115 (1067 female, 48 male) pSS patients. Severe extraglandular manifestations were detectable in 15% of the patients and were represented by active synovitis (11%), axonal sensory-motor neuropathy (2%), severe leucocytopenia (14%), cutaneous vasculitis (6%) and non-Hodgkin's lymphoma (4.5%). We found that low C3/C4, hypergammaglobulinaemia, RF and cryoglobulinaemia were markers of severity for pSS. According to the number of serological variables, the patients were subdivided into three distinct groups: favourable (no serological markers), intermediate (one serological marker) and poor (two or more serological markers). In comparison with the other two patient groups, pSS patients presenting with two or more adverse determinants had a higher frequency of severe visceral disease complications and required more aggressive therapeutic interventions.\n\nCONCLUSION: This study confirmed that the prevalence of the pSS high-risk subset for severe systemic manifestations is \u223c15%. Serological markers might help in the early identification of patients who are candidates to receive more aggressive treatments.", "author" : [ { "dropping-particle" : "", "family" : "Baldini", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pepe", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quartuccio", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priori", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartoloni", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alunno", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gattamelata", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maset", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Modesti", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavoni", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vita", "given" : "S.", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "12", "24" ] ] }, "page" : "839-844", "title" : "Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁷", "plainTextFormattedCitation" : "107", "previouslyFormattedCitation" : "¹⁰⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }107. Low C3/C4 levels, hypergammaglobulinaemia and cryoglobulins, positivity for RF and anti-Ro/SSA identified patients with a potentially more severe clinical expression of the disease who may deserve a more close follow-up over the time.[H2] Sicca symptomsDryness of the eyes and of the mouth are the classical and commonest presenting features of SjS. Patients with dry mouth usually complain of inability to swallow dry food without fluid, difficulty in speaking continuously, changes in sense of taste, burning mouth and the need to wake up in the night to take sips of water. Dry, erythematous and sticky oral mucosa and dried fissured tongue can be usually observed at physical examination, as well as accelerated dental caries, with a specific pattern of involvement (damage at the cervical region and/or smooth surface of the teeth, regions that are usually rather caries resistant due to the continuous flow of saliva over these surfaces). About half of the patients complain of recurrent parotid swelling, particularly relatively young patients in whom the inflammatory phase predominatesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1601-0825.2012.01930.x", "ISSN" : "1601-0825", "PMID" : "22490059", "abstract" : "Sj\u00f6gren's syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti-SSA/Ro and anti-SSB/La relevant for the diagnosis of SjS? (iv) Are the American-European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti-Ro/La autoantibodies, anti \u03b1-fodrin IgA and anti-MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS.", "author" : [ { "dropping-particle" : "", "family" : "Aframian", "given" : "D J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konttinen", "given" : "Y T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrozzo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "a G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral diseases", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "46-58", "title" : "Urban legends series: Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁸", "plainTextFormattedCitation" : "108", "previouslyFormattedCitation" : "¹⁰⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }108. Patients with dry eyes usually report gritty eyes, itchiness, redness, sandy sensation, intolerance of contact lenses and need to use tear substitutes. On examination, the eyes may be reddened and may present dilatation of the bulbar conjunctival vessels and irregularity of the corneal image. Exocrine glands other than the salivary and lachrymal glands may be affected. Dryness can affect the nose, the upper respiratory tract as well as the oropharynx causing rhinitis sicca, cough and hoarseness. Many patients also experience skin xerosis and vaginal drynessADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ophtha.2014.07.026", "ISBN" : "0161-6420", "ISSN" : "1549-4713", "PMID" : "25178806", "abstract" : "PURPOSE: To report vision-threatening ocular manifestations of primary Sj\u00f6gren's syndrome (SS).\\n\\nDESIGN: Retrospective review.\\n\\nPARTICIPANTS: Consecutive patients evaluated at an SS center between January 2007 and May 2011.\\n\\nMETHODS: Data collection was completed in March 2013. The 2002 American-European consensus criteria were used for diagnosis of SS.\\n\\nMAIN OUTCOME MEASURES: Frequency of extraglandular ocular findings and timing of their diagnosis relative to that of SS and dry eye were assessed.\\n\\nRESULTS: One hundred sixty-three patients were included. Almost all patients (98%) had a history of dry eye for an average of 10.4 years (median, 7.9 years) before presentation. One or more extraglandular ocular manifestations were present in 40 patients (25%), and vision-threatening findings were present in 22 patients (13%). Twelve patients (55%) with a vision-threatening ocular finding did not have a diagnosis of SS at presentation. Sixty-eight patients (42%) had extraglandular systemic manifestations of SS. Patients with vision-threatening ocular findings were 3.9 times more likely to have systemic involvement (95% confidence interval, 1.4-11.0; P\u00a0= 0.010). Peripheral neuropathy, interstitial nephritis, and vasculitis were more common in those with vision-threatening ocular findings compared with patients without (P < 0.05 for all).\\n\\nCONCLUSIONS: These results from a tertiary referral-based cohort demonstrate that primary SS frequently is associated with ocular and systemic complications. Dry eye precedes these findings on average by 1 decade. Therefore, ophthalmologists should consider assessing for SS in patients with clinically significant dry eye.", "author" : [ { "dropping-particle" : "", "family" : "Akpek", "given" : "Esen Karamursel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathews", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hessen", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grader-Beck", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birnbaum", "given" : "Julius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ophthalmology", "id" : "ITEM-1", "issue" : "May 2011", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-6", "title" : "Ocular and Systemic Morbidity in a Longitudinal Cohort of Sj\u00f6gren's Syndrome.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0392-856X", "ISSN" : "0392856X", "PMID" : "16466625", "abstract" : "This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sj\u00f6gren syndrome (SS), dermatomyositis (DM) and Beh\u00e7et syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis.", "author" : [ { "dropping-particle" : "", "family" : "Albrecht", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atzeni", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalakas", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demirkesen", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yazici", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mat", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werth", "given" : "V P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarzi-Puttini", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Exp Rheumatol", "id" : "ITEM-2", "issue" : "1 Suppl 40", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "S52-9", "title" : "Skin involvement and outcome measures in systemic autoimmune diseases", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^109,110", "plainTextFormattedCitation" : "109,110", "previouslyFormattedCitation" : "^109,110" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }109,110 .[H2] Systemic symptoms A long list of systemic features is reported in patients with primary SjS, that may be developed either at presentation or later (Figure 4); when systemic features appear before the onset of the characteristic features of dryness (or when patients report mild symptoms, often neglected by the patient or physician or both), we may talk of an “occult” SjS (non-sicca onset of the disease). According to the European SjS disease activity index (ESSDAI)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2009.110619", "ISBN" : "1468-2060 (Electronic)\r0003-4967 (Linking)", "ISSN" : "1468-2060", "PMID" : "19561361", "abstract" : "To develop a disease activity index for patients with primary Sj\u00f6gren's syndrome (SS): the European League Against Rheumatism (EULAR) Sj\u00f6gren's syndrome disease activity index (ESSDAI).", "author" : [ { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baron", "given" : "Gabriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1103-1109", "title" : "EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "69" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹¹", "plainTextFormattedCitation" : "111", "previouslyFormattedCitation" : "¹¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }111, SjS systemic features can be described recognizing different domains with different levels of activity:[H3] General symptoms. Low-grade fever and involuntary weight of loss are quite common in SjS, especially as presenting features of the disease. They are often associated with abnormal fatigue, defined as a sense of exhaustion that is not relieved by rest. Seropositive and seronegative patients are equally likely to report clinically significant fatigue; however, functional impairment seems to be greater in seronegative patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "PMID" : "24529195", "abstract" : "OBJECTIVES: To investigate in primary Sj\u00f6gren's syndrome, the differences between patients with and without widespread pain (WSP) with respect to the cumulative prevalence of extra-glandular manifestations (EGMs) and systemic auto-antibodies.\\n\\nMETHODS: All outpatients diagnosed with primary Sj\u00f6gren's syndrome (2) were included in a prospective follow-up, with at least one check up each year, from June 1991 until November 2011. Patients who also fulfilled criteria for concomitant connective tissue disorders were excluded. Widespread pain was defined as the presence of long-lasting (>one year) diffuse pain in all four body quadrants. Data were collected with respect to the cumulative prevalence of systemic auto-antibodies (anti-nuclear antibodies [ANA], anti-Sj\u00f6gren syndrome A antigen [anti-SSA], anti-Sj\u00f6gren syndrome B antigen [anti-SSB] and immunoglobulin M-Rheumatoid factor [IgM-RF]) and EGMs related to primary Sj\u00f6gren's syndrome.\\n\\nRESULTS: Eighty-three patients were included in the final analysis. Thirty-nine (34.9%) patients had widespread pain. Anti-SSB was found less frequently (p<0.05) in patients with WSP than in patients without WSP. The WSP-positive patients were more frequently negative for all four tested autoantibodies (p<0.05). The patients with WSP had fewer EGMs than the patients without WSP (p<0.01); more specifically, polyneuropathy occurred less frequently (p<0.05) in the patients with WSP. Cytopenia, uveitis, pericarditis, pleuritis, interstitial lung disease, vasculitis, monoclonal gammapathy of unknown significance and non-Hodgkin lymphoma only occurred in the patients without WSP.\\n\\nCONCLUSIONS: Primary Sj\u00f6gren's patients with WSP form a benign subgroup, with a lower prevalence of anti-SSB and EGMs (in particular polyneuropathy). We suggest a shorter period of follow-up for this subset than for the WSP-negative patients.", "author" : [ { "dropping-particle" : "", "family" : "Borg", "given" : "E J", "non-dropping-particle" : "ter", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelder", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "349-53", "title" : "Lower prevalence of extra-glandular manifestations and anti-SSB antibodies in patients with primary Sj\u00f6gren's syndrome and widespread pain: evidence for a relatively benign subset.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹²", "plainTextFormattedCitation" : "112", "previouslyFormattedCitation" : "¹¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Karageorgas T, Fragioudaki S, Nezos A, Karaiskos D, Moutsopoulos HM", "given" : "Mavragani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "CP", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Fatigue in primary Sjogren's syndrome: Clinical, laboratory, psychometric and biological associations. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹³", "plainTextFormattedCitation" : "113", "previouslyFormattedCitation" : "¹¹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }113. [H3] Lymphadenopathy.Reactive multiple lymphadenopathy can be often observed in patients with SjS and may prelude to the development of lymphoproliferative complicationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2015.03.004", "ISSN" : "1873-0183", "PMID" : "25808075", "abstract" : "The intrinsic and complex nature of primary Sj\u04e7gren's syndrome (pSS) makes it difficult to identify risk factors that can predict the development and outcome of non-Hodgkin's lymphoma (NHL), yet patients at high risk for such complication seem to bear certain clinic-serological characteristics that render them a unique profile. In the last decade, research focusing on B-cell hyperactivity as the hallmark of pSS-related lymphoproliferation has shed light on certain biological and molecular factors that participate in disease evolution and lymphoma development, thus indicating possible predictors of lymphoma development and outcome. In this review, we explore all the available data concerning the clinical picture, risk prognostication and outcome of pSS-associated NHLs.", "author" : [ { "dropping-particle" : "", "family" : "Papageorgiou", "given" : "Aristea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voulgarelis", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity reviews", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "641-649", "title" : "Clinical picture, outcome and predictive factors of lymphoma in Sj\u04e7gren syndrome.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁴", "plainTextFormattedCitation" : "114", "previouslyFormattedCitation" : "¹¹⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }114. [H3] Articular involvement. Arthralgias can be detected in up to 60-70% of patients at the diagnosis. Synovitis/arthritis is observed in 20-30% of patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket349", "ISBN" : "1462-0324", "ISSN" : "14620324", "PMID" : "24162151", "abstract" : "OBJECTIVE: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions.\\n\\nMETHODS: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated.\\n\\nRESULTS: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score \u2265 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain.\\n\\nCONCLUSION: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casanovas", "given" : "Arnau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sope\u00f1a", "given" : "Bernardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00edaz-L\u00f3pez", "given" : "Bernardino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n", "given" : "Francisco Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qanneta", "given" : "Rami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraile", "given" : "Guadalupe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-Alvarez", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callejas", "given" : "Jos\u00e9 Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripoll", "given" : "Mar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinilla", "given" : "Blanca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fonseca", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canora", "given" : "Jes\u00fas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nadal", "given" : "Mar\u00eda Elvira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "la Red", "given" : "Gloria", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fern\u00e1ndez-Regal", "given" : "In\u00e9s", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Heredia", "given" : "Iratxe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Josep Angel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ayala", "given" : "Mar\u00eda Del Mar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morera-Morales", "given" : "Lluisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maure", "given" : "Brenda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mera", "given" : "Arantxa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramentol", "given" : "Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "Belchin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (United Kingdom)", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "321-331", "title" : "Systemic involvement in primary Sj\u00f6gren's syndrome evaluated by the EULAR-SS disease activity index: Analysis of 921 spanish patients (GEAS-SS registry)", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁵", "plainTextFormattedCitation" : "115", "previouslyFormattedCitation" : "¹¹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }115 (Figure 5a); in contrast to RA, arthritis tends to be less erosive and more relapsing and remitting. Subclinical synovitis can be frequently observed by musculoskeletal ultrasound (MSUS)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "2787 [pii]", "ISBN" : "0392-856X (Print)\\r0392-856X (Linking)", "ISSN" : "0392-856X", "PMID" : "19917155", "abstract" : "OBJECTIVE: To study the frequency and features of joint and tendon involvement in the hand of patients with primary Sjogren's syndrome (pSS) by musculoskeletal ultrasound (US) examination., METHODS: Forty-eight patients with pSS diagnosed according to the preliminary classification criteria proposed by the American-European Classification Criteria Group were enrolled in the study. Bilateral US examination of the 1st-5th metacarpophalangeal (MCP), 2nd-5th proximal interphalangeal (PIP) joints and of flexor tendons were performed. A semi-quantitative grading method (0 to 3) for scoring joint effusion, synovial proliferation and intra-articular power Doppler (PD) signal was used., RESULTS: We observed clear evidence of inflammatory arthritis in 9 (18.7%) patients. Bone erosions at MCP and/or PIP joint were visualized in 6 out of 48 (12.5%) patients. In 10 (20.8%) patients we imaged flexor tenosynovitis which appeared more frequent than in healthy subjects even if no statistically significant difference was detected., CONCLUSION: US examination appears to be a useful imaging technique to study joint and soft tissue involvement in connective tissue diseases. The presence of bone erosions in pSS patients is unexpected. Future studies will hopefully concentrate more on defining the erosive capability of connective tissue disorders together with inflammatory involvement of tendons.", "author" : [ { "dropping-particle" : "", "family" : "Riente", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scire", "given" : "C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delle Sedie", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filippucci", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meenagh", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iagnocco", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montecucco", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grassi", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "747-750", "title" : "Ultrasound imaging for the rheumatologist. XXIII. Sonographic evaluation of hand joint involvement in primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁶", "plainTextFormattedCitation" : "116", "previouslyFormattedCitation" : "¹¹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }116. Articular involvement sometimes leads to Jaccoud’s arthropathyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.berh.2007.09.001", "ISBN" : "1521-6942; 1521-6942", "ISSN" : "15216942", "PMID" : "18068857", "abstract" : "Sj\u00f6gren's syndrome is a chronic inflammatory process that primarily involves the exocrine glands. Its clinical manifestations range from autoimmune exocrinopathy to extraglandular (systemic) involvement affecting the lungs, kidneys, blood vessels, and muscles; it can occur alone (primary Sj\u00f6gren's syndrome) or in association with other autoimmune diseases (secondary Sj\u00f6gren's syndrome). In recent years, clinical and laboratory observations have highlighted the central role of the epithelial cell and it has been suggested that the etiological name of the disease should be 'autoimmune epithelitis'. The extraglandular manifestations of the disease are divided in two groups: (1) lung, kidney (interstitial nephritis), and liver involvement as a result of lymphocytic invasion in epithelial tissues; and (2) skin vasculitis, peripheral neuropathy, and glomerulonephritis, with low C4 levels, which is the result of immune complex disease, are associated with increased morbidity and high risk for lymphoma. The diagnosis of the disease is based on the classification criteria, raised by the American-European Study Group and which have been built on the European preliminary classification criteria, developed in 1992. The association of Sj\u00f6gren's syndrome with lymphoma is well documented as in approximately 5% of patients the benign autoimmune process is transformed into a lymphoid malignancy. The salivary extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue type are the most common lymphoma in Sj\u00f6gren's syndrome. These tumors are antigen-stimulated B-cell lymphomas and are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Among the clinical and serological parameters that have been associated with lymphoma development in patients with Sj\u00f6gren's syndrome, the presence of palpable purpura, low C4 and mixed monoclonal cryoglobulinemia constitute the main predictive markers; patients displaying these risk factors should be monitored closely. The purpose of this review is to discuss the clinical picture, the diagnostic procedure, and the malignant lymphoproliferation in the disease. \u00a9 2007 Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voulgarelis", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best Practice and Research: Clinical Rheumatology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "989-1010", "title" : "Update on Sj\u00f6gren's syndrome autoimmune epithelitis: from classification to increased neoplasias", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁷", "plainTextFormattedCitation" : "117", "previouslyFormattedCitation" : "¹¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }117.[H3] Cutaneous involvement. Cutaneous vasculits includes a variety of lesions. The most common vasculitis lesions are: flat purpura which is seen in patients with hypergammaglobulinemia and palpable purpura which is associated with cryoglobulinaemic vasculitis and has been generally considered a potential risk factor for lymphoma development in SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Quartuccio L, Isola M, Baldini C, Priori R, Bartoloni E, Carubbi F", "given" : "Gregoraci", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G, Gandolfo S, Salvin S, Luciano N, Minniti A, Alunno A, Giacomelli R", "given" : "Gerli R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini G, Bombardieri S", "given" : "De Vita S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Clinical and biological differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sj\u00f6gren's syndrome: results of a large... - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁸", "plainTextFormattedCitation" : "118", "previouslyFormattedCitation" : "¹¹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }118 (Figure 5b). Annular erythema has been described mostly in SjS patients from JapanADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0392-856X", "ISSN" : "0392856X", "PMID" : "16466625", "abstract" : "This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sj\u00f6gren syndrome (SS), dermatomyositis (DM) and Beh\u00e7et syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis.", "author" : [ { "dropping-particle" : "", "family" : "Albrecht", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atzeni", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalakas", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demirkesen", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yazici", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mat", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werth", "given" : "V P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarzi-Puttini", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Exp Rheumatol", "id" : "ITEM-1", "issue" : "1 Suppl 40", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "S52-9", "title" : "Skin involvement and outcome measures in systemic autoimmune diseases", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁰", "plainTextFormattedCitation" : "110", "previouslyFormattedCitation" : "¹¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }110. Skin xerosis has a frequency varying from 23 to 68%. The most classical expression of skin xerosis is non-specific itching, sensation of dryness, and a “pin prick-like” feeling, which are associated with various objective signs such as rough or fine scaling skinADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0392-856X", "ISSN" : "0392856X", "PMID" : "16466625", "abstract" : "This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sj\u00f6gren syndrome (SS), dermatomyositis (DM) and Beh\u00e7et syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis.", "author" : [ { "dropping-particle" : "", "family" : "Albrecht", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atzeni", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalakas", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demirkesen", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yazici", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mat", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werth", "given" : "V P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarzi-Puttini", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Exp Rheumatol", "id" : "ITEM-1", "issue" : "1 Suppl 40", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "S52-9", "title" : "Skin involvement and outcome measures in systemic autoimmune diseases", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁰", "plainTextFormattedCitation" : "110", "previouslyFormattedCitation" : "¹¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }110.[H3] Pulmonary involvement. Lung involvement is quite common in SjS, but is rarely clinical relevant. The most common clinical presentation is represented by either dry cough secondary to xerotrachea or dyspnea from airway obstruction. The principal histopathological abnormality of airways is a peribronchial and /or peribronchiolar infiltration by CD4-positive T-lymphocytes, leading to small airway obstruction. Severe interstitial disease (ILD) in SjS is rare although lung biopsies from SjS patients with ILD have shown different patterns including non-specific interstitial pneumonia, usual interstitial pneumonitis, lymphocytic interstitial pneumonia (Figure 5c) and organizing pneumonia. Patients with ILD were more likely to have RF, anti-Ro/SSA and anti-La /SSB antibodies and lymphopeniaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jcma.2013.11.001", "ISSN" : "17264901", "PMID" : "24342542", "abstract" : "Background: Lung involvement is one of the major systemic manifestations of primary Sj\u00f6gren's syndrome (pSS). This study aims to demonstrate the correlation between high-resolution computed tomography (HRCT), pulmonary function test (PFT) results, and outcome in these patients. Methods: Forty-four pSS patients were enrolled and their PFT results and HRCT findings/scores were retrospectively investigated. Results: All patients had reduced carbon monoxide-diffusing capacity (DLCO; <75% of the predicted value); <60% of the predicted value of peak expiratory flow (PEF), of forced vital capacity (FVC), and of forced expiratory volume in the 1st second (FEV1) were noted in 15 (34.1%) patients, 13 (29.5%) patients, and 12 (27.3%) patients, respectively. HRCT scores had a negative correlation with DLCO (r = -0.376, p = 0.012), but not with other PFT results. Twelve patients (27.3%) expired during a mean follow-up of 3.7 years; 11 (91.7%) patients died of respiratory failure in the lung-involved patients, of which three were present with pneumonia. The expired patients had lower predicted values of FEV1 (63.1 \u00b1 19.4% vs. 79.0 \u00b1 22.7%, p = 0.017), FVC (58.7 \u00b1 20.4% vs. 77.1 \u00b1 17.5%, p = 0.005), and PEF (54.3 \u00b1 20.5% vs. 72.0 \u00b1 24.8%, p = 0.035), and higher HRCT scores (9.2 \u00b1 5.7 vs. 5.2 \u00b1 3.5, p = 0.033) than those patients who survived. Patients with FEV1, FVC, PEF < 60% of the predicted value, or high HRCT score (13-18) presented shorter median overall survival (p = 0.005, p < 0.001, p = 0.021, p < 0.001, respectively). Multivariate analysis adjusted for PFT results showed that HRCT \u226513 was an independent risk factor for mortality (p = 0.007). Conclusion: The clinical outcome of pSS patients with lung involvement in Taiwan is not very favorable. Although HRCT score was poorly correlated with PFT, high HRCT score was significantly associated with higher mortality. \u00a9 2013.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Ming Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Hsiao Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "Chien Chih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yu Dong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Ming Huang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Hsiao Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "De Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the Chinese Medical Association", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "75-82", "title" : "Lung involvement in primary Sj\u00f6gren's syndrome: Correlation between high-resolution computed tomography score and mortality", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁹", "plainTextFormattedCitation" : "119", "previouslyFormattedCitation" : "¹¹⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }119. [H3] Nephro-urological involvement. The kidney is potentially targeted by two distinct immunopathologic pathways: activated lymphocytes infiltrate tubular epithelium, resulting in interstitial nephritis, or an immune complex mediated membranous or membranoproliferative glomerulonephritis. Distal tubular acidosis might be clinically silent but may lead as well to compromised renal function. Glomerulonephritis has been described as a potentially paraneoplastic condition potentially associated with MALT lymphoma development. Chronic cystitis in the absence of bacterial infection may be observed as well during the disease courseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.38100", "ISSN" : "1529-0131 (Electronic)", "PMID" : "24166794", "abstract" : "OBJECTIVE: To estimate the prevalence and investigate the clinical features and the outcome of clinically significant renal involvement in a large cohort of patients with primary Sjogren's syndrome (SS). METHODS: Among 715 patients who met the American-European Consensus Group criteria for primary SS, those with clinically significant renal involvement were identified and their clinical and immunologic features were recorded. The prognosis in patients with primary SS with renal involvement was assessed by the clinical appearance of any of the following major outcomes: death, hemodialysis, chronic renal failure (CRF), and lymphoma. Kaplan-Meier analysis was applied to compare death rates between patients without and those with renal involvement. RESULTS: Thirty-five patients with primary SS (4.9%) had clinically significant renal involvement, representing a total followup time after renal diagnosis of 252.2 person-years. Thirteen patients (37.1%) had interstitial nephritis alone, 17 patients (48.6%) had glomerulonephritis (GN) alone, and 5 patients (14.3%) had both entities. Nine patients died (25.7%), 11 developed CRF (including 4 requiring chronic hemodialysis) (31.4%), and 9 developed lymphoma (25.7%). The overall 5-year survival rate was 85%. Kaplan-Meier analysis showed statistically significant reduced survival for patients with primary SS with renal involvement compared to those without renal involvement (P < 0.0001 by log rank test), with GN patients displaying increased mortality. Eight of 9 reported deaths (89%) and 8 of 9 lymphomas (89%) were observed among patients with GN. CONCLUSION: The long-term prognosis varies for patients with primary SS who have clinically significant renal involvement. Patients with interstitial nephritis display a favorable prognosis, while patients with GN are at high risk of developing lymphoma and have poor survival.", "author" : [ { "dropping-particle" : "V", "family" : "Goules", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tatouli", "given" : "Ioanna P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2945-2953", "title" : "Clinically significant renal involvement in primary Sjogren's syndrome: clinical presentation and outcome.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁰", "plainTextFormattedCitation" : "120", "previouslyFormattedCitation" : "¹²⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }120.[H3] Muscular involvement.Myalgias are quite common in SS patients but muscle enzymes are usually normal. Isolated cases of myositis have been described rarelyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Colafrancesco S, Priori R, Gattamelata A, Picarelli G, Minniti A", "given" : "Brancatisano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "F, D'Amati G, Giordano C, Cerbelli B, Maset M, Quartuccio L, Bartoloni E", "given" : "Carubbi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "F, Cipriani P, Baldini C, Luciano N, De Vita S, Gerli R", "given" : "Giacomelli R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri S", "given" : "Valesini G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Myositis in primary Sj\u00f6gren's syndrome: data from a multicentre cohort. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²¹", "plainTextFormattedCitation" : "121", "previouslyFormattedCitation" : "¹²¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }121.[H3] Peripheral nervous system (PNS) involvement. Sensory neuropathy is the most common neuropathy reported in SjS patients and include axonal sensory polyneuropathy (distal symmetric sensory involvement with absent or reduced sensory potentials on nerve conduction studies), small fiber sensory neuropathy (painful paresthesias with negative results in electrodiagnostic studies) and sensory ataxic neuronopathy (caused by the lymphocytic infiltration of thedorsal root ganglia). Other types of neuropathies nclude axonal sensorimotor polyneuropathy; trigeminal and other cranial neuropathy, mononeuritis multiplex, demyelinating polyradiculoneuropathy and autonomic neuropathyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392856X", "PMID" : "23020902", "abstract" : "OBJECTIVES: This paper aims to analyse the etiology, characterisation and outcomes of the different types of peripheral neuropathy in patients with primary Sjogren's syndrome (SS) and their association with clinical and immunological disease expression., METHODS: A total of 563 consecutive patients diagnosed with primary SS were evaluated. We retrospectively assessed the results of nerve conduction studies carried out in patients with suspected peripheral nervous system involvement. Peripheral neuropathies were classified into mononeuropathy, mononeuropathy multiplex, polyneuropathy and neuronopathy according to the patterns evidenced by electrodiagnostic studies., RESULTS: Nerve conduction studies were carried out in 158/563 (28%) SS patients. The results were normal in 49 and abnormal in 109 patients, in whom peripheral neuropathy was diagnosed in 102. After excluding patients with neuropathy associated with other diseases and patients with entrapment mononeuropathies, 55/563 (10%) patients were classified as having SS-related peripheral neuropathy, including axonal sensorimotor polyneuropathy (n=24), pure sensory neuronopathy (n=15), mononeuropathy multiplex (n=15) and demyelinating polyradiculoneuropathy (n=1). In spite of therapy, clinical progression measured by the MOHS scale was observed in 12% of patients with axonal polyneuropathy, 13% of those with mononeuropathy multiplex and 47% of those with neuronopathy. Survival was significantly reduced in patients with peripheral neuropathy (especially in those with mononeuropathy multiplex and axonal polyneuropathy) in comparison with the control group (log rank =0.001)., CONCLUSIONS: We found a prevalence of SS-related peripheral neuropathy of 10%. Classification of neuropathy according to the clinical presentation and electrodiagnostic tests may be useful in determining the functional outcome, therapeutic response and survival.", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bov\u00e9", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-De-Lis", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Lagares", "given" : "Candido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gand\u00eda", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-Alvarez", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto-C\u00e1rdenas", "given" : "Ma Jos\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valls-Sole", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graus", "given" : "Francesc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and Experimental Rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "103-110", "title" : "Classification and characterisation of peripheral neuropathies in 102 patients with primary Sj\u00f6gren's syndrome", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²²", "plainTextFormattedCitation" : "122", "previouslyFormattedCitation" : "¹²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }122.[H3] Central nervous system (CNS) involvement. The frequency of CNS involvement is controversial and its clinical presentation include cerebral lesions which may mimic multiple sclerosis (Figure 5d), myelitis and aseptic meningitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2009.11.004", "ISSN" : "1873-0183", "PMID" : "19903539", "abstract" : "Sjogren's syndrome (SS) is a slowly progressing autoimmune disease, affecting predominantly middle-aged women, with a female to male ratio reaching 9:1. It is characterized by lymphocytic infiltration of the exocrine glands, mainly the lacrimal and salivary glands, resulting in reduced secretory functions and oral and ocular dryness. The syndrome can present alone as primary SS (pSS) or in the context of underlying connective tissue disease as secondary SS (sSS). While the pathogenesis of the disease remains elusive, environmental, genetic and hormonal contributors seem to be involved. Over the last years, compelling evidence has suggested a pivotal role of the epithelium in orchestrating the immune response in the histopathological lesion of Sjogren's syndrome and the term \"autoimmune epithelitis\" has been proposed as an etiological term. Although the clinical manifestations of pSS patients are mainly those of an autoimmune exocrinopathy, almost half of patients develop extraglandular disease, which may be manifested either by epithelial lymphocytic invasion of lung, liver, or kidney (resulting in interstitial nephritis) or by skin vasculitis, peripheral neuropathy, glomerulonephritis, and low C4 levels. The latter reflect immune-complex mediated disease and confer increased risk for lymphoma development.", "author" : [ { "dropping-particle" : "", "family" : "Mavragani", "given" : "Clio P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity reviews", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "A305-10", "title" : "The geoepidemiology of Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁵", "plainTextFormattedCitation" : "105", "previouslyFormattedCitation" : "¹⁰⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }105. [H3] Haematological involvement. Around one third of SjS patients have cytopenias in the blood count (see “Laboratory abnormalities”). Lymphoma (Figure 5e) is the more severe complication of SjS (see Management section).[H3] Other systemic involvements. The list of organs affected by the disease is larger than that included in the ESSDAI scoreADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2009.110619", "ISBN" : "1468-2060 (Electronic)\r0003-4967 (Linking)", "ISSN" : "1468-2060", "PMID" : "19561361", "abstract" : "To develop a disease activity index for patients with primary Sj\u00f6gren's syndrome (SS): the European League Against Rheumatism (EULAR) Sj\u00f6gren's syndrome disease activity index (ESSDAI).", "author" : [ { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baron", "given" : "Gabriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1103-1109", "title" : "EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "69" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹¹", "plainTextFormattedCitation" : "111", "previouslyFormattedCitation" : "¹¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }111. Patients with primary SjS may present with Raynaud’s phenomenon (Figure 5f), serositis, pulmonary arterial hypertension, children with autoimmune congenital heart block or neonatal lupus, recurrent pancreatitis, neurosensorial hearing loss, dysautonomia or protein-losing enteropathy, among others.[H2] Diagnostic approaches[H3] Sicca component. Sicca symptoms are mainly related to hypofunction of the main exocrine glands and diagnostic tests not only try to measure glandular dysfunction, but also quantify the degree of involvement of the main glands affected (major salivary glands and lachrymal glands) (Table 5). The two main oral tests are salivary flow rates, which measure the quantity of saliva produced in a pre-defined time (with or without previous glandular stimulation), and salivary gland scan scintigraphy, a non-invasive nuclear medicine test that evaluates the function of the main major salivary glands (parotid and submandibular glands) by measuring the pattern of uptake and secretion of a radioactive tracerADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2009.02.027", "ISSN" : "1873-0183", "PMID" : "19245858", "abstract" : "Salivary gland scintigraphy (SGS) is a non invasive method of salivary gland function assessment. This technique is easy to perform, reproducible and well tolerated by patients. Additionally, an abnormal salivary gland scintigraphy result is accepted by the American-European consensus group as a criterion for the diagnosis of Sj\u00f6gren's syndrome. Scintigraphic evaluation of salivary gland function also plays an important role in therapeutic decision and patient follow-up. Schall's categorical classification is usually considered the standard method for salivary scintigraphy interpretation, though subjective and with limited capacity to discriminate borderline results. In order to improve the diagnostic accuracy of SGS, there has been an increasing interest in the quantification of glandular function. However, the debate on the most reliable and suitable parameters for the diagnosis of SS persists.", "author" : [ { "dropping-particle" : "", "family" : "Vinagre", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santos", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prata", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "J Canas", "non-dropping-particle" : "da", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santos", "given" : "a I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity reviews", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "672-6", "title" : "Assessment of salivary gland function in Sj\u00f6gren's syndrome: the role of salivary gland scintigraphy.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²³", "plainTextFormattedCitation" : "123", "previouslyFormattedCitation" : "¹²³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }123. Ultrasonography (US) and magnetic resonance are mainly used in daily practice to evaluate the most frequent complications that may arise in the parotid glands of SjS patients (infection and lymphoma). The main ocular tests include measurement of lachrymal gland output (Schirmer’s test) and analysis of the corneal surface by the use of dyes (fluorescein and lissamine green) that stain degenerated or dead cells (corneal stainings)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Barlett JD", "given" : "Jaanus SD", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Ocular Pharmacology", "editor" : [ { "dropping-particle" : "", "family" : "Barlett JD", "given" : "Jaanus SD", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "publisher" : "Butterworth Heinemann", "publisher-place" : "London", "title" : "Dyes", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁴", "plainTextFormattedCitation" : "124", "previouslyFormattedCitation" : "¹²⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }124; several scores are used to categorize the degree of corneal damage (Figure 6).[H3] Laboratory abnormalities. SjS patients often have a specific laboratory pattern defined by the triad of cytopenias, hypergammaglobulinemia, and raised erythrocyte sedimentation rate (ESR), abnormalities that may be confirmed by simple, routine laboratory tests. Around one third of SjS patients have cytopenias in the blood countADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Koh JH, Lee J, Chung SH, Kwok SK", "given" : "Park SH", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Relation of Autoimmune Cytopenia to Glandular and Systemic Manifestations in Primary Sj\u00f6gren Syndrome: Analysis of 113 Korean Patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n P, Kostov B, Solans R, Fraile G, Su\u00e1rez-Cuervo C", "given" : "Casanovas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n FJ, Qanneta R, P\u00e9rez-Alvarez R, Ripoll M, Akasbi M, Pinilla B", "given" : "Bosch JA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos J, D\u00edaz-L\u00f3pez B, Morera-Morales ML, Gheitasi H", "given" : "Retamozo S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals M; on behalf of the SS Study Group", "given" : "Autoimmune Diseases Study Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "(GEAS)", "given" : "Spanish Society of Internal Medicine (SEMI)", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Systemic activity and mortality in primary Sj\u00f6gren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^125,126", "plainTextFormattedCitation" : "125,126", "previouslyFormattedCitation" : "^125,126" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }125,126 (127,128), including normocytic anemia, leukopenia (related to lymphompenia and/or neutropenia) and thrombocytopenia, especially patients carrying anti-Ro/La antibodies. The cytopenias are overwhelmingly asymptomatic, but may be clinically overt in some casesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Expert Review of Clinical Immunology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Early Diagnosis of primary Sj\u00f6gren\u2019s Syndrome: EULAR-SS Task Force Clinical Recommendations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁷", "plainTextFormattedCitation" : "127", "previouslyFormattedCitation" : "¹²⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }127, and are closely associated with systemic disease and poor outcomesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket349", "ISBN" : "1462-0324", "ISSN" : "14620324", "PMID" : "24162151", "abstract" : "OBJECTIVE: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions.\\n\\nMETHODS: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated.\\n\\nRESULTS: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score \u2265 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain.\\n\\nCONCLUSION: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casanovas", "given" : "Arnau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sope\u00f1a", "given" : "Bernardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00edaz-L\u00f3pez", "given" : "Bernardino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n", "given" : "Francisco Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qanneta", "given" : "Rami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraile", "given" : "Guadalupe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-Alvarez", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callejas", "given" : "Jos\u00e9 Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripoll", "given" : "Mar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinilla", "given" : "Blanca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fonseca", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canora", "given" : "Jes\u00fas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nadal", "given" : "Mar\u00eda Elvira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "la Red", "given" : "Gloria", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fern\u00e1ndez-Regal", "given" : "In\u00e9s", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Heredia", "given" : "Iratxe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Josep Angel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ayala", "given" : "Mar\u00eda Del Mar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morera-Morales", "given" : "Lluisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maure", "given" : "Brenda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mera", "given" : "Arantxa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramentol", "given" : "Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "Belchin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (United Kingdom)", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "321-331", "title" : "Systemic involvement in primary Sj\u00f6gren's syndrome evaluated by the EULAR-SS disease activity index: Analysis of 921 spanish patients (GEAS-SS registry)", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n P, Kostov B, Solans R, Fraile G, Su\u00e1rez-Cuervo C", "given" : "Casanovas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n FJ, Qanneta R, P\u00e9rez-Alvarez R, Ripoll M, Akasbi M, Pinilla B", "given" : "Bosch JA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos J, D\u00edaz-L\u00f3pez B, Morera-Morales ML, Gheitasi H", "given" : "Retamozo S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals M; on behalf of the SS Study Group", "given" : "Autoimmune Diseases Study Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "(GEAS)", "given" : "Spanish Society of Internal Medicine (SEMI)", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Systemic activity and mortality in primary Sj\u00f6gren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0315-162X", "abstract" : "OBJECTIVE: Case reports have described an association between idiopathic CD4+ T-lymphocytopenia (ICL) and non-Hodgkin's malignant lymphoma (NHML), and both entities have an increased prevalence in patients with primary Sjogren's syndrome (SS). We investigated lymphocyte subset counts in patients with primary SS to determine if presence of different autoantibodies is associated with ICL and hence may represent an increased risk for development of NHML., METHODS: A total of 80 patients with primary SS according to the American-European Consensus Classification Criteria (AECC) and 37 non-AECC sicca patients were studied for presence of different autoantibodies, and lymphocyte subsets were investigated by flow cytometry., RESULTS: Absolute CD4+ T-lymphocyte counts were significantly lower among anti-SSA antibody seropositive SS patients compared to correlating seronegatives and non-AECC sicca patients (601/microl vs 956/microl and 1087/microl; p < 0.001 and p < 0.001, respectively). ICL was found in 16% of anti-SSA seropositive patients., CONCLUSION: ICL, a proposed risk factor for development of NHML, occurs frequently and presumably exclusively in patients with primary SS who are anti-SSA antibody seropositive. These findings support that this group comprises patients at risk for development of NHML.", "author" : [ { "dropping-particle" : "", "family" : "Mandl", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bredberg", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "Lennart T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manthorpe", "given" : "Rolf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henriksson", "given" : "Gunnel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "726-728", "title" : "CD4+ T-lymphocytopenia--a frequent finding in anti-SSA antibody seropositive patients with primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/MD.0b013e3181b76ab5", "ISBN" : "3021074626", "ISSN" : "0025-7974", "PMID" : "19745687", "abstract" : "The diverse hematologic manifestations of primary Sj\u00f6gren syndrome (pSS) have not been systematically investigated, and their prognostic relevance remains unclear. We conducted a retrospective study of 536 consecutive patients followed in our institution to assess the prevalence of hematologic abnormalities and their associations with various disease manifestations in pSS. We also aimed to identify risk factors for the development of non-Hodgkin lymphoma (NHL) overall and by subtype. Anemia of chronic disease and hypergammaglobulinemia were the most prevalent hematologic manifestations encountered at diagnosis and during the course of pSS. Univariate analysis between cytopenias and glandular manifestations revealed a statistically significant correlation between lymphocytopenia and parotid gland enlargement (p = 0.002), as well as between neutropenia and xerostomia (p = 0.019). Anemia, lymphocytopenia, thrombocytopenia, hypergammaglobulinemia, the presence of monoclonal serum proteins, and cryoglobulinemia correlated significantly with the presence of extraglandular symptoms such as palpable purpura, lymphadenopathy, and splenomegaly. Lymphoma was diagnosed in 7.5% (95% confidence interval [CI], 5.4%-10%) of patients. Marginal zone B-cell lymphomas (MZBCLs) were the predominant histologic type (65%; 95% CI, 48.3%-79.4%), while diffuse large B-cell lymphomas (DLBCLs) accounted for 17.5% (95% CI, 7.3%-32.8%) of all cases. The development of NHL in patients with pSS could be predicted by the presence of simple clinical and laboratory factors at diagnosis: neutropenia (p = 0.041), cryoglobulinemia (p = 0.008), splenomegaly (p = 0.006), lymphadenopathy (p = 0.021), and low C4 levels (p = 0.009). Patients carrying any of these factors had a more than 5-fold increased risk of NHL compared to patients with no risk factors at all. The above set of disease characteristics could predict subsequent development of MZBCL; the presence of lymphocytopenia (p = 0.044) at diagnosis served as a risk factor for the development of a non-MZBCL, most commonly DLBCL. Anemia of chronic disease and hypergammaglobulinemia are common hematologic manifestations at diagnosis and during the course of pSS. Neutropenia and cryoglobulinemia at diagnosis are significantly associated with an increased risk of lymphoma development.", "author" : [ { "dropping-particle" : "", "family" : "Baimpa", "given" : "Evangelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahabreh", "given" : "Issa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voulgarelis", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "284-293", "title" : "Hematologic manifestations and predictors of lymphoma development in primary Sj\u00f6gren syndrome: clinical and pathophysiologic aspects.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1016/j.semarthrit.2008.01.014", "ISSN" : "00490172", "PMID" : "18378278", "abstract" : "Objective: To analyze the prevalence of neutropenia in a large cohort of patients with primary Sj\u00f6gren's syndrome (SS) and its association with clinical and immunological disease expression and adverse outcomes. Methods: The study cohort included 300 patients diagnosed with primary SS in our department between 1984 and 2002. The outcomes measured after the first laboratory evidence of neutropenia (<2.5 \u00d7 109/L) were first hospital admission caused by infection, development of systemic manifestations, neoplasia, and death. Results: Ninety-nine (33%) patients had neutropenia during the follow-up, which was related to neoplasia or drugs in 9 (3%) patients and was considered idiopathic in the remaining 90 (30%). Patients with neutropenia had a lower mean age at diagnosis of SS (51.9 versus 59.4 years, P < 0.001) and a higher prevalence of anti-Ro/La antibodies (53% versus 22%, P < 0.001), rheumatoid factor (49% versus 32%, P = 0.009), and low C4 levels (17% versus 8%, P = 0.044) than those without neutropenia. Patients with neutropenia had a higher incidence of hospital admission caused by infection (24% versus 9%, P = 0.002), especially those with neutropenia <1 \u00d7 109/L (50% versus 9%, P = 0.002), and a higher rate of admission (log rank = 0.0023) in comparison with those without neutropenia. Agranulocytosis was found in 7 (2%) patients, predominantly related to neoplasia (5 cases). One (1%) of the 90 patients with SS-related neutropenia developed large granular lymphocyte T-cell leukemia. Conclusion: Neutropenia should be considered a relevant hematologic finding of primary SS, due both to its elevated prevalence and to its clinical significance (close association with anti-Ro/La antibodies, coexistence with other cytopenias, and development of severe infections). \u00a9 2009 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soria", "given" : "Natalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mu\u00f1oz", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bov\u00e9", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belenguer", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "389-395", "title" : "Prevalence and Clinical Relevance of Autoimmune Neutropenia in Patients with Primary Sj\u00f6gren's Syndrome", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{115,126,128\u2013130}", "plainTextFormattedCitation" : "115,126,128\u2013130", "previouslyFormattedCitation" : "^{115,126,128\u2013130}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }115,126,128–130. Polyclonal hypergammaglobulinemia is the laboratory reflection of the polyclonal B-cell activation involved in the disease pathogenesis, and the ESR often correlates with the quantity of circulating gamma globulins, while serum C-reactive protein levels are usually normal (elevated levels should raise the suspicion of an infection). Raised serum β2 microglobulin levels have been reported in one-third of patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0059868", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "23717383", "abstract" : "OBJECTIVES: To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sj\u00f6gren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment.\\n\\nMETHODS: Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the \"Assessment of Systemic Signs and Evolution of Sj\u00f6gren's Syndrome\" (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sj\u00f6gren's Syndrome Disease Activity Index (ESSDAI).\\n\\nRESULTS: Patient median age was 58 (25(th)-75(th): 51-67) and median disease duration was 5 (2-9) years. Median ESSDAI at enrollment was 2 (0-7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]-[11] vs 2 [0-7], P\u200a=\u200a0.03; 4 [1]-[11] vs 2 [0-7], P< 0.0001); 4 [2]-[10] vs 2 [0-6.6], P< 0.0001 and 4 [2-8.2] vs 2 [0-7.0], P\u200a=\u200a0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1-3665.5) vs 898.9 (715.9-1187.2) pg/ml, P\u200a=\u200a0.01 and 2.6 (2.2-2.9) vs 2.1 (1.8-2.6) mg/l, P\u200a=\u200a0.04, respectively).\\n\\nCONCLUSION: In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miceli-Richard", "given" : "Corinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benessiano", "given" : "Joelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dieude", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauchais", "given" : "Anne Laure", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larroche", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pu\u00e9chal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rist", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sene", "given" : "Damien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vittecoq", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nocturne", "given" : "Ga\u00e9tane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-6", "title" : "Serum Levels of Beta2-Microglobulin and Free Light Chains of Immunoglobulins Are Associated with Systemic Disease Activity in Primary Sj\u00f6gren's Syndrome. Data at Enrollment in the Prospective ASSESS Cohort", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³¹", "plainTextFormattedCitation" : "131", "previouslyFormattedCitation" : "¹³¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }131. Other laboratory abnormalities may suggest SjS-related renal involvement or associated liver disease.[H3] Immunological features. Autoantibodies are the key serological markers of an autoimmune disease and, in patients with SjS, may be present up to 20 years before the disease diagnosisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2013.278448", "ISSN" : "0098-7484", "PMID" : "24193084", "abstract" : "The article discusses a study on autoantibodies present before symptom onset in patients with Sj\u00f6gren syndrome. The study found that there was no statistically significant difference in the time between a positive test result and a symptom onset between autoantibodies. It also noted that most cases produced autoantibodies many years before clinical onset of Sj\u00f6gren syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Jama", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1854", "title" : "Autoantibodies Present Before Symptom Onset in Primary Sj\u00f6gren Syndrome", "type" : "article-journal", "volume" : "310" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.39214", "ISSN" : "2326-5205", "PMID" : "26109563", "abstract" : "OBJECTIVE: Autoantibodies are highly characteristic of primary Sj\u00f6gren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets.\n\nMETHODS: A nested case-control design linking data from the Malm\u00f6 primary SS registry and 3 Swedish healthcare biobanks was applied. In all, 175 serum samples obtained from 117 individuals before diagnosis of primary SS and 1 serum sample from each of 117 matched controls were analyzed for antinuclear antibodies (ANAs), rheumatoid factor (RF), and antibodies against Ro 60/SSA, Ro 52/SSA, and La/SSB.\n\nRESULTS: Considering all patients with primary SS who were autoantibody positive after diagnosis, at least one autoantibody specificity was detected in 81% up to 20 years (median 4.3-5.1 years) before diagnosis. Those found most often were ANAs, followed by RF, anti-Ro 60/SSA, anti-Ro 52/SSA, and anti-La/SSB. Anti-Ro/SSA and anti-La/SSB antibodies were strongly associated with the risk of developing primary SS, especially early-onset disease and a severe disease course. When Bayesian prior prevalence estimates for primary SS were included in the calculation, prediagnostic anti-Ro 60/SSA and anti-Ro 52/SSA had the highest positive predictive values (25% and 100%, respectively).\n\nCONCLUSION: Our findings indicate that autoantibodies are present for up to 18-20 years before the diagnosis of primary SS, but we cannot exclude even earlier seropositivity, since for most patients, the earliest sample analyzed was positive. In families with multiple cases of autoimmune disease, autoantibody profiling, along with assessment of genetic risk, enables identification of susceptible individuals in a predisease state.", "author" : [ { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6str\u00f6m", "given" : "Bitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brokstad", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henriksson", "given" : "Gunnel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "2427-36", "title" : "Prediction of Sj\u00f6gren's Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^86,87", "plainTextFormattedCitation" : "86,87", "previouslyFormattedCitation" : "^86,87" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86,87.- Antinuclear antibodies (ANA) and rheumatoid factor (FR). ANA are the most frequently detected autoantibodies in primary SjS (>80%), and are a useful immunological screening test for further diagnostic referralADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0007-1161", "abstract" : "AIMS: To assess the prevalence and determine predictors of Sjogren's syndrome (SS) in patients with clinically significant aqueous-deficient dry eye., METHODS: Patients enrolled in an industry-sponsored, multicentre clinical trial (NCT00784719) were assessed prospectively for the presence of SS. Ocular testing included Schirmer test, corneal fluorescein staining, conjunctival lissamine green staining, and tear-film breakup time. Review of systems questionnaire, medical history, dry eye questionnaire and laboratory work-up (Sjogren-specific antibody A (SSA), Sjogren-specific antibody B (SSB), rheumatoid factor (RF) and antinuclear antibody (ANA)) were obtained., RESULTS: Of 327 patients, 38 (11.6%) had SS: 21 (6.4%) with primary SS (pSS), and 17 (5.2%) with secondary SS. Nine patients (3%) were newly diagnosed using the applied diagnostic criteria based on American-European consensus criteria. Patients with SS had significantly worse conjunctival and corneal staining, Schirmer test (with and without anaesthesia), and symptoms compared with patients without SS. pSS Was significantly more likely to occur in patients with positive ANA (OR: 13.9) and RF (OR: 4.8)., CONCLUSIONS: Ophthalmologists caring for patients with clinically significant dry eye should have a high index of suspicion for underlying SS and low threshold for serological work-up. RF and ANA are recommended as useful tests in SSA/SSB-negative patients for further diagnostic referral.", "author" : [ { "dropping-particle" : "", "family" : "Liew MS Kim E, Akpek EK", "given" : "Zhang M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liew", "given" : "Melissa Shiao Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akpek", "given" : "Esen K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British journal of ophthalmology", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1498", "title" : "Prevalence and predictors of Sjogren's syndrome in a prospective cohort of patients with aqueous-deficient dry eye.", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³²", "plainTextFormattedCitation" : "132", "previouslyFormattedCitation" : "¹³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }132. RF is present in half the patients with primary SjS, has a similar sensitivity but a greater specificity than ANA for SjS classificationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.21591", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22563590", "abstract" : "OBJECTIVE: We propose new classification criteria for Sj\u00f6gren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.\\n\\nMETHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sj\u00f6gren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American\u2013European Consensus Group (AECG) criteria, a model-based \u201cgold standard\u201dobtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development.\\n\\nRESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications.\\n\\nCONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.", "author" : [ { "dropping-particle" : "", "family" : "Shiboski", "given" : "S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "L A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "A N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Challacombe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanfranchi", "given" : "H", "non-dropping-particle" : "", 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"suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "475-87", "title" : "American College of Rheumatology classification criteria for Sj\u00f6gren's syndrome: a data-driven, expert consensus approach in the Sj\u00f6gren's International Collaborative Clinical Alliance cohort.", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³³", "plainTextFormattedCitation" : "133", "previouslyFormattedCitation" : "¹³³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }133 and has been associated with the main clinical, histopathological and laboratory features of primary SjS.- Anti-Ro/SS-A antibodies. Ro/SS-A antibodies principally target two protein antigens (Ro60 and Ro52) associated with small RNA molecules. Anti-Ro/SSA antibodies are detected in up to 70% of SjS patients, although the prevalence may vary widely according to the method of detection due to their varying capacity to recognize the Ro52 and Ro60 antigens; 12-20% of patients with a negative Ro/SS-A determination may have specific antibodies against one of these antigensADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "5286 [pii]", "ISBN" : "0392-856X (Print)\\n0392-856X (Linking)", "ISSN" : "0392-856X (Print)", "PMID" : "22704838", "abstract" : "OBJECTIVES: To evaluate how determination of antibodies against the Ro52 antigen influences the classification and clinical characterisation of patients with suspected primary Sjogren's syndrome (SS). METHODS: The cohort study included 187 patients who fulfilled at least four of the six 1993 SS classification criteria, including positive autoantibodies (antinuclear antibodies [ANA], rheumatoid factor [RF], anti-Ro/SSA and/or anti-La/SS-B antibodies) as mandatory criterium. Anti-Ro/SSA antibodies were tested by qualitative ELISA using a commercial assay. Anti-Ro52 antibodies were detected by a semiquantitative ELISA. RESULTS: Anti-Ro52 antibodies were found in 70/187 (37%) patients. A significant percentage of patients with anti-Ro/SSA antibodies were negative for anti-Ro52 antibodies (22%), while 13 patients (12%) were negative for anti-Ro/SSA antibodies but positive for anti-Ro52 antibodies, meaning that they fulfilled the 2002 SS criteria while avoiding the need for a salivary biopsy. Higher mean titers of anti-Ro52 antibodies were associated with severe scintigraphic involvement, positive salivary gland biopsy, parotid enlargement, anaemia, leukopenia and RF. A statistical correlation was found between anti-Ro52 titers and age, gammaglobulin levels, RF titers and serum IgA and IgG. Patients with positive anti-Ro/SSA and anti-Ro52 antibodies had a higher frequency of positive salivary gland biopsy, parotid enlargement and positive RF, and higher levels of serum IgG and IgA levels in comparison with patients with positive anti-Ro/SSA but negative anti-Ro52 antibodies. CONCLUSIONS: Anti-Ro52 antibodies were closely associated with the main clinical, histopathological and immunological features of primary SS. Anti-Ro52 autoantibody testing may help to identify a specific subset of SS patients with more aggressive disease, in whom a closer follow-up and earlier, more robust therapeutic management may be necessary.", "author" : [ { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zeron", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bove", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez-de-Lis", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jimenez", "given" : "Iratxe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto-Cardenas", "given" : "Maria-Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gandia", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Lagares", "given" : "Candido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinas", "given" : "Odette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siso", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez-Alvarez", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yague", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "686-692", "title" : "Anti-Ro52 antibody testing influences the classification and clinical characterisation of primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/rheumatology/ket295", "ISSN" : "1462-0332", "PMID" : "24026249", "abstract" : "OBJECTIVE: The objective of this study was to assess the diagnostic value of anti-Ro52/60 antibodies by immunodot in patients with suspected SS., METHODS: All patients between 2008 and 2012 with suspected SS without anti-SSA/SSB antibodies by ELISA and who had a determination of anti-SSA (Ro52/Ro60) antibodies by immunodot (Euroimmun, Germany) were retrospectively analysed., RESULTS: Eighty-four patients (median age 62 years; males 35 cases) were included. Forty-five patients had associated interstitial lung disease (ILD). American-European Consensus Group (AECG) criteria for SS were fulfilled in 10 patients (12%) with a positive salivary gland biopsy, and among them 2 patients had anti-Ro52 antibodies by dot (20%). Among 74 patients with a negative salivary gland biopsy, 16 (22%) had anti-Ro52/60 antibodies and 10 (14%) fulfilled AECG criteria when including Ro52/60 antibodies. A comparison of patients with and without anti-Ro52/60 antibodies revealed no differences, except gamma globulin levels and more frequent steroid use in patients with anti-Ro52/60 antibodies (P < 0.05). In 45 patients with ILD and dry eye/mouth syndrome, 10 (22%) had positive anti-Ro52/60 antibodies. In these patients 2 (4%) fulfilled AECG criteria without anti-Ro52/60 antibodies vs 4 (8%) patients if anti-Ro52/60 antibodies were included., CONCLUSION: In patients with dry eye/mouth syndrome without anti-SSA/SSB antibodies by ELISA, the detection of anti-Ro52/Ro60 antibodies by dot could help in the diagnosis of SS. In patients with ILD, the lower frequency of a Chisholm score >3 enhances the interest of anti-Ro52/Ro60 screening.", "author" : [ { "dropping-particle" : "", "family" : "Mekinian", "given" : "Arsene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nicaise-Roland", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chollet-Martin", "given" : "Sylvie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crestani", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2223-2228", "title" : "Anti-SSA Ro52/Ro60 antibody testing by immunodot could help the diagnosis of Sjogren's syndrome in the absence of anti-SSA/SSB antibodies by ELISA.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^134,135", "plainTextFormattedCitation" : "134,135", "previouslyFormattedCitation" : "^134,135" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }134,135. Recent studies suggest that Ro60 and Ro52 represent two distinct autoantibody systems and that specific separate detection is desirable when SjS is suspectedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2009.02.010", "ISBN" : "1873-0183 (Electronic)\\r1568-9972 (Linking)", "ISSN" : "1873-0183", "PMID" : "19393201", "abstract" : "Anti-SS-A (Ro52/Ro60) autoantibodies have been described as serological marker for Sj\u00f6gren's syndrome but are also found in patients with other systemic autoimmune diseases. Historically, these autoantibodies were considered as a uniform autoantibody-system. However, recent studies provided evidence that Ro60 and Ro52 are not part of a stable macromolecular complex and that anti-Ro52 and anti-Ro60 (SS-A) antibodies have different clinical associations. The prevalence of anti-Ro52 in systemic sclerosis and myositis is significantly higher than anti-Ro60 (SS-A) and isolated anti-Ro52 can be found in up to 37% of myositis patients, often correlated with anti-Jo-1 reactivity (p=0.0002). Furthermore, recent developments have made significant improvements in the quality of recombinant Ro60 showing excellent performance in Ro60 (SS-A) ELISA (Dr. Fooke Laboratorien). Of note, single reactivity to either Ro52 or Ro60 (SS-A) can be missed when measured with a classical SS-A ELISA based on a mixture of both antigens. Approximately 20% of anti-Ro52 or Ro60 (SS-A) positive samples may remain undetected using a mixture of both antigens. Moreover, the international reference sera from the Centers for Disease Control and Prevention (CDC 2, 3, 7, 10) were further characterized. It was concluded that Ro60 (SS-A) and Ro52 represent two distinct autoantibody systems and that separate detection is desirable in a clinical diagnostic setting.", "author" : [ { "dropping-particle" : "", "family" : "Schulte-Pelkum", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritzler", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahler", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity reviews", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "632-7", "title" : "Latest update on the Ro/SS-A autoantibody system.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³⁶", "plainTextFormattedCitation" : "136", "previouslyFormattedCitation" : "¹³⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }136. In patients with a high clinical suspicion of primary SjS and negative results for the standard determination of ANA and anti-Ro/SS-A antibodies, specific detection of anti-Ro52/60 antibodies is recommended.- Anti-La/SS-B antibodies. La protein is involved in diverse aspects of RNA metabolism, and has also been related to the binding of viral-related RNAs. Anti-La/SSB antibodies are detected in up to 50% of patients with primary SjS, overwhelmingly in association with anti-Ro antibodies; double positivity is associated with a higher chance of testing positive for ANAADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Yang Z, Liang Y", "given" : "Zhong R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Is identification of anti-SSA and/or -SSB antibodies necessary in serum samples referred for antinuclear antibodies testing? - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³⁷", "plainTextFormattedCitation" : "137", "previouslyFormattedCitation" : "¹³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }137 and with systemic activityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "PMID" : "24529195", "abstract" : "OBJECTIVES: To investigate in primary Sj\u00f6gren's syndrome, the differences between patients with and without widespread pain (WSP) with respect to the cumulative prevalence of extra-glandular manifestations (EGMs) and systemic auto-antibodies.\\n\\nMETHODS: All outpatients diagnosed with primary Sj\u00f6gren's syndrome (2) were included in a prospective follow-up, with at least one check up each year, from June 1991 until November 2011. Patients who also fulfilled criteria for concomitant connective tissue disorders were excluded. Widespread pain was defined as the presence of long-lasting (>one year) diffuse pain in all four body quadrants. Data were collected with respect to the cumulative prevalence of systemic auto-antibodies (anti-nuclear antibodies [ANA], anti-Sj\u00f6gren syndrome A antigen [anti-SSA], anti-Sj\u00f6gren syndrome B antigen [anti-SSB] and immunoglobulin M-Rheumatoid factor [IgM-RF]) and EGMs related to primary Sj\u00f6gren's syndrome.\\n\\nRESULTS: Eighty-three patients were included in the final analysis. Thirty-nine (34.9%) patients had widespread pain. Anti-SSB was found less frequently (p<0.05) in patients with WSP than in patients without WSP. The WSP-positive patients were more frequently negative for all four tested autoantibodies (p<0.05). The patients with WSP had fewer EGMs than the patients without WSP (p<0.01); more specifically, polyneuropathy occurred less frequently (p<0.05) in the patients with WSP. Cytopenia, uveitis, pericarditis, pleuritis, interstitial lung disease, vasculitis, monoclonal gammapathy of unknown significance and non-Hodgkin lymphoma only occurred in the patients without WSP.\\n\\nCONCLUSIONS: Primary Sj\u00f6gren's patients with WSP form a benign subgroup, with a lower prevalence of anti-SSB and EGMs (in particular polyneuropathy). We suggest a shorter period of follow-up for this subset than for the WSP-negative patients.", "author" : [ { "dropping-particle" : "", "family" : "Borg", "given" : "E J", "non-dropping-particle" : "ter", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelder", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "349-53", "title" : "Lower prevalence of extra-glandular manifestations and anti-SSB antibodies in patients with primary Sj\u00f6gren's syndrome and widespread pain: evidence for a relatively benign subset.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Quartuccio L, Baldini C, Bartoloni E, Priori R, Carubbi F, Corazza L", "given" : "Alunno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "A, Colafrancesco S, Luciano N, Giacomelli R, Gerli R, Valesini G", "given" : "Bombardieri S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S", "given" : "De Vita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Anti-SSA/SSB-negative Sj\u00f6gren's syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1136/bjo.2011.202812", "ISBN" : "1468-2079 (Electronic)\\n0007-1161 (Linking)", "ISSN" : "0007-1161", "PMID" : "21558290", "abstract" : "AIMS: To determine whether prognostic immunological profiles predict the severity of keratoconjunctivitis sicca (KCS) in patients with Sjogren's syndrome (SS). METHODS: 121 patients diagnosed with SS and followed for at least 1 year were enrolled in this study. Patients were allocated to either a mild KCS group (Mi-KCS; n=65) or to a moderate to severe KCS group (MS-KCS; n=56) based on the Oxford scheme and response to treatment. These groups were each sub-divided into two groups based on the clinical severity of KCS and the presence of associated rheumatic disease (primary SS vs secondary SS). Anti-Ro/anti-La antibody, rheumatoid factor and tear interleukin (IL)-17 levels and Schirmer test results were compared between each group. RESULTS: Anti-Ro/SSA antibody and anti-La/SSB antibody concentrations were significantly higher in the MS-KCS group than in the Mi-KCS group for total and primary SS. The presence of anti-La/SSB antibody was significantly higher in the MS-KCS than the Mi-KCS group for total and primary SS. The mean tear IL-17 concentration in the MS-KCS group was significantly higher than in the Mi-KCS group for both total SS and primary SS patients. CONCLUSION: Serum anti-La/SSB antibody, serum anti-Ro/SSA antibody and tear IL-17 are likely to be strongly involved in the clinical severity of KCS in patients with primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Chung", "given" : "J. K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "M. K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wee", "given" : "W. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Ophthalmology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "240-245", "title" : "Prognostic factors for the clinical severity of keratoconjunctivitis sicca in patients with Sjogren's syndrome", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^112,138,139", "plainTextFormattedCitation" : "112,138,139", "previouslyFormattedCitation" : "^112,138,139" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112,138,139. The frequency of SjS patients with isolated anti-La/SS-B antibodies (without concomitant anti-Ro/SSA) ranges between 2.3% and 7%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s13075-015-0766-3", "ISSN" : "1478-6362", "PMID" : "26370711", "abstract" : "INTRODUCTION: We conducted a study to analyze how infection by hepatitis C virus (HCV) may influence the immunological serum pattern of patients with Sj\u00f6gren syndrome (SS).\n\nMETHODS: Since 1994, we have tested serum HCV-IgG antibodies in 783 patients with SS diagnosed according to the 1993 European classification criteria. The immunological profile at diagnosis was compared according to the presence or absence of HCV.\n\nRESULTS: Of the 783 patients with SS, 105 (13.4 %) tested positive for HCV-IgG antibodies (88 females, 17 males, mean age at SS diagnosis: 62.9 years). Multivariate analysis showed that patients with SS-HCV had a higher mean age and a higher frequency of low C3/C4 levels, cryoglobulins, and hematological neoplasia compared with patients without HCV. The frequency of anti-La antibodies compared with anti-Ro antibodies was higher in patients with SS-HCV (17 % vs. 15 %) and lower in patients without HCV infection (30 % vs. 43 %). The frequency of concomitant detection of the three main cryoglobulin-related markers (cryoglobulins, rheumatoid factor activity, and C4 consumption) was threefold higher in patients with SS-HCV compared with patients without HCV. SS-HCV patients with genotype 1b showed the highest frequencies of immunological abnormalities related to cryoglobulins and the lowest frequencies of anti-Ro/La antibodies.\n\nCONCLUSIONS: We found HCV infection in 13 % of a large series of Spanish patients with SS. The HCV-driven autoimmune response was characterized by a lower frequency of anti-Ro/La antibodies, an abnormal predominance of anti-La among anti-Ro antibodies, and a higher frequency of cryoglobulinemic-related immunological markers in comparison with patients without HCV infection. This immunological pattern may contribute to the poor outcomes found in patients with SS-HCV.", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gheitasi", "given" : "Hoda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bov\u00e9", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Londo\u00f1o", "given" : "Mar\u00eda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00e1nchez-Tapias", "given" : "Jose-Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caballero", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "Belchin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forns", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Kaveri", "given" : "Srini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "250", "title" : "How hepatitis C virus modifies the immunological profile of Sj\u00f6gren syndrome: analysis of 783 patients.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "TE", "family" : "Baer AN, McAdams DeMarco M, Shiboski SC, Lam MY, Challacombe S", "given" : "Daniels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong Y, Greenspan JS, Kirkham BW, Lanfranchi HE, Schi\u00f8dt M, Srinivasan M", "given" : "Umehara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H, Vivino FB, Vollenweider CF, Zhao Y, Criswell LA", "given" : "Shiboski CH; Sj\u00f6gren's", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groups", "given" : "International Collaborative Clinical Alliance (SICCA) Research", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sj\u00f6gren's syndrome. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Danda", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Rheum", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "abstract number 2542", "title" : "La Positive, Ro60 Negative Subset of Primary Sj\u00f6gren\u2019s Syndrome Is a Reality", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^84,140,141", "plainTextFormattedCitation" : "84,140,141", "previouslyFormattedCitation" : "^84,140,141" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84,140,141, and Baer et al have suggested performing a salivary gland biopsy in these patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "TE", "family" : "Baer AN, McAdams DeMarco M, Shiboski SC, Lam MY, Challacombe S", "given" : "Daniels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong Y, Greenspan JS, Kirkham BW, Lanfranchi HE, Schi\u00f8dt M, Srinivasan M", "given" : "Umehara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H, Vivino FB, Vollenweider CF, Zhao Y, Criswell LA", "given" : "Shiboski CH; Sj\u00f6gren's", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groups", "given" : "International Collaborative Clinical Alliance (SICCA) Research", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sj\u00f6gren's syndrome. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁰", "plainTextFormattedCitation" : "140", "previouslyFormattedCitation" : "¹⁴⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }140.- Cryoglobulins. Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures < 37°CADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60242-0", "ISSN" : "1474-547X", "PMID" : "21868085", "abstract" : "Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less than 37\u00b0C and produce organ damage through two main pathways: vascular sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune-mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia). Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped into infections, autoimmune disorders, and malignancies; the most common cause is infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed when a patient has typical organ involvement (mainly skin, kidney, or peripheral nerve) and circulating cryoglobulins. Cutaneous purpura is the most common manifestation of cryoglobulinaemic vasculitis. The most frequently affected internal organs are the peripheral nerves, kidneys, and joints. The course varies widely and prognosis is influenced by both cryoglobulinaemic damage to vital organs and by comorbidities associated with underlying diseases. More than 90% of cases of cryoglobulinaemia have a known underlying cause; therefore treatment is focused on the cause of the disorder rather than merely symptomatic relief. Studies suggest that both combined or sequential antiviral therapies and targeted biological treatments might be more effective than monotherapy.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "John H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cid", "given" : "Maria C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9813", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "348-60", "title" : "The cryoglobulinaemias.", "type" : "article-journal", "volume" : "379" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴²", "plainTextFormattedCitation" : "142", "previouslyFormattedCitation" : "¹⁴²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142. Nearly 10% of patients with primary SjS present with circulating cryoglobulins, which are overwhelmingly mixedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n P, Kostov B, Solans R, Fraile G, Su\u00e1rez-Cuervo C", "given" : "Casanovas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n FJ, Qanneta R, P\u00e9rez-Alvarez R, Ripoll M, Akasbi M, Pinilla B", "given" : "Bosch JA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos J, D\u00edaz-L\u00f3pez B, Morera-Morales ML, Gheitasi H", "given" : "Retamozo S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals M; on behalf of the SS Study Group", "given" : "Autoimmune Diseases Study Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "(GEAS)", "given" : "Spanish Society of Internal Medicine (SEMI)", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Systemic activity and mortality in primary Sj\u00f6gren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁶", "plainTextFormattedCitation" : "126", "previouslyFormattedCitation" : "¹²⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }126. Cryoglobulins are the principal immunological marker that antedates a poor prognosis in SjS, including a higher prevalence of extraglandular disease, an enhanced risk of B-cell lymphoma and poor survivalADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket427", "ISSN" : "1462-0324", "PMID" : "24369420", "abstract" : "OBJECTIVE: The aims of this study were to describe the clinical presentation of primary SS (pSS) in a large cohort of patients by assessing the prevalence of the patient subgroups at high risk for severe extraglandular manifestations and to explore the influence of the patients' serological profile on disease severity and on immunosuppressive drug utilization.\n\nMETHODS: Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent serological markers for glandular and extraglandular disease manifestations were identified by logistic regression.\n\nRESULTS: The cohort included 1115 (1067 female, 48 male) pSS patients. Severe extraglandular manifestations were detectable in 15% of the patients and were represented by active synovitis (11%), axonal sensory-motor neuropathy (2%), severe leucocytopenia (14%), cutaneous vasculitis (6%) and non-Hodgkin's lymphoma (4.5%). We found that low C3/C4, hypergammaglobulinaemia, RF and cryoglobulinaemia were markers of severity for pSS. According to the number of serological variables, the patients were subdivided into three distinct groups: favourable (no serological markers), intermediate (one serological marker) and poor (two or more serological markers). In comparison with the other two patient groups, pSS patients presenting with two or more adverse determinants had a higher frequency of severe visceral disease complications and required more aggressive therapeutic interventions.\n\nCONCLUSION: This study confirmed that the prevalence of the pSS high-risk subset for severe systemic manifestations is \u223c15%. Serological markers might help in the early identification of patients who are candidates to receive more aggressive treatments.", "author" : [ { "dropping-particle" : "", "family" : "Baldini", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pepe", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quartuccio", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priori", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartoloni", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alunno", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gattamelata", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maset", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Modesti", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavoni", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vita", "given" : "S.", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "12", "24" ] ] }, "page" : "839-844", "title" : "Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/rheumatology/ket349", "ISBN" : "1462-0324", "ISSN" : "14620324", "PMID" : "24162151", "abstract" : "OBJECTIVE: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions.\\n\\nMETHODS: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated.\\n\\nRESULTS: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score \u2265 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain.\\n\\nCONCLUSION: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casanovas", "given" : "Arnau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sope\u00f1a", "given" : "Bernardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", 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"suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n FJ, Qanneta R, P\u00e9rez-Alvarez R, Ripoll M, Akasbi M, Pinilla B", "given" : "Bosch JA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos J, D\u00edaz-L\u00f3pez B, Morera-Morales ML, Gheitasi H", "given" : "Retamozo S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals M; on behalf of the SS Study Group", "given" : "Autoimmune Diseases Study Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "(GEAS)", "given" : "Spanish Society of Internal Medicine (SEMI)", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Systemic activity and mortality in primary Sj\u00f6gren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Quartuccio L, Isola M, Baldini C, Priori R, Bartoloni Bocci E", "given" : "Carubbi F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maset M, Gregoraci G, Della Mea V, Salvin S, De Marchi G", "given" : "Luciano N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colafrancesco S, Alunno A, Giacomelli R, Gerli R, Valesini G, Bombardieri S", "given" : "De", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S", "given" : "Vita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Biomarkers of lymphoma in Sj\u00f6gren's syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{107,115,126,143}", "plainTextFormattedCitation" : "107,115,126,143", "previouslyFormattedCitation" : "^{107,115,126,143}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }107,115,126,143. Therefore, detection of cryoglobulins in patients with primary SjS is essential, both at diagnosis and during the follow-up; indirect laboratory data suggesting an underlying mixed cryoglobulinemia include low C4 levels, raised RF, and serum monoclonal IgM gammopathyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60242-0", "ISSN" : "1474-547X", "PMID" : "21868085", "abstract" : "Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less than 37\u00b0C and produce organ damage through two main pathways: vascular sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune-mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia). Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped into infections, autoimmune disorders, and malignancies; the most common cause is infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed when a patient has typical organ involvement (mainly skin, kidney, or peripheral nerve) and circulating cryoglobulins. Cutaneous purpura is the most common manifestation of cryoglobulinaemic vasculitis. The most frequently affected internal organs are the peripheral nerves, kidneys, and joints. The course varies widely and prognosis is influenced by both cryoglobulinaemic damage to vital organs and by comorbidities associated with underlying diseases. More than 90% of cases of cryoglobulinaemia have a known underlying cause; therefore treatment is focused on the cause of the disorder rather than merely symptomatic relief. Studies suggest that both combined or sequential antiviral therapies and targeted biological treatments might be more effective than monotherapy.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "John H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cid", "given" : "Maria C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9813", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "348-60", "title" : "The cryoglobulinaemias.", "type" : "article-journal", "volume" : "379" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴²", "plainTextFormattedCitation" : "142", "previouslyFormattedCitation" : "¹⁴²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142. - Hypocomplementemia. Low C3 and/or C4 levels are found in 10-25% of SjS patients. Like cryoglobulins, hypocomplementemia is closely associated with the main adverse outcomes of SjS (lymphoma and death)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keh407", "ISSN" : "1462-0324", "PMID" : "15381790", "abstract" : "OBJECTIVE: To analyse the prevalence and clinical significance of hypocomplementaemia in a large series of patients with primary Sjogren's syndrome (SS), focusing on the association of low complement levels with clinical manifestations, immunological features, lymphoproliferative disorders and mortality. METHODS: Complement determinations (C3 and C4 levels, CH50 activity) were made in 336 consecutive patients with primary SS (313 women and 23 men, mean age 58.5 yr). We also analysed complement levels in 46 patients with SS associated with hepatitis C virus (HCV) infection and 184 with HCV-related cryoglobulinaemia as control groups. RESULTS: Hypocomplementaemia was detected in 81 (24%) of patients with primary SS, low CH50 being detected in 51 (15%), low C3 values in 42 (12%) and low C4 values in 39 (12%). In the multivariate analysis, patients with low C4 levels showed a higher prevalence of peripheral neuropathy, cutaneous vasculitis, RF, cryoglobulins and lymphoma compared with those with normal C4 levels. The analysis of the 218 SS patients followed prospectively since 1994 showed a lower probability of survival in patients with hypocomplementaemia (with low C3, C4 or CH50 levels) at protocol entry. SS-HCV patients presented a higher frequency of hypocomplementaemia than patients with primary SS (76 vs 24%, P<0.001); nine (20%) of these patients had persistent, unquantifiable complement levels. CONCLUSION: Hypocomplementaemia is closely associated with systemic expression and adverse outcomes (lymphoma development and death) in patients with primary SS. Our results support the inclusion of complement determination at diagnosis as a predictor of the outcome of patients with primary SS and its routine determination in the clinical follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yag\u00fce", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bautista", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruano", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claver", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gil", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "89-94", "title" : "Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁴", "plainTextFormattedCitation" : "144", "previouslyFormattedCitation" : "¹⁴⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }144. - Monoclonal immunoglobulins. Studies have reported that up to 20% of patients with primary SjS may have associated monoclonal gammopathy of undetermined significance (MGUS)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.md.0000157398.37679.47", "ISSN" : "0025-7974", "PMID" : "15758838", "abstract" : "We conducted the current study to analyze the prevalence and clinical significance of circulating monoclonal immunoglobulins in patients with Sjo\u00f8gren syndrome (SS), focusing on the association with extraglandular features, immunologic markers, hematologic neoplasia, and hepatitis C virus (HCV) infection. We performed serum immunoelectrophoresis in 200 patients with primary SS and 37 patients with HCV-related SS. All patients fulfilled 4 or more of the 1993 European classification criteria for SS. Of the 200 patients with primary SS, 35 (18%) presented circulating monoclonal immunoglobulins. The monoclonal bands identified were 20 IgG (13 k, 7 l), 10 IgM (5 k, 5 l), 2 IgAk, and 3 free circulating light chains. Of the 37 SS-HCV patients, 16 (43%) had circulating monoclonal immunoglobulins. The monoclonal bands identified were 10 IgMk, 5 IgGl, and 1 free light l chain. Compared with primary SS patients, SS-HCV patients presented a higher frequency of monoclonal immunoglobulins (43% vs 18%, p = 0.001), with monoclonal IgMk being the most frequent monoclonal band. Six (12%) of the 51 SS patients with circulating monoclonal immunoglobulins presented hematologic neoplasia, compared with 3 (1.6%) of those without monoclonal immunoglobulins (p = 0.004; odds ratio = 8.13; 95% confidence intervals, 1.64\u201351.54). In 2 of the 6 patients with monoclonal immunoglobulins and lymphoproliferative disorders, a change of the monoclonal component was detected in previous immunoelectrophoresis determinations before the development of hematologic neoplasia. Circulating monoclonal immunoglobulins were detected in nearly 20% of patients with primary SS, with monoclonal IgG being the most frequent type of immunoglobulin detected. In SSHCV patients, the prevalence of monoclonal immunoglobulins was higher (43%), with monoclonal IgM being the most frequent type found. SS-HCV patients presented a more restrictive monoclonal expression (limited to either monoclonal IgMk or monoclonal IgGl) than primary SS patients, who showed all types of heavy and light chains.", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zeron", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nardi", "given" : "Norma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervera", "given" : "Ricard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yag??e", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "90-97", "title" : "Circulating Monoclonal Immunoglobulins in Sj\u00f8gren Syndrome", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁵", "plainTextFormattedCitation" : "145", "previouslyFormattedCitation" : "¹⁴⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }145, with mIgGκ being the most frequent type of band detectedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n P, Kostov B, Solans R, Fraile G, Su\u00e1rez-Cuervo C", "given" : "Casanovas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n FJ, Qanneta R, P\u00e9rez-Alvarez R, Ripoll M, Akasbi M, Pinilla B", "given" : "Bosch JA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos J, D\u00edaz-L\u00f3pez B, Morera-Morales ML, Gheitasi H", "given" : "Retamozo S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals M; on behalf of the SS Study Group", "given" : "Autoimmune Diseases Study Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "(GEAS)", "given" : "Spanish Society of Internal Medicine (SEMI)", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Systemic activity and mortality in primary Sj\u00f6gren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaut.2012.01.010", "ISBN" : "0896-8411", "ISSN" : "08968411", "PMID" : "22297146", "abstract" : "Objective: To analyze the monoclonal expression of SS through the detection of serum monoclonal immunoglobulins (mIgs) in a large series of patients with Sj\u00f6gren syndrome (SS), focusing on the etiology, characterization and evolution of the monoclonal band and the association with SS clinical expression and outcomes. Methods: Serum immunoelectrophoresis (IE) was performed to 408 consecutive patients who were evaluated by our unit between 1992 and 2011: 221 patients who fulfilled the 2002 American-European criteria for primary SS, 122 primary SS patients who fulfilled exclusively the 1993 European criteria and 65 patients with SS-associated hepatitis C virus infection. IE was performed at diagnosis and every year during the follow-up. Results: Of the 221 patients with primary SS, 48 (22%) had monoclonal gammopathy. In the control groups, the prevalence was 16% in patients with SS who fulfilled the 1993 criteria (p > 0.05) and 52% in SS-HCV patients (p < 0.001). Monoclonal bands were characterized in 47/48 patients with primary SS: IgG (n = 21), IgM (n = 16), IgA (n = 5) and free light chains (n = 5); the light chain was \u03ba in 28 patients and \u03bb in 19 (\u03ba:\u03bb ratio 1.5). Primary SS patients with monoclonal gammopathy had a higher prevalence of parotidomegaly (38% vs 20%, p = 0.021), vasculitis (21% vs 6%, p = 0.003), neurological involvement (42% vs 23%, p = 0.016), higher mean values of circulating gammaglobulins (23.4 vs 20.6%, p = 0.026), ESR (56.6 vs 37.6 mm/h, p = 0.003), a higher prevalence of RF (69% vs 50%, p = 0.022), low C3 levels (24% vs 11%, p = 0.028), low C4 levels (24% vs 7%, p = 0.003), low CH50 activity (28% vs 11%, p = 0.008) and cryoglobulins (23% vs 8%, p = 0.012) compared with those without monoclonal gammopathy. Of the 48 patients with primary SS and monoclonal gammopathy, 8 developed hematologic neoplasia after a mean follow-up of 10 years, a higher prevalence than observed in patients without monoclonal gammopathy (17% vs 5%, p = 0.009). Survival rates according to the presence or absence of monoclonal gammopathy were 83% and 97%, respectively (log rank 0.004). Conclusion: Monoclonal gammopathy was detected in 22% of patients with primary SS fulfilling the 2002 criteria, with mIgG\u03ba being the most frequent type of band detected. In HCV-associated SS patients, the prevalence was higher (52%) with IgM\u03ba being the most prevalent band detected. Monoclonal gammopathy was associated with a higher prevalence of parotid enlargement, extraglandula\u2026", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "Soledad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gand\u00eda", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-De-Lis", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Lagares", "given" : "Candido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bov\u00e9", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-Alvarez", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto-C\u00e1rdenas", "given" : "Mar\u00eda Jos\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Autoimmunity", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "43-48", "title" : "Monoclonal gammopathy related to Sj\u00f6gren syndrome: A key marker of disease prognosis and outcomes", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^126,146", "plainTextFormattedCitation" : "126,146", "previouslyFormattedCitation" : "^126,146" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }126,146.[H3] Salivary biopsy. Minor salivary gland biopsy remains the most specific test for the diagnosis of SjS, together with anti-Ro/SSA antibodiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2012.08.001", "ISSN" : "15689972", "PMID" : "22889617", "abstract" : "Objectives: To assess the diagnostic value of minor salivary gland biopsy (MSGB) for primary Sj\u00f6gren's syndrome (pSS). Methods: Systematic review of studies retrieved from PUBMED and EMBASE using the terms 'salivary glands' AND 'Sj\u00f6gren's syndrome' AND 'biopsy', conducted in patients with suspected pSS, and defining positive biopsies as a focus score (FS)\u22651 Sensitivity and specificity of MSGB were abstracted from the articles or calculated when possible. Results: Of 238 publications identified initially, 9 were included in the study. MSGB sensitivity ranged from 63.5% to 93.7% and specificity from 61.2% to 100%. Specificity was >89% in six studies. An attempt to separate patients with and without pSS without using MSGB findings or via clinical re-evaluation was made in only two studies, in 73 and 120 patients, respectively, with sicca syndrome in the first study and suspected pSS in the other. The reference standard for diagnosing pSS was a set of criteria that did not include MSGB in the first and patient re-evaluation by three experienced rheumatologists who were aware of MSGB findings in the other. In these studies, sensitivity was 63.9% and 85.7% and specificity was 91.9% and 89.7%, respectively. Conclusions: Few published studies have evaluated the diagnostic usefulness of MSGB in pSS. Only two studies used a methodology that precluded circular reasoning. Our study indicates a lack of information about the diagnostic value of MSGB. Specificity and positive predictive values (PPV) are high and sensitivity is variable. \u00a9 2012 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Guellec", "given" : "Dewi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornec", "given" : "Divi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marhadour", "given" : "Thierry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcorelles", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity Reviews", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "416-420", "title" : "Diagnostic value of labial minor salivary gland biopsy for Sj\u00f6gren's syndrome: A systematic review", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁷", "plainTextFormattedCitation" : "147", "previouslyFormattedCitation" : "¹⁴⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }147. The technique with the best balance between efficacy and safety is linear incision of the buccal side of the lower lip (Figure 7) rather than a punch biopsyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kel266", "ISBN" : "1462-0324; 1462-0324", "ISSN" : "1462-0324", "PMID" : "16891656", "abstract" : "OBJECTIVE: To assess the value of the parotid biopsy as a diagnostic tool for primary Sj\u00f6gren's syndrome (pSS), and to compare the parotid biopsy and the labial biopsy with regard to diagnostic value and biopsy-related morbidity. METHODS: In 15 consecutive patients with pSS and 20 controls, the parotid biopsy was assessed as a diagnostic tool based on the presence of lymphocytic foci, benign lymphoepithelial lesions and lymphoid follicles. These new histological criteria were compared with established diagnostic criteria for the labial biopsy in 35 consecutive patients suspected for pSS who underwent simultaneous biopsies from both sites. In addition, both biopsies were compared for morbidity. RESULTS: The first analysis revealed a focus score of >or=1 or lymphocytic infiltrates (not fulfilling the criterion of a focus score of 1) combined with benign lymphoepithelial lesions as diagnostic criteria for pSS. When comparing the parotid biopsy with the labial biopsy sensitivity and specificity were comparable (sensitivity 78%, specificity 86%). Level of pain was comparable and no loss of motor function was observed. No permanent sensory loss was observed after parotid biopsy, while labial biopsy led to permanent sensory loss in 6% of the patients. Malignant lymphoma was detected in one parotid biopsy by chance, without involvement of the labial salivary gland. CONCLUSION: A parotid biopsy has a diagnostic potential comparable with that of a labial biopsy in the diagnosis of pSS, and may be associated with less morbidity.", "author" : [ { "dropping-particle" : "", "family" : "Pijpe", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalk", "given" : "W W I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wal", "given" : "J E", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kluin", "given" : "Ph M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roodenburg", "given" : "J L N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "335-341", "title" : "Parotid gland biopsy compared with labial biopsy in the diagnosis of patients with primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁸", "plainTextFormattedCitation" : "148", "previouslyFormattedCitation" : "¹⁴⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }148, although parotid biopsy has also been used by some groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.30381", "ISBN" : "1529-0131 (Electronic)\\r0004-3591 (Linking)", "ISSN" : "1529-0131", "PMID" : "21480190", "abstract" : "OBJECTIVE: To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sj\u00f6gren's syndrome (SS).\\n\\nMETHODS: The database of the Sj\u00f6gren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features.\\n\\nRESULTS: LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of \u22651 per 4 mm\u00b2) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of \u22651 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of \u22651 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of \u22651 than were those with a higher flow rate, after controlling for other phenotypic features of SS.\\n\\nCONCLUSION: Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of \u22651 per 4 mm\u00b2, as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.", "author" : [ { "dropping-particle" : "", "family" : "Daniels", "given" : "Troy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Darren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "Caroline H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f8dt", "given" : "Morten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ava", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanfranchi", "given" : "Hector", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Challacombe", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam", "given" : "Mi Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Yvonne", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f8dt", "given" : "Julie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holm", "given" : "Helena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bisio", "given" : "Patricia a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gandolfo", "given" : "Mariana S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sawaki", "given" : "Toshioki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mengtao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varghese-Jacob", "given" : "Beni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibsen", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keszler", "given" : "Alicia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurose", "given" : "Nozomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nojima", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Odell", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "Lindsey a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jordan", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2021-30", "title" : "Associations between salivary gland histopathologic diagnoses and phenotypic features of Sj\u00f6gren's syndrome among 1,726 registry participants.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁹", "plainTextFormattedCitation" : "149", "previouslyFormattedCitation" : "¹⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }149. Focal lymphocytic sialadenitis (FLS), defined as ≥ 1 dense aggregate of ≥ 50 lymphocytes in perivascular or periductal areas is considered the key histopathologic feature of SjS (Figure 8)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.30381", "ISBN" : "1529-0131 (Electronic)\\r0004-3591 (Linking)", "ISSN" : "1529-0131", "PMID" : "21480190", "abstract" : "OBJECTIVE: To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sj\u00f6gren's syndrome (SS).\\n\\nMETHODS: The database of the Sj\u00f6gren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features.\\n\\nRESULTS: LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of \u22651 per 4 mm\u00b2) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of \u22651 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of \u22651 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of \u22651 than were those with a higher flow rate, after controlling for other phenotypic features of SS.\\n\\nCONCLUSION: Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of \u22651 per 4 mm\u00b2, as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.", "author" : [ { "dropping-particle" : "", "family" : "Daniels", "given" : "Troy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Darren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "Caroline H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f8dt", "given" : "Morten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ava", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanfranchi", "given" : "Hector", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Challacombe", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam", "given" : "Mi Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Yvonne", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f8dt", "given" : "Julie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holm", "given" : "Helena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bisio", "given" : "Patricia a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gandolfo", "given" : "Mariana S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sawaki", "given" : "Toshioki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mengtao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varghese-Jacob", "given" : "Beni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibsen", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keszler", "given" : "Alicia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurose", "given" : "Nozomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nojima", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Odell", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "Lindsey a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jordan", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2021-30", "title" : "Associations between salivary gland histopathologic diagnoses and phenotypic features of Sj\u00f6gren's syndrome among 1,726 registry participants.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁹", "plainTextFormattedCitation" : "149", "previouslyFormattedCitation" : "¹⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }149; the finding of germinal centre-like structures has been associated with a higher risk of lymphomaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keu453", "ISSN" : "1462-0332", "PMID" : "25433039", "abstract" : "OBJECTIVE: The aim of this study was to assess intraobserver and interobserver reliability of minor salivary gland biopsy (MSGB) in SS.\\n\\nMETHODS: All MSGBs available from the Tolerance and Efficacy of Rituximab in Primary Sj\u00f6gren's Syndrome (TEARS) study were subjected to a standardized blinded assessment by a single specifically trained pathologist twice at a 2 month interval; both the Chisholm-Mason (CM) grade and the focus score (FS) were determined. Baseline histopathological reports by local pathologists at each study centre were compared with the first standardized blinded assessment. Agreement was assessed for the dichotomized FS (dFS) and dichotomized CM (dCM) grade, as well as for nine other histopathological features.\\n\\nRESULTS: Eighty-nine MSGBs were studied. Intraobserver \u03ba values were 1 for dFS, 0.80 for dCM, 0.67 for germinal centre-like structures, 0.44 for fibrosis and 0.29 for confluent foci. Most of the local histopathological reports based their diagnosis on the CM grade, although the FS was often reported or the data needed to determine it were provided. Interobserver agreement \u03ba values were 0.71 for dFS, 0.64 for dCM, 0.46 for focal lymphocytic sialadenitis, 0.42 for non-specific chronic inflammation and 0.16 for fibrosis.\\n\\nCONCLUSION: Although FS reliability was good, disparities were noted in the assessment methods used by local pathologists. The protocol for FS determination was not followed routinely, with the result that the FS was often overestimated. Germinal centre-like structures, which predict lymphoma, showed good reliability but were inconsistently reported.", "author" : [ { "dropping-particle" : "", "family" : "Costa", "given" : "Sebastian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quintin-Rou\u00e9", "given" : "Isabelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lesourd", "given" : "Agn\u00e8s", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berthelot", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre-Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vittecoq", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcorelles", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-9", "title" : "Reliability of histopathological salivary gland biopsy assessment in Sj\u00f6gren's syndrome: a multicentre cohort study.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3899/jrheum.131527", "ISSN" : "0315-162X", "PMID" : "25274895", "abstract" : "OBJECTIVE: Germinal center (GC)-like structures have previously been observed in minor salivary glands (MSG) of patients with primary Sjogren syndrome (pSS). The aim of our study was to explore the prevalence and features of GC-like structures and B cell clonality in patients with pSS with and without lymphoma. METHODS: Based on a nationwide survey in Norway, we included 21 patients with pSS and with a concomitant lymphoma from whom MSG and/or lymphoma biopsies were available. Tonsil biopsies and MSG from 28 patients with pSS without lymphoma were used as controls. The presence of GC-like structures was investigated with H&E staining and double staining for CD21/IgD and CD38/IgD. B cell clonality in MSG and tumors were investigated with analysis of immunoglobulin gene rearrangements. RESULTS: H&E labeling of MSG revealed GC-like structures in 17/40 (43%) of the patients: 4/12 (33%) with and 13/28 (46%) without lymphoma. Staining for CD21/CD38/IgD demonstrated CD21+ networks in 27/40 (68%) of the patients. CD21+/CD38- infiltrates were seen in 25/40 (63%) of the patients, and 16 of these were IgD+ within the infiltrate. Five percent (2/40) of the patients presented with CD21+/CD38+ infiltrates resembling tonsillar GC. Monoclonal B cell infiltration in MSG was present in 5/12 patients (42%) with and 5/28 patients (18%) without lymphoma (p=0.12). In 2/10 (20%) of cases where both MSG and lymphoma biopsies were available, identical clonal rearrangements were detected. CONCLUSION: GC-like structures seen in H&E-stained MSG may represent various subtypes of CD21+ infiltrates. We were unable to detect a clear association between cellular infiltrates, B cell clonality, and lymphoma development.", "author" : [ { "dropping-particle" : "", "family" : "Johnsen", "given" : "S. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berget", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Jonsson", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helgeland", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omdal", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Rheumatology", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "2214-2222", "title" : "Evaluation of Germinal Center-like Structures and B Cell Clonality in Patients with Primary Sjogren Syndrome with and without Lymphoma", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.semarthrit.2014.05.015", "ISSN" : "1532-866X", "PMID" : "24935529", "abstract" : "OBJECTIVES: Several histological scoring systems, including the focus score, performed in minor salivary glands (MSGs) by hematoxylin-eosin (H&E) staining, have been employed in clinical practice to assess the inflammatory infiltrate and provide the diagnosis of primary Sjo\u00a8gren\u05f3s syndrome (pSS). Aims of this study were to integrate different scoring systems and identify potential differences in the molecular profile of lymphoid cytokines related to germinal center (GC) formation and clinical subsets in pSS.\\n\\nMETHODS: Overall, 104 pSS patients and 40 subjects with sicca non-pSS were retrospectively evaluated. MSG biopsies were evaluated by H&E and immunofluorescence to assess histological pattern, Chisholm and Mason grading system, Tarpley score, a grading for the severity of inflammatory infiltrate, T-/B-cell segregation, and the presence of GC. MSGs from 50 pSS patients and 30 sicca non-pSS patients were processed by real-time PCR to assess LT\u03b1, LT\u03b2, BAFF, CXCR4, CXCL12, CXCR5, CXCL13, CCR7, CCL19, and CCL21.\\n\\nRESULTS: GCs presence was associated with anti-Ro/SSA and anti-La/SSB antibodies, hypergammaglobulinemia, salivary gland swelling, higher Tarpley score and focus score, and extraglandular involvement but, at multivariate analysis, only extraglandular involvement was independently associated to GC. pSS patients displayed higher level of all cytokines compared to those with sicca symptoms. GC(+) pSS patients displayed higher level of all cytokines compared to those GC(-).\\n\\nCONCLUSIONS: Our study demonstrates that different histopathological patterns, including GC presence, reflect different cytokine expression and different clinical subsets. We believe that the combined immunofluorescence/molecular approach in MSGs would help to tailor diagnostic and therapeutic approach for different subsets of pSS patients.", "author" : [ { "dropping-particle" : "", "family" : "Carubbi", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alunno", "given" : "Alessia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cipriani", "given" : "Paola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benedetto", "given" : "Paola", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruscitti", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berardicurti", "given" : "Onorina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartoloni", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bistoni", "given" : "Onelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caterbi", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciccia", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Triolo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giacomelli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in arthritis and rheumatism", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "314-24", "title" : "Is minor salivary gland biopsy more than a diagnostic tool in primary Sjo\u00a8gren\u05f3s syndrome? Association between clinical, histopathological, and molecular features: A retrospective study.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.semarthrit.2012.07.003", "ISBN" : "1532-866X; 0049-0172", "ISSN" : "00490172", "PMID" : "22995442", "abstract" : "Objectives: To determine whether the presence of germinal centers (GCs) in salivary glands of patients with primary Sj??gren's syndrome (pSS) is related to the severity of disease course and distinct immunopathology features. Methods: A systematic search was performed in September 2011 for terms and synonyms of Sj??gren's syndrome and germinal centers. A total of 80 articles were retrieved, of which 16 were included for (meta-) analysis. Results: GC morphology was present in a mean ?? SD 25.1 ?? 5.0% of pSS patients. Mean lymphocyte focus scores were 1.25 points higher in patients with GCs as compared to those without GCs. Saliva production was reduced in patients with GCs, although this did not reach statistical significance. Percentages of patients positive for rheumatoid factor, anti-Sj??gren's syndrome A (SSA), and anti-Sj??gren's syndrome B (SSB) antibodies were significantly higher in patients with GCs (mean increase, 15%, 18%, and 18%, respectively). Additionally, patients with GCs were characterized by enhanced levels of local and systemic proinflammatory mediators. Importantly, these patients have a higher risk of lymphoma development (14% versus 1%). Conclusions: Patients with GCs are characterized by more severe disease, although the small number of studies and their design hamper generalizability of results. The precise mechanisms that contribute to the development and persistence of germinal centers in pSS are largely unknown. This and the strongly increased risk of lymphoma development warrant intensive studies for the role of germinal centers in the immunopathology of pSS. ?? 2013 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Risselada", "given" : "Anna P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Looije", "given" : "Marjolein F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "Aike a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijlsma", "given" : "Johannes W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roon", "given" : "Joel a G", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "368-376", "title" : "The Role of Ectopic Germinal Centers in the Immunopathology of Primary Sj??gren's Syndrome: A Systematic Review", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^150\u2013153", "plainTextFormattedCitation" : "150\u2013153", "previouslyFormattedCitation" : "^150\u2013153" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }150–153. The key requirements for a correct histological evaluation are an adequate number of informative glands (3–5) with a sufficient glandular surface to be evaluated, and the determination of an average focus score (FS)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.30381", "ISBN" : "1529-0131 (Electronic)\\r0004-3591 (Linking)", "ISSN" : "1529-0131", "PMID" : "21480190", "abstract" : "OBJECTIVE: To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sj\u00f6gren's syndrome (SS).\\n\\nMETHODS: The database of the Sj\u00f6gren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features.\\n\\nRESULTS: LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of \u22651 per 4 mm\u00b2) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of \u22651 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of \u22651 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of \u22651 than were those with a higher flow rate, after controlling for other phenotypic features of SS.\\n\\nCONCLUSION: Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of \u22651 per 4 mm\u00b2, as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.", "author" : [ { "dropping-particle" : "", "family" : "Daniels", "given" : "Troy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Darren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "Caroline H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f8dt", "given" : "Morten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ava", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanfranchi", "given" : "Hector", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Challacombe", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam", "given" : "Mi Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Yvonne", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f8dt", "given" : "Julie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holm", "given" : "Helena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bisio", "given" : "Patricia a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gandolfo", "given" : "Mariana S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sawaki", "given" : "Toshioki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mengtao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varghese-Jacob", "given" : "Beni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibsen", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keszler", "given" : "Alicia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurose", "given" : "Nozomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nojima", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Odell", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "Lindsey a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jordan", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2021-30", "title" : "Associations between salivary gland histopathologic diagnoses and phenotypic features of Sj\u00f6gren's syndrome among 1,726 registry participants.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁹", "plainTextFormattedCitation" : "149", "previouslyFormattedCitation" : "¹⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }149. FLS is considered the gold standard diagnostic test for SjS but should be interpreted with caution in the absence of a suggestive clinical scenario, since FLS has been reported in 2.5% of autopsy subjectsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0904-2512 (Print)\\r0904-2512 (Linking)", "ISSN" : "0904-2512", "PMID" : "11140903", "abstract" : "Investigation of age-related prevalence of various types of focal lymphocytic infiltration (FLI) and degrees of histomorphologic changes was conducted on 120 biopsies of palatal and labial salivary glands (PSG and LSG, respectively) obtained from autopsy subjects free of salivary gland tumors/diseases. Biopsies were divided into young (<30 years, n=30), adult (30-60 years, n=45) and old (>60 years, n=45) age groups. A modified Chisholm & Mason grading system was used to record grades of FLI and a modified Greenspan et al. system was used to evaluate the severity of histomorphologic changes. The prevalence of FLI in PSG increased significantly from 10% in the young group to 46.6% in the old group (P=0.0012). No significant changes were found with aging in LSG. FLI was significantly more prevalent in the adult and old age groups in PSG as compared with LSG (P=0.015 and P=0.003, respectively). Both glands demonstrated significant histomorphologic changes among age groups (p<0.0001); however, these changes were significantly less common in the old age group in PSG as compared to LSG (P=0.003). In cases showing severe histomorphologic changes, FLI was not present. Therefore, FLI should not be considered as part of the deteriorating histomorphologic changes that are usually encountered in salivary glands with aging. The immunologic profile of these infiltrates should be further clarified to understand their role, both in physiologic and pathologic conditions.", "author" : [ { "dropping-particle" : "", "family" : "Vered", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchner", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haimovici", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiss", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dayan", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "7-11", "title" : "Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵⁴", "plainTextFormattedCitation" : "154", "previouslyFormattedCitation" : "¹⁵⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }154 and 17% of young asymptomatic individualsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.10668", "ISSN" : "0004-3591", "PMID" : "12382301", "abstract" : "OBJECTIVE: To determine the prevalence and severity of focal lymphocytic sialadenitis in minor salivary glands of healthy, asymptomatic individuals, in whom Sj\u00f6gren's syndrome (SS) has been excluded. METHODS: Charts of 54 healthy volunteers who had salivary gland biopsies at the National Institutes of Health from January 1992 to August 1998 were reviewed. The healthy volunteers served as control subjects in various studies of salivary dysfunction. Significant medical conditions including SS were excluded. A biopsy with a focus score (FS) >1 was regarded as positive. Descriptive statistics were used to summarize the population's characteristics. RESULTS: The frequency of focal lymphocytic infiltration in the healthy volunteers was about 15% (8 of 54). None of these individuals had subjective xerostomia or dry eyes. The positive FS ranged from 2 to 6. FS did not correlate with age, smoking, serologic findings, or salivary flow in these patients. CONCLUSION: Lymphocytic infiltration in minor salivary glands is not uncommon among individuals without a history of salivary gland dysfunction. This finding is in agreement with the result of a previous autopsy survey study, indicating that focal sialadenitis may occur in the absence of SS.", "author" : [ { "dropping-particle" : "", "family" : "Radfar", "given" : "Lida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleiner", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Philip C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pillemer", "given" : "Stanley R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "520-524", "title" : "Prevalence and clinical significance of lymphocytic foci in minor salivary glands of healthy volunteers.", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵⁵", "plainTextFormattedCitation" : "155", "previouslyFormattedCitation" : "¹⁵⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }155. [H3] Classification criteria. The set of classification criteria used worldwide in the last 10 years is the AECG classification criteria proposed by Vitali et al in 2002ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.61.6.554", "ISBN" : "0003-4967 (Print)\\r0003-4967 (Linking)", "ISSN" : "0003-4967", "PMID" : "12006334", "abstract" : "Classification criteria for Sj\u00f6gren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.", "author" : [ { "dropping-particle" : "", "family" : "Vitali", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexander", "given" : "E L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carsons", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kassan", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pillemer", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weisman", "given" : "M H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "554-8", "title" : "Classification criteria for Sj\u00f6gren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵⁶", "plainTextFormattedCitation" : "156", "previouslyFormattedCitation" : "¹⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }156, which require evidence of an SjS-specific autoimmune process (either anti-Ro/SS-A and/or La/SSB antibodies or FLS in salivary gland biopsy) with a sensitivity of 93.5% and a specificity of 94%. In 2012, Shiboski et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.21591", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22563590", "abstract" : "OBJECTIVE: We propose new classification criteria for Sj\u00f6gren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.\\n\\nMETHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sj\u00f6gren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American\u2013European Consensus Group (AECG) criteria, a model-based \u201cgold standard\u201dobtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development.\\n\\nRESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications.\\n\\nCONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. 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"suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "475-87", "title" : "American College of Rheumatology classification criteria for Sj\u00f6gren's syndrome: a data-driven, expert consensus approach in the Sj\u00f6gren's International Collaborative Clinical Alliance cohort.", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³³", "plainTextFormattedCitation" : "133", "previouslyFormattedCitation" : "¹³³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }133 proposed a new set of classification criteria for SjS on behalf of the American College of Rheumatology (ACR criteria), which reached similar figures (sensitivity of 92.5%, specificity of 95.4%). Table 6 summarizes the individual values for sensitivity and specificity of the main criteria; only two criteria (anti-Ro/La antibodies and FLS) have a sensitivity and specificity >80% in all reported studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.21591", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22563590", "abstract" : "OBJECTIVE: We propose new classification criteria for Sj\u00f6gren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.\\n\\nMETHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sj\u00f6gren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American\u2013European Consensus Group (AECG) criteria, a model-based \u201cgold standard\u201dobtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development.\\n\\nRESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications.\\n\\nCONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.", "author" : [ { "dropping-particle" : "", "family" : "Shiboski", "given" : "S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "L A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "A N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Challacombe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanfranchi", "given" : "H", "non-dropping-particle" : "", 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"N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sack", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shirlaw", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugai", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcher", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "475-87", "title" : "American College of Rheumatology classification criteria for Sj\u00f6gren's syndrome: a data-driven, expert consensus approach in the Sj\u00f6gren's International Collaborative Clinical Alliance cohort.", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.1780360309", "ISSN" : "0004-3591", "PMID" : "8452579", "abstract" : "Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.", "author" : [ { "dropping-particle" : "", "family" : "Vitali", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balestrieri", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bencivelli", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernstein", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braga", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coll", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vita", "given" : "S", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "340-347", "title" : "Preliminary criteria for the classification of Sj\u00f6gren's syndrome. Results of a prospective concerted action supported by the European Community", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0003-4967", "PMID" : "7979575", "abstract" : "AIM: To establish a definitive set of diagnostic criteria in a multicentre European study a selected number of oral and ocular tests were performed on a large number of patients with Sj\u00f6grens Syndrome (SS) and controls. The diagnostic accuracy of each test for patients with primary and secondary SS and for controls at different ages, was studied. METHODS: Each centre received a clinical chart describing the series of tests to be conducted. The tests included: questionnaires for dry eye and dry mouth symptoms, Schirmer's-I-test (ScT), tear fluid lactoferrin level (TFLL), break-up time (BUT) and rose Bengal score (RBS) for the eye evaluation; unstimulated and stimulated whole saliva collection (UWSC and SWSC), salivary gland scintigraphy (SGS), parotid sialography (PS) and minor salivary gland biopsy (MSGB) for oral involvement. RESULTS: Data from 22 centres and 11 countries was collected on a total of 447 patients with SS (246 with primary SS and 201 with secondary SS) and 246 controls (of whom 113 had a connective tissue disease without SS). Among the ocular symptoms, the feeling of dry eye and 'sand in the eye' were the ones most commonly recorded in patients with SS. Similarly, the feeling of dry mouth, appearing either spontaneously or when the patient was eating or breathing, was the most frequent subjective oral symptom. Among the ocular tests, ScT showed the best balance between sensitivity and specificity (76.9% and 72.4% respectively), while RBS was the most specific test (81.7%). ScT and RBS gave also sufficiently concordant results. TFLL and BUT gave considerably less reliable results, which were not concordant with each other or with the other ocular tests. The quantitative lacrimal tests ScT and TFLL produced significantly different results in elderly controls, while RBS did not. Abnormal results for all of the ocular tests were less marked and less frequent in patients with secondary SS than in those with primary SS. The oral tests (except SWSC) were generally more reliable than the ocular tests in diagnosing SS. In particular, PS was the most specific diagnostic tools (100%), while MSGB (where the presence of at least one inflammatory focus was considered as indicative for the diagnosis) showed a good balance between sensitivity and specificity (82.4% and 86.2%, respectively). The tests showed a good degree of agreement, and, with the exception of UWSC, were not influenced by age. In the oral, as in the ocular tests, abnormal results were \u2026", "author" : [ { "dropping-particle" : "", "family" : "Vitali", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "637-647", "title" : "The European Community Study Group on diagnostic criteria for Sj\u00f6gren's syndrome. Sensitivity and specificity of tests for ocular and oral involvement in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Vitali C, Bombardieri S, Moutsopoulos HM, Coll J, Gerli R, Hatron PY", "given" : "Kater L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konttinen YT, Manthorpe R, Meyer O, Mosca M, Ostuni P, Pellerito RA", "given" : "Pennec Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porter SR, Richards A, Sauvezie B, Schi\u00f8dt M, Sciuto M, Shoenfeld Y", "given" : "Skopouli FN", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smolen JS, Soromenho F, Tishler M, Wattiaux MJ", "given" : "et al.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Assessment of the European classification criteria for Sj\u00f6gren's syndrome in a series of clinically defined cases: results of a prospective multice... - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/sj.eye.6702204", "ISSN" : "0950-222X", "PMID" : "16397619", "abstract" : "OBJECTIVE: To evaluate the diagnostic performance of the tests included in primary Sjogren's syndrome (SS-I) diagnostic criteria (Schirmer I, break-up time, vital dye staining) and to compare them with other examinations related to the ocular surface status. METHODS: Clinical and cytological data were collected from 177 patients (62 SS-1, 56 non-SS autoimmune diseases, 59 Sicca syndrome). Tear tests included: a validated questionnaire on symptoms, Schirmer I, Jones test, Ferning test, BUT, corneal aesthesiometry, tear clearance test, lissamine green staining, impression conjunctival cytology. Data were statistically evaluated and sensitivity, specificity, likelihood ratio (LR+), receiver-operating characteristics (ROC) curves were calculated for each test. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (sensitivity 0.42; specificity 0.76; LR+1.75) and BUT (sensitivity 0.92; specificity 0.17; LR+1.11) (area under the curve in ROC analysis <0.58). Validated subjective symptoms questionnaire (sensitivity 0.89; specificity 0.72; LR+3.18), Jones test (sensitivity 0.60; specificity 0.88; LR+5), corneal aesthesiometry (sensitivity 0.80; specificity 0.67; LR+2.42), and tear clearance test (sensitivity 0.63; specificity 0.84; LR+3.93), all exhibited a high diagnostic performance (area under the curve in the ROC analysis always >0.70). Lissamine green staining exhibited the best performance (sensitivity 0.63; specificity 0.89; LR+5.72) but the result could be distorted by an incorporation bias. CONCLUSIONS: Our data suggest to implement the items for ocular signs and symptoms contained in many SS-I diagnostic criteria with the use of a validated questionnaire, performance of Jones test, corneal aesthesiometry measurement, and tear clearance rate evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Versura", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frigato", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cellini", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mul\u00e8", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malavolta", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campos", "given" : "E C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eye (London, England)", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "229-237", "title" : "Diagnostic performance of tear function tests in Sjogren's syndrome patients.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "ISSN" : "1790-5427", "PMID" : "25097897", "abstract" : "Our aim was to validate eight scintigraphic salivary gland (SG) parameters, as diagnostic parameters in patients with Sj\u00f6gren's syndrome (SS). We used the standardized stimulated dynamic salivary gland scintigraphy (DSGS) protocol and correlated this with the unstimulated whole sialometry (UWS) functions. The DSGS and UWS tests meeting the European and the USA diagnostic classification criteria for SS were applied in twenty patients and in ten normal controls. The DSGS tests were performed 60min after the intravenous (i.v.) injection of 370MBq of technetium-99m-pertechnetate ((99m)TcO(-)4) and after per os stimulation with a 0.5g tablet of ascorbic acid administered 40min after the injection. Using time-activity curves, eight different parameters were calculated for each parotid gland (PG) and each submandibular salivary gland (SMG): a) time at maximum counts (Tmax), b) time at minimum counts (Tmin), c) maximum accumulation (MA), d) accumulation velocity (AV), e) maximum secretion (MS), f) maximum stimulated secretion (MSS), g) stimulated secretion velocity (SSV), and h) uptake ratio (UR). Values of UWS below 2.5mL/15min, were considered abnormal. All these parameters, as for the PG, showed significant abnormality in SS patients (P<0.001), especially of the secretion function. All SMG parameters also showed a significant abnormality (P<0.001), but especially of the accumulation function. There was a greater impairment of the above parameters in SMG than in PG in the SS patients. Sensitivity of the standardized DSGS was 100%, specificity 80%, negative prognostic value 100%, and positive prognostic value 91%. Sensitivity of UWS was 75%. In conclusion, this paper suggested that the best diagnostic parameters for the SS patients were those of: a) the maximum secretion, b) the maximum stimulated secretion for both the parotid and the submandibular glands, c) maximum accumulation and d) accumulation velocity of submandibular glands. The times at maximum and at minimum counts were non diagnostic.", "author" : [ { "dropping-particle" : "", "family" : "Dugonji\u0107", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefanovi\u0107", "given" : "Du\u0161an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ethurovi\u0107", "given" : "Branka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spasi\u0107-Joki\u0107", "given" : "Vesna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajdinovi\u0107", "given" : "Boris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hellenic journal of nuclear medicine", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "116-22", "title" : "Evaluation of diagnostic parameters from parotid and submandibular dynamic salivary glands scintigraphy and unstimulated sialometry in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{133,157\u2013161}", "plainTextFormattedCitation" : "133,157\u2013161", "previouslyFormattedCitation" : "^{133,157\u2013161}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }133,157–161.[H2] Screening and preventionSjS is a chronic, not preventable disease. But some screening approaches to specific subsets of patients may prevent, or ensure timely treatment, of the main complications of the disease. Oral and ocular dryness are the principal symptoms leading to a suspicion of SjS, as well as episodic parotid gland swelling. But current evidence suggests we cannot await the development of sicca features in order to diagnose SjS. A large number of non-sicca and laboratory features may appear up to 20 years before sicca symptoms become overtADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2013.278448", "ISSN" : "0098-7484", "PMID" : "24193084", "abstract" : "The article discusses a study on autoantibodies present before symptom onset in patients with Sj\u00f6gren syndrome. The study found that there was no statistically significant difference in the time between a positive test result and a symptom onset between autoantibodies. It also noted that most cases produced autoantibodies many years before clinical onset of Sj\u00f6gren syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Jama", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1854", "title" : "Autoantibodies Present Before Symptom Onset in Primary Sj\u00f6gren Syndrome", "type" : "article-journal", "volume" : "310" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.39214", "ISSN" : "2326-5205", "PMID" : "26109563", "abstract" : "OBJECTIVE: Autoantibodies are highly characteristic of primary Sj\u00f6gren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets.\n\nMETHODS: A nested case-control design linking data from the Malm\u00f6 primary SS registry and 3 Swedish healthcare biobanks was applied. In all, 175 serum samples obtained from 117 individuals before diagnosis of primary SS and 1 serum sample from each of 117 matched controls were analyzed for antinuclear antibodies (ANAs), rheumatoid factor (RF), and antibodies against Ro 60/SSA, Ro 52/SSA, and La/SSB.\n\nRESULTS: Considering all patients with primary SS who were autoantibody positive after diagnosis, at least one autoantibody specificity was detected in 81% up to 20 years (median 4.3-5.1 years) before diagnosis. Those found most often were ANAs, followed by RF, anti-Ro 60/SSA, anti-Ro 52/SSA, and anti-La/SSB. Anti-Ro/SSA and anti-La/SSB antibodies were strongly associated with the risk of developing primary SS, especially early-onset disease and a severe disease course. When Bayesian prior prevalence estimates for primary SS were included in the calculation, prediagnostic anti-Ro 60/SSA and anti-Ro 52/SSA had the highest positive predictive values (25% and 100%, respectively).\n\nCONCLUSION: Our findings indicate that autoantibodies are present for up to 18-20 years before the diagnosis of primary SS, but we cannot exclude even earlier seropositivity, since for most patients, the earliest sample analyzed was positive. In families with multiple cases of autoimmune disease, autoantibody profiling, along with assessment of genetic risk, enables identification of susceptible individuals in a predisease state.", "author" : [ { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6str\u00f6m", "given" : "Bitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brokstad", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henriksson", "given" : "Gunnel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "2427-36", "title" : "Prediction of Sj\u00f6gren's Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^86,87", "plainTextFormattedCitation" : "86,87", "previouslyFormattedCitation" : "^86,87" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86,87. Detecting the early immunological and histopathological signatures of the disease has the greatest clinical utility. Autoantibodies (especially anti-Ro) are clues to the early diagnosis of primary SjS. The development of annular erythema, autoimmune cytopenias, or CHB/neonatal lupus in babies of mothers carrying anti-Ro antibodies are good examplesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrrheum.2015.29", "ISSN" : "1759-4804", "PMID" : "25800217", "abstract" : "Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder.", "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izmirly", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buyon", "given" : "Jill P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khamashta", "given" : "Munther A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015", "5" ] ] }, "page" : "301-12", "title" : "The clinical spectrum of autoimmune congenital heart block.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶²", "plainTextFormattedCitation" : "162", "previouslyFormattedCitation" : "¹⁶²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }162. In contrast, neurological involvements are related to a lower frequency of autoantibodies and often require a salivary gland biopsy disclosing FLS in order to diagnose SjS earlyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Expert Review of Clinical Immunology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Early Diagnosis of primary Sj\u00f6gren\u2019s Syndrome: EULAR-SS Task Force Clinical Recommendations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁷", "plainTextFormattedCitation" : "127", "previouslyFormattedCitation" : "¹²⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }127. SjS is now being diagnosed earlier ? in the Spanish cohort, the mean age at diagnosis was 62 years in the first reported series in 1997 and is now 54 yearsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0025-7753 (Print)\\r0025-7753 (Linking)", "PMID" : "9312582", "abstract" : "BACKGROUND: To determine the clinical and immunologic characteristics of a large cohort of patients with primary Sjorgen's syndrome (SS) and to asses if the sex, the age at onset, the time of evolution and the immunologic pattern define different subsets with specific characteristics. PATIENTS AND METHODS: We included 80 patients (76 female and 4 male) that were prospectively studied at our Unit. All patients fulfilled the European Community criteria proposed in 1993 for the diagnosis of SS. RESULTS: Mean age of patients was 62 years with a mean disease duration of 8 years. The most frequently observed clinical manifestations were xerostomia (96%), xerophthalmia (94%) and parotidomegaly (46%). The main extraglandular manifestations were arthritis (45%), Raynaud's phenomenon (20%) and liver involvement (19%). The immunologic study showed antinuclear antibodies in 82% of patients, rheumatoid factor in 45%, anti-Ro/SS-A in 40% and anti-La/SS-B in 20%. In patients with an onset of disease before the age of 40 years, a higher prevalence of parotidomegaly, peripheral neuropathy, cutaneous vasculitis, rheumatoid factor, anti-Ro/SS-A and anti-La/SS-B antibodies was observed. A disease duration longer than 10 years was associated with a higher prevalence of pulmonary involvement and more focus of mononuclear cells in the minor salivary glands. Clinical manifestations associated to any one or more immunologic marker (rheumatoid factor, anti-Ro/SS-A and/or anti-La/SS-B) were Raynaud's phenomenon, arthritis, thyroid disease, cutaneous vasculitis and peripheral neuropathy. CONCLUSIONS: Primary SS is an autoimmune disease characterized by a marked heterogeneity in the clinical presentation and evolution, thus allowing the definition of several subsets of patients with their own clinical and immunological characteristics.", "author" : [ { "dropping-particle" : "", "family" : "Ramos", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garcia-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miret", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munoz", "given" : "F J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Espinosa", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Med Clin (Barc)", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "652-657", "title" : "[Primary Sjogren's syndrome: clinical and immunologic study of 80 patients]", "type" : "article-journal", "volume" : "108" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.intimp.2015.03.027", "ISSN" : "15675769", "PMID" : "25899085", "abstract" : "OBJECTIVE To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sj\u00f6gren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of systemic activity measured by ESSDAI score. PATIENTS AND METHODS By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins [IVIG] and/or rituximab [RTX]). RESULTS There were 1048 (94%) females and 72 (6%) males, with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255\u201423%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34\u20130.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents, patients as inadequately treated, mainly associated with articular involvement of low/moderate activity. CONCLUSION The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted.", "author" : [ { "dropping-particle" : "", "family" : "Gheitasi", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraile", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su\u00e1rez-Cuervo", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casanovas", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n", "given" : "F.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qanneta", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9rez-Alvarez", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripoll", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akasbi", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinilla", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "J.A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00edaz-L\u00f3pez", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morera-Morales", "given" : "M.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retamozo", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Immunopharmacology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "How we are treating our systemic patients with primary Sj\u00f6gren syndrome? Analysis of 1120 patients", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^163,164", "plainTextFormattedCitation" : "163,164", "previouslyFormattedCitation" : "^163,164" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }163,164.[H1] Management[H2] Follow-up and monitoring The clinical spectrum of SjS may vary from a very mild (probably there are non-symptomatic cases, which never become diagnosed) pure exocrine disease to a very severe systemic disorder complicated by life threatening organ dysfunctions or non-Hodgkin’s lymphomaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "(Canadian+Medical+Association+Journal)+2014", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Mavragani CP", "given" : "Moutsopoulos HM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Sj\u00f6gren syndrome. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁵", "plainTextFormattedCitation" : "165", "previouslyFormattedCitation" : "¹⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }165. Consequently, requirements for monitoring and follow-up will differ from patient to patient. A number of studies have shown that in many cases the character of the disease can be clarified successfully from the beginning, while in some patients the course of the disease may evolve into unexpected shape during follow-up. Thus a general monitoring and follow-up plan fitting all patients cannot be provided. Age at disease onset or diagnosis can be importantADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0961-2033", "PMID" : "9607645", "abstract" : "The objective of our study was to determine the clinical and immunological characteristics of primary Sj\u00f6gren's syndrome (SS) in patients with a young onset of the disease. We included 144 consecutive patients (134 female and 10 male; mean age at onset 53 y; range 20-87 y) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS, proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 13 (9%) patients, disease onset occurred before the age of 35. All were female and the disease onset occurred between 20-34 y (mean, 28 y). When compared with patients with older onset, patients with a young onset of the primary SS presented a higher prevalence of lymphadenopathy (54% vs 6%, P < 0.001), rheumatoid factor (70% vs 39%, P=0.034), anti-Ro/SS-A antibodies (70% vs 28%, P=0.004) and monoclonal immunoglobulins (23% vs 4%, P=0.02) in their sera. From the initial diagnosis of SS, three patients with a young-onset of the primary SS have developed lymphoproliferative disease at the time of the study, compared with one patient of the older-onset group (23% vs 1%, P=0.002). Our study shows several differences between younger and older onset patients, including a higher incidence of lymphomas in the younger, thus conferring to the age at onset of the disease a prognostic value.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Espinosa", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reino", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lupus", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "202-6", "title" : "Young onset of primary Sj\u00f6gren's syndrome: clinical and immunological characteristics.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁶", "plainTextFormattedCitation" : "166", "previouslyFormattedCitation" : "¹⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166. Younger patients, who develop seropositive SjS are often prone to more severe and systemic diseaseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.39214", "ISSN" : "2326-5205", "PMID" : "26109563", "abstract" : "OBJECTIVE: Autoantibodies are highly characteristic of primary Sj\u00f6gren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets.\n\nMETHODS: A nested case-control design linking data from the Malm\u00f6 primary SS registry and 3 Swedish healthcare biobanks was applied. In all, 175 serum samples obtained from 117 individuals before diagnosis of primary SS and 1 serum sample from each of 117 matched controls were analyzed for antinuclear antibodies (ANAs), rheumatoid factor (RF), and antibodies against Ro 60/SSA, Ro 52/SSA, and La/SSB.\n\nRESULTS: Considering all patients with primary SS who were autoantibody positive after diagnosis, at least one autoantibody specificity was detected in 81% up to 20 years (median 4.3-5.1 years) before diagnosis. Those found most often were ANAs, followed by RF, anti-Ro 60/SSA, anti-Ro 52/SSA, and anti-La/SSB. Anti-Ro/SSA and anti-La/SSB antibodies were strongly associated with the risk of developing primary SS, especially early-onset disease and a severe disease course. When Bayesian prior prevalence estimates for primary SS were included in the calculation, prediagnostic anti-Ro 60/SSA and anti-Ro 52/SSA had the highest positive predictive values (25% and 100%, respectively).\n\nCONCLUSION: Our findings indicate that autoantibodies are present for up to 18-20 years before the diagnosis of primary SS, but we cannot exclude even earlier seropositivity, since for most patients, the earliest sample analyzed was positive. In families with multiple cases of autoimmune disease, autoantibody profiling, along with assessment of genetic risk, enables identification of susceptible individuals in a predisease state.", "author" : [ { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6str\u00f6m", "given" : "Bitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brokstad", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henriksson", "given" : "Gunnel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "2427-36", "title" : "Prediction of Sj\u00f6gren's Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁷", "plainTextFormattedCitation" : "87", "previouslyFormattedCitation" : "⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }87, while they may not suffer too much from sicca complaints. The reason for the latter may be the well-preserved glandular tissue with a high functional capacity. The ESSPRI instrument seems less useful, although fatigue may be bothering from an early time pointADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2010.143743", "ISBN" : "1468-2060", "ISSN" : "0003-4967", "PMID" : "21345815", "abstract" : "To develop a score for assessment of patients' symptoms in primary Sj\u00f6gren's syndrome (SS): the EULAR SS Patient Reported Index (ESSPRI).", "author" : [ { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Arne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6rner", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "Aike a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Praprotnik", "given" : "Sonja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "Matija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devita", "given" : "Salvatore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandl", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carsons", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutcliffe", "given" : "Nurhan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "968-972", "title" : "EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁷", "plainTextFormattedCitation" : "167", "previouslyFormattedCitation" : "¹⁶⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }167. The ESSDAI on the other hand is a very important tool, and the complete spectrum including all the laboratory items (complement, blood cell counts, cryoglobulins, immunoglobulins, monoclonal components, muscle and liver enzymes, pulmonary and renal function) should be fully assessed at diagnosis and yearly during the first 5 to 10 years of follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n P, Kostov B, Solans R, Fraile G, Su\u00e1rez-Cuervo C", "given" : "Casanovas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasc\u00f3n FJ, Qanneta R, P\u00e9rez-Alvarez R, Ripoll M, Akasbi M, Pinilla B", "given" : "Bosch JA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nava-Mateos J, D\u00edaz-L\u00f3pez B, Morera-Morales ML, Gheitasi H", "given" : "Retamozo S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals M; on behalf of the SS Study Group", "given" : "Autoimmune Diseases Study Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "(GEAS)", "given" : "Spanish Society of Internal Medicine (SEMI)", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Systemic activity and mortality in primary Sj\u00f6gren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2014-206008", "ISBN" : "1468-2060; 0003-4967", "ISSN" : "1468-2060", "PMID" : "25480887", "abstract" : "OBJECTIVES: To define disease activity levels, minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) with the primary Sj\u00f6gren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patient-reported index (ESSPRI).\\n\\nMETHODS: For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI.\\n\\nRESULTS: Low-activity (ESSDAI<5), moderate-activity (5\u2264ESSDAI\u226413) and high-activity (ESSDAI\u226514) levels were defined. MCII of ESSDAI was defined as an improvement of at least three points. The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15%.\\n\\nCONCLUSIONS: This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI\u22655) and define response to treatment as an improvement of ESSDAI at least three points. 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Disease Activity Index (ESSDAI) and the EULAR SS Patient-Reported Index (ESSPRI) were recently developed. We aimed to determine whether patients' symptoms differed between patients with and without systemic involvement and if the disease-specific indices correlated with each other in primary SS.\\n\\nMETHODS: Fifteen French centers included 395 primary SS patients in the Assessment of Systemic Signs and Evolution in Sj\u00f6gren's Syndrome Cohort. At enrollment, physicians completed the ESSDAI, the SS Disease Activity Index (SSDAI), and the Sj\u00f6gren's Systemic Clinical Activity Index (SCAI), and patients completed the ESSPRI, the Sicca Symptoms Inventory, and the Profile of Fatigue and Discomfort. All scores were compared between patients with and without systemic involvement. Correlations between scores of systemic activity and patients' symptoms were obtained.\\n\\nRESULTS: At enrollment, 120 (30.4%) patients had never experienced systemic complication and 155 (39.2%) patients and 120 (30.4%) patients had, respectively, only past or current systemic manifestations. Past or current systemic patients had higher levels of symptoms, except dryness. The ESSDAI did not correlate with the patient-scored ESSPRI (rho = 0.06, P = 0.30), whereas the SSDAI and the SCAI, which include subjective items, did correlate (rho = 0.28 and 0.25, respectively; P < 0.0001 for both).\\n\\nCONCLUSION: Alterations of common patient-reported outcomes are present in all patients with primary SS, including those with systemic complications. However, patient symptoms and systemic complications are 2 different facets of primary SS. Therefore, the use of both systemic and patients' indices, such as the ESSDAI and ESSPRI, are useful. 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A subgroup of patients fulfilling the 2002 AECG criteriaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.61.6.554", "ISBN" : "0003-4967 (Print)\\r0003-4967 (Linking)", "ISSN" : "0003-4967", "PMID" : "12006334", "abstract" : "Classification criteria for Sj\u00f6gren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.", "author" : [ { "dropping-particle" : "", "family" : "Vitali", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexander", "given" : "E L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carsons", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kassan", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pillemer", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weisman", "given" : "M H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "554-8", "title" : "Classification criteria for Sj\u00f6gren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵⁶", "plainTextFormattedCitation" : "156", "previouslyFormattedCitation" : "¹⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }156 presents without measurable autoantibodies to Ro or La. While these are more often the middle aged or older patients, this form of SjS exists also among young individuals. Generally, they have a milder course in terms of systemic complications and usually there is no disease-related increased risk of lymphoma. This group however suffers heavily from sicca complaints and fatigue and the ESSPRI is the ideal instrument to catch the disease burdenADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2010.143743", "ISBN" : "1468-2060", "ISSN" : "0003-4967", "PMID" : "21345815", "abstract" : "To develop a score for assessment of patients' symptoms in primary Sj\u00f6gren's syndrome (SS): the EULAR SS Patient Reported Index (ESSPRI).", "author" : [ { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Arne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6rner", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "Aike a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Praprotnik", "given" : "Sonja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "Matija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devita", "given" : "Salvatore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandl", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carsons", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutcliffe", "given" : "Nurhan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "968-972", "title" : "EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁷", "plainTextFormattedCitation" : "167", "previouslyFormattedCitation" : "¹⁶⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }167. The ESSDAI would typically be very low (<3). After an initial repeated assessment after 1 or 2 years, a well-informed general practitioner might take over the yearly or two-yearly follow-up of these patients, focusing on supportive measures for fatigue and arthralgias and redirecting the patient in case of unexpected organ complications. Ro/La+ patients should be divided into those with risk factors for systemic complications or lymphoma (cryoglobulinemia, hypocomplementemia, purpura) or not. The 25-30% of high risk patients deserve closer follow-up. A clinical assessment every 3-6 months seems mandatory. However, the well-educated patient may be seen yearly and additionally on demand, when pre-defined symptoms/situations mirroring potential lymphoma appear. The physician on charge should follow the ESSDAI score, in particular complement and immunoglobulin levels, monoclonal components, the presence of cryoglobulins and cytopenias, the presence of salivary gland or lymph node swellings, the appearance of cryoglobulinemic or hypergammaglobulinemic vasculitis or of moderate to severe objectively verified peripheral neuropathy. A risk factor not included in the ESSDAI is the presence of either a high focus score (≥3) or germinal-center formation in the salivary gland biopsyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.131527", "ISSN" : "0315-162X", "PMID" : "25274895", "abstract" : "OBJECTIVE: Germinal center (GC)-like structures have previously been observed in minor salivary glands (MSG) of patients with primary Sjogren syndrome (pSS). The aim of our study was to explore the prevalence and features of GC-like structures and B cell clonality in patients with pSS with and without lymphoma. METHODS: Based on a nationwide survey in Norway, we included 21 patients with pSS and with a concomitant lymphoma from whom MSG and/or lymphoma biopsies were available. Tonsil biopsies and MSG from 28 patients with pSS without lymphoma were used as controls. The presence of GC-like structures was investigated with H&E staining and double staining for CD21/IgD and CD38/IgD. B cell clonality in MSG and tumors were investigated with analysis of immunoglobulin gene rearrangements. RESULTS: H&E labeling of MSG revealed GC-like structures in 17/40 (43%) of the patients: 4/12 (33%) with and 13/28 (46%) without lymphoma. Staining for CD21/CD38/IgD demonstrated CD21+ networks in 27/40 (68%) of the patients. CD21+/CD38- infiltrates were seen in 25/40 (63%) of the patients, and 16 of these were IgD+ within the infiltrate. Five percent (2/40) of the patients presented with CD21+/CD38+ infiltrates resembling tonsillar GC. Monoclonal B cell infiltration in MSG was present in 5/12 patients (42%) with and 5/28 patients (18%) without lymphoma (p=0.12). In 2/10 (20%) of cases where both MSG and lymphoma biopsies were available, identical clonal rearrangements were detected. CONCLUSION: GC-like structures seen in H&E-stained MSG may represent various subtypes of CD21+ infiltrates. We were unable to detect a clear association between cellular infiltrates, B cell clonality, and lymphoma development.", "author" : [ { "dropping-particle" : "", "family" : "Johnsen", "given" : "S. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berget", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Jonsson", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helgeland", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omdal", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Rheumatology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "2214-2222", "title" : "Evaluation of Germinal Center-like Structures and B Cell Clonality in Patients with Primary Sjogren Syndrome with and without Lymphoma", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.2010.144782", "ISBN" : "1468-2060; 0003-4967", "ISSN" : "0003-4967", "PMID" : "21715359", "abstract" : "The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sj\u00f6gren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker.", "author" : [ { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vasaitis", "given" : "Lilian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baecklund", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordmark", "given" : "Gunnel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warfvinge", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liedholm", "given" : "Rolf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brokstad", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "Malin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1363-1368", "title" : "Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^151,171", "plainTextFormattedCitation" : "151,171", "previouslyFormattedCitation" : "^151,171" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }151,171. The more of these factors present, the higher the risk for the patient, the tighter the follow-up should be. In case of suspicion of prevailing lymphoma, the further steps have to be determined in collaboration with oncologistsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.110077", "ISBN" : "0315-162X; 0315-162X", "ISSN" : "0315-162X", "PMID" : "21844152", "abstract" : "OBJECTIVE: To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sj\u00f6gren's syndrome (SS).\\n\\nMETHODS: All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical Center Groningen between January 1997 and January 2009 were analyzed. Clinical course and treatment outcome of SS and MALT lymphoma were evaluated.\\n\\nRESULTS: From a total of 329 patients with SS, 35 MALT-SS patients were identified, with a median followup of 76 months (range 16-153 mo). MALT lymphoma was localized in the parotid gland in all cases. Treatment consisted of \"watchful waiting\" (n = 10), surgery (n = 3), radiotherapy (n = 1), surgery combined with radiotherapy (n = 2), rituximab only (n = 13), or rituximab combined with chemotherapy (n = 6). Complete response was observed in 14 patients, partial response in 1 patient, and stable disease in 20 patients. In 6 of 7 patients with initially high SS disease activity (M-protein, cryoglobulins, IgM rheumatoid factor > 100 KIU/l, severe extraglandular manifestations), MALT lymphoma progressed and/or SS disease activity increased after a median followup of 39 months (range 4-98 mo), necessitating retreatment. Only 1 patient with MALT who had low SS disease activity showed progression of lymphoma when left untreated.\\n\\nCONCLUSION: An initially high SS disease activity likely constitutes an adverse prognostic factor for progression of lymphoma and/or SS. Such patients may require treatment for both MALT lymphoma and SS. In SS patients with localized asymptomatic MALT lymphoma and low SS disease activity, a \"watchful waiting\" strategy seems justified.", "author" : [ { "dropping-particle" : "", "family" : "Pollard", "given" : "Rodney P E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pijpe", "given" : "Justin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "Fred K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kluin", "given" : "Philip M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roodenburg", "given" : "Jan L N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "Cees G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "Arjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imhoff", "given" : "Gustaaf W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2198-208", "title" : "Treatment of mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: a retrospective clinical study.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷²", "plainTextFormattedCitation" : "172", "previouslyFormattedCitation" : "¹⁷²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }172. With regard to eye dryness and mouth dryness, monitoring and follow-up aim at prevention of irreversible damage which mainly derives from lack of saliva resulting in tooth damage. Regular visits to a dentist for prophylactic measures and early recognition of threat to the teeth are necessary at least bi-annuallyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Rhodus", "given" : "Nelson L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "An update on the management for the dental patient with Sj\u00f6gren's syndrome and xerostomia. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷³", "plainTextFormattedCitation" : "173", "previouslyFormattedCitation" : "¹⁷³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173. The ocular surface is not as often subject to irreversible damage and regular ophthalmologist visits seem only mandatory in the most severe and treatment resistant cases. [H2] Lymphoma managementSjS is the autoimmune disease where the risk of lymphoma is the highest, the standardized incidence ratio with the general population being between 15 and 20 in older studies and between 5 and 10 in more recent studies (174). Marginal Zone Lymphomas (MZL) and especially MALT lymphomas are the most common histological type of lymphoma encountered in the setting of SjS. Diffuse large B-cell lymphoma (DLBCL) often presents as a progression of a previous low-grade lymphomaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/bjh.13192", "ISBN" : "1365-2141; 0007-1048", "ISSN" : "00071048", "PMID" : "25316606", "abstract" : "Primary Sjogren Syndrome (pSS) is an autoimmune disease associated with an increased risk of lymphoma. Lymphomas complicating pSS are mostly low-grade B cell non-Hodgkin lymphomas, predominantly of marginal zone histological type. Mucosal localization is predominant, notably mucosa-associated lymphoid tissue lymphomas. Lymphomas often develop in organs where pSS is active, such as salivary glands. Germinal centre (GC)-like structures, high TNFSF13B (BAFF) and Flt3-ligand (FLT3LG) levels and genetic impairment of TNFAIP3 are new predictors of lymphoma development. These new findings allow a better understanding of the pathogenic mechanisms leading to lymphoma. We propose the following scenario: auto-immune B cells with rheumatoid factor (RF) activity are continuously stimulated by immune complexes containing antibodies against more specific auto-antigens, such as SSA/Ro, SSB/La or others. Germline abnormality of TNFAIP3 leads to a decreased control of the NF-kB pathway and thus promotes survival of B cells and oncogenic mutations especially in GC structure. Moreover, B cells are stimulated by a positive loop of activation induced by BAFF secretion. Thus, lymphomagenesis associated with pSS exemplifies the development of antigen-driven B-cell lymphoma. The control of disease activity by a well-targeted immunosuppressor is the primary objective of the management of the patient in order to repress chronic B cell stimulation.", "author" : [ { "dropping-particle" : "", "family" : "Nocturne", "given" : "Gaetane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Haematology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "317-327", "title" : "Sj\u00f6gren Syndrome-associated lymphomas: an update on pathogenesis and management", "type" : "article-journal", "volume" : "168" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁴", "plainTextFormattedCitation" : "174", "previouslyFormattedCitation" : "¹⁷⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }174. The salivary glands (overwhelmingly the parotids) are the most frequent localization of MALT lymphomas in patients with SjS, but lymphomas may arise in other mucosal sites. The most frequent presentation of lymphoma is a persistent parotid enlargement, which is clinically difficult to differentiate from a benign parotid enlargement, although some clinical findings may be helpful: benign parotid enlargement is often bilateral and goes up and down, while lymphoma is more often unilateral, tumefaction is fixed and sometimes hard. Salivary gland ultrasound (including Doppler) and magnetic resonance imaging may be helpful to differentiate benign and malign parotid enlargement. The main clinical predictors of lymphoma are persistent swelling of salivary glands, lymphadenopathy and palpable purpura (overwhelmingly related to cryoglobulinemia) (Table 7).Recently, it was found that a moderate (ESSDAI ≥ 5) and even more a high activity of the disease (ESSDAI≥14) was predictive of lymphoma occurrenceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Nocturne G, Virone A, Ng WF, Le Guern V, Hachulla E, Cornec D", "given" : "Daien C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vittecoq O, Bienvenu B, Marcelli C, Wendling D, Amoura Z, Dhote R", "given" : "Lavigne C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fior R, Gottenberg JE, Seror R", "given" : "Mariette X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sj\u00f6gren's Syndrome. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁵", "plainTextFormattedCitation" : "175", "previouslyFormattedCitation" : "¹⁷⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }175. The main biological predictors are cryoglobulinemia, lymphopenia and especially CD4 lymphopenia, low complement levels, a focus score≥3, germinal center-like structures a monoclonal component in serum or urine and presence of rheumatoid factorADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/bjh.13192", "ISBN" : "1365-2141; 0007-1048", "ISSN" : "00071048", "PMID" : "25316606", "abstract" : "Primary Sjogren Syndrome (pSS) is an autoimmune disease associated with an increased risk of lymphoma. Lymphomas complicating pSS are mostly low-grade B cell non-Hodgkin lymphomas, predominantly of marginal zone histological type. Mucosal localization is predominant, notably mucosa-associated lymphoid tissue lymphomas. Lymphomas often develop in organs where pSS is active, such as salivary glands. Germinal centre (GC)-like structures, high TNFSF13B (BAFF) and Flt3-ligand (FLT3LG) levels and genetic impairment of TNFAIP3 are new predictors of lymphoma development. These new findings allow a better understanding of the pathogenic mechanisms leading to lymphoma. We propose the following scenario: auto-immune B cells with rheumatoid factor (RF) activity are continuously stimulated by immune complexes containing antibodies against more specific auto-antigens, such as SSA/Ro, SSB/La or others. Germline abnormality of TNFAIP3 leads to a decreased control of the NF-kB pathway and thus promotes survival of B cells and oncogenic mutations especially in GC structure. Moreover, B cells are stimulated by a positive loop of activation induced by BAFF secretion. Thus, lymphomagenesis associated with pSS exemplifies the development of antigen-driven B-cell lymphoma. The control of disease activity by a well-targeted immunosuppressor is the primary objective of the management of the patient in order to repress chronic B cell stimulation.", "author" : [ { "dropping-particle" : "", "family" : "Nocturne", "given" : "Gaetane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Haematology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "317-327", "title" : "Sj\u00f6gren Syndrome-associated lymphomas: an update on pathogenesis and management", "type" : "article-journal", "volume" : "168" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2013-204634", "ISBN" : "1468-2060 (Electronic)\\r0003-4967 (Linking)", "ISSN" : "1468-2060", "PMID" : "24525912", "abstract" : "OBJECTIVES: To investigate the prognostic value of the lymphocytic focus score (LFS) and the percentages of IgA+, IgM+ and IgG+ plasma cells for disease severity of primary Sj\u00f6gren syndrome (pSS).\\n\\nMETHODS: Medical charts of 174 pSS patients were retrospectively analysed, comparing histology results (LFS and percentages of IgA+, IgM+ and IgG+ plasma cells) with disease outcomes as non-Hodgkin lymphoma (NHL) and clinical scores including cumulative EULAR (European League against Rheumatism) Sj\u00f6gren syndrome disease activity index (ESSDAI) and the total number of extraglandular manifestations.\\n\\nRESULTS: The mean LFS was significantly higher in patients developing NHL (3.0\u00b10.894 vs 2.25\u00b11.086; p=0.021). The threshold of \u22653 foci has a positive predictive value of 16% for lymphoma, and a negative predictive value of 98%. Only LFS \u22653 contributed significantly and independently to NHL development in a standard multiple regression model. Ig class distribution of plasma cells did not help to identify patients developing lymphoma. Patients with LFS \u22653, \u226440% IgA+ or \u226525% IgM+ plasma cells in salivary gland biopsy specimens had significantly enhanced systemic disease.\\n\\nCONCLUSIONS: Routine histopathological minor salivary gland assessment has important prognostic value. The LFS might help to identify patients with an increased risk for lymphoma.", "author" : [ { "dropping-particle" : "", "family" : "Risselada", "given" : "Anna P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "Aike a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldschmeding", "given" : "Roel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lafeber", "given" : "Floris P J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijlsma", "given" : "Johannes W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roon", "given" : "Joel a G", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1537-40", "title" : "The prognostic value of routinely performed minor salivary gland assessments in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "73" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^174,176", "plainTextFormattedCitation" : "174,176", "previouslyFormattedCitation" : "^174,176" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }174,176. Of note, all these predisposing factors are easy to check in daily practice and should be included in the management of SjS patients.The therapeutic approach must be evaluated according to the lymphoma type. Some authors recommend a watchful policy in patients with low-grade lymphomas affecting exclusively the exocrine glandsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : ".\tNocturne+G,+Tarn+J,+Boudaoud+S,+Locke+J,+Miceli-Richard+C,+Hachulla+E,+Dubost+JJ,+Bowman+S,+Gottenberg+JE,+Criswell+LA,+Lessard+CJ,+Sivils+KL,+Carapito+R,+Bahram+S,+Seror+R,+Ng+", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Nocturne G, Tarn J, Boudaoud S, Locke J, Miceli-Richard C, Hachulla E", "given" : "Dubost", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "JJ, Bowman S, Gottenberg JE, Criswell LA, Lessard CJ, Sivils KL", "given" : "Carapito R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahram S, Seror R, Ng WF", "given" : "Mariette X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Germline variation of TNFAIP3 in primary Sj\u00f6gren's syndrome-associated lymphoma. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁷", "plainTextFormattedCitation" : "177", "previouslyFormattedCitation" : "¹⁷⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }177. In contrast, patients with disseminated MALT lymphoma or those with concomitant high disease activity have an increased risk of progression and might benefit from early treatment at least for avoiding transformation into more aggressive lymphomasADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : ".\tNocturne+G,+Tarn+J,+Boudaoud+S,+Locke+J,+Miceli-Richard+C,+Hachulla+E,+Dubost+JJ,+Bowman+S,+Gottenberg+JE,+Criswell+LA,+Lessard+CJ,+Sivils+KL,+Carapito+R,+Bahram+S,+Seror+R,+Ng+", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Nocturne G, Tarn J, Boudaoud S, Locke J, Miceli-Richard C, Hachulla E", "given" : "Dubost", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "JJ, Bowman S, Gottenberg JE, Criswell LA, Lessard CJ, Sivils KL", "given" : "Carapito R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahram S, Seror R, Ng WF", "given" : "Mariette X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Germline variation of TNFAIP3 in primary Sj\u00f6gren's syndrome-associated lymphoma. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁷", "plainTextFormattedCitation" : "177", "previouslyFormattedCitation" : "¹⁷⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }177.The best therapeutic regimen is the combination of alkylating agents (cyclophosphamide/chlorambucil), fludarabine or bendamustine with rituximabADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.110077", "ISBN" : "0315-162X; 0315-162X", "ISSN" : "0315-162X", "PMID" : "21844152", "abstract" : "OBJECTIVE: To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sj\u00f6gren's syndrome (SS).\\n\\nMETHODS: All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical Center Groningen between January 1997 and January 2009 were analyzed. Clinical course and treatment outcome of SS and MALT lymphoma were evaluated.\\n\\nRESULTS: From a total of 329 patients with SS, 35 MALT-SS patients were identified, with a median followup of 76 months (range 16-153 mo). MALT lymphoma was localized in the parotid gland in all cases. Treatment consisted of \"watchful waiting\" (n = 10), surgery (n = 3), radiotherapy (n = 1), surgery combined with radiotherapy (n = 2), rituximab only (n = 13), or rituximab combined with chemotherapy (n = 6). Complete response was observed in 14 patients, partial response in 1 patient, and stable disease in 20 patients. In 6 of 7 patients with initially high SS disease activity (M-protein, cryoglobulins, IgM rheumatoid factor > 100 KIU/l, severe extraglandular manifestations), MALT lymphoma progressed and/or SS disease activity increased after a median followup of 39 months (range 4-98 mo), necessitating retreatment. Only 1 patient with MALT who had low SS disease activity showed progression of lymphoma when left untreated.\\n\\nCONCLUSION: An initially high SS disease activity likely constitutes an adverse prognostic factor for progression of lymphoma and/or SS. Such patients may require treatment for both MALT lymphoma and SS. In SS patients with localized asymptomatic MALT lymphoma and low SS disease activity, a \"watchful waiting\" strategy seems justified.", "author" : [ { "dropping-particle" : "", "family" : "Pollard", "given" : "Rodney P E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pijpe", "given" : "Justin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "Fred K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kluin", "given" : "Philip M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roodenburg", "given" : "Jan L N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "Cees G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "Arjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imhoff", "given" : "Gustaaf W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2198-208", "title" : "Treatment of mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: a retrospective clinical study.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/S0140-6736(12)61763-2", "ISBN" : "1474-547X (Electronic)\\n0140-6736 (Linking)", "ISSN" : "01406736", "PMID" : "23433739", "abstract" : "Background: Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. Methods: We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m2 on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1\u00b74 mg/m2 on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m2 on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with , number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. Findings: 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69\u00b75 months [26\u00b71 to not yet reached] vs 31\u00b72 months [15\u00b72-65\u00b77]; hazard ratio 0\u00b758, 95% CI 0\u00b744-0\u00b774; p<0\u00b70001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved \u22653 cycles; p<0\u00b70001), haematological toxicity (77 [30%] vs 173 [68%]; p<0\u00b70001), infections (96 [37%] vs 127 [50%]); p=0\u00b70025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0\u00b70001), and stomatitis (16 [6%] vs 47 [19%]; p<0\u00b70001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab\u2026", "author" : [ { "dropping-particle" : "", "family" : "Rummel", "given" : "Mathias J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niederle", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maschmeyer", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banat", "given" : "G. Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00fcnhagen", "given" : "Ulrich", "non-dropping-particle" : "Von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Losem", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kofahl-Krause", "given" : "Dorothea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heil", "given" : "Gerhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welslau", "given" : "Manfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balser", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaiser", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weidmann", "given" : "Eckhart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00fcrk", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ballo", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stauch", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roller", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Juergen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoelzer", "given" : "Dieter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinke", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brugger", "given" : "Wolfram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet", "id" : "ITEM-2", "issue" : "9873", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1203-1210", "title" : "Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: An open-label, multicentre, randomised, phase 3 non-inferiority trial", "type" : "article-journal", "volume" : "381" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/acr.21856", "ISBN" : "2151-4658 (Electronic)\\n2151-464X (Linking)", "PMID" : "22972527", "abstract" : "OBJECTIVE: Treatment of refractory mixed cryoglobulinemia (MC) with severe organ involvement remains challenging. Fludarabine, cyclophosphamide, and rituximab (FCR) treatment is highly effective for patients with chronic lymphocytic leukemia and marginal-zone lymphoma. We first report the safety and efficacy of FCR treatment in severe and refractory MC vasculitis associated with lymphoma. METHODS: We report the safety and efficacy of fludarabine (40 mg/m(2) orally on days 2-4), cyclophosphamide (250 mg/m(2) orally on days 2-4), and rituximab (375 mg/m(2) on day 1), every 4 weeks, for 3 to 6 cycles in 7 consecutive patients with severe and refractory MC. RESULTS: Clinical features of MC included purpura (n = 7), polyneuropathy (n = 6), and kidney (n = 4) and cardiac involvement (n = 2). Previous treatment included rituximab (n = 5), corticosteroids (n = 5), antiviral therapy (n = 5), cyclophosphamide (n = 3), and plasmapheresis (n = 2). All patients achieved clinical response, with 3 patients (42.9%) achieving a complete remission and 4 patients (57.1%) a partial remission. Cryoglobulin decreased from 0.94 to 0.41 gm/liter (P = 0.015). After a followup of 27 months, 2 patients experienced a relapse of MC. Five patients (71.4%) experienced side effects, including cytopenia (n = 5), pneumopathy (n = 2), and serum sickness (n = 1). CONCLUSION: The FCR regimen represents an effective treatment in severe and refractory MC.", "author" : [ { "dropping-particle" : "", "family" : "Saadoun", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pineton de Chambrun", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermine", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karras", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choquet", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jego", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Decaux", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cacoub", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Care Res (Hoboken)", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "643-647", "title" : "Using rituximab plus fludarabine and cyclophosphamide as a treatment for refractory mixed cryoglobulinemia associated with lymphoma", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Zucca E, Conconi A, Laszlo D, L\u00f3pez-Guillermo A, Bouabdallah R", "given" : "Coiffier B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C", "given" : "Campo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F", "given" : "Martinelli G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "C", "given" : "Thieblemont", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymph... - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{172,178\u2013180}", "plainTextFormattedCitation" : "172,178\u2013180", "previouslyFormattedCitation" : "^{172,178\u2013180}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }172,178–180. This later combination of rituximab and bendamustine has been evaluated favorably both on effectiveness and on safety in recent studies concerning MZ and MALT lymphomasADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(12)61763-2", "ISBN" : "1474-547X (Electronic)\\n0140-6736 (Linking)", "ISSN" : "01406736", "PMID" : "23433739", "abstract" : "Background: Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. Methods: We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m2 on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1\u00b74 mg/m2 on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m2 on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with , number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. Findings: 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69\u00b75 months [26\u00b71 to not yet reached] vs 31\u00b72 months [15\u00b72-65\u00b77]; hazard ratio 0\u00b758, 95% CI 0\u00b744-0\u00b774; p<0\u00b70001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved \u22653 cycles; p<0\u00b70001), haematological toxicity (77 [30%] vs 173 [68%]; p<0\u00b70001), infections (96 [37%] vs 127 [50%]); p=0\u00b70025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0\u00b70001), and stomatitis (16 [6%] vs 47 [19%]; p<0\u00b70001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab\u2026", "author" : [ { "dropping-particle" : "", "family" : "Rummel", "given" : "Mathias J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niederle", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maschmeyer", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banat", "given" : "G. Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00fcnhagen", "given" : "Ulrich", "non-dropping-particle" : "Von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Losem", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kofahl-Krause", "given" : "Dorothea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heil", "given" : "Gerhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welslau", "given" : "Manfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balser", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaiser", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weidmann", "given" : "Eckhart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00fcrk", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ballo", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stauch", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roller", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Juergen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoelzer", "given" : "Dieter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinke", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brugger", "given" : "Wolfram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet", "id" : "ITEM-1", "issue" : "9873", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1203-1210", "title" : "Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: An open-label, multicentre, randomised, phase 3 non-inferiority trial", "type" : "article-journal", "volume" : "381" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁸", "plainTextFormattedCitation" : "178", "previouslyFormattedCitation" : "¹⁷⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }178. In patients with diffuse large B-cell lymphomas, the treatment has to be adapted to the histologic grade and is based on the association of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2005.046193", "ISBN" : "0003-4967", "ISSN" : "0003-4967", "PMID" : "16322082", "abstract" : "BACKGROUND: Primary Sj\u00f6gren's syndrome (SS) is associated with an increased frequency of non-Hodgkin's lymphomas (NHLs), mainly of low histological grade. However, aggressive diffuse large B cell lymphomas (DLBCL) characterised by poor treatment outcome can also be encountered in SS. It has recently been shown that rituxan has significant therapeutic activity in this type of lymphoma. OBJECTIVE: To evaluate the efficacy of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in combination with rituxan in SS patients with DLBCL, and to determine the outcome in such patients. METHODS: In an open, single case trial, six SS patients with DLBCL were assigned to receive eight cycles of CHOP every three weeks plus rituxan given on day 1 of each cycle. In a retrospective study, conducted by the European Concerted Action for SS, nine cases were diagnosed as DLBCL, all of whom had been treated with CHOP alone. These patients were used as historical controls. RESULTS: The difference in the overall survival between the two treatment groups was significant. The group treated with rituxan plus CHOP had a 100% two year overall survival rate, while the historical controls had only a 37% survival rate. Extraglandular manifestations serving as predictors for lymphoma development such as palpable purpura and peripheral neuropathy disappeared. The remission of these signs was accompanied by a decrease in both circulating monoclonal cryoglobulins and rheumatoid factor activity and an increase in C4 levels. Clinically relevant toxicity was not detected. CONCLUSIONS: The addition of rituxan to standard CHOP chemotherapy results in improved treatment outcome in SS patients with aggressive DLBCL, without increasing toxicity.", "author" : [ { "dropping-particle" : "", "family" : "Voulgarelis", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giannouli", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "a G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "1033-1037", "title" : "Long term remission of Sj\u00f6gren's syndrome associated aggressive B cell non-Hodgkin's lymphomas following combined B cell depletion therapy and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸¹", "plainTextFormattedCitation" : "181", "previouslyFormattedCitation" : "¹⁸¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }181. [H2] Therapeutic management Whereas for other autoimmune diseases a wide variety of non-biological and biological agents is available, systemic treatment options for SjS are still limitedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrrheum.2012.53", "ISBN" : "1759-4804 (Electronic)\\r1759-4790 (Linking)", "ISSN" : "1759-4804", "PMID" : "22549247", "abstract" : "The treatment of primary Sj\u00f6gren's syndrome (SS) is based principally on the management of sicca features and systemic manifestations. Sicca manifestations are treated symptomatically through administration of topical therapies, such as saliva substitutes and artificial tears; in patients with residual salivary gland function, stimulation of salivary flow with a sialogogue is the therapy of choice. The management of extraglandular features must be tailored to the specific organ or organs involved; however, limited data have been obtained from controlled trials in SS to guide the treatment of systemic symptoms using therapies including antimalarials, glucocorticoids, immunosuppressive drugs and biologic agents. Nevertheless, randomised controlled trials of biologic agents that target molecules and receptors involved in the aetiopathogenesis of primary SS have initiated a new era in the therapeutic management of the disease, although the potential risks and benefits of these agents must be carefully considered. In this Review, we analyse the evidence regarding the efficacy of the therapeutic agents currently available to treat the manifestations of SS. On the basis of this evidence, we provide guidance on the use of these agents in different clinical scenarios.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3-Almirall", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Rheumatology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "399-411", "title" : "Topical and systemic medications for the treatment of primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸²", "plainTextFormattedCitation" : "182", "previouslyFormattedCitation" : "¹⁸²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182 (Figure 3).[H3] Symptomatic treatment. Symptomatic treatment of SjS is usually limited to sicca symptoms. With regard to dry eyes, substitution therapy consisting of high-viscosity eye drops and gels, in combination with mucolytic agents, is the mainstay. Topical nonpreserved corticosteroids and topical antibiotics are used in more severe cases of keratoconjunctivitis sicca with secondary bacterial infectionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1088-0224", "ISSN" : "1088-0224", "abstract" : "The management of dry eye disease (DED) encompasses both pharmacologic and nonpharmacologic approaches, including avoidance of exacerbating factors, eyelid hygiene, tear supplementation, tear retention, tear stimulation, and anti-inflammatory agents. Artificial tears are the mainstay of DED therapy but, although they improve symptoms and objective findings, there is no evidence that they can resolve the underlying inflammation in DED. Topical corticosteroids are effective anti-inflammatory agents, but are not recommended for long-term use because of their adverse-effect profiles. Topical cyclosporine - currently the only pharmacologic treatment approved by the US Food and Drug Administration specifically for DED - is safe for long-term use and is disease-modifying rather than merely palliative. Treatment selection is guided primarily by DED severity. Recently published guidelines propose a severity classification based on clinical signs and symptoms, with treatment recommendations according to severity level.", "author" : [ { "dropping-particle" : "", "family" : "M.A.", "given" : "Lemp", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Managed Care", "id" : "ITEM-1", "issue" : "SUPPL. 3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "S88-S101", "title" : "Management of dry eye disease", "type" : "article", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸³", "plainTextFormattedCitation" : "183", "previouslyFormattedCitation" : "¹⁸³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }183. Local management of the oral component is focused on moistering of oral surfaces and preventive measures to preserve or obtain optimal oral health. Proper oral hygiene combined with frequent application of fluorides in dentate subjects is important. Several saliva substitutes are available, but are not appreciated over time by many patients. Systemic symptomatic management of sicca symptoms consists of the secretagogues pilocarpine and cevimeline. Both drugs are muscarine agonists, inducing a transient increase in salivary and lacrimal output, but only in patients who have residual functional gland tissue. Both drugs are approved by the Food and Drug Administration in the USA for the treatment of dry eyes and mouth, but cevimeline is not available worldwide. Common side effects include sweating, flushing, urinary urgency and gastrointestinal discomfort, which may limit the application of these drugsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrrheum.2012.53", "ISBN" : "1759-4804 (Electronic)\\r1759-4790 (Linking)", "ISSN" : "1759-4804", "PMID" : "22549247", "abstract" : "The treatment of primary Sj\u00f6gren's syndrome (SS) is based principally on the management of sicca features and systemic manifestations. Sicca manifestations are treated symptomatically through administration of topical therapies, such as saliva substitutes and artificial tears; in patients with residual salivary gland function, stimulation of salivary flow with a sialogogue is the therapy of choice. The management of extraglandular features must be tailored to the specific organ or organs involved; however, limited data have been obtained from controlled trials in SS to guide the treatment of systemic symptoms using therapies including antimalarials, glucocorticoids, immunosuppressive drugs and biologic agents. Nevertheless, randomised controlled trials of biologic agents that target molecules and receptors involved in the aetiopathogenesis of primary SS have initiated a new era in the therapeutic management of the disease, although the potential risks and benefits of these agents must be carefully considered. In this Review, we analyse the evidence regarding the efficacy of the therapeutic agents currently available to treat the manifestations of SS. On the basis of this evidence, we provide guidance on the use of these agents in different clinical scenarios.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3-Almirall", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Rheumatology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "399-411", "title" : "Topical and systemic medications for the treatment of primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2013-204615", "ISBN" : "1468-2060; 0003-4967", "ISSN" : "1468-2060", "PMID" : "24442883", "abstract" : "OBJECTIVES: To validate the two recently developed disease activity indexes for assessment of primary Sj\u00f6gren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). METHODS: A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sj\u00f6gren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores. RESULTS: Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores. CONCLUSIONS: ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.", "author" : [ { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valim", "given" : "Valeria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6rner", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans-Laqu\u00e9", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandl", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivils", "given" : "Kathy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Wan-Fai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauchais", "given" : "Anne-Laure", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartoloni", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "Matija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sumida", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishiyama", "given" : "Sumusu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caporali", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "Aike a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "annrheumdis-2013-204615", "title" : "Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI).", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^182,184", "plainTextFormattedCitation" : "182,184", "previouslyFormattedCitation" : "^182,184" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182,184. [H3] Systemic treatment. Of all clinical trials in SjS the effect of systemic treatment on extraglandular manifestations is conducted in only a few of them. The lack of data can be explained by several factors. First, the heterogeneity of the extraglandular symptoms ranging from skin involvement and arthritis to glomerulonephritis and myelitis. Second, the inclusion of patients with low systemic disease activity in clinical trials, e.g., by excluding patients with MALT lymphomas. Third, the former lack of validated outcome measures to evaluate the systemic manifestationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrrheum.2012.53", "ISBN" : "1759-4804 (Electronic)\\r1759-4790 (Linking)", "ISSN" : "1759-4804", "PMID" : "22549247", "abstract" : "The treatment of primary Sj\u00f6gren's syndrome (SS) is based principally on the management of sicca features and systemic manifestations. Sicca manifestations are treated symptomatically through administration of topical therapies, such as saliva substitutes and artificial tears; in patients with residual salivary gland function, stimulation of salivary flow with a sialogogue is the therapy of choice. The management of extraglandular features must be tailored to the specific organ or organs involved; however, limited data have been obtained from controlled trials in SS to guide the treatment of systemic symptoms using therapies including antimalarials, glucocorticoids, immunosuppressive drugs and biologic agents. Nevertheless, randomised controlled trials of biologic agents that target molecules and receptors involved in the aetiopathogenesis of primary SS have initiated a new era in the therapeutic management of the disease, although the potential risks and benefits of these agents must be carefully considered. In this Review, we analyse the evidence regarding the efficacy of the therapeutic agents currently available to treat the manifestations of SS. On the basis of this evidence, we provide guidance on the use of these agents in different clinical scenarios.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3-Almirall", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Rheumatology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "399-411", "title" : "Topical and systemic medications for the treatment of primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸²", "plainTextFormattedCitation" : "182", "previouslyFormattedCitation" : "¹⁸²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182. The need for treating patients with extraglandular manifestations is obvious. [H3] Non-biological therapies. These drugs are still used despite the fact that there are no studies showing high levels of evidence for using these drugs in SjS. Corticosteroids and hydroxychloroquine are the most widely representors of them. The use of prednisone in SjS is extrapolated from its effectiveness in other autoimmune diseases. Based on clinical experience, low dose prednisone is used for the treatment of fatigue, arthritis and cutaneous symptoms. High dose of prednisone showed efficacy in the treatment of kidney, lung and central nervous system features. Prednisone may improve the hypergammaglobulinemia which is more pronounced in patients with SjS and extraglandular manifestationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0392-856X", "abstract" : "Primary Sjogren's syndrome is a systemic autoimmune exocrinopathy characterized by a lymphoplasmacytic infiltrate and destruction of salivary and lacrimal glandular tissues. There is no widely accepted or effective systemic therapy for this disorder. The purpose of this 6-month randomized, double-blinded, placebo-controlled study was to examine the effects of prednisone (30 mg, alternate days), piroxicam (20 mg, daily), or placebo on the salivary, lacrimal and immunologic alterations of primary Sjogren's syndrome. Eight patients were enrolled in each group. Salivary and lacrimal function were assessed at entry and at the completion of treatment. Labial minor salivary gland tissue was obtained at these times and examined for intensity of infiltration (focus scores) and for the relative proportion of glandular elements. Serologic and subjective evaluations were done as well, and patients were monitored for therapy-related side effects. Neither active treatment led to significant improvement in salivary or lacrimal function, although prednisone improved salivary flow in selected patients and was associated with positive subjective responses. Prednisone also significantly decreased the serum total protein, IgG, IgA, and sedimentation rate and increased the white cell count. There were no significant alterations in either focus scores or the percentage of glandular component tissues of minor glands with either active treatment. This study demonstrated that 6 months of prednisone or piroxicam at the doses utilized failed to improve the histological or functional parameters of salivary and lacrimal glands in primary Sjogren's syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Fox PC Atkinson JC, Macynski AA, Scott J, Fletcher D, Valdez IH, Kurrasch RH, Delapenha R, Jackson W", "given" : "Datiles M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "149", "title" : "Prednisone and piroxicam for treatment of primary Sjogren's syndrome.", "type" : "article", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁵", "plainTextFormattedCitation" : "185", "previouslyFormattedCitation" : "¹⁸⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }185. Long-term use of corticosteroids may harm the patient as result of its side effects (osteoporosis, diabetes, weight gain, dyslipidemia). In SjS deregulated IFN production is a key pathogenic factor in the disease process. The effect of hydroxychloroquine is based on the inhibition of TLR7 and TLR9 which affects the innate immune response including pro-inflammatory cytokines as type I IFN. This mechanism of action is reflected by a decrease in serological parameters (IL-6, IgG, ESR, RF)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2014.7682", "ISBN" : "1538-3598; 0098-7484", "ISSN" : "1538-3598", "PMID" : "25027140", "abstract" : "IMPORTANCE: Primary Sj\u00f6gren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome. However, evidence regarding its efficacy is limited. OBJECTIVE: To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sj\u00f6gren syndrome: dryness, pain, and fatigue. DESIGN, SETTING, AND PARTICIPANTS: From April 2008 to May 2011, 120 patients with primary Sj\u00f6gren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012. INTERVENTIONS: Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 [best] to 10 [worst]) evaluating dryness, pain, and fatigue. RESULTS: At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2% (11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group. CONCLUSIO\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pu\u00e9chal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larroche", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean-Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rist", "given" : "St\u00e9phanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sene", "given" : "Damien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batouche", "given" : "Djilali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furlan", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benessiano", "given" : "Joelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perrodeau", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Raphaele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "249-58", "title" : "Effects of hydroxychloroquine on symptomatic improvement in primary Sj\u00f6gren syndrome: the JOQUER randomized clinical trial.", "type" : "article-journal", "volume" : "312" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0003-4967", "abstract" : "OBJECTIVES: In 1985 and 1988 a positive effect of treatment of primary Sjogren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjogren's syndrome a two year study was performed., METHODS: The design of the study included a prospective, placebo controlled, two year double blind crossover trial in 19 patients., RESULTS: A significant decrease in IgG and IgM and a tendency for a decrease in the erythrocyte sedimentation rate (ESR) during treatment with hydroxychloroquine compared with treatment with placebo were found. No beneficial clinical effect of the use of hydroxychloroquine as expressed in preference for treatment with hydroxychloroquine or placebo with regard to symptoms and signs of primary Sjogren's syndrome could be shown, however, nor any relevant change in tear gland activity and sequelae of peripheral tear function deficiency, nor salivary gland scintigraphy., CONCLUSIONS: The use of hydroxychloroquine at a dose of 400 mg daily taken over a 12 month period does not have a worthwhile clinical benefit in patients with primary Sjogren's syndrome despite an improvement of hyperglobulinaemia and slight changes in the ESR and IgM.", "author" : [ { "dropping-particle" : "", "family" : "Kruize AA Kallenberg CG, van Bijsterveld OP, van der Heide A, Kater L, Bijlsma JW", "given" : "Hene R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hene", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijsterveld", "given" : "O P", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heide", "given" : "A", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kater", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijlsma", "given" : "J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "360", "title" : "Hydroxychloroquine treatment for primary Sjogren's syndrome: a two year double blind crossover trial.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^186,187", "plainTextFormattedCitation" : "186,187", "previouslyFormattedCitation" : "^186,187" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }186,187. Hydroxychloroquine is used as maintenance therapy in SjS based on its positive effect observed in patients with SLE and RA and the improvement on serological parametersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0003-4967", "abstract" : "OBJECTIVES: In 1985 and 1988 a positive effect of treatment of primary Sjogren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjogren's syndrome a two year study was performed., METHODS: The design of the study included a prospective, placebo controlled, two year double blind crossover trial in 19 patients., RESULTS: A significant decrease in IgG and IgM and a tendency for a decrease in the erythrocyte sedimentation rate (ESR) during treatment with hydroxychloroquine compared with treatment with placebo were found. No beneficial clinical effect of the use of hydroxychloroquine as expressed in preference for treatment with hydroxychloroquine or placebo with regard to symptoms and signs of primary Sjogren's syndrome could be shown, however, nor any relevant change in tear gland activity and sequelae of peripheral tear function deficiency, nor salivary gland scintigraphy., CONCLUSIONS: The use of hydroxychloroquine at a dose of 400 mg daily taken over a 12 month period does not have a worthwhile clinical benefit in patients with primary Sjogren's syndrome despite an improvement of hyperglobulinaemia and slight changes in the ESR and IgM.", "author" : [ { "dropping-particle" : "", "family" : "Kruize AA Kallenberg CG, van Bijsterveld OP, van der Heide A, Kater L, Bijlsma JW", "given" : "Hene R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hene", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijsterveld", "given" : "O P", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heide", "given" : "A", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kater", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijlsma", "given" : "J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "360", "title" : "Hydroxychloroquine treatment for primary Sjogren's syndrome: a two year double blind crossover trial.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁷", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "¹⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187. However, a recent RCT found that hydroxychloroquine was not superior to placebo in SjS patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2014.7682", "ISBN" : "1538-3598; 0098-7484", "ISSN" : "1538-3598", "PMID" : "25027140", "abstract" : "IMPORTANCE: Primary Sj\u00f6gren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome. However, evidence regarding its efficacy is limited. OBJECTIVE: To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sj\u00f6gren syndrome: dryness, pain, and fatigue. DESIGN, SETTING, AND PARTICIPANTS: From April 2008 to May 2011, 120 patients with primary Sj\u00f6gren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012. INTERVENTIONS: Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 [best] to 10 [worst]) evaluating dryness, pain, and fatigue. RESULTS: At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2% (11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group. CONCLUSIO\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pu\u00e9chal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larroche", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean-Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rist", "given" : "St\u00e9phanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sene", "given" : "Damien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batouche", "given" : "Djilali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furlan", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benessiano", "given" : "Joelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perrodeau", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Raphaele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "249-58", "title" : "Effects of hydroxychloroquine on symptomatic improvement in primary Sj\u00f6gren syndrome: the JOQUER randomized clinical trial.", "type" : "article-journal", "volume" : "312" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁶", "plainTextFormattedCitation" : "186", "previouslyFormattedCitation" : "¹⁸⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }186. From all immunosuppressive agents no clear benefit is shown in SjS patients. These drugs include methotrexate, azathioprine, sulphasalazine, mycophenolic acid and leflunomideADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2010.1014", "ISSN" : "1538-3598; 0098-7484", "abstract" : "CONTEXT: A variety of topical and systemic drugs are available to treat primary Sjogren syndrome, although no evidence-based therapeutic guidelines are currently available. OBJECTIVE: To summarize evidence on primary Sjogren syndrome drug therapy from randomized controlled trials. DATA SOURCES: We searched MEDLINE and EMBASE for articles on drug therapy for primary Sjogren syndrome published between January 1, 1986, and April 30, 2010. STUDY SELECTION: Controlled trials of topical and systemic drugs including adult patients with primary Sjogren syndrome were selected as the primary information source. RESULTS: The search strategy yielded 37 trials. A placebo-controlled trial found significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use in patients treated with topical ocular 0.05% cyclosporine. Three placebo-controlled trials found that pilocarpine was associated with improvements in dry mouth (61%-70% vs 24%-31% in the placebo group) and dry eye (42%-53% vs 26%). Two placebo-controlled trials found that cevimeline was associated with improvement in dry mouth (66%-76% vs 35%-37% in the placebo group) and dry eye (39%-72% vs 24%-30%). Small trials (<20 patients) found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents (azathioprine and cyclosporine). A large trial found limited benefits for oral interferon alfa-2a. Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness); neither did 2 small trials (<30 patients) testing rituximab, although significant results were observed in some secondary outcomes and improvement compared with baseline. CONCLUSIONS: In primary Sjogren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye. Anti-tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siso", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "452-460", "title" : "Treatment of primary Sjogren syndrome: a systematic review", "type" : "article-journal", "volume" : "304" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁸", "plainTextFormattedCitation" : "188", "previouslyFormattedCitation" : "¹⁸⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }188. The high rate of adverse events and the high chance to develop a MALT lymphoma in SjS patients raises concerns to the off-label use of these drugs [H3] Biological therapies. Recently, promising results have been reported with several biological agents, especially for those targeting B-cells. B-cell depletion therapy with rituximab (anti-CD20) showed efficacy in SjS in several RCTs and open label trialsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2007.083865", "ISBN" : "0003-4967", "ISSN" : "1468-2060", "PMID" : "18276741", "abstract" : "OBJECTIVE: Primary Sjogren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS., METHODS: A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy., RESULTS: There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group., CONCLUSIONS: This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.", "author" : [ { "dropping-particle" : "", "family" : "Dass S Vital EM, Ikeda K, Pease CT, Hamburger J, Richards A, Rauz S, Emery P", "given" : "Bowman S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1541", "title" : "Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.", "type" : "article", "volume" : "67" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.27314", "ISBN" : "0004-3591 (ISSNLinking)", "ISSN" : "00043591", "PMID" : "20131246", "abstract" : "OBJECTIVE: To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sj\u00f6gren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. METHODS: Patients with active primary SS, as determined by the revised American-European Consensus Group criteria, and a rate of stimulated whole saliva secretion of > or =0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. RESULTS: Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean +/- SD age of the patients receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50 months, while patients in the placebo group were age 43 +/- 17 years and had a disease duration of 67 +/- 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness-like disease. CONCLUSION: These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Meijer", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meiners", "given" : "P. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F. K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdulahad", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamminga", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brouwer", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C. G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and Rheumatism", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "960-968", "title" : "Effectiveness of rituximab treatment in primary sj??gren's syndrome: A randomized, double-blind, placebo-controlled trial", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "1539-3704", "ISSN" : "1539-3704", "abstract" : "BACKGROUND: Primary Sjogren syndrome (pSS) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations., OBJECTIVE: To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS., DESIGN: Randomized, placebo-controlled, parallel-group trial conducted between March 2008 and January 2011. Study personnel (except pharmacists), investigators, and patients were blinded to treatment group. (: NCT00740948)., SETTING: 14 university hospitals in France., PATIENTS: 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS., INTERVENTION: Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo., MEASUREMENTS: Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24., RESULTS: No significant difference between groups in the primary end point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab., LIMITATION: Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes., CONCLUSION: Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points.", "author" : [ { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berthelot", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puechal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "Veronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiche", "given" : "Laurent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Internal Medicine", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "233-242", "title" : "Treatment of primary Sjogren syndrome with rituximab: a randomized trial", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/art.21260", "ISBN" : "0004-3591; 0004-3591", "ISSN" : "00043591", "PMID" : "16142737", "abstract" : "OBJECTIVE: To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sj\u00f6gren's syndrome of short duration (early primary SS) and patients with primary SS and mucosa-associated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS). METHODS: Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/primary SS group were primary SS and an associated MALT-type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m2) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion. RESULTS: Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human anti-chimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1. CONCLUSION: Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Pijpe", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imhoff", "given" : "G. W.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F. K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roodenburg", "given" : "J. L N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolbink", "given" : "G. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mansour", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C. G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and Rheumatism", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2740-2750", "title" : "Rituximab treatment in patients with primary Sj\u00f6gren's syndrome: An open-label phase II study", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1136/annrheumdis-2012-202293", "ISBN" : "1468-2060 (Electronic)\\r0003-4967 (Linking)", "ISSN" : "1468-2060", "PMID" : "23264337", "abstract" : "OBJECTIVES: To evaluate the efficacy and safety of rituximab in patients with primary Sj\u00f6gren's syndrome (pSS).\\n\\nMETHODS: The AutoImmune and Rituximab registry has included 86 patients with pSS treated with rituximab, prospectivey followed up every 6 months for 5 years.\\n\\nRESULTS: Seventy-eight patients with pSS (11 men, 67 women), who already had at least one follow-up visit, were analysed. Median age was 59.8 years (29-83), median duration of disease was 11.9 years (3-32). Indications for treatment were systemic involvement for 74 patients and only severe glandular involvement in four patients. The median European Sj\u00f6gren's Syndrome disease activity index (ESSDAI) was 11 (2-31). 17 patients were concomitantly treated with another immunosuppressant agent. Median follow-up was 34.9 months (6-81.4) (226 patient-years). Overall efficacy according to the treating physician was observed in 47 patients (60%) after the first cycle of rituximab. Median ESSDAI decreased from 11 (2-31) to 7.5 (0-26) (p<0.0001). Median dosage of corticosteroid decreased from 17.6 mg/day (3-60) to 10.8 mg/day (p=0.1). Forty-one patients were retreated with rituximab. Four infusion reactions and one delayed serum sickness-like disease resulted in rituximab discontinuation. Three serious infections (1.3/100 patient-years) and two cancer-related deaths occurred.\\n\\nCONCLUSIONS: In common practice, the use of rituximab in pSS is mostly restricted to patients with systemic involvement. This prospective study shows good efficacy and tolerance of rituximab in patients with pSS and systemic involvement.", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cinquetti", "given" : "Gael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larroche", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Combe", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pertuiset", "given" : "Edouard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplanski", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiche", "given" : "Laurent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berthelot", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gombert", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goupille", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcelli", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feuillet", "given" : "S\u00e9verine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leone", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carli", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rist", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudin", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salliot", "given" : "Carine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piperno", "given" : "Muriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deplas", "given" : "Adeline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Breban", "given" : "Maxime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lequerre", "given" : "Thierry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richette", "given" : "Pascal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghiringhelli", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamidou", "given" : "Mohamed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1026-31", "title" : "Efficacy of rituximab in systemic manifestations of primary Sjogren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1186/ar4359; 10.1186/ar4359", "ISSN" : "1478-6362; 1478-6354", "abstract" : "INTRODUCTION: Primary Sjogren's syndrome (pSS) is an autoimmune disorder affecting exocrine glands; however, a subgroup of pSS patients experience systemic extra-glandular involvement leading to a worsening of disease prognosis. Current therapeutic options are mainly empiric and often translated by other autoimmune diseases. In the last few years growing evidence suggests that B-cell depletion by rituximab (RTX) is effective also in pSS. Patients with early active disease appear to be those who could benefit the most from RTX. The aim of this study was to investigate the efficacy and safety of RTX in comparison to disease modifying anti-rheumatic drugs (DMARDs) in early active pSS patients. METHODS: Forty-one patients with early pSS and active disease (EULAR Sjogren's syndrome disease activity index, ESSDAI >/= 6) were enrolled in the study. Patients were treated with either RTX or DMARDs in two different Rheumatology centers and followed up for 120 weeks. Clinical assessment was performed by ESSDAI every 12 weeks up to week 120 and by self-reported global disease activity pain, sicca symptoms and fatigue on visual analogic scales, unstimulated saliva flow and Schirmer's I test at week 12, 24, 48, 72, 96, and 120. Laboratory assessment was performed every 12 weeks to week 120. Two labial minor salivary gland (MSG) biopsies were obtained from all patients at the time of inclusion in the study and at week 120. RESULTS: Our study demonstrated that RTX treatment results in a faster and more pronounced decrease of ESSDAI and other clinical parameters compared to DMARDs treatment. No adverse events were reported in the two groups. We also observed that RTX is able to reduce glandular infiltrate, interfere with B/T compartmentalization and consequently with the formation of ectopic lymphoid structures and germinal center-like structures in pSS-MSGs. CONCLUSIONS: To our knowledge, this is the first study performed in a large cohort of early active pSS patients for a period of 120 weeks. We showed that RTX is a safe and effective agent to be employed in pSS patients with systemic, extra-glandular involvement. Furthermore, our data on pSS-MSGs provide additional biological basis to employ RTX in this disease.", "author" : [ { "dropping-particle" : "", "family" : "Carubbi", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cipriani", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marrelli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benedetto", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruscitti", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berardicurti", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantano", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liakouli", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alvaro", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alunno", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manzo", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciccia", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Triolo", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giacomelli", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-6", "issue" : "5", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "R172", "title" : "Efficacy and safety of rituximab treatment in early primary Sjogren's syndrome: a prospective, multi-center, follow-up study", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^189\u2013194", "plainTextFormattedCitation" : "189\u2013194", "previouslyFormattedCitation" : "^189\u2013194" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }189–194. Fatigue was reduced in most studies. Improvement of salivary flow was reported in two trialsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.27314", "ISBN" : "0004-3591 (ISSNLinking)", "ISSN" : "00043591", "PMID" : "20131246", "abstract" : "OBJECTIVE: To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sj\u00f6gren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. METHODS: Patients with active primary SS, as determined by the revised American-European Consensus Group criteria, and a rate of stimulated whole saliva secretion of > or =0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. RESULTS: Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean +/- SD age of the patients receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50 months, while patients in the placebo group were age 43 +/- 17 years and had a disease duration of 67 +/- 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness-like disease. CONCLUSION: These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Meijer", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meiners", "given" : "P. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F. K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdulahad", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamminga", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brouwer", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C. G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and Rheumatism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "960-968", "title" : "Effectiveness of rituximab treatment in primary sj??gren's syndrome: A randomized, double-blind, placebo-controlled trial", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.21260", "ISBN" : "0004-3591; 0004-3591", "ISSN" : "00043591", "PMID" : "16142737", "abstract" : "OBJECTIVE: To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sj\u00f6gren's syndrome of short duration (early primary SS) and patients with primary SS and mucosa-associated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS). METHODS: Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/primary SS group were primary SS and an associated MALT-type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m2) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion. RESULTS: Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human anti-chimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1. CONCLUSION: Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Pijpe", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imhoff", "given" : "G. W.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F. K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roodenburg", "given" : "J. L N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolbink", "given" : "G. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mansour", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C. G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and Rheumatism", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2740-2750", "title" : "Rituximab treatment in patients with primary Sj\u00f6gren's syndrome: An open-label phase II study", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^190,192", "plainTextFormattedCitation" : "190,192", "previouslyFormattedCitation" : "^190,192" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }190,192. ESSDAI pointed towards a significant response on extraglandular manifestations in most trials, but not in one large RCT, the TEARS studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1539-3704", "ISSN" : "1539-3704", "abstract" : "BACKGROUND: Primary Sjogren syndrome (pSS) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations., OBJECTIVE: To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS., DESIGN: Randomized, placebo-controlled, parallel-group trial conducted between March 2008 and January 2011. Study personnel (except pharmacists), investigators, and patients were blinded to treatment group. (: NCT00740948)., SETTING: 14 university hospitals in France., PATIENTS: 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS., INTERVENTION: Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo., MEASUREMENTS: Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24., RESULTS: No significant difference between groups in the primary end point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab., LIMITATION: Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes., CONCLUSION: Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points.", "author" : [ { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berthelot", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puechal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "Veronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiche", "given" : "Laurent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Internal Medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "233-242", "title" : "Treatment of primary Sjogren syndrome with rituximab: a randomized trial", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹¹", "plainTextFormattedCitation" : "191", "previouslyFormattedCitation" : "¹⁹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }191. When posthoc applying the SjS response index (SSRI), a significant response rate difference between rituximab and placebo was also found in TEARSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kev114", "ISSN" : "1462-0332", "PMID" : "25957440", "abstract" : "OBJECTIVES: To determine which outcome measures detected rituximab efficacy in the Tolerance and Efficacy of Rituximab in Sj\u00f6gren's Disease (TEARS) trial and to create a composite endpoint for future trials in primary SS (pSS).\n\nMETHODS: Post hoc analysis of the multicentre randomized placebo-controlled double-blind TEARS trial. The results were validated using data from two other randomized controlled trials in pSS, assessing rituximab (single-centre trial in the Netherlands) and infliximab, respectively.\n\nRESULTS: Five outcome measures were improved by rituximab in the TEARS trial: patient-assessed visual analogue scale scores for fatigue, oral dryness and ocular dryness, unstimulated whole salivary flow and ESR. We combined these measures into a composite endpoint, the SS Responder Index (SSRI), and we defined an SSRI-30 response as a \u226530% improvement in at least two of five outcome measures. In TEARS, the proportions of patients with an SSRI-30 response in the rituximab and placebo groups at 6, 16 and 24 weeks were 47% vs 21%, 50% vs 7% and 55% vs 20%, respectively (P < 0.01 for all comparisons). SSRI-30 response rates after 12 and 24 weeks in the single-centre rituximab trial were 68% (13/19) vs 40% (4/10) and 74% (14/19) vs 40% (4/10), respectively. No significant differences in SSRI-30 response rates were found between infliximab and placebo at any of the time points in the infliximab trial.\n\nCONCLUSION: A core set of outcome measures used in combination suggests that rituximab could be effective and infliximab ineffective in pSS. The SSRI might prove useful as the primary outcome measure for future therapeutic trials in pSS.", "author" : [ { "dropping-particle" : "", "family" : "Cornec", "given" : "Divi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berthelot", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pu\u00e9chal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiche", "given" : "Laurent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques-Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meiners", "given" : "Petra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "Arjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "1699-708", "title" : "Development of the Sj\u00f6gren's Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁵", "plainTextFormattedCitation" : "195", "previouslyFormattedCitation" : "¹⁹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }195. Analyses on serological and histological parameters showed a complete B-cell depletion in serum, a partial depletion of B-cells in the salivary glandsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.24903", "ISBN" : "00043591", "ISSN" : "00043591", "PMID" : "19877054", "abstract" : "OBJECTIVE: To assess the effect of rituximab (anti-CD20 antibody) therapy on the (immuno)histopathology of parotid tissue in patients with primary Sj\u00f6gren's syndrome (SS) and the correlation of histologic findings with the flow rate and composition of parotid saliva. METHODS: In a phase II study, an incisional parotid biopsy specimen was obtained from 5 patients with primary SS before and 12 weeks after rituximab treatment (4 infusions of 375 mg/m(2)). The relative amount of parotid parenchyma, lymphocytic infiltrate, and fat, and the presence/quantity of germinal centers and lymphoepithelial duct lesions were evaluated. Immunohistochemical characterization was performed to analyze the B:T cell ratio of the lymphocytic infiltrate (CD20, CD79a, CD3) and cellular proliferation in the acinar parenchyma (by double immunohistologic labeling for cytokeratin 14 and Ki-67). Histologic data were assessed for correlations with the parotid flow rate and saliva composition. RESULTS: Four patients showed an increased salivary flow rate and normalization of the initially increased salivary sodium concentration. Following rituximab treatment, the lymphocytic infiltrate was reduced, with a decreased B:T cell ratio and (partial) disappearance of germinal centers. The amount and extent of lymphoepithelial lesions decreased in 3 patients and was completely absent in 2 patients. The initially increased proliferation of acinar parenchyma in response to inflammation was reduced in all patients. CONCLUSION: Sequential parotid biopsy specimens obtained from patients with primary SS before and after rituximab treatment demonstrated histopathologic evidence of reduced glandular inflammation and redifferentiation of lymphoepithelial duct lesions to regular striated ducts as a putative morphologic correlate of increased parotid flow and normalization of the salivary sodium content. These histopathologic findings in a few patients underline the efficacy of B cell depletion and indicate the potential for glandular restoration in SS.", "author" : [ { "dropping-particle" : "", "family" : "Pijpe", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meijer", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wal", "given" : "J. E.", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F. K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C. G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ihrler", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and Rheumatism", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "3251-3256", "title" : "Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sj??gren's syndrome", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁶", "plainTextFormattedCitation" : "196", "previouslyFormattedCitation" : "¹⁹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }196 and an effect on the T-cell arm by reducing the absolute numbers of T follicular helper (Tfh) cells and its hallmark cytokine IL-21. All observations were in parallel with the clinical change in ESSDAI. Despite pretreatment with corticosteroids, antihistamines and acetaminophen, some patients developed a serum sickness-like syndrome which may be associated with the hypergammaglobulinemia making SjS patients prone to formation of anti-chimeric antibodies against rituximabADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.27314", "ISBN" : "0004-3591 (ISSNLinking)", "ISSN" : "00043591", "PMID" : "20131246", "abstract" : "OBJECTIVE: To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sj\u00f6gren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. METHODS: Patients with active primary SS, as determined by the revised American-European Consensus Group criteria, and a rate of stimulated whole saliva secretion of > or =0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. RESULTS: Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean +/- SD age of the patients receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50 months, while patients in the placebo group were age 43 +/- 17 years and had a disease duration of 67 +/- 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness-like disease. CONCLUSION: These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Meijer", "given" : "J. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meiners", "given" : "P. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F. K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdulahad", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamminga", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brouwer", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "C. G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and Rheumatism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "960-968", "title" : "Effectiveness of rituximab treatment in primary sj??gren's syndrome: A randomized, double-blind, placebo-controlled trial", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁰", "plainTextFormattedCitation" : "190", "previouslyFormattedCitation" : "¹⁹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }190. Yet, rituximab is prescribed off-label in the management of severe extraglandular manifestation, including lymphomaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2010.1014", "ISSN" : "1538-3598; 0098-7484", "abstract" : "CONTEXT: A variety of topical and systemic drugs are available to treat primary Sjogren syndrome, although no evidence-based therapeutic guidelines are currently available. OBJECTIVE: To summarize evidence on primary Sjogren syndrome drug therapy from randomized controlled trials. DATA SOURCES: We searched MEDLINE and EMBASE for articles on drug therapy for primary Sjogren syndrome published between January 1, 1986, and April 30, 2010. STUDY SELECTION: Controlled trials of topical and systemic drugs including adult patients with primary Sjogren syndrome were selected as the primary information source. RESULTS: The search strategy yielded 37 trials. A placebo-controlled trial found significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use in patients treated with topical ocular 0.05% cyclosporine. Three placebo-controlled trials found that pilocarpine was associated with improvements in dry mouth (61%-70% vs 24%-31% in the placebo group) and dry eye (42%-53% vs 26%). Two placebo-controlled trials found that cevimeline was associated with improvement in dry mouth (66%-76% vs 35%-37% in the placebo group) and dry eye (39%-72% vs 24%-30%). Small trials (<20 patients) found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents (azathioprine and cyclosporine). A large trial found limited benefits for oral interferon alfa-2a. Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness); neither did 2 small trials (<30 patients) testing rituximab, although significant results were observed in some secondary outcomes and improvement compared with baseline. CONCLUSIONS: In primary Sjogren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye. Anti-tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siso", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "452-460", "title" : "Treatment of primary Sjogren syndrome: a systematic review", "type" : "article-journal", "volume" : "304" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁸", "plainTextFormattedCitation" : "188", "previouslyFormattedCitation" : "¹⁸⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }188. Results of the TRACTISS study (ISCTN65360827), a large multicenter RCT, are soon expected. Epratuzumab (anti-CD22) acts via B-cell antigen receptor signaling, leading to a partial B-cell depletion. A beneficial effect was observed for fatigue, but the effect on extraglandular manifestations was not evaluatedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/ar2018", "ISSN" : "1478-6362", "PMID" : "16859536", "abstract" : "This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sj\u00f6gren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33-72 years) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a > or = 20% improvement in at least two of the aforementioned parameters, with > or = 20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at > or = 20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%-50% responded at the > or = 30% level, while 10%-45% responded at the > or = 50% level for 10-32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted.", "author" : [ { "dropping-particle" : "", "family" : "Steinfeld", "given" : "Serge D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tant", "given" : "Laure", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burmester", "given" : "Gerd R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teoh", "given" : "Nick K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wegener", "given" : "William a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldenberg", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pradier", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "1 - 11", "title" : "Epratuzumab (humanised anti-CD22 antibody) in primary Sj\u00f6gren's syndrome: an open-label phase I/II study.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁷", "plainTextFormattedCitation" : "197", "previouslyFormattedCitation" : "¹⁹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }197. BAFF (B-cell activating factor) is involved in B-cell survival, activation and differentiation of B-cells. Serum levels of BAFF reflect ESSDAI scores. In an open label trial with belimumab, a BAFF(Blys) blocking drug, 60% of the patients were responders reflected by a decrease in ESSDAI scoresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2013-203991 [doi]", "ISSN" : "1468-2060; 0003-4967", "abstract" : "BACKGROUND: Increased expression of B cell activating factor (BAFF or B lymphocyte stimulator) may explain the B cell activation characteristic of primary Sjogren's syndrome (pSS). OBJECTIVES: To evaluate the efficacy and safety of belimumab, targeting BAFF, in patients with pSS. METHODS: Patients were included in this bi-centric prospective 1-year open-label trial if they fulfilled American European Consensus group criteria, were anti-Sjogren's syndrome A-positive and had current systemic complications or salivary gland enlargement, or early disease (/=30% in dryness score on a visual analogue scale (VAS), >/=30% in fatigue VAS score, >/=30% in VAS pain score, >/=30% in systemic activity VAS assessed by the physician and/or >25% improvement in any B cell activation biomarker values. RESULTS: Among 30 patients included, the primary end-point was achieved in 18 (60%). The mean (SD) European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6) (p=0.0015) and EULAR) Sjogren's Syndrome Patient Reported Index from 6.4 (1.1) to 5.6 (2.0) (p=0.0174). The mean dryness, fatigue and pain VAS varied from 7.8 (1.8) to 6.2 (2.9) (p=0.0021), 6.9 (1.8) to 6.0 (2.2) (p=0.0606) and 4.6 (2.6) to 4.7 (2.4) (p=0.89), respectively. Salivary flow and Schirmer's test did not change. CONCLUSIONS: These encouraging results justify future randomised controlled trials of belimumab in a selected target population of pSS patients most likely to benefit from treatment.", "author" : [ { "dropping-particle" : "", "family" : "Mariette", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quartuccio", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baron", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salvin", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabris", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desmoulins", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nocturne", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vita", "given" : "S", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the Rheumatic Diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the BELISS open-label phase II study", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁸", "plainTextFormattedCitation" : "198", "previouslyFormattedCitation" : "¹⁹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }198.With respect to T-cell targeting, abatacept, a fusion molecule, prevents CD28 co-stimulation between antigen presenting cells, including B-cells and T-cells. Abatacept is presumed to inhibit full T-cell activation and T-cell dependent B-cell activation. In two open label trials abatacept reduced glandular and extra-glandular manifestations reflected by a significant improvement in ESSDAI, and IgG and RF levels and Tfh cellsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.22052", "ISSN" : "2151-4658", "PMID" : "23740889", "abstract" : "Objectives To prospectively evaluate histopathologic, blood cellular, serological and clinical changes in response to abatacept treatment in patients with primary Sj\u00f6gren's syndrome (pSS). Methods Blood, saliva and minor salivary gland biopsies were obtained before and after the last of 8 doses of abatacept in 11 pSS patients. The histologic data evaluated the number of lymphocytic foci and of B- and T-cell subtypes (CD20(+) , CD3(+) , CD4(+) , CD8(+) ). The numbers of FoxP3(+) regulatory T-cells were measured and the FoxP3 /CD 3 ratio was calculated. Histologic data were compared with results from peripheral blood and with changes in saliva secretion. Results The numbers of lymphocytic foci decreased significantly (p=0.041). Numbers of local FoxP3(+) T-cells decreased significantly in percentage of total lymphocytic infiltrates (p=0.037). In the peripheral blood B-cells increased (p=0.038). This was due to an expansion of the na\u00efve B cell pool (p=0.034). When adjusting for disease duration, an increase was also noted for total lymphocytes (p=0.044) and for CD 4 cells (p=0.009). Gamma globulins decreased significantly (p=0.005), but IgG reduction did not reach significance. Adjusted for disease duration, saliva production increased significantly (p=0.029). Conclusions CTLA4-Ig treatment significantly reduces glandular inflammation in pSS, induces several celluar changes and increases saliva production. Remarkably, this increase in saliva production is significantly influenced by disease duration. \u00a9 2013 American College of Rheumatology.", "author" : [ { "dropping-particle" : "", "family" : "Adler", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6rner", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "F\u00f6rger", "given" : "Frauke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huscher", "given" : "D\u00f6rte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caversaccio", "given" : "Marco-Domenico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Villiger", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1862-1868", "title" : "Evaluation of histological, serological and clinical changes in response to abatacept treatment of primary Sj\u00f6gren's syndrome: A pilot study.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2013-204653; 10.1136/annrheumdis-2013-204653", "ISBN" : "1468-2060 (Electronic)\\n0003-4967 (Linking)", "ISSN" : "1468-2060; 0003-4967", "PMID" : "24473674", "abstract" : "OBJECTIVE: To assess the efficacy and safety of abatacept in patients with early and active primary Sjogren's syndrome (pSS). METHODS: All 15 patients (12 women, three men) included in the open-label Active Sjogren Abatacept Pilot study met the revised American-European Consensus Group criteria for pSS and were biological disease-modifying antirheumatic drug-naive. Patients were treated with eight intravenous abatacept infusions on days 1, 15 and 29 and every 4 weeks thereafter. Follow-up was conducted at 4, 12, 24 (on treatment), 36 and 48 weeks (off treatment). Disease activity was assessed with European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI). Several other functional, laboratory and subjective variables were analysed. Generalised estimating equations were used to analyse parameters over time. RESULTS: ESSDAI, ESSPRI, rheumatoid factor and IgG levels decreased significantly during abatacept treatment and increased post-treatment. Salivary and lacrimal gland function did not change during treatment. Fatigue and health-related quality of life (HR-QoL) improved significantly during treatment. No serious side effects or infections were seen. CONCLUSIONS: In this open-label study, abatacept treatment is effective, safe and well tolerated, and results in improved disease activity, laboratory parameters, fatigue and HR-QoL in patients with early and active pSS. TRIAL REGISTRATION NUMBER: 2009-015558-40.", "author" : [ { "dropping-particle" : "", "family" : "Meiners", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kroese", "given" : "F G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smitt-Kamminga", "given" : "N Sillevis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdulahad", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulthuis-Kuiper", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brouwer", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arends", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the Rheumatic Diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-4", "title" : "Abatacept treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study)", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^199,200", "plainTextFormattedCitation" : "199,200", "previouslyFormattedCitation" : "^199,200" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }199,200. A phase III RCT (ASAP III trial) is in progress (NCT02067910).Until now none of the biological agents has been approved for SjS. Timely treatment and stratified approaches are needed to prevent complications and damage in involved organs and to improve quality of life.[H1] Quality of lifeThe principle symptoms of SjS, namely dryness (particularly oral and ocular), fatigue and pain (of limbs – arthralgic/myalgic) are unpleasant and for many individuals, debilitating. It is hardly surprising, therefore, that many patients might report a reduced ‘quality of life (QoL)’, or, more particularly, of reduced ‘Health-related quality of life (HRQoL)’. Quality of life is defined as the overall well-being of individuals and societies. QoL covers a broad range of concepts from personal well-being, to the environment, levels of happiness, personal freedom etc that are not necessarily specifically relevant to SjS. The World Health Organization has developed questionnaires to measure QoLADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Szabo", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "editor" : [ { "dropping-particle" : "", "family" : "B", "given" : "Spilker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "publisher" : "Lippincott-Raven Publishers", "publisher-place" : "New York", "title" : "The World Health Organisation Quality of Life (WHOQOL) Assessment Instrument. In Quality of Life and Pharmaeconomics in Clinical Trials", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰¹", "plainTextFormattedCitation" : "201", "previouslyFormattedCitation" : "²⁰¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }201 that at its simplest asks ‘how would you rate your quality of life?’ (over the last 2 weeks on a five-point scale; 1= very poor, 2=poor, 3=neither poor nor good, 4=good and 5=very good). There is also an overall question for health-related Qol, namely; ‘how satisfied are you with your health?’ (over the last 2 weeks on a five-point scale; 1=very dissatisfied, 2=dissatisfied, 3=neither satisfied nor dissatisfied, 4=satisfied, 5=very satisfied). The WHOQoL-BREF is a 24-item (plus the 2 overall items above) questionnaire with 4 domains; 1=physical health, 2=psychological wellbeing, 3=social relationships and 4=the environmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "The WHOQOL Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychol Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "551-8", "title" : "Development of the World Health Organization WHOQOL-BREF quality of life assessment", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰²", "plainTextFormattedCitation" : "202", "previouslyFormattedCitation" : "²⁰²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }202. In a study evaluating QoL, HRQoL and symptoms in SjS, patients demonstrated reduced QoL (and HRQoL) comparable to patients with RA or SLEADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keh170", "ISBN" : "1462-0324 (Print)\\r1462-0324 (Linking)", "ISSN" : "1462-0324", "PMID" : "15039495", "abstract" : "Objective. Fatigue is a prominent symptom in primary Sjo?gren's syndrome (PSS). We set out to compare existing instruments and a new tool for measuring fatigue and general discomfort in PSS, with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. Methods. Groups of female Caucasian PSS patients completed a new questionnaire developed from PSS patients' own vocabulary, as well as the SF-36, WHOQOL-BREF and HAD scales. For comparison, the questionnaire was also completed by group of SLE and RA patients and healthy controls. Results. Each disease group differed significantly from healthy controls on each facet of fatigue and general discomfort in the new tool. Somatic fatigue was worst in RA, while mental fatigue was worst in PSS and SLE. The facets of somatic fatigue and discomfort in the new tool correlated well with comparable domains in existing scales. Conclusions. Fatigue in PSS can be measured using this new Sjo?gren's-based psychometric instrument. The new questionnaire tool was more sensitive than the SF-36, WHOQOL-BREF and HAD at distinguishing the three rheumatic disorders from controls. \u00a9 British Society for Rheumatology 2004; all rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Bowman", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Booth", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platts", "given" : "R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Situnayake", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanu-Cernat", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heaton", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speculand", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ainsworth", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bawendi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamburger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maddison", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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"properties" : { "noteIndex" : 0 }, "schema" : "" }203 with a profile closely similar to that of SLE patients. Other groups have found similar results with reduced QoL measured by the WHOQoL-BREF linked to psychological distress such as anxiety and somatasizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10165-010-0329-z", "ISSN" : "1439-7609", "PMID" : "20585824", "abstract" : "The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with primary Sj\u00f6gren's syndrome (pSS) using both Short-Form 36 (SF-36) and World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF) questionnaires and to determine the effects of anxiety and depression on HR-QOL using the Hospital Anxiety-Depression Scale (HADS). In this cross-sectional study, 107 female patients with pSS (mean age 54.10 \u00b1 10.2 years), fulfilling US-European Consensus Criteria and 109 female controls (mean age 53.4 \u00b1 10.9 years) were included. Student's t test, Mann-Whitney U test, and analysis of variance (ANOVA) were used for statistical analysis. P values > 0.05 were accepted as significant. All domains of the SF-36, with the exception of \"Vitality\", and all domains of the WHOQOL-BREF with the exception of \"Environment\", were significantly lower in pSS patients compared with healthy controls. In pSS patients having anxiety according to HADS, the scores of all domains of WHOQOL-BREF were significantly lower, and in patients having depression according to HADS, three of four domains of WHOQOL-BREF were significantly lower compared with the rest of the group. However, the scores of two domains of the SF-36, namely \"Role-Physical\" and \"Role-Emotional\" domains, were significantly higher in pSS patients having depression according to HADS. We confirmed the presence of impaired HR-QOL in pSS. Whereas the presence of anxiety and/or depression generally showed a negative affect on HR-QOL, interestingly, depression seemed to improve the scores of \"Role-Physical\" and \"Role-Emotional\" domains of the SF-36. This surprising finding might be related to adaptation to changing health. Social support based upon cultural traditions might also have contributed.", "author" : [ { "dropping-particle" : "", "family" : "Inal", "given" : "Vedat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "Gul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karabulut", "given" : "Gonca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keser", "given" : "G\u00f6khan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kabasakal", "given" : "Yasemin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "588-97", "title" : "Evaluation of quality of life in relation to anxiety and depression in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0392-856X", "abstract" : "OBJECTIVES: We aimed to assess the defensive profile of primary Sjogren's syndrome (SS) patients and to investigate the independent associations of psychological distress and personality variables with health-related quality of life (HRQOL)., METHODS: In 40 primary SS patients we assessed psychological distress (SCL-90-R), ego defense mechanisms (Defense Style Questionnaire), hostility features (HDHQ) and HRQOL (WHOQOL-BREF). Fifty-six patients with Systemic Lupus Erythematosous (SLE) and 80 healthy participants matched for age and sex served as controls., RESULTS: Primary SS patients presented higher rates of general psychological distress compared to SLE and healthy participants. Symptoms of somatisation were more prominent in SS than SLE or healthy controls. SS patients presented less use of humour defense and more help-rejecting complains and delusional guilt hostility, compared to controls. Primary SS patients' HRQOL was more impaired than healthy participants and comparable to SLE. Psychological distress was a constant independent correlate of SS patients' HRQOL, while less use of humour (p<0.001) and higher rates of delusional guilt (p=0.032) were also significantly associated with Physical HRQOL independently of psychological distress; more use of schizoid fantasy was also independently associated with impaired Environment HRQOL (p=0.005)., CONCLUSIONS: Primary SS patients exhibit several specific psychological difficulties in adaptation to life stressors, and clinicians and consultation-liaison psychiatrists, apart from the early assessment and treatment of psychological distress and somatisation symptoms, should consider the patients' underlying defensive profile and coping capacities, since such personality traits, although usually underestimated, are also independently associated with the disease outcome.", "author" : [ { "dropping-particle" : "", "family" : "Hyphantis", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mantis", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Voulgari", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "485-493", "title" : "The psychological defensive profile of primary Sjogren's syndrome patients and its relationship to health-related quality of life.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^204,205", "plainTextFormattedCitation" : "204,205", "previouslyFormattedCitation" : "^204,205" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }204,205.Most work in this field, however, has focused on health-related QoL using the Medical Outcomes Short-Form 36-tem questionnaire (SF-36). This is an eight-domain questionnaire and many studies have used this to demonstrate reduced HRQoL in SjS patients similar to that seen in patients with RA or SLE (patients with RA tend to have particularly reduced physical/pain domains, but otherwise profiles are similar between the diseasesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "PMID" : "9825745", "abstract" : "OBJECTIVE: Using the European Community (EC) criteria for classification\\nVitali et al. Arthritis Rheum 1993;36:340 7, we report the prevalence\\nestimates of Sjogren's syndrome (SS) from a general population and\\npresent the first population data to assess the impact of the syndrome.\\nMETHODS: A cross-sectional population-based survey performed on 1000\\nadults, aged 18-75 yr, randomly selected from a population register.\\nResponders to the initial postal phase were invited for an interview.\\nThe five criteria measured at interview were: (1) the reporting of\\nsubjective oral symptoms lasting for > 3 months; (2) the reporting\\nof subjective ocular symptoms lasting for >3 months; (3) Schirmer-I\\ntest; (4) unstimulated salivary flow; (5) autoantibodies [Ro (SS-A),\\nLa (SS-B), rheumatoid factor (RF), antinuclear antibodies (ANA)].\\nSS was diagnosed if at least four of these five criteria were positive.\\nThe MOS Short-form 36 (SF-36), General Health Questionnaire (GHQ)\\nand the Health and Fatigue Questionnaire (HFQ) were completed by\\nsubjects after the interview, and scores were compared between those\\nwith and without a diagnosis of SS. RESULTS: A total of 341 subjects\\ncompleted both the postal questionnaire and home visit. A diagnosis\\nof SS could be given to 13 subjects. After adjusting for the presence\\nof possible bias due to non-response, our best estimate of the prevalence\\nof SS in the study population was 33 per 1000 subjects (95% CI 22\\n44). The prevalence of the disorder was higher in females (38; 95%\\nCI 27-52) and for those subjects aged > or = 55 yr (46; 95% CI 34-61).\\nThose subjects diagnosed positively were more impaired for each of\\nthe eight dimensions of the SF-36 than those without a diagnosis,\\nand also suffered from higher levels of depression and fatigue. CONCLUSIONS:\\nSS affects approximately 3-4% of adults and in the general population\\nappears to be associated with a clinically significant impairment\\nof a subject's health and well-being.", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajeer", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silman", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Br J Rheumatol", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "1069-1076", "title" : "Sj\ufffdgren's syndrome: a community-based study of prevalence and impact.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/rheumatology/keh170", "ISBN" : "1462-0324 (Print)\\r1462-0324 (Linking)", "ISSN" : "1462-0324", "PMID" : "15039495", "abstract" : "Objective. Fatigue is a prominent symptom in primary Sjo?gren's syndrome (PSS). We set out to compare existing instruments and a new tool for measuring fatigue and general discomfort in PSS, with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. Methods. Groups of female Caucasian PSS patients completed a new questionnaire developed from PSS patients' own vocabulary, as well as the SF-36, WHOQOL-BREF and HAD scales. For comparison, the questionnaire was also completed by group of SLE and RA patients and healthy controls. Results. Each disease group differed significantly from healthy controls on each facet of fatigue and general discomfort in the new tool. Somatic fatigue was worst in RA, while mental fatigue was worst in PSS and SLE. The facets of somatic fatigue and discomfort in the new tool correlated well with comparable domains in existing scales. Conclusions. Fatigue in PSS can be measured using this new Sjo?gren's-based psychometric instrument. The new questionnaire tool was more sensitive than the SF-36, WHOQOL-BREF and HAD at distinguishing the three rheumatic disorders from controls. \u00a9 British Society for Rheumatology 2004; all rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Bowman", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Booth", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platts", "given" : "R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Situnayake", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanu-Cernat", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heaton", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speculand", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ainsworth", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bawendi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamburger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maddison", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulherin", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shirlaw", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snaith", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akil", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeoman", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Field", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rostron", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dawson", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longman", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffiths", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davidson", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McHugh", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waldron", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pease", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tyas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isenberg", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leandro", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutcliffe", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "758-764", "title" : "Measurement of fatigue and discomfort in primary Sjo?gren's syndrome using a new questionnaire tool", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0300-9742 (Print) 0300-9742 (Linking)", "PMID" : "10722254", "abstract" : "OBJECTIVE: To investigate the health-related quality of life in women with primary Sjogren's syndrome (prim SS) and compare with normative data and the health-related quality of life in women with rheumatoid arthritis (RA) and women with fibromyalgia. METHODS: A questionnaire including the MOS Short-Form 36 (SF-36) was completed by 42 prim SS women, 59 RA women, and 44 women with fibromyalgia. RESULTS: All three patient groups experienced a decreased quality of life level ranging from 5 to 65 % in all SF-36 scales compared to normative data. Differences between groups were seen in 7 of the 8 scales (p< or = 0.004). The prim SS patients experienced a higher quality of life level with regard to physical function than the women with RA and fibromyalgia, whereas in the psychological dimensions the quality of life level was comparable to that of the two other groups. CONCLUSION: The health-related quality of life was significantly decreased as compared to norms in prim SS women and comparable to the levels of women with RA and fibromyalgia.", "author" : [ { "dropping-particle" : "", "family" : "Strombeck", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ekdahl", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manthorpe", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wikstrom", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scand J Rheumatol", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "20-28", "title" : "Health-related quality of life in primary Sjogren's syndrome, rheumatoid arthritis and fibromyalgia compared to normal population data using SF-36", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/art.21990", "ISBN" : "0004-3591 (Print)\\r0004-3591 (Linking)", "PMID" : "16739213", "abstract" : "OBJECTIVE: To compare pain, fatigue, and sicca symptoms; quality of life; and psychological status between patients with primary Sjogren's syndrome (SS) and those with sicca symptoms but no autoimmune features (sicca asthenia polyalgia syndrome [SAPS]), and to determine whether a psychological pattern can be detected in patients with SAPS, which could suggest psychological distress as the cause. METHODS: This cross-sectional, prospective study included 111 patients with primary SS according to the American-European Consensus Group criteria and 65 SAPS patients with no focus on lip biopsy and no anti-SSA/SSB antibodies. Pain, fatigue, and sicca symptoms were assessed using visual analog scales; quality of life was assessed using the Short Form 36 (SF-36); and psychological distress by the Symptom Checklist-90-Revised (SCL-90-R) questionnaire. RESULTS: No difference was observed between primary SS and SAPS patients for pain, fatigue, sicca symptoms, quality of life, and psychological status. Fatigue and pain, but not dryness, were correlated with both quality of life and psychological distress in both groups. For primary SS patients, physical and mental composite scores on the SF-36 correlated well with global severity index (GSI) scores of the SCL-90-R (r = -0.29, P = 0.006 and r = -0.61, P < 0.0001, respectively). CONCLUSION: Patients with primary SS and SAPS do not differ in quality of life or psychological status. Although both diseases probably have a different origin, they may require the same psychological support or psychiatric care. The strong correlation between the composite physical and mental scores of the SF-36 and the GSI scores of the SCL-90-R in primary SS patients emphasizes the importance of the psychological dimension in results of the SF-36.", "author" : [ { "dropping-particle" : "", "family" : "Champey", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corruble", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buhl", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caudmont", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berge", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pellet", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hardy", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Rheum", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "451-457", "title" : "Quality of life and psychological status in patients with primary Sjogren's syndrome and sicca symptoms without autoimmune features", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1186/1477-7525-7-46", "ISBN" : "1477-7525 (Electronic)\\n1477-7525 (Linking)", "ISSN" : "1477-7525", "PMID" : "19473510", "abstract" : "OBJECTIVE: To assess the health related quality of life of patients with primary Sj\u00f6gren's Syndrome (PSS) in a large US sample. METHODS: Questionnaires were mailed to 547 patients with a confirmed diagnosis of PSS (PhysR-PSS) and all active members of the Sj\u00f6gren's Syndrome Foundation USA (SSF-PSS), half of whom identified a friend without PSS to also complete the survey. RESULTS: 277 PhysR-PSS patients were compared to 606 controls. The mean age was 62 years in the PhysR-PSS group and 61 years in the control group. 90% in both groups were women. Time from first symptom to diagnosis of PSS was a mean of 7 years. Sicca related morbidity, fatigue severity, depression and pain (assessed by validated questionnaires, PROFAD-SSI, FACIT-F, CES-D, BPI) were significantly greater, and all eight SF-36 domains were significantly diminished, in patients compared to controls. Somatic fatigue was the dominant predictor of physical function and of general health. Depression was the dominant predictor of emotional well being. Health care utilization was higher in patients than controls, including out of pocket dental expenses (mean: PhysR-PSS = $1473.3, controls = $503.6), dental visits (mean: PhysR-PSS = 4.0, controls = 2.3), current treatments (mean: PhysR-PSS = 6.6, controls = 2.5), and hospitalizations (53% PhysR-PSS, vs. 40% controls). CONCLUSION: Diminished health quality and excess health costs are prevalent among PSS patients. Health experiences and functional impact of PSS is similar among US and European patients. Delayed diagnosis, sicca related morbidity, fatigue, pain and depression are substantial suggesting unmet health needs and the importance of earlier recognition of PSS.", "author" : [ { "dropping-particle" : "", "family" : "Segal", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Philip C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vivino", "given" : "Frederick B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murukutla", "given" : "Nandita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brodscholl", "given" : "Jeff", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogale", "given" : "Sarika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McLean", "given" : "Lachy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Health and quality of life outcomes", "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "46", "title" : "Primary Sj\u00f6gren's Syndrome: health experiences and predictors of health quality among patients in the United States.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1093/rheumatology/kep141", "ISSN" : "1462-0332", "PMID" : "19553376", "abstract" : "OBJECTIVE: To compare health-related quality of life (HR-QOL), employment and disability of primary and secondary SS (pSS and sSS, respectively) patients with the general Dutch population.\\n\\nMETHODS: HR-QOL, employment and disability were assessed in SS patients regularly attending the University Medical Center Groningen (n = 235). HR-QOL, employment and disability were evaluated with the Short Form-36 questionnaire (SF-36) and an employment and disability questionnaire. Results were compared with Dutch population data (matched for sex and age). Demographical and clinical data associated with HR-QOL, employment and disability were assessed.\\n\\nRESULTS: Response rate was 83%. SS patients scored lower on HR-QOL than the general Dutch population. sSS patients scored lower on physical functioning, bodily pain and general health than pSS patients. Predictors for reduced HR-QOL were fatigue, tendomyalgia, articular involvement, use of artificial saliva, use of anti-depressants, comorbidity, male sex and eligibility for disability compensation (DC). Employment was lower and DC rates were higher in SS patients compared with the Dutch population.\\n\\nCONCLUSION: SS has a large impact on HR-QOL, employment and disability.", "author" : [ { "dropping-particle" : "", "family" : "Meijer", "given" : "Jiska M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meiners", "given" : "Petra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huddleston Slater", "given" : "James J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "Fred K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "Cees G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "Arjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-6", "issue" : "9", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1077-82", "title" : "Health-related quality of life, employment and disability in patients with Sjogren's syndrome.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{22,203,206\u2013209}", "plainTextFormattedCitation" : "22,203,206\u2013209", "previouslyFormattedCitation" : "^{22,203,206\u2013209}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22,203,206–209). Generally, fatigue, pain and low mood tend to better predict SF-36 scores in SjS patients than levels of dryness symptomsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.21990", "ISBN" : "0004-3591 (Print)\\r0004-3591 (Linking)", "PMID" : "16739213", "abstract" : "OBJECTIVE: To compare pain, fatigue, and sicca symptoms; quality of life; and psychological status between patients with primary Sjogren's syndrome (SS) and those with sicca symptoms but no autoimmune features (sicca asthenia polyalgia syndrome [SAPS]), and to determine whether a psychological pattern can be detected in patients with SAPS, which could suggest psychological distress as the cause. METHODS: This cross-sectional, prospective study included 111 patients with primary SS according to the American-European Consensus Group criteria and 65 SAPS patients with no focus on lip biopsy and no anti-SSA/SSB antibodies. Pain, fatigue, and sicca symptoms were assessed using visual analog scales; quality of life was assessed using the Short Form 36 (SF-36); and psychological distress by the Symptom Checklist-90-Revised (SCL-90-R) questionnaire. RESULTS: No difference was observed between primary SS and SAPS patients for pain, fatigue, sicca symptoms, quality of life, and psychological status. Fatigue and pain, but not dryness, were correlated with both quality of life and psychological distress in both groups. For primary SS patients, physical and mental composite scores on the SF-36 correlated well with global severity index (GSI) scores of the SCL-90-R (r = -0.29, P = 0.006 and r = -0.61, P < 0.0001, respectively). CONCLUSION: Patients with primary SS and SAPS do not differ in quality of life or psychological status. Although both diseases probably have a different origin, they may require the same psychological support or psychiatric care. The strong correlation between the composite physical and mental scores of the SF-36 and the GSI scores of the SCL-90-R in primary SS patients emphasizes the importance of the psychological dimension in results of the SF-36.", "author" : [ { "dropping-particle" : "", "family" : "Champey", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corruble", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buhl", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caudmont", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berge", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pellet", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hardy", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Rheum", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "451-457", "title" : "Quality of life and psychological status in patients with primary Sjogren's syndrome and sicca symptoms without autoimmune features", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/rheumatology/kep141", "ISSN" : "1462-0332", "PMID" : "19553376", "abstract" : "OBJECTIVE: To compare health-related quality of life (HR-QOL), employment and disability of primary and secondary SS (pSS and sSS, respectively) patients with the general Dutch population.\\n\\nMETHODS: HR-QOL, employment and disability were assessed in SS patients regularly attending the University Medical Center Groningen (n = 235). HR-QOL, employment and disability were evaluated with the Short Form-36 questionnaire (SF-36) and an employment and disability questionnaire. Results were compared with Dutch population data (matched for sex and age). Demographical and clinical data associated with HR-QOL, employment and disability were assessed.\\n\\nRESULTS: Response rate was 83%. SS patients scored lower on HR-QOL than the general Dutch population. sSS patients scored lower on physical functioning, bodily pain and general health than pSS patients. Predictors for reduced HR-QOL were fatigue, tendomyalgia, articular involvement, use of artificial saliva, use of anti-depressants, comorbidity, male sex and eligibility for disability compensation (DC). Employment was lower and DC rates were higher in SS patients compared with the Dutch population.\\n\\nCONCLUSION: SS has a large impact on HR-QOL, employment and disability.", "author" : [ { "dropping-particle" : "", "family" : "Meijer", "given" : "Jiska M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meiners", "given" : "Petra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huddleston Slater", "given" : "James J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "Fred K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallenberg", "given" : "Cees G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "Arjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1077-82", "title" : "Health-related quality of life, employment and disability in patients with Sjogren's syndrome.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^207,209", "plainTextFormattedCitation" : "207,209", "previouslyFormattedCitation" : "^207,209" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }207,209. More recently, another measure of HRQoL, the EuroQol 5-domain questionnaire (EQ-5D) has also confirmed reduced HRQoL in SjS patients and linked this to higher levels of patient symptoms (particularly pain levels) and the presence of systemic diseaseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keu361", "ISBN" : "1462-0324", "ISSN" : "1462-0332 (Electronic)", "PMID" : "25240612", "abstract" : "OBJECTIVE: This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. METHODS: Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearman's rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. RESULTS: This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. CONCLUSION: This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.", "author" : [ { "dropping-particle" : "", "family" : "Lendrem", "given" : "Dennis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Sheryl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McMeekin", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gompels", "given" : "Luke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hackett", "given" : "Katie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pease", "given" : "Colin T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emery", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Jacqueline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanyon", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutcliffe", "given" : "Nurhan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pitzalis", "given" : "Costantino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McLaren", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Annie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Regan", "given" : "Marian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giles", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isenberg", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saravanan", "given" : "Vadivelu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coady", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dasgupta", "given" : "Bhaskar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McHugh", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young-Min", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moots", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gendi", "given" : "Nagui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akil", "given" : "Mohammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffiths", "given" : "Bridget", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Wan-Fai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-5", "title" : "Do the European League Against Rheumatism Sjogren's syndrome outcome measures correlate with health status in primary Sjogren's syndrome?", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁰", "plainTextFormattedCitation" : "210", "previouslyFormattedCitation" : "²¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }210. Although there are some differences between these studies regarding the worst-affected domains of HRQoL in SjS and associations with other disease features, the consistent features are: 1. HRQoL is reduced in SjS and 2. Systemic features including fatigue, pain and low mood are associated with reduced HRQoL in SjS, whereas dryness features appear less closely associated if at all. In terms of taking things forward one key question is whether intervention can lead to improvement in HRQoL. In particular, as we enter the era of biologics usage in SjS, it will be of considerable interest to see whether therapies that lead to clinical and symptomatic improvements are also associated with improvement in HRQoLADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2013-204653; 10.1136/annrheumdis-2013-204653", "ISBN" : "1468-2060 (Electronic)\\n0003-4967 (Linking)", "ISSN" : "1468-2060; 0003-4967", "PMID" : "24473674", "abstract" : "OBJECTIVE: To assess the efficacy and safety of abatacept in patients with early and active primary Sjogren's syndrome (pSS). METHODS: All 15 patients (12 women, three men) included in the open-label Active Sjogren Abatacept Pilot study met the revised American-European Consensus Group criteria for pSS and were biological disease-modifying antirheumatic drug-naive. Patients were treated with eight intravenous abatacept infusions on days 1, 15 and 29 and every 4 weeks thereafter. Follow-up was conducted at 4, 12, 24 (on treatment), 36 and 48 weeks (off treatment). Disease activity was assessed with European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI). Several other functional, laboratory and subjective variables were analysed. Generalised estimating equations were used to analyse parameters over time. RESULTS: ESSDAI, ESSPRI, rheumatoid factor and IgG levels decreased significantly during abatacept treatment and increased post-treatment. Salivary and lacrimal gland function did not change during treatment. Fatigue and health-related quality of life (HR-QoL) improved significantly during treatment. No serious side effects or infections were seen. CONCLUSIONS: In this open-label study, abatacept treatment is effective, safe and well tolerated, and results in improved disease activity, laboratory parameters, fatigue and HR-QoL in patients with early and active pSS. TRIAL REGISTRATION NUMBER: 2009-015558-40.", "author" : [ { "dropping-particle" : "", "family" : "Meiners", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kroese", "given" : "F G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spijkervet", "given" : "F K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smitt-Kamminga", "given" : "N Sillevis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abdulahad", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulthuis-Kuiper", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brouwer", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arends", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the Rheumatic Diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-4", "title" : "Abatacept treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study)", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0392-856X 0392-856X (ISSNLinking)", "ISSN" : "0392856X", "PMID" : "21345287", "abstract" : "To assess the efficacy of the anti-CD20 antibody rituximab in improving physical function and health-related quality of life (HRQoL) in patients with active primary Sj\u00f6gren's syndrome (pSS), as well as the duration and sources of HRQoL improvements.", "author" : [ { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morvan", "given" : "Johanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rat", "given" : "Anne-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennec", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jaques-Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jamin", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renaudineau", "given" : "Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quintin-Rou\u00e9", "given" : "Isabelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cochener", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Youinou", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "6-12", "title" : "Effects of rituximab therapy on quality of life in patients with primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^200,211", "plainTextFormattedCitation" : "200,211", "previouslyFormattedCitation" : "^200,211" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }200,211.Outlook Clinical knowledge of primary SjS has evolved rapidly in recent years, but not sufficiently to permit significant changes in daily patient management. The areas where the biggest changes have occurred are: [H2] Novel etiopathogenic pathways and antigens Studies are investigating novel IFN-related mechanisms involving microRNA expression and interferon-inducible proteins such as IFI16 and cytokines (IL17, IL-21)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/cei.12664", "ISSN" : "1365-2249", "PMID" : "26201309", "abstract" : "The elevated tissue expression of Ro/SSA and La/SSB autoantigens appears to be crucial for the generation and perpetuation of autoimmune humoral responses against these autoantigens in Sj\u00f6gren's syndrome (SS). The mechanisms that govern their expression are not known. miRNAs, the post-transcriptional regulators of gene expression, might be implicated. We have identified previously the miRNAs let7b, miR16, miR181a, miR200b-3p, miR200b-5p, miR223 and miR483-5p that are predicted to target Ro/SSA [Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2)] and La/SSB mRNAs. To study possible associations with autoantigen mRNA expression and disease features, their expression was investigated in minor salivary gland (MSG) tissues, peripheral blood mononuclear cells (PBMC) and long-term cultured non-neoplastic salivary gland epithelial cells (SGEC) from 29 SS patients (20 of 29 positive for autoantibodies to Ro/SSA and La/SSB) and 24 sicca-complaining controls. The levels of miR16 were up-regulated in MSGs, miR200b-3p in SGECs and miR223 and miR483-5p in PBMCs of SS patients compared to sicca-complaining controls. The MSG levels of let7b, miR16, miR181a, miR223 and miR483-5p were correlated positively with Ro52/TRIM21-mRNA. miR181a and miR200b-3p were correlated negatively with Ro52/TRIM21 and Ro60/TROVE2 mRNAs in SGECs, respectively, whereas let7b, miR200b-5p and miR223 associated with La/SSB-mRNA. In PBMCs, let7b, miR16, miR181a and miR483-5p were correlated with Ro52/TRIM21, whereas let7b, miR16 and miR181a were also associated with La/SSB-mRNA expression. Significantly lower miR200b-5p levels were expressed in SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma compared to those without. Our findings indicate that miR16, miR200b-3p, miR223 and miR483-5p are deregulated in SS, but the exact role of this deregulation in disease pathogenesis and autoantigen expression needs to be elucidated.", "author" : [ { "dropping-particle" : "", "family" : "Gourzi", "given" : "V C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyriakidis", "given" : "N C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental immunology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "page" : "14-22", "title" : "Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sj\u00f6gren's Syndrome.", "type" : "article-journal", "volume" : "182" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/s13075-015-0722-2", "ISSN" : "1478-6362", "PMID" : "26271464", "abstract" : "INTRODUCTION: There is evidence that interferon is involved in the pathogenesis of primary Sj\u00f6gren's syndrome (pSS). The interferon-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders. This leads to tolerance breaking to this self-protein with consequent development of anti-IFI16 antibodies. The aim of this study was to identify the pathogenic and clinical significance of IFI16 and anti-IFI16 in pSS.\n\nMETHODS: IFI16 and anti-IFI16 were assessed in the serum of 67 pSS patients and over 100 healthy donors by enzyme-linked immunosorbent assay. IFI16 was also evaluated by immunohistochemistry in minor salivary glands of 15 pSS patients and 10 subjects with sicca symptoms but without any clinical, serological or histological features of pSS.\n\nRESULTS: pSS patients display higher serum levels of both IFI16 and anti-IFI16 compared to healthy donors. IFI16 concentration was directly correlated with disease duration and focus score and inversely correlated with age at diagnosis. Moreover, IFI16 positivity was associated with concurrent positivity for rheumatoid factor. Interestingly, the direct correlation between IFI16 positivity and focus score was independent of disease duration and age at diagnosis. pSS minor salivary glands display marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intralesional endothelium compared to minor salivary glands with normal architecture or nonspecific chronic sialadenitis. Within the mononuclear cell infiltrate, IFI16 expression appears to parallel the distribution of T lymphocytes.\n\nCONCLUSION: Our data suggest that the IFI16 protein may be involved in the pathogenesis of glandular inflammation occurring in pSS.", "author" : [ { "dropping-particle" : "", "family" : "Alunno", "given" : "Alessia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caneparo", "given" : "Valeria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carubbi", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bistoni", "given" : "Onelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caterbi", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartoloni", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giacomelli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gariglio", "given" : "Marisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landolfo", "given" : "Santo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "208", "title" : "Interferon gamma-inducible protein 16 in primary Sj\u00f6gren's syndrome: a novel player in disease pathogenesis?", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/acr.22632", "ISSN" : "2151-4658", "PMID" : "26037655", "abstract" : "OBJECTIVE: Interferon inducible protein-16 (IFI16) is an intracellular DNA receptor involved in innate immunity. We evaluated the frequency, phenotypic characteristics and clinical associations of anti-IFI16 antibodies in patients with primary Sj\u00f6gren's syndrome (SS), and quantitated expression levels of IFI16 in SS and control salivary gland lysates.\n\nMETHODS: Anti-IFI16 antibodies were assayed by ELISA using sera from patients with primary SS (n=133) and from healthy controls (n=47). Sera from SLE patients (n=132) were included as disease controls. Immunoprecipitation of in vitro transcription translated IFI16 was used to determine which portion of IFI16 the antibodies recognized. Expression of IFI16 in salivary gland lysates was quantitated by immunoblotting.\n\nRESULTS: Anti-IFI16 antibodies were present in 38/133 (29%) of SS patient sera compared to 1/47 (2.1%) healthy controls (SS vs controls, p<0.0002) and 31/132 (24%) SLE controls. In SS, anti-IFI16 antibodies were associated with an abnormal Schirmer's test (p=0.003), hyperglobulinemia (p=0.02), ANA\u22651:320 (p=0.01), germinal center-like structures in labial salivary gland lymphoid infiltrates (p=0.01), and higher focus scores (3.4 vs 2.4, p=0.005). High titer IFI16 antibodies were directed against an epitope outside the N-terminus in 9/13 (69%) of SS patients. IFI16 was expressed in 4/5 (80%) of SS and 1/6 (17%) of control labial salivary glands.\n\nCONCLUSION: Anti-IFI16 antibodies are a prominent specificity in primary SS, and are associated with markers of severe disease. IFI16 is expressed at higher levels in SS salivary glands compared to controls. These high levels in disease target tissue may contribute to the ongoing anti-IFI16 immune response. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petri", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sohn", "given" : "Jungsan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosen", "given" : "Antony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casciola-Rosen", "given" : "Livia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2015", "6", "2" ] ] }, "title" : "Antibodies to interferon-inducible protein-16 in primary Sj\u00f6gren's syndrome are associated with markers of more severe disease.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/ICO.0000000000000363", "ISBN" : "1536-4798 (Electronic)\\r0277-3740 (Linking)", "ISSN" : "1536-4798", "PMID" : "25603233", "abstract" : "PURPOSE:: IL-21 plays an important role in primary Sj\u00f6gren syndrome (SS) pathogenesis. The purpose of this study was to evaluate IL-21 expression in tears and the conjunctiva and to analyze the impact of IL-21 on primary SS dry eyes.\\n\\nMETHODS:: Eighty subjects were enrolled in this study: 30 patients with primary SS dry eye (30 eyes); 30 patients with non-SS dry eye (30 eyes), and 20 normal controls. Tear IL-21 levels were measured by flow cytometry, and IL-21 gene expression in the conjunctiva from impression cytology was evaluated by quantitative polymerase chain reaction. Ocular Surface Disease Index, tear film breakup time, Schirmer I test, and ocular surface staining scores were obtained for all patients.\\n\\nRESULTS:: Primary SS dry eyes had significantly higher tear IL-21 levels than non-SS dry eyes and normal controls (P < 0.01). In addition, IL-21 gene expression in the conjunctiva was also higher in primary SS dry eyes than in non-SS dry eyes and normal controls (P < 0.01). However, there were no significant differences in IL-21 expression in tears and the conjunctiva between non-SS dry eyes and controls. The tear IL-21 level was significantly correlated with ocular surface stain scores (r = 0.54, P < 0.01) and Schirmer I test values (r = -0.23, P < 0.05) in primary SS dry eyes.\\n\\nCONCLUSIONS:: Our findings suggest that severity of primary SS dry eye is associated with IL-21.", "author" : [ { "dropping-particle" : "", "family" : "Lim", "given" : "Sung A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "Doo Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jee Hye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwok", "given" : "Seung-Ki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Sung-Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chung", "given" : "So-Hyang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cornea", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Association of IL-21 Cytokine With Severity of Primary Sj\u00f6gren Syndrome Dry Eye.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^212\u2013215", "plainTextFormattedCitation" : "212\u2013215", "previouslyFormattedCitation" : "^212\u2013215" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212–215. Other etiopathogenic pathways under investigation include autophagy, the role of aromatase and, especially, epigenetic dysregulation, which might be restricted to the main cellular components involved in the etiopathogenesis of SjS (epithelial cells and lymphocytes)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/cei.12638", "ISSN" : "1365-2249", "PMID" : "25845745", "abstract" : "The aim of this study was to examine the levels of endoplasmic reticulum (ER) stress in minor salivary glands, to investigate the interplay between ER stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to test the effect of ER stress-induced apoptosis on the cellular redistribution of the two major Sj\u00f6gren's syndrome (SS) autoantigens Ro/Sj\u00f6gren's syndrome-related antigen A (SSA) and La/Sj\u00f6gren's syndrome-related antigen B (SSB). Minor salivary gland biopsies from SS patients and sicca controls were examined by immunohistochemistry for the expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell viability, autophagy and apoptosis were assessed. Immunoblot was applied to detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal epithelial cells in salivary glands of patients and sicca controls. TG treatment induced autophagy, as indicated by enhanced protein expression of LC3II. The protein levels of UPR marker XBP-1 were increased after TG treatment, while GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the cytoplasm in resting cells, while they were redistributed to cell membrane and blebs in the apoptotic cells. In conclusion, ER stress is activated in minor salivary gland epithelial cells from SS patients and controls. ER stress-induced apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization of Ro/SSA and La/SSB autoantigens.", "author" : [ { "dropping-particle" : "", "family" : "Katsiougiannis", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tenta", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skopouli", "given" : "F N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental immunology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015", "8" ] ] }, "page" : "244-52", "title" : "Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sj\u00f6gren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells.", "type" : "article-journal", "volume" : "181" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ajpath.2014.09.006", "ISSN" : "1525-2191", "PMID" : "25447050", "abstract" : "Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is an enzyme that converts androgens to estrogens. Herein, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 increased in white adipose tissue of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M1 macrophages was observed in white adipose tissue of ArKO mice. A significantly increased monocyte chemotactic protein-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sj\u00f6gren syndrome were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play a key role in the pathogenesis of Sj\u00f6gren syndrome-like lesions by controlling the target organ and adipose tissue-associated macrophage.", "author" : [ { "dropping-particle" : "", "family" : "Iwasa", "given" : "Akihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arakaki", "given" : "Rieko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Honma", "given" : "Naoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ushio", "given" : "Aya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamada", "given" : "Akiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kondo", "given" : "Tomoyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurosawa", "given" : "Emi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kujiraoka", "given" : "Satoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsunematsu", "given" : "Takaaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kudo", "given" : "Yasusei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Eiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshimura", "given" : "Noriko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harada", "given" : "Nobuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayashi", "given" : "Yoshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishimaru", "given" : "Naozumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of pathology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "151-61", "title" : "Aromatase controls Sj\u00f6gren syndrome-like lesions through monocyte chemotactic protein-1 in target organ and adipose tissue-associated macrophages.", "type" : "article-journal", "volume" : "185" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3389/fgene.2014.00071", "ISSN" : "1664-8021", "PMID" : "24765104", "abstract" : "Sj\u00f6gren's syndrome (SS) is a chronic autoimmune epithelitis that combines exocrine gland dysfunctions and lymphocytic infiltrations. While the pathogenesis of SS remains unclear, its etiology is multifunctional and includes a combination of genetic predispositions, environmental factors, and epigenetic factors. Recently, interest has grown in the involvement of epigenetics in autoimmune diseases. Epigenetics is defined as changes in gene expression, that are inheritable and that do not entail changes in the DNA sequence. In SS, several epigenetic mechanisms are defective including DNA demethylation that predominates in epithelial cells, an abnormal expression of microRNAs, and abnormal chromatin positioning-associated with autoantibody production. Last but not least, epigenetic modifications are reversible as observed in minor salivary glands from SS patients after B cell depletion using rituximab. Thus epigenetic findings in SS open new perspectives for therapeutic approaches as well as the possible identification of new biomarkers.", "author" : [ { "dropping-particle" : "", "family" : "Konsta", "given" : "Orsia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thabet", "given" : "Yosra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dantec", "given" : "Christelle", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brooks", "given" : "Wesley H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques-Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renaudineau", "given" : "Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in genetics", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "71", "title" : "The contribution of epigenetics in Sj\u00f6gren's Syndrome.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^216\u2013218", "plainTextFormattedCitation" : "216\u2013218", "previouslyFormattedCitation" : "^216\u2013218" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }216–218. Epigenetic mechanisms involving the modification of histones, non-coding RNAs and, especially, the methylation process of DNA, could play an etiopathogenic role in SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2014-206998", "ISSN" : "1468-2060", "PMID" : "26183421", "abstract" : "BACKGROUND: Beyond genetics, epigenetics alterations and especially those related to DNA methylation, play key roles in the pathogenesis of autoimmune diseases such as primary Sj\u00f6gren's syndrome (pSS) and systemic lupus erythematosus. This study aimed to assess the role of methylation deregulation in pSS pathogeny through a genome-wide methylation approach.\n\nPATIENTS AND METHODS: 26 female patients with pSS and 22 age-matched controls were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and their genome-wide DNA methylation profiles were analysed using Infinium Human Methylation 450\u2005K BeadChips. Probes with a median DNA methylation difference of at least 7% and p<0.01 between patients and controls were considered significantly differentially methylated.\n\nRESULTS: Methylation alterations were mainly present in B cells compared with T cells. In B cells, an enrichment of genes with differentially methylated probes in genetic at-risk loci was observed, suggesting involvement of both genetic and epigenetic abnormalities in the same genes. Methylation alterations in B cells were more frequent in some specific pathways including Interferon Regulated Genes, mainly among patients who were autoantibody positive. Moreover, genes with differentially methylated probes were over-represented in B cells from patients with active disease.\n\nCONCLUSIONS: This study demonstrated more important deregulation of DNA methylation patterns in B cells compared with T cells, emphasising the importance of B cells in the pathogenesis of the disease. Overlap between genes with differentially methylated probes in B lymphocytes and genetic at-risk loci is a new finding highlighting their importance in pSS.", "author" : [ { "dropping-particle" : "", "family" : "Miceli-Richard", "given" : "Corinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang-Renault", "given" : "Shu-Fang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boudaoud", "given" : "Saida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busato", "given" : "Florence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lallemand", "given" : "C\u00e9line", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bethune", "given" : "Kevin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belkhir", "given" : "Rakiba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nocturne", "given" : "Ga\u00e9tane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tost", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "7", "16" ] ] }, "title" : "Overlap between differentially methylated DNA regions in blood B lymphocytes and genetic at-risk loci in primary Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1586/1744666X.2014.901888", "ISSN" : "1744-8409", "PMID" : "24646085", "abstract" : "Primary Sj\u00f6gren's syndrome (pSS) is characterized by lymphoid infiltration of lacrimal and salivary glands leading to xerophthalmia and xerostomia. pSS is a complex disease involving both genetic and environmental risk factors. Technological advances over the past 10 years have revolutionized genetics and genomics research enabling high-throughput characterization and analysis of DNA and RNA in patient samples on a genome-wide scale. Further, application of high-throughput methods for characterization of epigenetic variation, such as DNA methylation status, is increasingly being applied to AID populations and will likely further define additional risk factors for disease risk and outcome. Main results obtain in pSS through these various approaches are reviewed here.", "author" : [ { "dropping-particle" : "", "family" : "Miceli-Richard", "given" : "Corinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "Lindsey a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Expert review of clinical immunology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "437-44", "title" : "Genetic, genomic and epigenetic studies as tools for elucidating disease pathogenesis in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^219,220", "plainTextFormattedCitation" : "219,220", "previouslyFormattedCitation" : "^219,220" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }219,220. With respect to novel antigens, some new molecules have recently been proposed (PUF60, carbamylated proteins)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2015-207509", "ISSN" : "1468-2060", "PMID" : "26253095", "abstract" : "OBJECTIVES: Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60\u2005kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody.\n\nMETHODS: A new 60\u2005kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sj\u00f6gren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38).\n\nRESULTS: PUF60 was identified as a new autoantigen. Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race.\n\nCONCLUSIONS: PUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases.", "author" : [ { "dropping-particle" : "", "family" : "Fiorentino", "given" : "David F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Presby", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petri", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rieger", "given" : "Kerri E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soloski", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosen", "given" : "Antony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mammen", "given" : "Andrew L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christopher-Stine", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casciola-Rosen", "given" : "Livia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "8", "7" ] ] }, "title" : "PUF60: a prominent new target of the autoimmune response in dermatomyositis and Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2015-207751", "ISSN" : "1468-2060", "PMID" : "26350884", "abstract" : "OBJECTIVES: Herein, we investigate the presence and prognostic value of autoantibodies against carbamylated proteins (anti-CarP) in the serum of patients with primary Sj\u00f6gren's syndrome (pSS).\n\nPATIENTS AND METHODS: Serum levels of anti-CarP antibodies were measured in Norwegian patients with pSS (n=78) and corresponding controls (n=74) using ELISA and analysed in relation with exocrine gland function, degree of salivary gland inflammation, signs of ectopic germinal centre (GC) formation and immunological markers. For univariate comparisons, the Mann-Whitney U test and \u03c7(2) or Fisher's exact tests were used. Correlations were assessed with Spearman's rank testing. Multivariate regression analyses were used to assess the effect of anti-CarP positivity on clinical manifestations.\n\nRESULTS: Of the patients with pSS, 27% were positive for anti-CarP IgG antibodies. Levels of anti-CarP correlated positively with total IgG, IgM, rheumatoid factor and \u03b22-microglobulin. Importantly, after adjusting for confounding factors, patients positive for anti-CarP had significantly higher focus score. Furthermore, positive anti-CarP status coincided with 9.2-fold higher odds of having developed GC-like structures in the minor salivary glands. As a patient group considered having worse disease outcome, individuals with ectopic GC-like structures also presented with significantly higher levels of anti-CarP antibodies.\n\nCONCLUSIONS: Presence of anti-CarP in patients with pSS is strongly associated with increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands, and diminished salivary gland function. Even taking into consideration our relatively small cohort we believe that anti-CarP antibodies offer new possibilities for identifying patients with more active disease and at risk of developing additional comorbidity.", "author" : [ { "dropping-particle" : "", "family" : "Bergum", "given" : "Brith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koro", "given" : "Catalin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delaleu", "given" : "Nicolas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solheim", "given" : "Magne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hellvard", "given" : "Annelie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binder", "given" : "Veronika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valim", "given" : "Valeria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammenfors", "given" : "Daniel S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "Malin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mydel", "given" : "Piotr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015", "9", "8" ] ] }, "title" : "Antibodies against carbamylated proteins are present in primary Sj\u00f6gren's syndrome and are associated with disease severity.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^221,222", "plainTextFormattedCitation" : "221,222", "previouslyFormattedCitation" : "^221,222" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }221,222 but, at present, no study has suggested a candidate to replace the role of Ro/La as the key autoantigens in SjS. [H2] Environmental factors The classic debate on the pathogenesis of human disease (genetics vs. environment) is also present in systemic autoimmune diseases such as SjS; a recent study has estimated the heritability of SjS to be around 54%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.39127", "ISSN" : "2326-5205", "PMID" : "25940005", "abstract" : "OBJECTIVE: To investigate familial aggregation of Sj\u00f6gren's syndrome (SS) and the relative risks (RRs) of other autoimmune disease in relatives of patients with SS.\n\nMETHODS: We identified 23,658,577 beneficiaries enrolled in the Taiwan National Health Insurance system in 2010, of whom 12,754 had SS. We identified 21,009,551 parent-child relationships and 17,168,340 pairs of full siblings. The familial risks of SS and other autoimmune diseases, tetrachoric correlation, and familial transmission were estimated.\n\nRESULTS: We identified 105 patients with SS who had an affected first-degree relative. The RR of SS was 18.99 (95% confidence interval [95% CI] 9.76-36.93) in siblings of patients with SS, 11.31 (95% CI 8.34-15.33) in offspring, and 12.46 (95% CI 9.34-16.62) in parents. Tetrachoric correlation coefficients were 0.53 (95% CI 0.41-0.65) for cotwins of affected individuals and 0.21 (95% CI 0.16-0.26) for full siblings. The familial transmission (heritability plus shared environmental contribution) was 0.54 (95% CI 0.44-0.77). In first-degree relatives of patients with SS, the RRs were 2.95 (95% CI 2.33-3.73) for rheumatoid arthritis, 6.25 (95% CI 5.15-7.58) for systemic lupus erythematosus, 2.39 (95% CI 0.77-7.41) for systemic sclerosis, 0.71 (95% CI 0.10-5.07) for idiopathic inflammatory myopathy, 1.97 (95% CI 1.29-3.02) for type 1 diabetes mellitus, 3.38 (95% CI 1.26-9.05) for multiple sclerosis, 1.67 (95% CI 0.83-3.33) for myasthenia gravis, 1.25 (95% CI 1.04-1.50) for psoriasis, 1.21 (95% CI 0.39-3.76) for inflammatory bowel disease, and 2.29 (95% CI 1.19-4.40) for vasculitis.\n\nCONCLUSION: The risk of SS and other autoimmune diseases is increased in relatives of patients with SS, and more than one-half of phenotypic variance in SS can be explained by familial factors.", "author" : [ { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang-Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grainge", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valdes", "given" : "Ana M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "See", "given" : "Lai-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luo", "given" : "Shue-Fen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weiya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doherty", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015", "7" ] ] }, "page" : "1904-12", "title" : "Familial Risk of Sj\u00f6gren's Syndrome and Co-aggregation of Autoimmune Diseases in Affected Families: A Nationwide Population Study.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²³", "plainTextFormattedCitation" : "223", "previouslyFormattedCitation" : "²²³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }223. Some recent studies have focused on the effect of environmental factors. An example is the role of the human microbiota, which consists of the 10-100 trillion symbiotic microbial cells harbored by each personADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.coi.2015.09.004", "ISSN" : "1879-0372", "PMID" : "26460968", "abstract" : "The trillions of microorganisms populating the mammalian mucosal surfaces (i.e. the microbiome) participate in the development and function of the host immune system that acts to balance clearance of pathogens with tolerance of beneficial commensals. Recent advances in mucosal immunology and culture-independent sequencing of microbial communities provide support for the hypothesis that the alterations in commensal microbiota alter the host immune response and can enhance risk for autoimmune disease in distant organs. Further explorations of the host-microbiota relationship will improve our understanding of autoimmune disorders and facilitate the discovery of a bacterial-based immunomodulators.", "author" : [ { "dropping-particle" : "", "family" : "Paun", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danska", "given" : "Jayne S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current opinion in immunology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "10", "10" ] ] }, "page" : "34-39", "title" : "Immuno-ecology: how the microbiome regulates tolerance and autoimmunity.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²⁴", "plainTextFormattedCitation" : "224", "previouslyFormattedCitation" : "²²⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }224; in SjS, the first studies have centered on the ocular and oral microbiotaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1089/jop.2015.0017", "ISSN" : "1557-7732", "PMID" : "26352162", "abstract" : "PURPOSE: The potential role of commensals as triggering factors that promote inflammation in dry eye disease has not been explored. The objective of this study was to evaluate whether ocular microbiota changes with the onset of dry eye disease in thrombospondin-1-deficient (TSP-1(-/-)) mice, a strain that develops Sj\u00f6gren's syndrome-like disease.\n\nMETHODS: Conjunctival swabs were collected from TSP-1(-/-) and C57BL/6 mice and analyzed for bacterial presence. Opsonophagocytosis of the bacterial conjunctival isolates derived from the aged TSP-1(-/-) mice by neutrophils derived from either TSP-1(-/-) or C57BL/6 bone marrow was evaluated. The bactericidal activities of TSP-1-derived peptide were examined.\n\nRESULTS: We found that in TSP-1(-/-) mice, the conjunctival colonization with Staphylococcus aureus and coagulase negative staphylococci sp (CNS) species was significantly increased with aging and preceded that of the wild-type C57BL/6 control mice. This correlated with increased neutrophil infiltration into the conjunctiva of the TSP-1(-/-) mice, suggesting that TSP-1 plays a significant role in regulating immunity to commensals. Accordingly, the TSP-1(-/-) PMNs opsonophagocytozed the ocular commensals less efficiently than the TSP-1-sufficient neutrophils. Furthermore, a TSP-1-derived peptide, 4N1K, exhibited significant antimicrobial activity when compared to a control peptide against commensal sp.\n\nCONCLUSION: These studies illustrate that alterations in the commensal frequency occur in the early stages of development of Sj\u00f6gren's-like pathology and suggest that interventions that limit commensal outgrowth such as the use of TSP-1-derived peptides could be used for treatment during the early stages of the disease to reduce the commensal burden and ensuing inflammation.", "author" : [ { "dropping-particle" : "", "family" : "Terzulli", "given" : "Marielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruiz", "given" : "Laura Contreras", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kugadas", "given" : "Abirami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masli", "given" : "Sharmila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gadjeva", "given" : "Mihaela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "413-8", "title" : "TSP-1 Deficiency Alters Ocular Microbiota: Implications for Sj\u00f6gren's Syndrome Pathogenesis.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.clim.2014.02.004", "ISBN" : "1521-7035", "ISSN" : "1521-7035", "PMID" : "24576620", "abstract" : "This study was undertaken to test the hypothesis that Sjogren's syndrome Antigen A (SSA)/Ro60-reactive T cells are activated by peptides originating from oral and gut bacteria. T cell hybridomas generated from HLA-DR3 transgenic mice recognized 3 regions on Ro60, with core epitopes mapped to amino acids 228-238, 246-256 and 371-381. BLAST analysis identified several mimicry peptides, originating from human oral, intestinal, skin and vaginal bacteria, as well as environmental bacteria. Amongst these, a peptide from the von Willebrand factor type A domain protein (vWFA) from the oral microbe Capnocytophaga ochracea was the most potent activator. Further, Ro60-reactive T cells were activated by recombinant vWFA protein and whole Escherichia coli expressing this protein. These results demonstrate that peptides derived from normal human microbiota can activate Ro60-reactive T cells. Thus, immune responses to commensal microbiota and opportunistic pathogens should be explored as potential triggers for initiating autoimmunity in SLE and Sj\u00f6gren's syndrome.", "author" : [ { "dropping-particle" : "", "family" : "Szymula", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenthal", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szczerba", "given" : "Barbara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagavant", "given" : "Harini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "Shu Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshmukh", "given" : "Umesh S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical immunology (Orlando, Fla.)", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-9", "title" : "T cell epitope mimicry between Sj\u00f6gren's syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria.", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^225,226", "plainTextFormattedCitation" : "225,226", "previouslyFormattedCitation" : "^225,226" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }225,226. Another fresh line of etiopathogenic investigation is the potential effect of exposure to environmental toxins, including both occupational toxins (solvents, aerozolised dust)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jaut.2015.04.004", "ISSN" : "1095-9157", "PMID" : "25963068", "abstract" : "OBJECTIVES: A case-control study was carried out to investigate the relation between primary Sj\u00f6gren's syndrome (pSS) and occupational exposure.\n\nMETHODS: One hundred seventy five cases of pSS followed up into the internal medicine departments of three French university hospitals from 2010 to 2013 were included. For each case, two age and gender matched controls were selected during the same period in the same departments. Occupational exposure was assessed retrospectively by industrial hygienists and occupational practitioners. Exposure to occupational factors such as organic solvents or silica was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment.\n\nRESULTS: Significant associations with pSS were observed for dichloromethane (OR 9.28, 95%CI 2.60-33.03), perchlorethylene (OR 2.64, 95%CI 1.20-5.77) chlorinated solvents (OR 2.95, 95%CI 1.77-4.93), benzene (OR 3.30, 95%CI 1.07-10.26), toluene (OR 4.18 95%CI 1.41-12.43), white spirit (OR 3.60, 95%CI 1.39-9.33), aromatic solvents (OR 3.03, 95%CI 1.41-6.50) and any types of solvents (OR 2.76, 95%CI 1.70-4.47). Risk of pSS was significantly associated with a high cumulative exposure score of occupational exposure to toluene (OR 4.69, 95%CI 1.42-15.45), white spirit (OR 3.30, 95%CI 1.07-10.26), aromatic solvents (OR 2.50, 95%CI 1.06-5.91) and any types of solvents (OR 2.25, 95%CI 1.20-4.22).\n\nCONCLUSION: This work suggests the influence of occupational risk factors in the occurrence of pSS.", "author" : [ { "dropping-particle" : "", "family" : "Chaigne", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lasfargues", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marie", "given" : "Isabelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenberger", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavigne", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchand-Adam", "given" : "Sylvain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maillot", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diot", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of autoimmunity", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "6" ] ] }, "page" : "80-5", "title" : "Primary Sj\u00f6gren's syndrome and occupational risk factors: A case-control study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.39059", "ISBN" : "2326-5191", "ISSN" : "2326-5191", "abstract" : "Objective. To test the a priori hypothesis that acute and chronic work\\nexposures to the World Trade Center (WTC) site on or after September 11,\\n2001 were associated with risk of new-onset systemic autoimmune\\ndiseases.\\nMethods. A nested case-control study was performed in WTC\\nrescue/recovery workers who had received a rheumatologist-confirmed\\nsystemic autoimmune disease diagnosis between September 12, 2001 and\\nSeptember 11, 2013 (n = 59), each of whom was individually matched to 4\\nrandomly selected controls (n = 236) on the basis of year of hire (+/- 1\\nyear), sex, race, and work assignment (firefighter or emergency medical\\nservice). Acute exposure was defined according to the earliest time of\\narrival (morning of 9/11 versus later) at the WTC site, and chronic\\nexposure was defined as duration (number of months) of WTC site-related\\nwork. Rheumatologists were blinded with regard to each subject's\\nexposure status. The conditional odds ratios (CORs) with 95% confidence\\nintervals (95% CIs) for incident autoimmune disease were derived from\\nexact conditional logistic regression models.\\nResults. Rheumatoid arthritis was the most common autoimmune diagnosis\\n(37% of subjects), followed by spondyloarthritis (22%), inflammatory\\nmyositis (14%), systemic lupus erythematosus (12%), systemic sclerosis\\n(5%), Sjogren's syndrome (5%), antiphospholipid syndrome (3%), and\\ngranulomatosis with polyangiitis (Wegener's) (2%). The COR for incident\\nautoimmune disease increased by 13% (COR 1.13, 95% CI 1.02-1.26) for\\neach additional month worked at the WTC site. These odds were\\nindependent of the association between high acute exposure (working\\nduring the morning of 9/11) and disease outcome, which conveyed an\\nelevated, but not statistically significant, risk (COR 1.85, 95% CI\\n0.86-3.89).\\nConclusion. Prolonged work at the WTC site, independent of acute\\nexposure, was an important predictor of post-9/11 systemic autoimmune\\ndiseases. The WTC Health Program should expand surveillance efforts for\\nthose with extended exposures, as early detection can facilitate early\\ntreatment, which has been shown to minimize organ damage and improve\\nquality of life.", "author" : [ { "dropping-particle" : "", "family" : "Webber", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moir", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeig-Owens", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glaser", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaber", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berman", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qayyum", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loupasakis", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prezant", "given" : "D J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "ARTHRITIS & RHEUMATOLOGY", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1369-1376", "title" : "Nested Case-Control Study of Selected Systemic Autoimmune Diseases in World Trade Center Rescue/Recovery Workers", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^227,228", "plainTextFormattedCitation" : "227,228", "previouslyFormattedCitation" : "^227,228" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }227,228, and airborne pollution (fine particulates)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.envres.2015.05.007", "ISSN" : "1096-0953", "PMID" : "25988990", "abstract" : "OBJECTIVE: To estimate the association between fine particulate (PM2.5) and nitrogen dioxide (NO2) pollution and systemic autoimmune rheumatic diseases (SARDs).\n\nMETHODS: Associations between ambient air pollution (PM2.5 and NO2) and SARDs were assessed using land-use regression models for Calgary, Alberta and administrative health data (1993-2007). SARD case definitions were based on \u22652 physician claims, or \u22651 rheumatology billing code; or \u22651 hospitalization code (for systemic lupus, Sjogren's Syndrome, scleroderma, polymyositis, dermatomyositis, or undifferentiated connective tissue disease). Bayesian hierarchical latent class regression models estimated the probability that each resident was a SARD case, based on these case definitions. The sum of individual level probabilities provided the estimated number of cases in each area. The latent class model included terms for age, sex, and an interaction term between age and sex. Bayesian logistic regression models were used to generate adjusted odds ratios (OR) for NO2 and PM2.5. pollutant models, adjusting for neighbourhood income, age, sex, and an interaction between age and sex. We also examined models stratified for First-Nations (FN) and non-FN subgroups.\n\nRESULTS: Residents that were female and/or aged >45 had a greater probability of being a SARD case, with the highest OR estimates for older females. Independently, the odds of being a SARDs case increased with PM2.5 levels, but the results were inconclusive for NO2. The results stratified by FN and non-FN groups were not distinctly different.\n\nCONCLUSION: In this urban Canadian sample, adjusting for demographics, exposure to PM2.5 was associated with an increased risk of SARDs. The results for NO2 were inconclusive.", "author" : [ { "dropping-particle" : "", "family" : "Bernatsky", "given" : "Sasha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smargiassi", "given" : "Audrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Markey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "Gilaad G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnabe", "given" : "Cheryl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Svenson", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bertazzon", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudson", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Ann E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fortin", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edworthy", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00e9lisle", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joseph", "given" : "Lawrence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Environmental research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "7" ] ] }, "page" : "474-8", "title" : "Fine particulate air pollution, nitrogen dioxide, and systemic autoimmune rheumatic disease in Calgary, Alberta.", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²⁹", "plainTextFormattedCitation" : "229", "previouslyFormattedCitation" : "²²⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }229.[H2] Quality of life Most studies have reported non-specific general complaints as the key contributors to the poor HRQoL of primary SjS patients, including fatigue, chronic pain, and depression. Ongoing studies are investigating other features that could contribute to poorer HRQOL, including inadequate dental and periodontal healthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jbspin.2015.02.015", "ISSN" : "1778-7254", "PMID" : "26194741", "author" : [ { "dropping-particle" : "", "family" : "Gall", "given" : "Malo", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornec", "given" : "Divi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques-Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cochener", "given" : "B\u00e9atrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roguedas-Contios", "given" : "Anne-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boisram\u00e9", "given" : "Sylvie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Joint, bone, spine : revue du rhumatisme", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "7", "17" ] ] }, "title" : "A prospective evaluation of dental and periodontal status in patients with suspected Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁰", "plainTextFormattedCitation" : "230", "previouslyFormattedCitation" : "²³⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }230, the impact of gynecological involvement on womens' sex livesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.141475", "ISSN" : "0315-162X", "PMID" : "26136488", "abstract" : "OBJECTIVE: To assess the quality of sexual life of women with primary Sj\u00f6gren syndrome (pSS) and to identify its correlations with disease activity and damage, quality of life, and mood disorders.\n\nMETHODS: The quality of sexual life of 24 women with pSS was assessed with the Female Sexual Function Index (FSFI). Twenty-four healthy women, matched by age and hormonal status, were enrolled as controls. Mood disorders and quality of life were investigated using the Hospital Anxiety and Depression Scale (HADS) and the Medical Outcomes Study Short Form-36. Patients underwent a gynecological visit with vaginal pH measurement, cervicovaginal swabs, and Pap smears. Disease activity and damage were assessed by the European League Against Rheumatism Sj\u00f6gren syndrome disease activity and damage indexes.\n\nRESULTS: Patients with pSS showed a pathological mean FSFI score (19.1 \u00b1 7.33) significantly different from controls (p = 0.004), both in menstruating women (p = 0.006) and in menopausal women (p = 0.03). Major differences between the 2 groups were detected in dyspareunia (p < 0.005), lubrication (p = 0.006), desire (p = 0.004), and arousal (p = 0.018). The FSFI score was inversely correlated with age (p = 0.008) and anxiety HADS (p = 0.031). No early anatomical changes, swabs, and Pap smear alterations were revealed in patients with pSS; however, vaginal pH was higher than normal in premenopausal patients (6.0 \u00b1 0.77).\n\nCONCLUSION: Both premenopausal and postmenopausal women with pSS have a worse sexual quality of life. We reported a greater prevalence of dyspareunia that is statistically significant when compared with controls. The FSFI could be a useful tool to assess this topic, but has been neglected in the care of patients with pSS heretofore.", "author" : [ { "dropping-particle" : "", "family" : "Priori", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minniti", "given" : "Antonina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Derme", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antonazzo", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brancatisano", "given" : "Filippo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghirini", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Framarino-dei-Malatesta", "given" : "Marialuisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "8" ] ] }, "page" : "1427-31", "title" : "Quality of Sexual Life in Women with Primary Sj\u00f6gren Syndrome.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/rheumatology/keu522", "ISSN" : "1462-0332", "PMID" : "25652072", "abstract" : "OBJECTIVE: Prevalence of vaginal dryness and dyspareunia is high in women with primary SS (pSS). Our aim was to compare sexual function and sexual distress in women with pSS with healthy controls, as well as to assess parameters that are associated with sexual dysfunction and distress in pSS. METHODS: Forty-six women fulfilling the American-European Consensus Group criteria for pSS [mean age 46.3 years (s.d. 10.5)] and 43 age-matched healthy controls were included. Participants completed self-administered questionnaires, namely the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), Multidimensional Fatigue Inventory (MFI), Hospital Anxiety and Depression Scale (HADS), Maudsley Marital Questionnaire (MMQ) and RAND 36-item Health Survey (RAND-36). In addition, the European League Against Rheumatism Sj\u00f6gren's Syndrome Disease Activity Index (ESSDAI) and Patient Reported Index (ESSPRI) were recorded in patients. RESULTS: Women with pSS had impaired sexual function compared with healthy controls (median FSFI 20.6 vs 30.3, P < 0.001), as reflected by significantly lower scores in the domains of desire, arousal, orgasm, lubrication and pain. Furthermore, pSS patients experienced more sexual distress (median FSDS 7 vs 4, P < 0.05) and were sexually active less frequently than controls (76% vs 93%, P < 0.05). Sexual dysfunction correlated significantly with patient-reported symptoms of pSS (ESSPRI), symptoms of fatigue (MFI), depressive symptoms (HADS), relationship dissatisfaction (MMQ) and lower mental quality of life (RAND-36), but not with systemic disease activity (ESSDAI). CONCLUSION: Women with pSS have impaired sexual function and more sexual distress compared with healthy controls. Sexual function and distress are influenced by vaginal dryness and patient-reported symptoms of pSS as well as psychosocial factors.", "author" : [ { "dropping-particle" : "", "family" : "Nimwegen", "given" : "Jolien F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arends", "given" : "Suzanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zuiden", "given" : "Greetje S", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissink", "given" : "Arjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kroese", "given" : "Frans G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1286-93", "title" : "The impact of primary Sj\u00f6gren's syndrome on female sexual function.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^231,232", "plainTextFormattedCitation" : "231,232", "previouslyFormattedCitation" : "^231,232" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }231,232 or the potential effect of voice disorders and other ENT symptoms on occupational and social activitiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0003489415579911", "ISSN" : "0003-4894", "PMID" : "25841042", "abstract" : "OBJECTIVES: This study examined quality of life burden of voice disorders in Sj\u00f6gren's syndrome (SS).\n\nMETHODS: Patients with SS (n = 101) completed interviews involving patient-reported histories of voice disorders, specific voice symptoms, SS disease severity, the Voice-Related Quality of Life (V-RQOL), and the general health-related quality of life Short Form 36 (SF-36) questionnaires. Relationships among voice symptoms, disease severity, and quality-of-life measures were examined and compared with patient-reported voice disorders.\n\nRESULTS: Significant correlations were observed among voice symptoms, disease severity, V-RQOL, SF-36, and patient-reported voice disorders (P < .05). Patients with SS who reported a voice disorder experienced a greater burden on general quality of life as compared with those without voice disorders. Specific voice symptoms significantly correlated with reduced SF-36 scores included frequent throat-clearing, throat soreness, difficulty projecting, and vocal discomfort. Despite the added burden of a voice disorder on quality of life in SS, voice-related treatment seeking was low (15.8%). However, the majority of patients who received voice treatment reported voice improvement.\n\nCONCLUSIONS: Individuals with SS frequently experience voice disorders and specific voice-related symptoms that are associated with reduced quality of life. These findings have important implications for voice referral practices and voice disorder symptom management in this population.", "author" : [ { "dropping-particle" : "", "family" : "Tanner", "given" : "Kristine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pierce", "given" : "Jenny L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merrill", "given" : "Ray M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Karla L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kendall", "given" : "Katherine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roy", "given" : "Nelson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Annals of otology, rhinology, and laryngology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "721-7", "title" : "The Quality of Life Burden Associated With Voice Disorders in Sj\u00f6gren's Syndrome.", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³³", "plainTextFormattedCitation" : "233", "previouslyFormattedCitation" : "²³³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }233. More detailed analysis of these symptoms by the correct specialist could be of great value to patients.[H2] Systemic diseaseThe increasing use of the ESSDAI and the recent publication of large European cohorts have definitively confirmed that SjS is a systemic disease. Unfortunately, the heterogeneous diagnostic approach used until now has contributed to the current ineffective approach to systemic SjS. The need for consensus is clear, and the EULAR-SS Task Force Group is working on developing organ-by-organ recommendationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kev200", "ISSN" : "1462-0332", "PMID" : "26231345", "abstract" : "OBJECTIVE: To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.\n\nMETHODS: The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features.\n\nRESULTS: The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ.\n\nCONCLUSION: The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6rner", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vita", "given" : "Salvatore", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandl", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Wan-Fai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruize", "given" : "Aike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitali", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2015", "12" ] ] }, "page" : "2230-8", "title" : "Characterization of systemic disease in primary Sj\u00f6gren's syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁴", "plainTextFormattedCitation" : "234", "previouslyFormattedCitation" : "²³⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234 and new scores for the better characterization and measurement of systemic diseaseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2014-206008", "ISBN" : "1468-2060; 0003-4967", "ISSN" : "1468-2060", "PMID" : "25480887", "abstract" : "OBJECTIVES: To define disease activity levels, minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) with the primary Sj\u00f6gren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patient-reported index (ESSPRI).\\n\\nMETHODS: For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI.\\n\\nRESULTS: Low-activity (ESSDAI<5), moderate-activity (5\u2264ESSDAI\u226413) and high-activity (ESSDAI\u226514) levels were defined. MCII of ESSDAI was defined as an improvement of at least three points. The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15%.\\n\\nCONCLUSIONS: This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI\u22655) and define response to treatment as an improvement of ESSDAI at least three points. For addressing patient-reported outcomes, inclusion of patients with unsatisfactory symptom state (ESSPRI\u22655) and defining response as an improvement of ESSPRI at least one point or 15% seems reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bootsma", "given" : "Hendrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theander", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Johan G", 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rheumatic diseases", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Development of clinESSDAI score (Clinical EULAR Sj\u00f6gren's Syndrome Disease Activity Index) without the biological domain: a tool for biological studies", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^168,169,235", "plainTextFormattedCitation" : "168,169,235", "previouslyFormattedCitation" : "^168,169,235" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }168,169,235. The scoring of systemic disease may provide diagnostic clues, since patients with the greatest systemic activity at diagnosis have a poorer prognosisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket349", "ISBN" : "1462-0324", "ISSN" : "14620324", "PMID" : "24162151", "abstract" : "OBJECTIVE: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions.\\n\\nMETHODS: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated.\\n\\nRESULTS: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score \u2265 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain.\\n\\nCONCLUSION: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. 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Disease Activity Index (ESSDAI) in 1045 patients. - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^115,126", "plainTextFormattedCitation" : "115,126", "previouslyFormattedCitation" : "^115,126" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }115,126.[H2] Improving diagnostic testsStudies are investigating how current diagnostic techniques can be improved. For ocular tests, studies are now using double staining, following the OSS scoreADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajo.2015.08.021", "ISSN" : "1879-1891", "PMID" : "26302236", "abstract" : "PURPOSE: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists.\n\nDESIGN: Reliability analysis within a prospective, observational, multicenter cohort study.\n\nMETHODS: Those enrolled in the National Institutes of Health-funded Sj\u00f6gren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining.\n\nRESULTS: Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90).\n\nCONCLUSIONS: Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sj\u00f6gren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.", "author" : [ { "dropping-particle" : "", "family" : "Rose-Nussbaumer", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lietman", "given" : "Thomas M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "Caroline H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "Stephen C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bunya", "given" : "Vatinee Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akpek", "given" : "Esen K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinivasan", "given" : "Muthiah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mascarenhas", "given" : "Jeena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massaro-Giordano", "given" : "Giacomina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNamara", "given" : "Nancy A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcher", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaynor", "given" : "Bruce D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of ophthalmology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2015", "12" ] ] }, "page" : "1150-1153.e3", "title" : "Inter-grader Agreement of the Ocular Staining Score in the Sj\u00f6gren's International Clinical Collaborative Alliance (SICCA) Registry.", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁶", "plainTextFormattedCitation" : "236", "previouslyFormattedCitation" : "²³⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }236, and have investigated specific damage in some corneal areas (central optical zone)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1167/iovs.11-8412", "ISBN" : "1552-5783 (Electronic)\\n0146-0404 (Linking)", "ISSN" : "01460404", "PMID" : "22110071", "abstract" : "PURPOSE: To investigate the changes in functional visual acuity (VA) and higher order aberrations in dry eye patients.\\n\\nMETHODS: In this prospective comparative case series, 22 right eyes were classified into those with or without superficial punctate keratopathy (SPK) in the central cornea of 22 patients with Sj\u00f6gren syndrome; 10 right eyes of 10 normal subjects served as the control. Serial measurements of VAs using a functional VA measurement system and higher order aberrations using a wavefront sensor were performed under blink-free conditions without topical anesthesia over a 10-second period. The parameters for each measurement were compared among the SPK-positive and -negative and normal groups. The correlation between those parameters was also analyzed.\\n\\nRESULTS: Dry eye with SPK showed significant deterioration of visual function and optical quality compared with dry eye without SPK and in normal eyes, as detected by both the visual maintenance ratio (VMR; P < 0.05) and the variation of VA (P < 0.05) and by comalike and total higher order aberrations (P < 0.05). Moreover, the severity of epithelial damage at the central cornea correlated significantly with VMR (P < 0.01) and variation of VA (P < 0.01) as well as comalike (P < 0.05) and total higher order aberrations (P < 0.05). The dry eye group without SPK showed minor visual deterioration compared with normal eyes, as detected only by VMR (P < 0.05).\\n\\nCONCLUSIONS: Optical disturbances at the central optical zone of the cornea in dry eye disease may affect visual performance. Functional VA measurement may be an applicable method of evaluating visual performance in dry eyes that is as efficient as wavefront aberration measurements.", "author" : [ { "dropping-particle" : "", "family" : "Kaido", "given" : "Minako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsumoto", "given" : "Yukihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shigeno", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishida", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dogru", "given" : "Murat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsubota", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Investigative Ophthalmology and Visual Science", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "9516-9522", "title" : "Corneal fluorescein staining correlates with visual function in dry eye patients", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁷", "plainTextFormattedCitation" : "237", "previouslyFormattedCitation" : "²³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }237 or the influence of desiccating environmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1790-5427", "PMID" : "25097897", "abstract" : "Our aim was to validate eight scintigraphic salivary gland (SG) parameters, as diagnostic parameters in patients with Sj\u00f6gren's syndrome (SS). We used the standardized stimulated dynamic salivary gland scintigraphy (DSGS) protocol and correlated this with the unstimulated whole sialometry (UWS) functions. The DSGS and UWS tests meeting the European and the USA diagnostic classification criteria for SS were applied in twenty patients and in ten normal controls. The DSGS tests were performed 60min after the intravenous (i.v.) injection of 370MBq of technetium-99m-pertechnetate ((99m)TcO(-)4) and after per os stimulation with a 0.5g tablet of ascorbic acid administered 40min after the injection. Using time-activity curves, eight different parameters were calculated for each parotid gland (PG) and each submandibular salivary gland (SMG): a) time at maximum counts (Tmax), b) time at minimum counts (Tmin), c) maximum accumulation (MA), d) accumulation velocity (AV), e) maximum secretion (MS), f) maximum stimulated secretion (MSS), g) stimulated secretion velocity (SSV), and h) uptake ratio (UR). Values of UWS below 2.5mL/15min, were considered abnormal. All these parameters, as for the PG, showed significant abnormality in SS patients (P<0.001), especially of the secretion function. All SMG parameters also showed a significant abnormality (P<0.001), but especially of the accumulation function. There was a greater impairment of the above parameters in SMG than in PG in the SS patients. Sensitivity of the standardized DSGS was 100%, specificity 80%, negative prognostic value 100%, and positive prognostic value 91%. Sensitivity of UWS was 75%. In conclusion, this paper suggested that the best diagnostic parameters for the SS patients were those of: a) the maximum secretion, b) the maximum stimulated secretion for both the parotid and the submandibular glands, c) maximum accumulation and d) accumulation velocity of submandibular glands. The times at maximum and at minimum counts were non diagnostic.", "author" : [ { "dropping-particle" : "", "family" : "Dugonji\u0107", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefanovi\u0107", "given" : "Du\u0161an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ethurovi\u0107", "given" : "Branka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spasi\u0107-Joki\u0107", "given" : "Vesna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajdinovi\u0107", "given" : "Boris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hellenic journal of nuclear medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "116-22", "title" : "Evaluation of diagnostic parameters from parotid and submandibular dynamic salivary glands scintigraphy and unstimulated sialometry in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶¹", "plainTextFormattedCitation" : "161", "previouslyFormattedCitation" : "¹⁶¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }161. Technical developments are promoting more-accurate quantitative evaluation in scintigraphic studies although there remains no clear consensusADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajo.2015.09.039", "ISSN" : "1879-1891", "PMID" : "26456254", "abstract" : "PURPOSE: To evaluate the response of the lacrimal function unit in Sj\u00f6gren syndrome (SS)-associated dry eye patients exposed to 2 simulated daily life environmental conditions.\n\nDESIGN: Prospective crossover pilot study.\n\nMETHODS: Fourteen female SS dry eye patients were exposed for 2 hours to a controlled normal condition (23 C, 45% relative humidity, and air flow 0.10\u00a0m/s) and a controlled adverse condition that simulates desiccating stress (23 C, 5% relative humidity, and air flow 0.10\u00a0m/s). The following dry eye tests were performed before and after the exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear break-up time, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test. Levels of 16 molecules were analyzed in tears by multiplex immunobead analysis.\n\nRESULTS: Clinical evaluation showed lacrimal functional unit impairment after the desiccating stress: significantly increased tear osmolarity (315.7 \u00b1 3.0 vs 327.7 \u00b1 5.1 mOsm/L, P\u00a0= .03), conjunctival hyperemia (1.3 \u00b1 0.1 vs 1.6 \u00b1 0.1, P\u00a0= .05), and corneal staining in temporal (3.5 \u00b1 0.5 vs 4.7 \u00b1 0.4, P\u00a0= .01) and nasal (3.6 \u00b1 0.5 vs 4.5 \u00b1 0.5, P\u00a0= .04) areas. Tear concentrations increased for interleukin-1 receptor antagonist (16 557.1 \u00b1 4047.8 vs 31 895.3 \u00b1 5916.5 pg/mL, P\u00a0= .01), interleukin-6 (63.8 \u00b1 20.2 vs 111.5 \u00b1 29.6 pg/mL, P\u00a0= .02), interleukin-8 (2196.1 \u00b1 737.9 vs 3753.2 \u00b1 1106.0 pg/mL, P\u00a0= .03), and matrix metalloproteinase-9 (101 515.6 \u00b1 37 088.4 vs 145 867.1 \u00b1 41 651.5 pg/mL, P\u00a0= .03). After the simulated normal condition, only a significant increase in nasal corneal staining (2.9 \u00b1 0.5 vs 3.6 \u00b1 0.5, P\u00a0= .03) was observed.\n\nCONCLUSIONS: Even a short exposure to a desiccating environment can produce a significant deterioration of the lacrimal function unit in female SS dry eye patients. The often unnoticed exposure to these conditions during daily life may increase inflammatory activity rapidly, triggering an ocular surface deterioration.", "author" : [ { "dropping-particle" : "", "family" : "L\u00f3pez-Miguel", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tes\u00f3n", "given" : "Marisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00edn-Monta\u00f1ez", "given" : "Vicente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enr\u00edquez-de-Salamanca", "given" : "Amalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Garc\u00eda", "given" : "Mar\u00eda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calonge", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of ophthalmology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "10", "8" ] ] }, "title" : "Clinical and Molecular Inflammatory Response in Sj\u00f6gren Syndrome-Associated Dry Eye Patients Under Desiccating Stress.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁸", "plainTextFormattedCitation" : "238", "previouslyFormattedCitation" : "²³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }238. With respect to salivary biopsy, it may be time to develop an international consensus on updating the classic histopathological classification, used with minimal variations for more than 40 years, and promoting close cooperation between clinicians and pathologists to facilitate the integration of pathological results into the clinical spectrum of each patient. Histopathological findings that do not fit the current criteria (focal aggregates of < 50 lymphocytes, chronic atrophic sialadenitis, GC) could have some diagnostic value if they are integrated in the appropriate clinical scenarioADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Retamozo S, Brito-Zer\u00f3n P, Bov\u00e9 A, Gheitasi H, Grant C, Superville D, Kostov B, Sis\u00f3-Almirall A, Al\u00f3s L", "given" : "Ramos-Casals M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Rheumatol", "id" : "ITEM-1", "issue" : "Suppl 10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Usefulness of the Minimally-Invasive Minor Salivary Gland Biopsy in Patients Presenting with Sicca Syndrome: Prospective Evaluation of 200 Patients", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁹", "plainTextFormattedCitation" : "239", "previouslyFormattedCitation" : "²³⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }239. [H2] New diagnostic tests Ultrasonography is an increasingly-used diagnostic area. Several studies have found a potential role for US in the early non-invasive diagnosis of SjS, a correlation with the main clinical features and a high diagnostic accuracyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0392-856X", "ISSN" : "0392-856X", "abstract" : "OBJECTIVES: To investigate major salivary gland ultrasonography (US) in relation to symptoms and findings of oral and ocular dryness, and autoimmune disease, for potential use in diagnosis and follow-up of patients with primary Sjogren's syndrome (pSS)., METHODS: Patients with pSS were recruited from the Department of Rheumatology, Haukeland University Hospital. The parotid and submandibular salivary glands were examined by US using a simplified scoring system for glandular homogeneity and hypoechogenic areas. Scans were graded on a scale 0-3, grades 0-1 considered corresponding to normal/non-specific changes and grades 2-3 to pathological changes. Sicca symptoms of the mouth and eyes, salivary gland capacity, tear secretion, minor salivary gland inflammation, serum autoantibodies, and fatigue were also investigated., RESULTS: US was performed in 97 patients. Oral and ocular sicca symptoms correlated with US score and decreased saliva levels. Fatigue VAS correlated with oral sicca symptoms but was inversely correlated with age. Patients with normal/non-specific US findings tended to be older than patients with pathological US findings. US score correlated with unstimulated and stimulated salivary secretion and tear secretion. Minor salivary gland inflammation correlated with major salivary gland US findings, and lymphoid organisation, germinal centre (GC)-like structures, in the minor salivary gland tissue biopsies was seemingly related to US pathology. Serum autoantibodies against Ro/SSA and/or La/SSB were associated with US pathology., CONCLUSIONS: US findings in major salivary glands correlate with subjective and objective oral and ocular items as well as systemic autoimmune features of pSS. US represents a useful imaging tool for diagnostics and follow-up of pSS.", "author" : [ { "dropping-particle" : "", "family" : "DS", "given" : "Hammenfors", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "JG", "given" : "Brun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MV", "given" : "Jonsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammenfors", "given" : "Daniel S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "Malin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "56-62", "title" : "Diagnostic utility of major salivary gland ultrasonography in primary Sjogren's syndrome.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/s13075-015-0657-7", "ISSN" : "1478-6362", "PMID" : "26022533", "abstract" : "INTRODUCTION: Recently, a great interest has arisen for salivary gland ultrasonography (SGUS) as a valuable tool for the assessment of major salivary gland involvement in primary Sj\u00f6gren's syndrome (pSS. The aims of this study were to test the accuracy of SGUS for the early detection of pSSand to compare the diagnostic performance of SGUS with minor salivary gland biopsy (MSGB) and unstimulated salivary flow (USFR) in this context.\n\nMETHOD: Patients with suspected pSS and symptoms duration of \u22645 years were consecutively enrolled in this study. The diagnosis of pSS was made according to the AECG criteria. SGUS was performed by two radiologists blinded to the diagnosis and a previously reported ultrasound scoring system (De Vita et al. 1992, cut-off \u2265 1) was used to grade the echostructure alterations of the salivary glands. Statistical analysis was performed using SPSS v16.\n\nRESULTS: This study included 50 pSS patients and 57 controls with no-SS sicca symptoms. The mean(SD) age of the pSS group was lower than non-SS group (47(13) vs 53(12)yrs, p = 0.006). No further differences between the two groups were observed. Patients with pSS showed a significantly higher SGUS score in comparison with controls (mean(SD) = 2.1(1.8) vs 0.0(0.4), p = 0.000). The SGUS cut-off \u2265 1 showed a sensitivity (SE) of 66 %, a specificity (SP) of 98 %, a positive predictive value (PPV) of 97 % and a negative predictive value (NPV) of 73 % for pSS diagnosis. The SGUS score correlated also with patients' MSGB/FS and USFR.\n\nCONCLUSIONS: This study confirmed the good performance of SGUS for the early non-invasive diagnosis of pSS. Further research in larger international cohort of patients is mandatory in order to assess the role of SGUS in the diagnostic algorithm of pSS.", "author" : [ { "dropping-particle" : "", "family" : "Baldini", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luciano", "given" : "Nicoletta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarantini", "given" : "Gaia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pascale", "given" : "Rachele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sernissi", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mosca", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caramella", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "146", "title" : "Salivary gland ultrasonography: a highly specific tool for the early diagnosis of primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/rheumatology/kev253", "ISSN" : "1462-0332", "PMID" : "26206346", "abstract" : "OBJECTIVES: Recently, convincing data have been published on the value of salivary gland ultrasonography (SGUS) in differentiating primary SS from non-immune-mediated sicca syndrome. Limited data are available regarding the diagnostic accuracy of SGUS in distinguishing SS from other rheumatic diseases. The purpose of this study was to assess the usefulness of SGUS in distinguishing patients with SS from those with xerostomia and/or xerophthalmia and a diagnosis of stable UCTD.\n\nMETHODS: This cross-sectional study consecutively enrolled 150 patients either diagnosed with SS (as established by the American-European Consensus Group criteria) or affected by UCTD but not SS. Parotid and submandibular glands on both sides were assessed for size, parenchymal echogenicity and inhomogeneity by means of SGUS, which was performed by a radiologist blinded to the diagnosis. Echostructural alterations of the salivary glands were graded from 0 to 3 (cut-off >2).\n\nRESULTS: This study included 109 patients: 55 with SS and 54 with UCTD. Patients with SS showed a higher SGUS score in comparison with those with UCTD [mean 2.2 (s.d. 1.8) vs 0.2 (s.d. 0.5), P < 0.0001]. The SGUS cut-off >2 showed a sensitivity of 65%, a specificity of 96%, a positive predictive value of 95% and a negative predictive value of 73% for SS diagnosis. A significant correlation was also found between the SGUS score and the minor salivary gland biopsy/focus score (r = 0.484, P < 0.0001).\n\nCONCLUSION: This study confirmed the good sensitivity and the high specificity of SGUS in differentiating SS from other CTDs.", "author" : [ { "dropping-particle" : "", "family" : "Luciano", "given" : "Nicoletta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarantini", "given" : "Gaia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferro", "given" : "Ferro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sernissi", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varanini", "given" : "Valentina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donati", "given" : "Valentina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martini", "given" : "Daniela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mosca", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caramella", "given" : "Davide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2015", "12" ] ] }, "page" : "2198-204", "title" : "Ultrasonography of major salivary glands: a highly specific tool for distinguishing primary Sj\u00f6gren's syndrome from undifferentiated connective tissue diseases.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^240\u2013242", "plainTextFormattedCitation" : "240\u2013242", "previouslyFormattedCitation" : "^240\u2013242" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }240–242. In 2012, an international task force began work on the standardization of the use of US in the diagnosis of SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keu397", "ISSN" : "1462-0332", "PMID" : "25288782", "author" : [ { "dropping-particle" : "", "family" : "Cornec", "given" : "Divi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "199-200", "title" : "Salivary gland ultrasound to diagnose Sj\u00f6gren's syndrome: a claim to standardize the procedure.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴³", "plainTextFormattedCitation" : "243", "previouslyFormattedCitation" : "²⁴³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }243. Other imaging techniques (3D-magnetic resonance, 18F-fluorodeoxyglucose positron emission tomography) are increasingly used to improve the non-invasive diagnosis of some organ-specific involvementsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1940-5901", "PMID" : "26064299", "abstract" : "AIM: To investigate the value of conventional MRI techniques combined with MR sialography on T2-3D-DRIVE in the diagnosis of Sj\u00f6gren syndrome (SS).\n\nMETHODS: 107 patients were divided into SS group and non-SS group. Conventional MRI techniques, such as T1WI, T2WI, and STIR images were used for changes of fat signal in the parotid gland, while the MR sialography were used for ducts dilation of the parotid gland.\n\nRESULTS: Among 93 SS patients, MRI identified abnormal fat deposit in the parotid glands in 86 patients. The fat signal based on MRI images showed 7 patients were in stage 0, 28 in stage 1, 14 in stage 2, 32 in stage 3 and 12 in stage 4. T2-3D-DRIVEMR MR sialography identified peripheral ducts dilation in 86 patients. The duct dilation based on MR sialography showed 7 patients in stage 0, 14 patients in stage 1, 44 patients in stage 2, 26 patients in stage 3, and 2 patients in stage 4. On MRI and MR sialography, both had a positive diagnostic rate of 92.5%. When MRI and MR sialography techniques were used together, the positive diagnostic rate increased to 96.8%. However, Kappa test showed that the MRI fat signal staging and MR sialogrpahy duct dilation staging had statistical difference (Kappa = 0.241, P = 0.000).\n\nCONCLUSION: T2-3D-DRIVE MR sialography detects peripheral ducts dilation in parotid glands with unmatched spatial resolution, also MRI fat suppression techniques detect diffusive fat deposit in parotid glands with high accuracy. Combining two techniques will provide optimal diagnosis workup for SS.", "author" : [ { "dropping-particle" : "", "family" : "Ren", "given" : "Yan-De", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xiang-Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Li-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Wei-Xiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Yao-Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of clinical and experimental medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "3974-82", "title" : "Conventional MRI techniques combined with MR sialography on T2-3D-DRIVE in Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/MD.0000000000000024", "ISSN" : "1536-5964", "PMID" : "24797167", "abstract" : "The diagnosis and treatment of patients with Sj\u00f6gren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional \"stocking-and-glove\" distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system-the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain.We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients whose neuropathic pain resolved with intravenous immunoglobulin (IVIg) therapy had improvement of MRN DRG abnormalities.We have developed a novel MRN protocol that can detect DRG abnormalities in SS patients with neuropathic pain who do not have markers of peripheral neuropathy. We found that SS patients with MRN DRG abnormalities had statistically significant, increased IENFD on skin biopsy studies, which may suggest a relationship between trophic mediators and neuropathic pain. Given that our literature review h\u2026", "author" : [ { "dropping-particle" : "", "family" : "Birnbaum", "given" : "Julius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "Trisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owoyemi", "given" : "Kristie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Kenneth C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrino", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chhabra", "given" : "Avneesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "121-34", "title" : "Use of a novel high-resolution magnetic resonance neurography protocol to detect abnormal dorsal root Ganglia in Sj\u00f6gren patients with neuropathic pain: case series of 10 patients and review of the literature.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.autrev.2013.06.012", "ISSN" : "15689972", "PMID" : "23810977", "abstract" : "Objective: This study aims to determine the value of FDG-PET/CT to assess disease activity in patients with Sj\u00f6gren's syndrome (SS). Methods: Thirty-two patients with SS who underwent PET/CT were retrospectively analyzed. PET/CT activity score was measured using a 6-point scale including the 6 following items (0/1: absence or presence of an item): lymphadenopathy on CT, high-resolution CT (HRCT) evidence of interstitial lung disease (ILD), parotid glands SUVmax >. 3, submandibular glands SUVmax >. 3, lymph node uptake, ILD uptake. Combined PET/CT score was correlated to ESSDAI (EULAR Sj\u00f6gren's Syndrome Disease Activity Index) score and other parameters of SS activity. Results: Pathological FDG uptake was observed in 75% of patients (24/32): lymph-nodes (n=19, 60%), salivary glands (n=17, 53%), lungs (n=9, 28%), and thyroid (n=2). Median ESSDAI and PET/CT activity scores were 9.5 [5-12] and 2 [0-3], respectively. PET/CT activity score correlated with ESSDAI (r=0.49, p=0.005), unlike SUVmax. Patients with a high ESSDAI score had a higher PET/CT activity score than patients with a low ESSDAI score (3 vs 1, p=0.004). PET was also correlated with gammaglobulin levels (r=0.43, p=0.02), but not with the presence of cryoglobulinemia, activated complement or beta-2 microglobulin levels. The FDG uptake in patients with lymphoma (n=4) was higher than in patients without lymphoma (SUVmax=5.4 vs. 3.2, p=0.05). Conclusion: We described a new PET/CT activity score, which correlates to ESSDAI and could help to assess disease activity in SS patients. PET can also help in the diagnosis of lymphoma, even if inflammatory lymph nodes can be frequently observed in SS patients. \u00a9 2013 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Cohen", "given" : "Camille", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mekinian", "given" : "Ars\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uzunhan", "given" : "Yurdagul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauchais", "given" : "Anne Laure", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhote", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pop", "given" : "Gabriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eder", "given" : "V\u00e9ronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nunes", "given" : "Hilario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brillet", "given" : "Pierre Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeyre", "given" : "Dominique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soussan", "given" : "Micha\u00ebl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity Reviews", "id" : "ITEM-3", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1109-1114", "title" : "18F-fluorodeoxyglucose positron emission tomography/computer tomography as an objective tool for assessing disease activity in Sj\u00f6gren's syndrome", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^244\u2013246", "plainTextFormattedCitation" : "244\u2013246", "previouslyFormattedCitation" : "^244\u2013246" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }244–246.[H2] Classification criteria The existence of two sets of classification criteria (AECG and ACR) with very similar figures of diagnostic accuracy has induced some scientific confusion. An international ACR-EULAR study group is now searching for a consensual set of criteria that maintain the same approach as previous sets of criteria: namely, the mandatory presence of either anti-Ro antibodies (anti-La are overwhelmingly associated with anti-Ro) or FLS. Future efforts should explore the potential usefulness of incorporating features other than Ro and glandular involvement, including organ-specific ESSDAI involvements (both clinical, laboratory and immunological) and novel imaging techniques (especially US, but also CT/MRI). [H2] Complexity and chronicity SjS has a significant “overload” of co-morbidity, principally the higher risk of hematological neoplasia, but also including other systemic or organ-specific autoimmune diseases, non-hematological cancer, and cardiovascular and infectious complicationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/joim.12346", "ISSN" : "1365-2796 (Electronic)", "PMID" : "25582881", "abstract" : "OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjogren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of 1343 pSS patients. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events were compared between a subgroup of 788 female pSS patients aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in pSS patients. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Bartoloni", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldini", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schillaci", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quartuccio", "given" : "Luca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priori", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carubbi", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bini", "given" : "Vittorio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alunno", "given" : "Alessia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Vita", "given" : "Salvatore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valesini", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giacomelli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerli", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of internal medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Cardiovascular disease risk burden in primary Sjogren's syndrome: results of a population-based multicentre cohort study.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.semarthrit.2006.08.007", "abstract" : "To analyze the main diagnostic problems caused by the overlap between Sj\u00f6gren's syndrome (SS) and other systemic autoimmune diseases (SAD).", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Semin Arthritis Rheum", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "246-55", "title" : "The overlap of Sj\u00f6gren's syndrome with other systemic autoimmune diseases.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1186/s13075-015-0613-6", "ISSN" : "1478-6362", "PMID" : "25886059", "abstract" : "INTRODUCTION: To determine the prevalence and clinical/laboratory associations of subclinical atherosclerosis and impaired bone health in primary Sjogren's syndrome (SS).\n\nMETHODS: 64 consecutive patients with primary SS, 77 with rheumatoid arthritis (RA) and 60 healthy controls (HC) \u03bff similar age and sex distribution were enrolled. Demographics, clinical/laboratory features, classical risk factors for atherosclerosis and osteoporosis (OP) were recorded. Intima-medial thickness scores (IMT) and carotid/femoral (C/F) plaque formation, as well as bone mineral density (BMD) and fractures were evaluated. Determinants of IMT/BMD levels and the presence of plaque were assessed by univariate and multivariate models. Serum levels of the Wnt signaling mediators Dickkopf-related protein 1(DKK1) and sclerostin were determined in primary SS patients and HC.\n\nRESULTS: Increased arterial wall thickening (IMT\u2009>\u20090.90\u00a0mm) and impaired bone health (defined as OP or osteopenia), were detected in approximately two-thirds of primary SS and RA patients, with a mean IMT value being significantly increased compared to HC. The presence of primary SS emerged as an independent risk factor for arterial wall thickening when traditional risk factors for cardiovascular disease (CVD) including age, sex, hypertension, smoking (pack/years), LDL and HDL levels were taken into account in a multivariate model [adjusted OR 95% (CI): 2.8 (1.04-7.54)]. In primary SS, age was revealed as independent predictor of increased IMT scores; age and lymphopenia as well as increased urine pH as independent determinants of C/F plaque formation and OP/osteopenia, respectively. An independent association of OP/osteopenia with plaque formation was observed when independent predictors for both variables were considered, with low DKK1 levels being associated with both plaque formation and lower BMD levels.\n\nCONCLUSIONS: Comorbidities such as subclinical atherosclerosis and impaired bone health occur frequently in primary SS, in association with disease related features and traditional risk factors. Wnt signaling mediators are potentially involved in the pathogenesis of both entities.", "author" : [ { "dropping-particle" : "", "family" : "Gravani", "given" : "Fotini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papadaki", "given" : "Ioanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antypa", "given" : "Eleni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nezos", "given" : "Andrianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masselou", "given" : "Kyriaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ioakeimidis", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koutsilieris", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "Haralampos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mavragani", "given" : "Clio P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis research & therapy", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "99", "title" : "Subclinical atherosclerosis and impaired bone health in patients with primary Sjogren's syndrome: prevalence, clinical and laboratory associations.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "2151-4658", "abstract" : "OBJECTIVE: To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjogren's syndrome (SS) patients and to compare them to healthy controls., METHODS: Data on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group., RESULTS: Primary SS patients had a higher prevalence of hypertension (28-50% versus 15.5-25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it., CONCLUSION: Primary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Juarez", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toms", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pablo", "given" : "P", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nightingale", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffiths", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutdliffe", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pitzalis", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pease", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emery", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Regan", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giles", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isenberg", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moots", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "K S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "W F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitas", "given" : "G D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Registry", "given" : "U K Primary Sjogren's Syndrome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "757-764", "title" : "Cardiovascular risk factors in women with primary Sjogren's syndrome: United Kingdom primary Sjogren's syndrome registry results.", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1111/1759-7714.12216", "ISSN" : "1759-7706", "PMID" : "26273404", "abstract" : "BACKGROUND: A retrospective analysis of clinical data from primary Sjogren's syndrome (pSS) patients with lung cancer was conducted in order to guide further clinical work.\n\nMETHODS: From January 1993 to December 2010, 10 pSS patients with lung cancer were hospitalized at the Peking Union Medical College Hospital. One hundred and three pSS patients were recruited as the controls. Patients' clinical data was retrospectively analyzed.\n\nRESULT: The incidence rate of lung cancer in pSS patients was 0.477%. The duration from diagnosis of pSS to lung cancer in the 10 patients was 0.92\u223c42 years. The pSS patients with lung cancer were significantly older than those without lung cancer (60.8 \u00b1 8.9 vs. 44.9 \u00b1 12.1, P < 0.001). Eight of the pSS patients with lung cancer (80%) were female nonsmokers; five pSS patients with lung cancer (50%) had lung involvement, exhibiting diffuse parenchymal lung disease. Adenocarcinoma was the most common pathological type of lung cancer (90%). Tumor node metastasis staging of lung cancer included: four cases of Ib (40%), one case of IIIb (10%), four cases of IV (40%) and one case undetermined (10%).\n\nCONCLUSION: The incidence rate of lung cancer in pSS patients was higher with respect to the normal population. Physicians should closely observe lung cancer incidence during the pSS follow-up period. Adenocarcinoma was the most frequently seen lung cancer pathology in pSS patients. Clinical stages and individualized treatment for pSS patients with lung cancer should be carefully determined.", "author" : [ { "dropping-particle" : "", "family" : "Xu", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fei", "given" : "Yunyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Longyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Mengzhao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Thoracic cancer", "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "7" ] ] }, "page" : "475-9", "title" : "The Prevalence and clinical characteristics of primary Sjogren's syndrome patients with lung cancer: An analysis of ten cases in China and literature review.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1371/journal.pone.0134930", "ISSN" : "1932-6203", "PMID" : "26305359", "abstract" : "BACKGROUND: Primary Sj\u00f6gren's syndrome (pSS) is associated with immunological dysfunctions--a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.\n\nMETHODS: This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.\n\nRESULTS: During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50-1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged \u226760; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14-5.45) > immunosuppressants alone (3.24; 95% CI 2.36-4.45) > steroids alone (2.54; 95% CI 2.16-2.97) > no pharmacological drugs (2.06; 95% CI 1.76-2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.\n\nCONCLUSIONS: Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Jen-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Li-Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feng", "given" : "Ping-Hsun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chu", "given" : "Chin-Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Tain-Junn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weng", "given" : "Shih-Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Su-Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Tsung-Hsueh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Chia-Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-6", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "e0134930", "title" : "Risk of Shingles in Adults with Primary Sjogren's Syndrome and Treatments: A Nationwide Population-Based Cohort Study.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{89,247\u2013251}", "plainTextFormattedCitation" : "89,247\u2013251", "previouslyFormattedCitation" : "^{89,247\u2013251}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89,247–251. This constellation of associated processes often provokes considerable concern and doubt in patients and physicians alike, and is responsible for the high degree of complexity and chronicity of SjS, which leads to increased hospitalization and outpatient visitsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "PMID" : "26315557", "abstract" : "OBJECTIVES: To identify the causes and risk factors for hospitalisation in primary Sj\u00f6gren's syndrome (pSS).\n\nMETHODS: We included 170 pSS patients who regularly attended our Institution (2000-2013) and retrospectively collected demographic, clinical (glandular and extraglandular features) and serological (anti-Ro/SSA, anti-La/SSB, RF, low C3 or C4 and immunoglobulin levels) data. If they were hospitalised, a rheumatologist determined the primary cause. We registered the length of hospitalisation, need for Intensive Care Unit (ICU) admission, number of hospitalisations and death. The Disease Damage Index (SSDDI) (excluding the oral and ocular items) and the Charlson comorbidity Index were assessed. We used a logistic regression analysis and multiple imputation method for missing data.\n\nRESULTS: Fifty-five (32%) patients were hospitalised, representing 111 hospitalisations (28 patients had \u22651 hospital admission). The hospitalisation incidence density rate was 6.49/100 patient / years. The median length of hospital stay was 9 days (IQR 6-15), there were 7 ICU admissions and 6 deaths. The main causes of admissions were disease activity (33.3%) and infection (32.4%). At the multivariate analysis, the variables associated with hospitalisation were hepatic involvement (OR=5.4; 95% CI 1.61-18.15; p=0.006), vasculitis (OR=3.8; 95% CI 1.11-13.09; p=0.03), the SSDDI (OR=1.3; 95% CI 1.01-1.66; p=0.03) and the use of antimalarials (OR=0.08; 95% CI 0.02-0.22; p<0.001).\n\nCONCLUSIONS: The major causes for hospitalisation were disease activity and infection. Patients with hepatic involvement, vasculitis and more damage accrual had the highest risk for being hospitalised, while the use of antimalarials was protective.", "author" : [ { "dropping-particle" : "", "family" : "Atisha-Fregoso", "given" : "Yemil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera-Vicencio", "given" : "Yahaira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ba\u00f1os-Pelaez", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hern\u00e1ndez-Molina", "given" : "Gabriela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "721-5", "title" : "Main causes and risk factors for hospitalisation in patients with primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵²", "plainTextFormattedCitation" : "252", "previouslyFormattedCitation" : "²⁵²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }252. Studies focusing on the complexity and chronicity of SjS are required for better understanding of disease outcomes.[H2] Drug-free management Drug-free therapeutic interventions often receive little attention and resources: a recent systematic review found that all drug-free therapeutic studies in SjS were of low quality and at high risk of biasADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kev227", "ISSN" : "1462-0332", "PMID" : "26135587", "abstract" : "OBJECTIVE: To evaluate the effects of non-pharmacological interventions for primary SS (pSS) on outcomes falling within the World Health Organization International Classification of Functioning Disability and Health domains.\\n\\nMETHODS: We searched the following databases from inception to September 2014: Cochrane Database of Systematic Reviews; Medline; Embase; PsychINFO; CINAHL; and clinical trials registers. We included randomized controlled trials of any non-pharmacological intervention. Two authors independently reviewed titles and abstracts against the inclusion/exclusion criteria and independently assessed trial quality and extracted data.\\n\\nRESULTS: A total of 1463 studies were identified, from which 17 full text articles were screened and 5 studies were included in the review; a total of 130 participants were randomized. The included studies investigated the effectiveness of an oral lubricating device for dry mouth, acupuncture for dry mouth, lacrimal punctum plugs for dry eyes and psychodynamic group therapy for coping with symptoms. Overall, the studies were of low quality and at high risk of bias. Although one study showed punctum plugs to improve dry eyes, the sample size was relatively small.\\n\\nCONCLUSION: Further high-quality studies to evaluate non-pharmacological interventions for PSS are needed.", "author" : [ { "dropping-particle" : "", "family" : "Hackett", "given" : "Katie L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deane", "given" : "Katherine H O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strassheim", "given" : "Victoria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deary", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rapley", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newton", "given" : "Julia L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Wan-Fai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "kev227-", "title" : "A systematic review of non-pharmacological interventions for primary Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵³", "plainTextFormattedCitation" : "253", "previouslyFormattedCitation" : "²⁵³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }253. Future studies should evaluate the disease from a holistic perspective focusing on the influence of determinants involving personal life and work on the phenotypic expression of SjS, including the effects of healthy (Mediterranean, Japanese) vs. unhealthy (high-sugar, processed food) diets, regular aerobic exercise (principally for non-sicca general symptoms) and stress (which acts not only to worsen the intensity of sicca features, but also as a potential trigger of systemic flares). [H2] Biological therapies Direct and indirect B-cell blockade seems to be the most-promising approach, although other therapeutic targets are under investigation (Table 8). IL-6 blockade is a promising option, since IL-6 induces polarization of Tfh-cells and is important for the induction of IL-21 productionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1084/jem.20120994", "ISBN" : "1540-9538 (Electronic)\\r0022-1007 (Linking)", "ISSN" : "0022-1007", "PMID" : "22753927", "abstract" : "The generation of high-affinity antibodies (Abs) plays a critical role in the neutralization and clearance of pathogens and subsequent host survival after natural infection with a variety of microorganisms. Most currently available vaccines rely on the induction of long- lived protective humoral immune responses by memory B cells and plasma cells, underscoring the importance of Abs in host protection. Ab responses against most antigens (Ags) require interactions between B cells and CD4+ T helper cells, and it is now well recognized that T follicular helper cells (Tfh) specialize in providing cognate help to B cells and are fundamentally required for the generation of T cell\u2013dependent B cell responses. Perturba- tions in the development and/or function of Tfh cells can manifest as immunopathologies, such as immunodeficiency, autoimmunity, and malignancy. Unraveling the cellular and molecular requirements underlying Tfh cell formation and maintenance will help to identify molecules that could be targeted for the treatment of immunological diseases that are characterized by insufficient or excessive Ab responses.", "author" : [ { "dropping-particle" : "", "family" : "Ma", "given" : "C. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deenick", "given" : "E. K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batten", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tangye", "given" : "S. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Experimental Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1241-1253", "title" : "The origins, function, and regulation of T follicular helper cells", "type" : "article-journal", "volume" : "209" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵⁴", "plainTextFormattedCitation" : "254", "previouslyFormattedCitation" : "²⁵⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }254. A phase III RCT is ongoing (NCT01782235). Other co-stimulatory pathways, such as CD40-CD40L, which crosslinks innate and adaptive immune cells and pathways, are also promising optionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4049/jimmunol.1303239", "ISBN" : "1550-6606; 0022-1767", "ISSN" : "1550-6606", "PMID" : "24670803", "abstract" : "CD40-CD40L interactions play a critical role in regulating immune responses. Blockade of CD40L by Abs, such as the anti-CD40L Ab 5c8, demonstrated positive clinical effects in patients with autoimmune diseases; however, incidents of thromboembolism (TE) precluded further development of these molecules. In this study, we examined the role of the Fc domain interaction with Fc\u03b3Rs in modulating platelet activation and potential for TE. Our results show that the interaction of the 5c8 wild-type IgG1 Fc domain with Fc\u03b3Rs is responsible for platelet activation, as measured by induction of PAC-1 and CD62P. A version of 5c8 with a mutated IgG1 tail was identified that showed minimal Fc\u03b3R binding and platelet activation while maintaining full binding to CD40L. To address whether Fc effector function is required for immunosuppression, a potent Ab fragment, termed a \"domain Ab\" (dAb), against murine CD40L was identified and fused to a murine IgG1 Fc domain containing a D265A mutation that lacks Fc effector function. In vitro, this dAb-Fc demonstrated comparable potency to the benchmark mAb MR-1 in inhibiting B cell and dendritic cell activation. Furthermore, the anti-CD40L dAb-Fc exhibited a notable efficacy comparable to MR-1 in various preclinical models, such as keyhole limpet hemocyanin-induced Ab responses, alloantigen-induced T cell proliferation, \"heart-to-ear\" transplantation, and NZB \u00d7 NZW F1 spontaneous lupus. Thus, our data show that immunosuppression and TE can be uncoupled and that a CD40L dAb with an inert Fc tail is expected to be efficacious for treating autoimmune diseases, with reduced risk for TE.", "author" : [ { "dropping-particle" : "", "family" : "Xie", "given" : "Jenny H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamniuk", "given" : "Aaron P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borowski", "given" : "Virna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhn", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Susulic", "given" : "Vojkan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rex-Rabe", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Xiaoxia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhou", "given" : "Xiadi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yifan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillooly", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brosius", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravishankar", "given" : "Rathna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waggie", "given" : "Kimberly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mink", "given" : "Kathy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehfuss", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamura", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Yongmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abramczyk", "given" : "Bozena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ignatovich", "given" : "Olga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drew", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bryson", "given" : "James W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suchard", "given" : "Suzanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salter-Cid", "given" : "Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nadler", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suri", "given" : "Anish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of immunology (Baltimore, Md. : 1950)", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "4083-92", "title" : "Engineering of a novel anti-CD40L domain antibody for treatment of autoimmune diseases.", "type" : "article-journal", "volume" : "192" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵⁵", "plainTextFormattedCitation" : "255", "previouslyFormattedCitation" : "²⁵⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }255. Isolated studies are exploring other drugs (fingolimod in patients with MS-like CNS involvement, bortezomib)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/ane.12357", "ISBN" : "0001-6314", "ISSN" : "00016314", "abstract" : "Background: Sjogren syndrome (SS) is a common autoimmune disease characterized by lymphocytic infiltration of the exocrine glands with neurological involvement in about 20% of patients. The neurological manifestations in the central nervous system CNS may vary and include a multiple sclerosis (MS)-like disease, and the treatments with immunosuppressive drugs have been undertaken. Case presentation: We describe a case of 40-year-old woman with clinical and instrumental evidence of an MS characterized by numerous relapses and demyelinating lesions prevailing in the infratentorial and spinal cord. Immunological analysis showed biological data that were consistent with an SS. The treatment with fingolimod showed not only an optimal response to the demyelinating events but also biological parameters. Conclusion: These data allow us to hypothesize possible combined efficacy of treatment with fingolimod in SS associated with definite MS.", "author" : [ { "dropping-particle" : "", "family" : "Signoriello", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sagliocchi", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fratta", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lus", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Neurologica Scandinavica", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "140-143", "title" : "Fingolimod efficacy in multiple sclerosis associated with Sjogren syndrome", "type" : "article-journal", "volume" : "131" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1536-7355", "abstract" : "Primary Sjogren syndrome (PSS) is a chronic autoimmune disease characterized by sicca complex and various systemic manifestations. Although it is well accepted to use corticosteroids for the treatment of systemic manifestations, there is scarce information available regarding the use of targeted therapy for refractory cases. We describe a case of a severe PSS patient refractory to conventional treatment with a response to bortezomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma. Bortezomib administration resulted in a notable improvement of the general symptoms, particularly fatigue, and a decrease in serum globulin levels as well as in serum viscosity. Hyperglobulinemic purpura disappeared, and prednisone tapering succeeded. Because of chronicity, no clinical changes were observed in sicca symptoms. As far as we know, this is the first report on the use of bortezomib in a refractory case of PSS.", "author" : [ { "dropping-particle" : "", "family" : "J.", "given" : "Jakez-Ocampo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Y.", "given" : "Atisha-Fregoso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L.", "given" : "Llorente", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Rheumatology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "31-32", "title" : "Refractory primary sjogren syndrome successfully treated with bortezomib", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^256,257", "plainTextFormattedCitation" : "256,257", "previouslyFormattedCitation" : "^256,257" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }256,257. However, the disappointing results of the two largest RCTs carried out in primary SjS until now, together with the recently-reported negative results of the TRACTISS trialADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Bowman S, Everett C, Bombardieri M, Busch R, Emery P, Hall F, Pease CT, Pitzalis C, Price E, Dawson L, Smith P, Sutcliffe N, Ng WF, Fernandez C, Ruddock S, Sharples L, Reynolds C", "given" : "Pavitt S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & Rheumatology", "id" : "ITEM-1", "issue" : "Suppl 10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Preliminary Results of a Double-Blind Randomised Trial of Rituximab Anti-B-Cell Therapy in Patients with Primary Sjogrens Syndrome", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵⁸", "plainTextFormattedCitation" : "258", "previouslyFormattedCitation" : "²⁵⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }258, which evaluated two drugs considered effective in daily practice (hydroxychloroquine and rituximab), have opened a debate about RCTs in SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2014.7682", "ISBN" : "1538-3598; 0098-7484", "ISSN" : "1538-3598", "PMID" : "25027140", "abstract" : "IMPORTANCE: Primary Sj\u00f6gren syndrome is a systemic autoimmune disease characterized by mouth and eye dryness, pain, and fatigue. Hydroxychloroquine is the most frequently prescribed immunosuppressant for the syndrome. However, evidence regarding its efficacy is limited. OBJECTIVE: To evaluate the efficacy of hydroxychloroquine for the main symptoms of primary Sj\u00f6gren syndrome: dryness, pain, and fatigue. DESIGN, SETTING, AND PARTICIPANTS: From April 2008 to May 2011, 120 patients with primary Sj\u00f6gren syndrome according to American-European Consensus Group Criteria from 15 university hospitals in France were randomized in a double-blind, parallel-group, placebo-controlled trial. Participants were assessed at baseline, week 12, week 24 (primary outcome), and week 48. The last follow-up date for the last patient was May 15, 2012. INTERVENTIONS: Patients were randomized (1:1) to receive hydroxychloroquine (400 mg/d) or placebo until week 24. All patients were prescribed hydroxychloroquine between weeks 24 and 48. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with a 30% or greater reduction between weeks 0 and 24 in scores on 2 of 3 numeric analog scales (from 0 [best] to 10 [worst]) evaluating dryness, pain, and fatigue. RESULTS: At 24 weeks, the proportion of patients meeting the primary end point was 17.9% (10/56) in the hydroxychloroquine group and 17.2% (11/64) in the placebo group (odds ratio, 1.01; 95% CI, 0.37-2.78; P = .98). Between weeks 0 and 24, the mean (SD) numeric analog scale score for dryness changed from 6.38 (2.14) to 5.85 (2.57) in the placebo group and 6.53 (1.97) to 6.22 (1.87) in the hydroxychloroquine group. The mean (SD) numeric analog scale score for pain changed from 4.92 (2.94) to 5.08 (2.48) in the placebo group and 5.09 (3.06) to 4.59 (2.90) in the hydroxychloroquine group. The mean (SD) numeric analog scale for fatigue changed from 6.26 (2.27) to 5.72 (2.38) in the placebo group and 6.00 (2.52) to 5.94 (2.40) in the hydroxychloroquine group. All but 1 patient in the hydroxychloroquine group had detectable blood levels of the drug. Hydroxychloroquine had no efficacy in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. During the first 24 weeks, there were 2 serious adverse events in the hydroxychloroquine group and 3 in the placebo group; in the last 24 weeks, there were 3 serious adverse events in the hydroxychloroquine group and 4 in the placebo group. CONCLUSIO\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravaud", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pu\u00e9chal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larroche", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean-Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rist", "given" : "St\u00e9phanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sene", "given" : "Damien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batouche", "given" : "Djilali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furlan", "given" : "Val\u00e9rie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benessiano", "given" : "Joelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perrodeau", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Raphaele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "249-58", "title" : "Effects of hydroxychloroquine on symptomatic improvement in primary Sj\u00f6gren syndrome: the JOQUER randomized clinical trial.", "type" : "article-journal", "volume" : "312" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "1539-3704", "ISSN" : "1539-3704", "abstract" : "BACKGROUND: Primary Sjogren syndrome (pSS) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations., OBJECTIVE: To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS., DESIGN: Randomized, placebo-controlled, parallel-group trial conducted between March 2008 and January 2011. Study personnel (except pharmacists), investigators, and patients were blinded to treatment group. (: NCT00740948)., SETTING: 14 university hospitals in France., PATIENTS: 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS., INTERVENTION: Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo., MEASUREMENTS: Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24., RESULTS: No significant difference between groups in the primary end point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab., LIMITATION: Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes., CONCLUSION: Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points.", "author" : [ { "dropping-particle" : "", "family" : "Devauchelle-Pensec", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousse-Joulin", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berthelot", "given" : "Jean-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perdriger", "given" : "Aleth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puechal", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "Veronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibilia", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottenberg", "given" : "Jacques-Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiche", "given" : "Laurent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Pierre Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goeb", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayem", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morel", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarnitsky", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubost", "given" : "Jean Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pers", "given" : "Jacques Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraux", "given" : "Alain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Internal Medicine", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "233-242", "title" : "Treatment of primary Sjogren syndrome with rituximab: a randomized trial", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^186,191", "plainTextFormattedCitation" : "186,191", "previouslyFormattedCitation" : "^186,191" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }186,191. These trials used a composite primary outcome based on the subjective evaluation of dryness, fatigue, and pain. The strong influence of personal and environmental factors on the intensity of this triad of symptoms could explain the lack of significant differences between the therapeutic and placebo arms, together with an inadequate selection of patients (absence or low disease activity, influence of concomitant drugs, heterogeneity of diagnostic tests). The EULAR-SS Task Force and other international groups are working on finding more solid, objective outcomes for future RCTs in SjSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2014-206008", "ISBN" : "1468-2060; 0003-4967", "ISSN" : "1468-2060", "PMID" : "25480887", "abstract" : "OBJECTIVES: To define disease activity levels, minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) with the primary Sj\u00f6gren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patient-reported index (ESSPRI).\\n\\nMETHODS: For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI.\\n\\nRESULTS: Low-activity (ESSDAI<5), moderate-activity (5\u2264ESSDAI\u226413) and high-activity (ESSDAI\u226514) levels were defined. MCII of ESSDAI was defined as an improvement of at least three points. The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15%.\\n\\nCONCLUSIONS: This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI\u22655) and define response to treatment as an improvement of ESSDAI at least three points. 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recruitment.\n\nMETHODS: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data.\n\nRESULTS: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sj\u00f6gren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sj\u00f6gren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sj\u00f6gren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sj\u00f6gren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sj\u00f6gren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sj\u00f6gren's Syndrome Patient Reported Index (ESSPRI) score \u2a7e5 (measure of patient symptoms) and the EULAR Sj\u00f6gren's Syndrome Disease Activity Index (ESSDAI) score \u2a7e5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%.\n\nCONCLUSION: The UKPSSR identified a number of options for trial design, including selection on ESSDAI \u2a7e5, ESSPRI \u2a7e5 and serological and other parameters.", "author" : [ { "dropping-particle" : "", "family" : "Oni", "given" : "Clare", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Sheryl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Katherine", 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"dropping-particle" : "", "family" : "Rauz", "given" : "Saaeha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richards", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowman", "given" : "Simon J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015", "10", "27" ] ] }, "title" : "Eligibility for clinical trials in primary Sj\u00f6gren's syndrome: lessons from the UK Primary Sj\u00f6gren's Syndrome Registry.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0133907", "ISSN" : "1932-6203", "PMID" : "26368934", "abstract" : "OBJECTIVE: The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sj\u00f6gren's syndrome (pSS).\n\nMETHODS: We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo.\n\nRESULTS: We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study.\n\nCONCLUSION: This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. 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[H2] Disruptive innovations Disruptive innovations that displace earlier technologies or working methods are rapidly emerging in this century, and health is one of the areas with the greatest potential for dramatic change. In SjS, the most innovative therapeutic approaches are those investigating the use of minimally-invasive endoscopic techniquesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jcms.2015.06.036", "ISSN" : "1878-4119", "PMID" : "26297422", "abstract" : "PURPOSE: To evaluate, on the basis of our clinical experience, the reliability of an endoscopic approach to the management of obstructive salivary diseases related to Sj\u00f6gren's syndrome.\n\nMATERIAL AND METHODS: A retrospective review of all patients affected by Sj\u00f6gren's syndrome who were followed up at the Maxillo-Facial Unit of the Second University of Naples Hospital and referred from the Reumatology Unit of the same hospital from September 2007 to July 2012 for chronic obstructive sialadenitis unresponsive to medical therapy. A total of 34 patients (29 women and 5 men) were recruited for this study. After the detection of the impaired gland, under local anesthesia with lidocaine 2% to the orifice region and a gradual dilation of the duct orifice, the diagnostic unit was introduced into the duct and was advanced forward until reaching the ductal system, with continuous lavage with isotonic saline solution. The plaques were washed out, and any strictures were dilated. Mucus plugs and debris were removed with irrigation or with a forceps if necessary.\n\nRESULTS: Our cohort included 34 patients with a mean age of 51.76 years. A total of 60 parotid glands and 25 submandibular glands were explored and treated. Strictures were found in 38 glands (38 of 85; 45%), mucus plugs in 47 glands (47 of 85; 55%), mucus plugs and strictures together in three glands (3 of 85; 4%), and kinks in two glands (2 of 85; 2%). In 32 parotid glands (32 of 60; 53%) the Stensen duct was affected, in two (2 of 60; 3%) only secondary ducts, and in 18 (18 of 60; 30%) both. In submandibular glands explored, strictures and mucus plugs were mainly observed in Wharton ducts. Symptomatic improvement was achieved in 29 patients (29 of 34; 85%), in a follow-up period ranging from 5 months to 3 years.\n\nCONCLUSIONS: Interventional sialoendoscopy is a viable technique to treat acute symptomatology in patients with obstructive salivary gland diseases related to Sj\u00f6gren's syndrome and refractory to conventional management.", "author" : [ { "dropping-particle" : "", "family" : "Luca", "given" : "Roberto", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trodella", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vicidomini", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colella", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tartaro", "given" : "Gianpaolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "page" : "1643-9", "title" : "Endoscopic management of salivary gland obstructive diseases in patients with Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁶¹", "plainTextFormattedCitation" : "261", "previouslyFormattedCitation" : "²⁶¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }261, the use of gene therapyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1517/14712598.2015.1064894", "ISSN" : "1744-7682", "PMID" : "26149284", "abstract" : "INTRODUCTION: Much research demonstrates the feasibility and efficacy of gene transfer to salivary glands. Recently, the first clinical trial targeting a salivary gland was completed, yielding positive safety and efficacy results.\n\nAREAS COVERED: There are two major disorders affecting salivary glands: radiation damage following treatment for head and neck cancers and Sj\u00f6gren's syndrome (SS). Salivary gland gene transfer has also been employed in preclinical studies using transgenic secretory proteins for exocrine (upper gastrointestinal tract) and endocrine (systemic) applications.\n\nEXPERT OPINION: Salivary gland gene transfer is safe and can be beneficial in humans. Applications to treat and prevent radiation damage show considerable promise. A first-in-human clinical trial for the former was recently successfully completed. Studies on SS suffer from an inadequate understanding of its etiology. Proof of concept in animal models has been shown for exocrine and endocrine disorders. Currently, the most promising exocrine application is for the management of obesity. Endocrine applications are limited, as it is currently impossible to predict if systemically required transgenic proteins will be efficiently secreted into the bloodstream. This results from not understanding how secretory proteins are sorted. Future studies will likely employ ultrasound-assisted and pseudotyped adeno-associated viral vector-mediated gene transfer.", "author" : [ { "dropping-particle" : "", "family" : "Baum", "given" : "Bruce J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alevizos", "given" : "Ilias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiorini", "given" : "John A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cotrim", "given" : "Ana P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Changyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Expert opinion on biological therapy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "1443-54", "title" : "Advances in salivary gland gene therapy - oral and systemic implications.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁶²", "plainTextFormattedCitation" : "262", "previouslyFormattedCitation" : "²⁶²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }262, the role of robotic/bioartificial techniques, including tissue engineering-based organ regenerationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1159/000371873", "ISSN" : "1422-6421", "PMID" : "25824480", "abstract" : "Salivary gland hypofunction resulting in xerostomia occurs as a result of various pathological conditions such as radiotherapy for head and neck cancers, Sj\u00f6gren's syndrome or salivary gland tumor resection. It can induce a large number of problems, including dental decay, periodontitis, dysgeusia, difficulty with mastication and swallowing and a reduced quality of life. Current therapies for xerostomia mostly focus on saliva substitutes, oral lubricants and medications which stimulate salivation from residual glands. However, these treatments are not sufficient to restore gland secretory function. Tissue engineering-based organ regeneration has emerged as a potential therapeutic alternative for end- organ failure. Here, we decellularized rat submandibular glands (SMG) by detergent immersion. Histological, immunofluorescent, Western blot, DNA and collagen quantitative analyses demonstrated that our protocol effectively removed cellular components and that extracellular matrix proteins and native structures were well preserved. We then reseeded the decellularized SMG as scaffolds with rat primary SMG cells in a rotary cell culture system. Histological staining and electron microscopy analyses illustrated that the decellularized SMG could support cellular adhesion. Furthermore, with immunofluorescent staining, we proved that bioartificially generated SMG showed some differentiation markers in vitro. Taken together, our findings might provide a potential scaffold for tissue-engineered regeneration of the salivary glands.", "author" : [ { "dropping-particle" : "", "family" : "Gao", "given" : "Zhenhua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Tingting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Junji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Guolin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Yilin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Chunmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jinsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Songlin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cells, tissues, organs", "id" : "ITEM-1", "issue" : "3-4", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "171-80", "title" : "Generation of Bioartificial Salivary Gland Using Whole-Organ Decellularized Bioscaffold.", "type" : "article-journal", "volume" : "200" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁶³", "plainTextFormattedCitation" : "263", "previouslyFormattedCitation" : "²⁶³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }263, and the proteomic/genomic analysis of salivaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrrheum.2015.10", "ISSN" : "1759-4804", "PMID" : "25668140", "abstract" : "Examination of biopsy-obtained salivary gland tissue provides valuable insights for the diagnosis, classification and treatment of patients with primary Sj\u00f6gren syndrome. Could the study of biomarkers present in saliva provide a noninvasive alternative?", "author" : [ { "dropping-particle" : "", "family" : "Tzioufas", "given" : "Athanasios G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kapsogeorgou", "given" : "Efstathia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Rheumatology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "page" : "202-3", "title" : "Biomarkers. Saliva proteomics is a promising tool to study Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.39015", "ISSN" : "2326-5205", "PMID" : "25545990", "abstract" : "OBJECTIVE: Dependence on invasive procedures for classification of patients with Sj\u00f6gren's syndrome (SS) hampers timely diagnosis and suitable patient followup. The aim of this study was to recapitulate the diagnosis of SS through noninvasive means and to define the biologic state of SS patients' salivary glands.\n\nMETHODS: Using a 187-plex capture antibody-based assay, salivary proteomic biomarker profiles were generated from patients with primary SS, patients with rheumatoid arthritis, and asymptomatic controls. Discriminant function analyses and Gene Ontology-based network analyses allowed data analyses with a reductionist approach and with a focus on systems biology.\n\nRESULTS: Characterized by significant changes in 61 and 55 proteins, respectively, the salivary proteome of SS patients appeared profoundly altered compared to that of individuals without SS. On this basis, 4-plex and 6-plex biomarker signatures, both including interleukin-4 (IL-4), IL-5, and clusterin, achieved accurate prediction of an individual's group membership for at least 94% of cases. Of note, all misclassified SS patients presented with ectopic germinal center-like structures. Systematic inference of biologic meaning identified SS-related protein patterns delineating B cell-dominated immune responses, macrophage differentiation, and signs of T cell chemotaxis. In addition, proteomic Multi-Analyte Profiles provided insight about proteins related to collagen, cytokine, and growth factor synthesis as well as lipid transport.\n\nCONCLUSION: The SS-related molecular landscape conveyed by saliva showed great congruence with histopathologic features found in SS and advances understanding of this disease at a molecular level. Such salivary biomarker signatures harbor great potential for improving timeliness of SS diagnosis and enabling suitable patient followup.", "author" : [ { "dropping-particle" : "", "family" : "Delaleu", "given" : "Nicolas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mydel", "given" : "Piotr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwee", "given" : "Ivo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "Malin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & rheumatology (Hoboken, N.J.)", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "page" : "1084-95", "title" : "High fidelity between saliva proteomics and the biologic state of salivary glands defines biomarker signatures for primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^264,265", "plainTextFormattedCitation" : "264,265", "previouslyFormattedCitation" : "^264,265" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }264,265. Novel research approaches are also emerging in this digital era, of which Big Data is the best exampleADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.autrev.2015.03.008", "ISBN" : "1568-9972", "ISSN" : "15689972", "PMID" : "25842074", "abstract" : "Systemic autoimmune diseases (SAD) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1,000 patients) of SAD reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SAD. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sj\u00f6gren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodefficiencies and Schonlein-Henoch disease), young people (SLE Beh\u00e7et disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SAD with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a \u201cbig data\u201d approach enabled hitherto unseen connections in SAD to emerge.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostov", "given" : "Belchin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sis\u00f3-Almirall", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buss", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilla", "given" : "Antoni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "John H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khamashta", "given" : "Munther a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shoenfeld", "given" : "Yehuda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Autoimmunity Reviews", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "670-679", "title" : "Google-driven search for big data in autoimmune geoepidemiology: Analysis of 394,827 patients with systemic autoimmune diseases", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁸", "plainTextFormattedCitation" : "28", "previouslyFormattedCitation" : "²⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28; a current international project has collected the key diagnostic features of more than 8000 patients with primary SjS from the five continents, data that could serve as a new way of investigating the disease across the worldADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Brito-Zer\u00f3n P, Retamozo S, Zeher M, Rasmussen A, Theander E, Gottenberg J, Baldini C, Quartuccio L, Priori R, Valim V, Kvarnstr\u00f6m M, Kruize A, Hernandez-Molina G, Bartoloni-Bocci E, Praprotnik S, Isenberg DA, Nordmark G, Bombardieri M, Suzuki Y, Solans R,", "given" : "Ramos-Casals M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & Rheumatology", "id" : "ITEM-1", "issue" : "Suppl. 10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Big Data International Primary Sj\u00f6gren Syndrome Registry: Baseline Characterization and Diagnostic Approach in 6047 Patients Fulfilling the 2002 AE Criteria", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁶⁶", "plainTextFormattedCitation" : "266", "previouslyFormattedCitation" : "²⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }266.The present is a good time to witness disruptive advances in autoimmune diseases like SjS. Better understanding of the influence of factors external to the disease, the etiopathogenic mechanisms of extraglandular damage, a more holistic approach to individual patient management, active international collaborations promoting multicenter registries and consensus on homogeneous diagnostic and therapeutic approaches, and application of new disruptive technologies (Big Data and analytics, wearable devices, bioartificial research) have the potential to be gamechangers in our understanding of the disease and providing a solid improvement in the quality of life and the prognosis of patients with SjS.Figures[Editorial note to peer reviewers: All figuers will be re-drawn by the Nature Reviews art editors following peer review. As such, we kindly ask that you focus your attention and comments to the content of the figures rather than their overall appearance] Figure 1. Milestones in the history of Sj?gren syndrome compressed in 100 years (1882-1982)[Editorial note to peer reviewers - this table will be redrawn as a timeline following peer review] YEARAUTHORFIRST DESCRIPTION1882LeberFilamentary keratitis1888Hadden, HutchinsonUse of the term “xerostomia” for dry mouth1889FischerAssociation of filamentary keratitis with arthritis deformans1903SchirmerLacrimal blotting paper test1919FuchsFailure of lacrimal secretion in women (post-climateric period)1925GougerotSicca syndrome (oral, ocular & vaginal dryness)1925StockFilamentary keratitis is caused by deficiency of tears1933Sj?gren"About Keratoconjunctivitis Sicca" Thesis (association between sicca syndrome & arthritis)1937Schluter, WeberUse of the term “Sj?gren’s syndrome”1939SheldonAssociation with scleroderma1948KoumrouyanSialographic studies1949KleinLacrimal strip and precorneal film study1951RothmanAssociation with lymphoblastoma and hypersplenism1951O’DayRose Bengal use1952BartsocasFirst case in a child1954GaulhoferEffect of cortisone1958JonesSearch for organ-specific antibodies 1959HeatonUse of antimalarials1959BucherDeath by systemic features (renal & pulmonary)1960BainAssociation with lupus1960BlochDifferentiated study with and without rheumatoid arthritis1961AttwoodNeurological complications1962AndersonPrecipitating autoantibodies1963Von FeltenAssociation with cryoglobulinemic vasculitis1964Talal & BunimAssociation with lymphoma1965BlochDivision between primary and secondary1965BeckAntinuclear antibodies titers, anti-SjD and antiSjT precipitins1967MasonSalivary flow rates1968Sj?grenSicca syndrome is an autoimmune disease1968WhaleyLymphocytic sialadenitis1968Chisholm & MasonLabial salivary gland biopsy1969AbramsonSalivary gland scintigraphy with 99 Technetium1970RuchelmanUse of the term “systemic manifestations of SS”1971SchallScintigraphic classification1973Alarcon-SegoviaAssociation with primary biliary cirrhosis1975TalalRaised levels of beta2 microglobulin1975Alspaugh & TanIdentification of the SS precipitating antibodies A, B & C1976LichtenfeldFamilial SS1978MoutsopoulosB lymphocyte antigens1978KassanIncreased risk of lymphoma1978MoutsopoulosGenetic differences between primary & secondary SS1979TalalLymphomas are of B-cell origin1982FontClassification of the disease1982AlexanderRo and La antibodiesFigure 2. Prevalence of primary Sj?gren’s syndrome in studies using the 1996/2002 criteriaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4065/76.6.593", "ISSN" : "0025-6196", "PMID" : "11393497", "abstract" : "OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sj\u00f6gren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients.\n\nPATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk.\n\nRESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia.\n\nCONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.", "author" : [ { "dropping-particle" : "", "family" : "Pillemer", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "E L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "L T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "P B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melton", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Fallon", "given" : "W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mayo Clinic proceedings", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001", "6" ] ] }, "page" : "593-9", "title" : "Incidence of physician-diagnosed primary Sj\u00f6gren syndrome in residents of Olmsted County, Minnesota.", "type" : "article-journal", "volume" : "76" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.2003.014027", "ISSN" : "0003-4967", "PMID" : "15194588", "abstract" : "OBJECTIVE: To determine the annual incidence of primary Sj\u00f6gren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.", "author" : [ { "dropping-particle" : "", "family" : "Plesivcnik Novljan", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rozman", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hocevar", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "874-876", "title" : "Incidence of primary Sjogren's syndrome in Slovenia.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/rheumatology/kei107", "ISSN" : "14620324", "PMID" : "16332955", "abstract" : "OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sj\u00f6gren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.", "author" : [ { "dropping-particle" : "", "family" : "Alamanos", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Voulgari", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venetsanopoulou", "given" : "a. I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siozos", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "a. a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "187-191", "title" : "Epidemiology of primary Sj??gren's syndrome in north-west Greece, 1982-2003", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3899/jrheum.100883", "ISSN" : "0315-162X", "PMID" : "21239759", "abstract" : "To estimate the incidence and mortality of treated primary Sj\u00f6gren's syndrome (pSS) by sex and age group in Taiwan.", "author" : [ { "dropping-particle" : "", "family" : "Weng", "given" : "Meng-Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Yu-Tung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ming-Fei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Tsung-Hsueh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "706-708", "title" : "Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: a population-based study.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/acr.21820", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22899470", "abstract" : "OBJECTIVE: The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population-based database.\\n\\nMETHODS: We used the longitudinal health insurance database (comprising 1,000,000 beneficiaries) of the Taiwan National Health Insurance from 2000 to 2008 and the National Death Registry of Taiwan from 2000 to 2008.\\n\\nRESULTS: The overall prevalence of major ARDs was 101.3 (95% confidence interval [95% CI] 27.5-107.9) per 100,000 populations; the prevalence was 165.1 (95% CI 44.8-177.1) in women and 40.1 (95% CI 10.9-46.1) in men. The prevalences of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis, vasculitis, and Beh\u00e7et's disease were 52.4 (95% CI 14.2-57.2), 37.0 (95% CI 10.0-41.0), 16.0 (95% CI 4.3-18.7), 3.8 (95% CI 1.0-5.3), 2.9 (95% CI 0.8-4.2), 5.7 (95% CI 1.6-7.4), and 1.4 (95% CI 0.4-2.3) per 100,000 persons, respectively. Between 2001 and 2008, the incidence rates (per 100,000 person-years) for these diseases were 17.3, 8.4, 10.6, 1.5, 1.5, 1.2, and 0.8, respectively. The incident cases with ARDs had a higher risk of mortality, with the standardized mortality ratio (SMR) ranging from 1.3 to 3.7.\\n\\nCONCLUSION: In 2000, the prevalence of major ARDs was 1.4-52.4 per 100,000 persons in Taiwan. Between 2000 and 2008, the incidence rates of various ARDs were 0.8-17.3 per 100,000 person-years. The prevalence and incidence of RA were the highest, followed by SLE and Sj\u00f6gren's syndrome, and those of Beh\u00e7et's disease were the lowest. Patients with different types of ARDs had higher mortality and SMR than those of the general population.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "See", "given" : "Lai-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang-Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I-Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Meng-Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "244-50", "title" : "Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.semarthrit.2013.06.001", "ISBN" : "0049-0172", "ISSN" : "00490172", "PMID" : "23916348", "abstract" : "Objectives: The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. Methods: A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. Results: Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sj\u00f6gren's syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Beh\u00e7et disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sj\u00f6gren's syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). Conclusions: ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sj\u00f6gren's syndrome and SLE, while the incidence of Beh\u00e7et disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases. \u00a9 2013 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "See", "given" : "Lai Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I. Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiou", "given" : "Meng Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "381-386", "title" : "Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1136/bmjopen-2013-003569", "ISSN" : "2044-6055", "PMID" : "24282246", "abstract" : "OBJECTIVE: A very few studies describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). METHODS: A population-based incidence cohort of patients diagnosed with pSS in 1976-2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. RESULTS: 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18-44 years: 2.1/100 000 vs \u226575 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (\u00b13%) at 1 year after diagnosis of pSS and increased to 20% (\u00b14%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). CONCLUSIONS: pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.", "author" : [ { "dropping-particle" : "", "family" : "Nannini", "given" : "Carlotta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jebakumar", "given" : "Adlene J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crowson", "given" : "Cynthia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryu", "given" : "Jay H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "Eric L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-7", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "e003569", "title" : "Primary Sjogren's syndrome 1976-2005 and associated interstitial lung disease: a population-based study of incidence and mortality.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.3109/03009742.2014.931457 [doi]", "ISBN" : "0300-9742", "ISSN" : "1502-7732; 0300-9742", "PMID" : "25222653", "abstract" : "Objectives: To define the incidence rate of primary Sjogren's syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. Method: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. Results: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3-4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89-0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. Conclusions: The incidence rate of pSS is 3.1 (95% CI 2.3-4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.", "author" : [ { "dropping-particle" : "", "family" : "Kvarnstrom", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ottosson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordmark", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahren-Herlenius", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-8", "title" : "Incident cases of primary Sjogren's syndrome during a 5-year period in Stockholm County: a descriptive study of the patients and their characteristics", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1186/1471-2474-11-98", "ISBN" : "1471-2474 (Electronic) 1471-2474 (Linking)", "ISSN" : "1471-2474", "PMID" : "20504294", "abstract" : "BACKGROUND: Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece.\\n\\nMETHODS: In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases.\\n\\nRESULTS: The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sj\u00f6gren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension.\\n\\nCONCLUSIONS: Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.", "author" : [ { "dropping-particle" : "", "family" : "Anagnostopoulos", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinzaras", "given" : "Elias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexiou", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papathanasiou", "given" : "Aphrodite a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davas", "given" : "Evangelos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koutroumpas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barouta", "given" : "Georgia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakkas", "given" : "Lazaros I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC musculoskeletal disorders", "id" : "ITEM-9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "98", "title" : "The prevalence of rheumatic diseases in central Greece: a population survey.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1111/j.1742-1241.2008.01749.x", "ISSN" : "1742-1241", "PMID" : "18422594", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.", "author" : [ { "dropping-particle" : "", "family" : "Birlik", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gurler", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sari", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birlik", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarioglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oktem", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Can", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayahan", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akkoc", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onen", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of clinical practice", "id" : "ITEM-10", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "954-61", "title" : "Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "ISBN" : "1395-3907 (Print) 1395-3907 (Linking)", "ISSN" : "1395-3907", "PMID" : "9253975", "abstract" : "PURPOSE: To investigate the presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome a sample of 504 persons aged 30-60 years from Copenhagen was studied. METHODS: The presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome was estimated according to both the Copenhagen set of criteria and the preliminary European criteria. RESULTS: Symptoms of dry eye and oral dryness were very common and with no significant correlation to age or sex. Keratoconjuncitivis sicca was most frequent in persons aged 50-59 years and was equally common in men and women. Primary Sj\u00f6gren's syndrome could only be diagnosed in one person according to the Copenhagen criteria (cut-off the Schirmer-1 test < or = 5 mm/5 min), and in three persons according to the preliminary European criteria. CONCLUSION: The frequency of keratoconjunctivitis sicca in persons aged 30-60 years in Copenhagen may be estimated to be 11% according to the Copenhagen criteria and 8% according to the preliminary European criteria. The frequency of primary Sj\u00f6gren's syndrome in persons aged 30-60 years in Copenhagen may be estimated to be between 0.2% and 0.8% according to the Copenhagen criteria and between 0.6% and 2.1% according to the preliminary European criteria.", "author" : [ { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta ophthalmologica Scandinavica", "id" : "ITEM-11", "issue" : "3", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "281-286", "title" : "Keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome in a Danish population aged 30-60 years.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "ISSN" : "0300-9742", "PMID" : "15124941", "abstract" : "To establish the prevalence among women of primary Sj\u00f6gren's syndrome (PSS) in Birmingham, UK.", "author" : [ { "dropping-particle" : "", "family" : "Bowman", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibrahim", "given" : "G H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamburger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ainsworth", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-12", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "39-43", "title" : "Estimating the prevalence among Caucasian women of primary Sj\u00f6gren's syndrome in two general practices in Birmingham, UK.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-13", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9370875", "abstract" : "OBJECTIVE: To define the prevalence of Sj\u00f6gren's syndrome (SS) through an epidemiological survey in a closed rural community. The classification of SS is based on the validated criteria reported by a multicentre study performed in Europe and supported by the Epidemiology Committee of the European Community (EEC-COMAC Epidemiology).\\n\\nMETHODS: The population under study consisted of 837 women aged 18 years or older, residing in the Astakos community of Aitoloakarnania, Greece. The study protocol was subdivided in two parts. In part I, an exhaustive epidemiological survey of these women was conducted in July and August of 1992. The validated questionnaire used in the survey assesses both ocular and oral involvement. In part II, 45 of the women reporting symptoms of both dry eye and dry mouth were approached for a full examination based on the validated set of classification criteria of SS. The full complement of the diagnostic tests was performed on 35 of these women. A subject is classified as a definite primary SS case if at least four of six items of the subject's test items are positive. If three of six items are positive the subject is classified as a probable primary SS case.\\n\\nRESULTS: The classification criteria for definite primary SS were satisfied by five women. This number corresponds to an estimated prevalence of 0.60% (exact 95% CI 0.19%, 1.39%). Probable primary SS was diagnosed for 25 women (prevalence = 2.99%).\\n\\nCONCLUSION: Because of the loss of follow up (10 of 45) and the use of slightly stricter criteria for inclusion of possible SS cases in part II of the study, we consider our estimate of the prevalence of SS to be conservative. This study concurring with other recent reports, suggests that SS is more prevalent than previously thought.", "author" : [ { "dropping-particle" : "", "family" : "Dafni", "given" : "U G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staikos", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skopouli", "given" : "F N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-13", "issue" : "9", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "521-5", "title" : "Prevalence of Sj\u00f6gren's syndrome in a closed rural community.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-14", "itemData" : { "DOI" : "10.1007/s12026-009-8153-2", "ISBN" : "0257-277X", "ISSN" : "0257277X", "PMID" : "20066507", "abstract" : "Epidemiologic studies of autoimmune diseases have not considered them in the aggregate. The objective was to estimate the prevalence of 30 autoimmune diseases separately and in aggregate according to ICD-10 classification. The lifetime prevalence of the entire population of 5,506,574 persons alive in Denmark on October 31, 2006, was estimated by linking records of all visitors to hospitals and specialty clinics via National Patient Registers from January 1, 1977 through October 31, 2006. The prevalences vary from 0.06/1,000 for Pemphigus to 8.94/1,000 for Type 1 diabetes. Nearly 4% of the population had one or more autoimmune disease. The general conclusion is that autoimmune diseases as an aggregate are common.", "author" : [ { "dropping-particle" : "", "family" : "Eaton", "given" : "William W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Marianne G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atlad\u00f3ttir", "given" : "Hj\u00f6rd\u00eds \u00d3sk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregory", "given" : "Patricia E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Noel R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mortensen", "given" : "Preben Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Immunologic Research", "id" : "ITEM-14", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "228-231", "title" : "The prevalence of 30 ICD-10 autoimmune diseases in Denmark", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-15", "itemData" : { "DOI" : "10.3109/03009742.2010.536164", "ISSN" : "1502-7732", "PMID" : "21231797", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (PSS) is a chronic autoimmune inflammatory disease characterized by exocrine gland inflammation producing clinical symptoms such as dryness of the mouth and eyes. The reported prevalence of PSS is variable, probably because of different classification criteria used and selection bias. The aim of this study was to determine the prevalence of PSS in a well-defined Norwegian Caucasian population using the revised American-European Consensus Group (AECG) criteria.\\n\\nMETHODS: Three hospitals and three private rheumatology practices provide all of the rheumatology services to the local population in Hordaland and Rogaland counties, which included 852 342 Caucasian inhabitants as of 1 January 2009. Patients on file fulfilling the new revised AECG criteria for PSS were included, and patients with incomplete data were invited to a screening visit.\\n\\nRESULTS: A total of 424 PSS patients were identified. Their mean age was 61.6 \u00b1 13.2 years; 28 (7%) were men and 396 (93%) were women. The point estimate for the proportion of PSS was 0.050% [95% confidence interval (CI) 0.048-0.052].\\n\\nCONCLUSION: The prevalence of PSS in this Norwegian population of Caucasians is lower than previously reported when less stringent criteria for identifying PSS were used, but is in line with more recent studies using the same criteria and methods as in this study.", "author" : [ { "dropping-particle" : "", "family" : "G\u00f8ransson", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haldorsen", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harboe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skarstein", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Time", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omdal", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-15", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "221-4", "title" : "The point prevalence of clinically relevant primary Sj\u00f6gren's syndrome in two Norwegian counties.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-16", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-16", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-17", "itemData" : { "DOI" : "10.1080/03009740600759704", "ISSN" : "0300-9742", "PMID" : "17062438", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sj\u00f6gren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey.\\n\\nMATERIALS AND METHOD: The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive.\\n\\nRESULTS: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria.\\n\\nCONCLUSION: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.", "author" : [ { "dropping-particle" : "", "family" : "Kabasakal", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turk", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oder", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durusoy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mete", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egrilmez", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akalin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-17", "issue" : "5", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "379-83", "title" : "The prevalence of Sj\u00f6gren's syndrome in adult women.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-18", "itemData" : { "DOI" : "10.1002/acr.22115", "ISSN" : "2151-4658", "PMID" : "23983119", "abstract" : "Purpose: To describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS) in a multi-racial/ethnic population. Methods: A cross-sectional study, with 5 case-retrieval sources, identified adults with pSS living in the Greater Paris area (population 1,172,482 adults) in 2007. Diagnoses were verified by the American-European Consensus Group (AECG) criteria and study-specific enlarged criteria based on the presence of \u22653/4 AECG items among subjective oral or ocular dryness, anti-SSA/SSB positivity and positive minor salivary-gland biopsy results. Prevalence estimates were standardized to those for the world population and 5-source capture-recapture analysis (CRA) was used. Racial/ethnic differences in pSS features were evaluated. Results: In all, 133 subjects met the AECG criteria and 203 the enlarged criteria. The 2007 prevalence of pSS was 1.02 per 10,000 adults (95% confidence interval 0.85-1.22) for AECG criteria and 1.52 per 10,000 adults (1.30-1.76) for enlarged criteria. CRA indicated completeness of case findings of ~90%. Compared to subjects with European background, those with non-European background had 2.1-2.3 times higher pSS prevalence and were younger (P < 0.0001) and more likely to have polyclonal hypergammaglobulinemia (P < 0.0001) and SSA/SSB-antibodies (P = 0.0005 and < 0.0001 for AECG and enlarged criteria, respectively). Conclusion: The figure of 1.02-1.52 per 10,000 adults we found and estimates from the few other population-based census surveys support that the prevalence of diagnosed pSS is between 1 and 10 per 10,000 (0.01-0.1%) of the general population. Non-European race/ethnicity may be associated with increased pSS risk and a distinct disease profile. \u00a9 2013 American College of Rheumatology.", "author" : [ { "dropping-particle" : "", "family" : "Maldini", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhote", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amoura", "given" : "Zahir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandt", "given" : "Michel", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delassus", "given" : "Jean-Luc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falgarone", "given" : "G\u00e9raldine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guillevin", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lhote", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanoelina", "given" : "Jacky", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacr\u00e9", "given" : "Karim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uzunhan", "given" : "Yurdagul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leroux", "given" : "Jean-Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahr", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-18", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Epidemiology of primary Sj\u00f6gren's syndrome in a French Multi-Racial/Ethnic area.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-19", "itemData" : { "ISSN" : "0047-1852", "PMID" : "8531339", "abstract" : "A nationwide epidemiological survey of Japanese Sj\u00f6gren's syndrome (SS) patients was conducted in 1994 by the Research Committee on Epidemiology of Intractable Diseases and the Research Committee of Autoimmune diseases, Ministry of Health and Welfare, Japan. The total number of patients treated for SS in 1993, in Japan, was estimated as 17,000 (95% confidence interval 15,000-20,000). The estimated crude prevalence rates were 1.9 and 25.6 per 100,000 population in males and females, respectively. The ratio of female to male patients was 13.7. The peak of age distribution was in their fifties. New research trends to explore the pathogenesis of SS are also discussed here.", "author" : [ { "dropping-particle" : "", "family" : "Miyasaka", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nihon rinsho. Japanese journal of clinical medicine", "id" : "ITEM-19", "issue" : "10", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "2367-70", "title" : "Epidemiology and pathogenesis of Sj\u00f6gren's syndrome", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-20", "itemData" : { "DOI" : "10.1371/journal.pone.0032487", "ISBN" : "1932-6203", "ISSN" : "1932-6203", "PMID" : "22396771", "abstract" : "BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases.\\n\\nMETHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals.\\n\\nRESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted.\\n\\nCONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.", "author" : [ { "dropping-particle" : "", "family" : "Sardu", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cocco", "given" : "Eleonora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mereu", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massa", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuccu", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marrosu", "given" : "Maria Giovanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Contu", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-20", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e32487", "title" : "Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-21", "itemData" : { "PMID" : "9825745", "abstract" : "OBJECTIVE: Using the European Community (EC) criteria for classification\\nVitali et al. Arthritis Rheum 1993;36:340 7, we report the prevalence\\nestimates of Sjogren's syndrome (SS) from a general population and\\npresent the first population data to assess the impact of the syndrome.\\nMETHODS: A cross-sectional population-based survey performed on 1000\\nadults, aged 18-75 yr, randomly selected from a population register.\\nResponders to the initial postal phase were invited for an interview.\\nThe five criteria measured at interview were: (1) the reporting of\\nsubjective oral symptoms lasting for > 3 months; (2) the reporting\\nof subjective ocular symptoms lasting for >3 months; (3) Schirmer-I\\ntest; (4) unstimulated salivary flow; (5) autoantibodies [Ro (SS-A),\\nLa (SS-B), rheumatoid factor (RF), antinuclear antibodies (ANA)].\\nSS was diagnosed if at least four of these five criteria were positive.\\nThe MOS Short-form 36 (SF-36), General Health Questionnaire (GHQ)\\nand the Health and Fatigue Questionnaire (HFQ) were completed by\\nsubjects after the interview, and scores were compared between those\\nwith and without a diagnosis of SS. RESULTS: A total of 341 subjects\\ncompleted both the postal questionnaire and home visit. A diagnosis\\nof SS could be given to 13 subjects. After adjusting for the presence\\nof possible bias due to non-response, our best estimate of the prevalence\\nof SS in the study population was 33 per 1000 subjects (95% CI 22\\n44). The prevalence of the disorder was higher in females (38; 95%\\nCI 27-52) and for those subjects aged > or = 55 yr (46; 95% CI 34-61).\\nThose subjects diagnosed positively were more impaired for each of\\nthe eight dimensions of the SF-36 than those without a diagnosis,\\nand also suffered from higher levels of depression and fatigue. CONCLUSIONS:\\nSS affects approximately 3-4% of adults and in the general population\\nappears to be associated with a clinically significant impairment\\nof a subject's health and well-being.", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajeer", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silman", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Br J Rheumatol", "id" : "ITEM-21", "issue" : "10", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "1069-1076", "title" : "Sj\ufffdgren's syndrome: a community-based study of prevalence and impact.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-22", "itemData" : { "DOI" : "10.1093/rheumatology/38.2.164", "ISSN" : "14602172", "abstract" : "Objective. The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia., Methods. A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results. Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions. The estimated prevalence of definite SS in Slovenia is 0.60%", "author" : [ { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Logar", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkovic", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-22", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "164-170", "title" : "Prevalence of Sjogren's syndrome in Slovenia", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-23", "itemData" : { "ISSN" : "0315-162X", "PMID" : "12858464", "abstract" : "OBJECTIVE:To assess the prevalence of rheumatic diseases in Greek urban, suburban, and rural adult general populations.METHODS:This cross-sectional population based epidemiological study of rheumatic diseases in Greece (the ESORDIG Study) was conducted on the total adult population of 2 urban, one suburban, and 4 rural communities (8547 subjects), as well as on 2100 out of 5686 randomly selected subjects in one suburban and one rural community. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Either established classification criteria or criteria set for the purposes of the study were used for diagnosis.RESULTS:A total of 8740 subjects participated in the study (response rate 82.1%). The overall age and sex adjusted prevalence (prevalence(asa)) of rheumatic diseases in the total target adult population was 26.9% (95% CI 26.2-27.6), being significantly higher among women (33.7%) than men (19.9%) (p &lt; 0.0005). Disease prevalence(asa) increased significantly with age (p &lt; 0.0005). The most common disease group was low back pain, with a prevalence(asa) of 11.0%, followed by symptomatic peripheral osteoarthritis (7.9%), neck pain (4.8%), miscellaneous rheumatic disorders (4.4%), soft tissue rheumatism disorders (4.3%), and inflammatory rheumatic disease (2.1%). Logistic regression analysis showed a significant positive association of female or male sex, age &gt;or= 50 years, high body mass index, low level of education, moderate or heavy alcohol consumption, and high socioeconomic level with particular diseases or disease groups.CONCLUSION:These findings indicate rheumatic diseases are very common in the general adult population of Greece; 26.9% of adults currently have active or chronic rheumatic disease in remission.", "author" : [ { "dropping-particle" : "", "family" : "Andrianakos", "given" : "Alexandros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trontzas", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christoyannis", "given" : "Fotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dantis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voudouris", "given" : "Costas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgountzos", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaziolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vafiadou", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelidou", "given" : "Kyriaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamitsos", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontelis", "given" : "Leonidas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krachtis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nikolia", "given" : "Zouboulio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaskani", "given" : "Evaggelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavaniotou", "given" : "Elpiniki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antoniades", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karanikolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontoyanni", "given" : "Anastasia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Study", "given" : "ESORDIG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Rheumatology", "id" : "ITEM-23", "issue" : "7", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "1589-1601", "title" : "Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-24", "itemData" : { "DOI" : "10.3109/14397595.2013.843765", "ISSN" : "1439-7609", "PMID" : "24252039", "abstract" : "Abstract Objective. To characterize the epidemiology of Sj\u00f6gren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan. Methods. The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments. Results. The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 \u00b1 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%). Conclusion. The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.", "author" : [ { "dropping-particle" : "", "family" : "Tsuboi", "given" : "Hiroto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asashima", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takai", "given" : "Chinatsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiwara", "given" : "Shinya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiya", "given" : "Chihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosawa", "given" : "Masahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirota", "given" : "Tomoya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawakami", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sano", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsubota", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Yoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takamura", "given" : "Etsuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Ichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inoue", "given" : "Hiroko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Seiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moriyama", "given" : "Masafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Tsutomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yoshiya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirata", "given" : "Shintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mimori", "given" : "Tsuneyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshifuji", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohta", "given" : "Akiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsumoto", "given" : "Isao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sumida", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-24", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "464-70", "title" : "Primary and secondary surveys on epidemiology of Sj\u00f6gren's syndrome in Japan.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-25", "itemData" : { "abstract" : "There has been no previous prevalence study about of Sjogren's syndrome (SS) in Brazil. The aim was to evaluate the SS prevalence in a general population in Vitoria, ES, Brazil. This was an epidemiological, observational, and cross-sectional study conducted on 1,205 randomized people, aged 18-65 years, who lived in Vitoria. The subjects were screened for xerostomia and xerofphthalmia through home interviews. Those with sicca symptoms were asked to report to a hospital for further medical evaluation, unstimulated salivary flow, Schirmer I test, blood analysis and minor labial salivary biopsy. Sicca symptoms were found in 18% (217 subjects) of the sample. Of the 217 subjects with sicca symptoms, 127 (58%) were available for examination. In this sample, 61.7% were female and 46.8% were under medication. Sicca syndrome was confirmed in 12% by at least one examination (salivary flow or Schirmer I). Two patients (0.17%) matched four criteria according to American-European Criteria (95% CI = 0.020-0.5983)", "author" : [ { "dropping-particle" : "", "family" : "Valim", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zandonade", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira", "given" : "a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito", "given" : "O H", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Serrano", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musso", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giovelli", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciconelli", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista Brasileira de Reumatologia", "id" : "ITEM-25", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "24-34", "title" : "Primary Sjogren's syndrome prevalence in a major metropolitan area in Brazil", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-26", "itemData" : { "ISSN" : "0315-162X", "PMID" : "7791159", "abstract" : "OBJECTIVE: To determine the prevalence rate of primary Sj\u00f6gren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sj\u00f6gren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sj\u00f6gren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sj\u00f6gren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "N Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Q P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "G X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "L L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Z X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "X C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-26", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "659-61", "title" : "Prevalence of primary Sj\u00f6gren's syndrome in China.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^2\u201327", "plainTextFormattedCitation" : "2\u201327", "previouslyFormattedCitation" : "^2\u201327" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2–27Figure 3. Autoimmune epitelitis: linking etiopathogenic mechanisms and therapeutic targets [Editorial note to peer reviewers: Please note this is a draft figur. We would appreciate any comments you may have on content/details the authors could add, change or remove from this figure.] Figure 4. Organ-by-organ systemic manifestations[Editorial note to peer reviewers: Please note this table will be converted to a figure following peer review, with a diagram of the body and each list of manifestations pointing to the relevant organ/system.] OrganManifestationGeneral symptomsFatigueChronic painFeverSkinPurpuraCutaneous ulcers Annular erythemaJoints and musclesArthralgiasNon-erosive symmetric arthritisSubclinical synovitisJaccoud arthropathyMyalgiasMyositisLungsChronic obstructive lung diseaseBronchiectasis Interstitial lung diseasesPleuritisCardiovascularRaynaud phenomenonPericarditisPulmonary arterial hypertensionDysautonomiaPancreasRecurrent acute pancreatitisNephro-urologicalRenal tubular acidosis Glomerulonephritis Interstitial cystitisOsteomalaciaRecurrent renal colic due to renal stones Peripheral nervesMixed polyneuropathy Pure sensory neuronopathy Mononeuritis multiplex Small-fibre neuropathyCentral nervous systemWhite matter lesions (MS-like disease)Cranial nerve involvementNeuromyelitis optica spectrum disorder (NMOSD)Recurrent meningitisHematologicalHemolytic anemiaUnexplained leukopenia (lymphopenia, neutropenia)Unexplained thrombocytopeniaEvans syndromeUnexplained monoclonal gammopathyThrombotic thrombocytopenic purpuraB-cell lymphomaObstetricsAutoimmune congenital heart blockCardiac fibroelastosisUnexplained fetal valvular diseaseNeonatal lupusENTRecurrent parotid enlargementBilateral multicystic parotid massesNeurosensorial hearing lossParotid lymphomaFigure 5. Systemic involvement in patients with Sj?gren’s syndrome:5a. Synovitis (swelling of extensor tendón sheath, single arrows) and arthritis (fusiform swelling of PIP joints, doublé arrows)5b. Cutaneous vasculitis: raised reddish-purple spots on the legs5c. Biopsy-proven lymphocytic interstitial pneumonia: multiple areas of ground-glass attenuation on pulmonary CT (arrows)5d. Cerebral MS-like involvement: bright spots represent demyelinating lesions on cerebral MRI.5e. Parotid MALT lymphoma: enlarged right parotid gland with diffuse cystic replacement (arrows)5f. Raynaud phenomenon: White fingers (inadequate blood flow, single arrows) and red fingers (return of the blood flow, doublé arrows)Figure 6. Study of the corneal surface by the use of dyes (fluorescein, rose Bengal and lissamine green) that stains degenerate or dead cells. Several scores are used to categorize the degree of corneal damage: 6a. van Bijsterveld score, in which each area of the eye (nasal, central, temporal) is scored semi-quantitatively from 0 to 3, depending on the extent of the surface staining; the sum of the different scores ranks from 0 to 9 for each eye; an score ≥ 4 in both eyes is included as one of the 2002 AE criteria.6b. The Oxford scale evaluates the presence of keratitis after fluorescein staining, with a 5-grade scale (0 to 4).6c. The OSS score consists in the sequential use of two stains (corneal and conjunctival stainings). The total ocular staining score was determined by adding the conjunctival and corneal staining with scores ranging from 0 to 12 for each eye.Figure 7. Minor salivary gland biopsy7a. Linear incision of the buccal side of the lower lip7b. Adequate number of informative glands.Figure 8. Minor salivary gland biopsy: main histopathological scenarios (reference 152)8a. Within normal limits: normal appearing architecture and scattered plasma cells, but without acinar atrophy and few if any lymphocytes.8b. Non-Specific chronic sialadenitis (NSCS): scattered or focal infiltrates of lymphocytes, macrophages and plasma cells that are not adjacent to normal-appearing acini and located in gland lobules that exhibit some combination of acinar atrophy, interstitial fibrosis, duct dilation and luminal inspissated mucus.8c. Focal lymphocytic sialadenitis (FLS): presence of one or more dense aggregates of 50 or more lymphocytes (usually several hundred or more) usually located in perivascular or periductal locations. The foci are located adjacent to normal-appearing mucous acini in gland lobes or lobules lacking duct dilation or interstitial fibrosis and contain no more than a minority proportion of plasma cells. Focus score (FS) is calculated assessing the number of lymphocytic foci present per 4 mm2 of glandular area examined.8d. Sclerosing chronic sialadenitis (SCS): the main features are interstitial fibrosis, various patterns of chronic inflammation and acinar atrophy; Daniels et al (152) suggest that SCS could be an advanced stage of NSCS [Awaiting image] Table 1. Incidence and prevalence of primary Sj?gren’s syndrome: main studies classified according to the classification criteria appliedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4065/76.6.593", "ISSN" : "0025-6196", "PMID" : "11393497", "abstract" : "OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sj\u00f6gren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients.\n\nPATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk.\n\nRESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia.\n\nCONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.", "author" : [ { "dropping-particle" : "", "family" : "Pillemer", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "E L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "L T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "P B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melton", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Fallon", "given" : "W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mayo Clinic proceedings", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001", "6" ] ] }, "page" : "593-9", "title" : "Incidence of physician-diagnosed primary Sj\u00f6gren syndrome in residents of Olmsted County, Minnesota.", "type" : "article-journal", "volume" : "76" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.2003.014027", "ISSN" : "0003-4967", "PMID" : "15194588", "abstract" : "OBJECTIVE: To determine the annual incidence of primary Sj\u00f6gren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.", "author" : [ { "dropping-particle" : "", "family" : "Plesivcnik Novljan", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rozman", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hocevar", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "874-876", "title" : "Incidence of primary Sjogren's syndrome in Slovenia.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/rheumatology/kei107", "ISSN" : "14620324", "PMID" : "16332955", "abstract" : "OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sj\u00f6gren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.", "author" : [ { "dropping-particle" : "", "family" : "Alamanos", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Voulgari", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venetsanopoulou", "given" : "a. I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siozos", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "a. a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "187-191", "title" : "Epidemiology of primary Sj??gren's syndrome in north-west Greece, 1982-2003", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3899/jrheum.100883", "ISSN" : "0315-162X", "PMID" : "21239759", "abstract" : "To estimate the incidence and mortality of treated primary Sj\u00f6gren's syndrome (pSS) by sex and age group in Taiwan.", "author" : [ { "dropping-particle" : "", "family" : "Weng", "given" : "Meng-Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Yu-Tung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ming-Fei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Tsung-Hsueh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "706-708", "title" : "Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: a population-based study.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/acr.21820", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22899470", "abstract" : "OBJECTIVE: The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population-based database.\\n\\nMETHODS: We used the longitudinal health insurance database (comprising 1,000,000 beneficiaries) of the Taiwan National Health Insurance from 2000 to 2008 and the National Death Registry of Taiwan from 2000 to 2008.\\n\\nRESULTS: The overall prevalence of major ARDs was 101.3 (95% confidence interval [95% CI] 27.5-107.9) per 100,000 populations; the prevalence was 165.1 (95% CI 44.8-177.1) in women and 40.1 (95% CI 10.9-46.1) in men. The prevalences of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis, vasculitis, and Beh\u00e7et's disease were 52.4 (95% CI 14.2-57.2), 37.0 (95% CI 10.0-41.0), 16.0 (95% CI 4.3-18.7), 3.8 (95% CI 1.0-5.3), 2.9 (95% CI 0.8-4.2), 5.7 (95% CI 1.6-7.4), and 1.4 (95% CI 0.4-2.3) per 100,000 persons, respectively. Between 2001 and 2008, the incidence rates (per 100,000 person-years) for these diseases were 17.3, 8.4, 10.6, 1.5, 1.5, 1.2, and 0.8, respectively. The incident cases with ARDs had a higher risk of mortality, with the standardized mortality ratio (SMR) ranging from 1.3 to 3.7.\\n\\nCONCLUSION: In 2000, the prevalence of major ARDs was 1.4-52.4 per 100,000 persons in Taiwan. Between 2000 and 2008, the incidence rates of various ARDs were 0.8-17.3 per 100,000 person-years. The prevalence and incidence of RA were the highest, followed by SLE and Sj\u00f6gren's syndrome, and those of Beh\u00e7et's disease were the lowest. Patients with different types of ARDs had higher mortality and SMR than those of the general population.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "See", "given" : "Lai-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang-Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I-Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Meng-Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "244-50", "title" : "Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.semarthrit.2013.06.001", "ISBN" : "0049-0172", "ISSN" : "00490172", "PMID" : "23916348", "abstract" : "Objectives: The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. Methods: A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. Results: Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sj\u00f6gren's syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Beh\u00e7et disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sj\u00f6gren's syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). Conclusions: ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sj\u00f6gren's syndrome and SLE, while the incidence of Beh\u00e7et disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases. \u00a9 2013 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "See", "given" : "Lai Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I. Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiou", "given" : "Meng Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "381-386", "title" : "Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1136/bmjopen-2013-003569", "ISSN" : "2044-6055", "PMID" : "24282246", "abstract" : "OBJECTIVE: A very few studies describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). METHODS: A population-based incidence cohort of patients diagnosed with pSS in 1976-2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. RESULTS: 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18-44 years: 2.1/100 000 vs \u226575 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (\u00b13%) at 1 year after diagnosis of pSS and increased to 20% (\u00b14%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). CONCLUSIONS: pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.", "author" : [ { "dropping-particle" : "", "family" : "Nannini", "given" : "Carlotta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jebakumar", "given" : "Adlene J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crowson", "given" : "Cynthia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryu", "given" : "Jay H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "Eric L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-7", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "e003569", "title" : "Primary Sjogren's syndrome 1976-2005 and associated interstitial lung disease: a population-based study of incidence and mortality.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.3109/03009742.2014.931457 [doi]", "ISBN" : "0300-9742", "ISSN" : "1502-7732; 0300-9742", "PMID" : "25222653", "abstract" : "Objectives: To define the incidence rate of primary Sjogren's syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. Method: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. Results: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3-4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89-0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. Conclusions: The incidence rate of pSS is 3.1 (95% CI 2.3-4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.", "author" : [ { "dropping-particle" : "", "family" : "Kvarnstrom", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ottosson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordmark", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahren-Herlenius", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-8", "title" : "Incident cases of primary Sjogren's syndrome during a 5-year period in Stockholm County: a descriptive study of the patients and their characteristics", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1186/1471-2474-11-98", "ISBN" : "1471-2474 (Electronic) 1471-2474 (Linking)", "ISSN" : "1471-2474", "PMID" : "20504294", "abstract" : "BACKGROUND: Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece.\\n\\nMETHODS: In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases.\\n\\nRESULTS: The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sj\u00f6gren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension.\\n\\nCONCLUSIONS: Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.", "author" : [ { "dropping-particle" : "", "family" : "Anagnostopoulos", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinzaras", "given" : "Elias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexiou", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papathanasiou", "given" : "Aphrodite a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davas", "given" : "Evangelos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koutroumpas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barouta", "given" : "Georgia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakkas", "given" : "Lazaros I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC musculoskeletal disorders", "id" : "ITEM-9", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "98", "title" : "The prevalence of rheumatic diseases in central Greece: a population survey.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1111/j.1742-1241.2008.01749.x", "ISSN" : "1742-1241", "PMID" : "18422594", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.", "author" : [ { "dropping-particle" : "", "family" : "Birlik", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gurler", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sari", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birlik", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarioglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oktem", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Can", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayahan", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akkoc", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onen", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of clinical practice", "id" : "ITEM-10", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "954-61", "title" : "Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "ISBN" : "1395-3907 (Print) 1395-3907 (Linking)", "ISSN" : "1395-3907", "PMID" : "9253975", "abstract" : "PURPOSE: To investigate the presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome a sample of 504 persons aged 30-60 years from Copenhagen was studied. METHODS: The presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome was estimated according to both the Copenhagen set of criteria and the preliminary European criteria. RESULTS: Symptoms of dry eye and oral dryness were very common and with no significant correlation to age or sex. Keratoconjuncitivis sicca was most frequent in persons aged 50-59 years and was equally common in men and women. Primary Sj\u00f6gren's syndrome could only be diagnosed in one person according to the Copenhagen criteria (cut-off the Schirmer-1 test < or = 5 mm/5 min), and in three persons according to the preliminary European criteria. CONCLUSION: The frequency of keratoconjunctivitis sicca in persons aged 30-60 years in Copenhagen may be estimated to be 11% according to the Copenhagen criteria and 8% according to the preliminary European criteria. The frequency of primary Sj\u00f6gren's syndrome in persons aged 30-60 years in Copenhagen may be estimated to be between 0.2% and 0.8% according to the Copenhagen criteria and between 0.6% and 2.1% according to the preliminary European criteria.", "author" : [ { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta ophthalmologica Scandinavica", "id" : "ITEM-11", "issue" : "3", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "281-286", "title" : "Keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome in a Danish population aged 30-60 years.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "ISSN" : "0300-9742", "PMID" : "15124941", "abstract" : "To establish the prevalence among women of primary Sj\u00f6gren's syndrome (PSS) in Birmingham, UK.", "author" : [ { "dropping-particle" : "", "family" : "Bowman", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibrahim", "given" : "G H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamburger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ainsworth", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-12", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "39-43", "title" : "Estimating the prevalence among Caucasian women of primary Sj\u00f6gren's syndrome in two general practices in Birmingham, UK.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-13", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9370875", "abstract" : "OBJECTIVE: To define the prevalence of Sj\u00f6gren's syndrome (SS) through an epidemiological survey in a closed rural community. The classification of SS is based on the validated criteria reported by a multicentre study performed in Europe and supported by the Epidemiology Committee of the European Community (EEC-COMAC Epidemiology).\\n\\nMETHODS: The population under study consisted of 837 women aged 18 years or older, residing in the Astakos community of Aitoloakarnania, Greece. The study protocol was subdivided in two parts. In part I, an exhaustive epidemiological survey of these women was conducted in July and August of 1992. The validated questionnaire used in the survey assesses both ocular and oral involvement. In part II, 45 of the women reporting symptoms of both dry eye and dry mouth were approached for a full examination based on the validated set of classification criteria of SS. The full complement of the diagnostic tests was performed on 35 of these women. A subject is classified as a definite primary SS case if at least four of six items of the subject's test items are positive. If three of six items are positive the subject is classified as a probable primary SS case.\\n\\nRESULTS: The classification criteria for definite primary SS were satisfied by five women. This number corresponds to an estimated prevalence of 0.60% (exact 95% CI 0.19%, 1.39%). Probable primary SS was diagnosed for 25 women (prevalence = 2.99%).\\n\\nCONCLUSION: Because of the loss of follow up (10 of 45) and the use of slightly stricter criteria for inclusion of possible SS cases in part II of the study, we consider our estimate of the prevalence of SS to be conservative. This study concurring with other recent reports, suggests that SS is more prevalent than previously thought.", "author" : [ { "dropping-particle" : "", "family" : "Dafni", "given" : "U G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staikos", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skopouli", "given" : "F N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-13", "issue" : "9", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "521-5", "title" : "Prevalence of Sj\u00f6gren's syndrome in a closed rural community.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-14", "itemData" : { "DOI" : "10.1007/s12026-009-8153-2", "ISBN" : "0257-277X", "ISSN" : "0257277X", "PMID" : "20066507", "abstract" : "Epidemiologic studies of autoimmune diseases have not considered them in the aggregate. The objective was to estimate the prevalence of 30 autoimmune diseases separately and in aggregate according to ICD-10 classification. The lifetime prevalence of the entire population of 5,506,574 persons alive in Denmark on October 31, 2006, was estimated by linking records of all visitors to hospitals and specialty clinics via National Patient Registers from January 1, 1977 through October 31, 2006. The prevalences vary from 0.06/1,000 for Pemphigus to 8.94/1,000 for Type 1 diabetes. Nearly 4% of the population had one or more autoimmune disease. The general conclusion is that autoimmune diseases as an aggregate are common.", "author" : [ { "dropping-particle" : "", "family" : "Eaton", "given" : "William W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Marianne G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atlad\u00f3ttir", "given" : "Hj\u00f6rd\u00eds \u00d3sk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregory", "given" : "Patricia E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Noel R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mortensen", "given" : "Preben Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Immunologic Research", "id" : "ITEM-14", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "228-231", "title" : "The prevalence of 30 ICD-10 autoimmune diseases in Denmark", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-15", "itemData" : { "DOI" : "10.3109/03009742.2010.536164", "ISSN" : "1502-7732", "PMID" : "21231797", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (PSS) is a chronic autoimmune inflammatory disease characterized by exocrine gland inflammation producing clinical symptoms such as dryness of the mouth and eyes. The reported prevalence of PSS is variable, probably because of different classification criteria used and selection bias. The aim of this study was to determine the prevalence of PSS in a well-defined Norwegian Caucasian population using the revised American-European Consensus Group (AECG) criteria.\\n\\nMETHODS: Three hospitals and three private rheumatology practices provide all of the rheumatology services to the local population in Hordaland and Rogaland counties, which included 852 342 Caucasian inhabitants as of 1 January 2009. Patients on file fulfilling the new revised AECG criteria for PSS were included, and patients with incomplete data were invited to a screening visit.\\n\\nRESULTS: A total of 424 PSS patients were identified. Their mean age was 61.6 \u00b1 13.2 years; 28 (7%) were men and 396 (93%) were women. The point estimate for the proportion of PSS was 0.050% [95% confidence interval (CI) 0.048-0.052].\\n\\nCONCLUSION: The prevalence of PSS in this Norwegian population of Caucasians is lower than previously reported when less stringent criteria for identifying PSS were used, but is in line with more recent studies using the same criteria and methods as in this study.", "author" : [ { "dropping-particle" : "", "family" : "G\u00f8ransson", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haldorsen", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harboe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skarstein", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Time", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omdal", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-15", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "221-4", "title" : "The point prevalence of clinically relevant primary Sj\u00f6gren's syndrome in two Norwegian counties.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-16", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-16", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-17", "itemData" : { "DOI" : "10.1080/03009740600759704", "ISSN" : "0300-9742", "PMID" : "17062438", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sj\u00f6gren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey.\\n\\nMATERIALS AND METHOD: The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive.\\n\\nRESULTS: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria.\\n\\nCONCLUSION: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.", "author" : [ { "dropping-particle" : "", "family" : "Kabasakal", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turk", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oder", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durusoy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mete", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egrilmez", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akalin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-17", "issue" : "5", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "379-83", "title" : "The prevalence of Sj\u00f6gren's syndrome in adult women.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-18", "itemData" : { "DOI" : "10.1002/acr.22115", "ISSN" : "2151-4658", "PMID" : "23983119", "abstract" : "Purpose: To describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS) in a multi-racial/ethnic population. Methods: A cross-sectional study, with 5 case-retrieval sources, identified adults with pSS living in the Greater Paris area (population 1,172,482 adults) in 2007. Diagnoses were verified by the American-European Consensus Group (AECG) criteria and study-specific enlarged criteria based on the presence of \u22653/4 AECG items among subjective oral or ocular dryness, anti-SSA/SSB positivity and positive minor salivary-gland biopsy results. Prevalence estimates were standardized to those for the world population and 5-source capture-recapture analysis (CRA) was used. Racial/ethnic differences in pSS features were evaluated. Results: In all, 133 subjects met the AECG criteria and 203 the enlarged criteria. The 2007 prevalence of pSS was 1.02 per 10,000 adults (95% confidence interval 0.85-1.22) for AECG criteria and 1.52 per 10,000 adults (1.30-1.76) for enlarged criteria. CRA indicated completeness of case findings of ~90%. Compared to subjects with European background, those with non-European background had 2.1-2.3 times higher pSS prevalence and were younger (P < 0.0001) and more likely to have polyclonal hypergammaglobulinemia (P < 0.0001) and SSA/SSB-antibodies (P = 0.0005 and < 0.0001 for AECG and enlarged criteria, respectively). Conclusion: The figure of 1.02-1.52 per 10,000 adults we found and estimates from the few other population-based census surveys support that the prevalence of diagnosed pSS is between 1 and 10 per 10,000 (0.01-0.1%) of the general population. Non-European race/ethnicity may be associated with increased pSS risk and a distinct disease profile. \u00a9 2013 American College of Rheumatology.", "author" : [ { "dropping-particle" : "", "family" : "Maldini", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhote", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amoura", "given" : "Zahir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandt", "given" : "Michel", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delassus", "given" : "Jean-Luc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falgarone", "given" : "G\u00e9raldine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guillevin", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lhote", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanoelina", "given" : "Jacky", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacr\u00e9", "given" : "Karim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uzunhan", "given" : "Yurdagul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leroux", "given" : "Jean-Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahr", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-18", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Epidemiology of primary Sj\u00f6gren's syndrome in a French Multi-Racial/Ethnic area.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-19", "itemData" : { "ISSN" : "0047-1852", "PMID" : "8531339", "abstract" : "A nationwide epidemiological survey of Japanese Sj\u00f6gren's syndrome (SS) patients was conducted in 1994 by the Research Committee on Epidemiology of Intractable Diseases and the Research Committee of Autoimmune diseases, Ministry of Health and Welfare, Japan. The total number of patients treated for SS in 1993, in Japan, was estimated as 17,000 (95% confidence interval 15,000-20,000). The estimated crude prevalence rates were 1.9 and 25.6 per 100,000 population in males and females, respectively. The ratio of female to male patients was 13.7. The peak of age distribution was in their fifties. New research trends to explore the pathogenesis of SS are also discussed here.", "author" : [ { "dropping-particle" : "", "family" : "Miyasaka", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nihon rinsho. Japanese journal of clinical medicine", "id" : "ITEM-19", "issue" : "10", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "2367-70", "title" : "Epidemiology and pathogenesis of Sj\u00f6gren's syndrome", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-20", "itemData" : { "DOI" : "10.1371/journal.pone.0032487", "ISBN" : "1932-6203", "ISSN" : "1932-6203", "PMID" : "22396771", "abstract" : "BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases.\\n\\nMETHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals.\\n\\nRESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted.\\n\\nCONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.", "author" : [ { "dropping-particle" : "", "family" : "Sardu", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cocco", "given" : "Eleonora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mereu", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massa", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuccu", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marrosu", "given" : "Maria Giovanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Contu", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-20", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e32487", "title" : "Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-21", "itemData" : { "PMID" : "9825745", "abstract" : "OBJECTIVE: Using the European Community (EC) criteria for classification\\nVitali et al. Arthritis Rheum 1993;36:340 7, we report the prevalence\\nestimates of Sjogren's syndrome (SS) from a general population and\\npresent the first population data to assess the impact of the syndrome.\\nMETHODS: A cross-sectional population-based survey performed on 1000\\nadults, aged 18-75 yr, randomly selected from a population register.\\nResponders to the initial postal phase were invited for an interview.\\nThe five criteria measured at interview were: (1) the reporting of\\nsubjective oral symptoms lasting for > 3 months; (2) the reporting\\nof subjective ocular symptoms lasting for >3 months; (3) Schirmer-I\\ntest; (4) unstimulated salivary flow; (5) autoantibodies [Ro (SS-A),\\nLa (SS-B), rheumatoid factor (RF), antinuclear antibodies (ANA)].\\nSS was diagnosed if at least four of these five criteria were positive.\\nThe MOS Short-form 36 (SF-36), General Health Questionnaire (GHQ)\\nand the Health and Fatigue Questionnaire (HFQ) were completed by\\nsubjects after the interview, and scores were compared between those\\nwith and without a diagnosis of SS. RESULTS: A total of 341 subjects\\ncompleted both the postal questionnaire and home visit. A diagnosis\\nof SS could be given to 13 subjects. After adjusting for the presence\\nof possible bias due to non-response, our best estimate of the prevalence\\nof SS in the study population was 33 per 1000 subjects (95% CI 22\\n44). The prevalence of the disorder was higher in females (38; 95%\\nCI 27-52) and for those subjects aged > or = 55 yr (46; 95% CI 34-61).\\nThose subjects diagnosed positively were more impaired for each of\\nthe eight dimensions of the SF-36 than those without a diagnosis,\\nand also suffered from higher levels of depression and fatigue. CONCLUSIONS:\\nSS affects approximately 3-4% of adults and in the general population\\nappears to be associated with a clinically significant impairment\\nof a subject's health and well-being.", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajeer", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silman", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Br J Rheumatol", "id" : "ITEM-21", "issue" : "10", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "1069-1076", "title" : "Sj\ufffdgren's syndrome: a community-based study of prevalence and impact.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-22", "itemData" : { "DOI" : "10.1093/rheumatology/38.2.164", "ISSN" : "14602172", "abstract" : "Objective. The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia., Methods. A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results. Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions. The estimated prevalence of definite SS in Slovenia is 0.60%", "author" : [ { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Logar", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkovic", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-22", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "164-170", "title" : "Prevalence of Sjogren's syndrome in Slovenia", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-23", "itemData" : { "ISSN" : "0315-162X", "PMID" : "12858464", "abstract" : "OBJECTIVE:To assess the prevalence of rheumatic diseases in Greek urban, suburban, and rural adult general populations.METHODS:This cross-sectional population based epidemiological study of rheumatic diseases in Greece (the ESORDIG Study) was conducted on the total adult population of 2 urban, one suburban, and 4 rural communities (8547 subjects), as well as on 2100 out of 5686 randomly selected subjects in one suburban and one rural community. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Either established classification criteria or criteria set for the purposes of the study were used for diagnosis.RESULTS:A total of 8740 subjects participated in the study (response rate 82.1%). The overall age and sex adjusted prevalence (prevalence(asa)) of rheumatic diseases in the total target adult population was 26.9% (95% CI 26.2-27.6), being significantly higher among women (33.7%) than men (19.9%) (p &lt; 0.0005). Disease prevalence(asa) increased significantly with age (p &lt; 0.0005). The most common disease group was low back pain, with a prevalence(asa) of 11.0%, followed by symptomatic peripheral osteoarthritis (7.9%), neck pain (4.8%), miscellaneous rheumatic disorders (4.4%), soft tissue rheumatism disorders (4.3%), and inflammatory rheumatic disease (2.1%). Logistic regression analysis showed a significant positive association of female or male sex, age &gt;or= 50 years, high body mass index, low level of education, moderate or heavy alcohol consumption, and high socioeconomic level with particular diseases or disease groups.CONCLUSION:These findings indicate rheumatic diseases are very common in the general adult population of Greece; 26.9% of adults currently have active or chronic rheumatic disease in remission.", "author" : [ { "dropping-particle" : "", "family" : "Andrianakos", "given" : "Alexandros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trontzas", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christoyannis", "given" : "Fotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dantis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voudouris", "given" : "Costas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgountzos", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaziolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vafiadou", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelidou", "given" : "Kyriaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamitsos", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontelis", "given" : "Leonidas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krachtis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nikolia", "given" : "Zouboulio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaskani", "given" : "Evaggelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavaniotou", "given" : "Elpiniki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antoniades", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karanikolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontoyanni", "given" : "Anastasia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Study", "given" : "ESORDIG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Rheumatology", "id" : "ITEM-23", "issue" : "7", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "1589-1601", "title" : "Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-24", "itemData" : { "DOI" : "10.3109/14397595.2013.843765", "ISSN" : "1439-7609", "PMID" : "24252039", "abstract" : "Abstract Objective. To characterize the epidemiology of Sj\u00f6gren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan. Methods. The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments. Results. The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 \u00b1 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%). Conclusion. The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.", "author" : [ { "dropping-particle" : "", "family" : "Tsuboi", "given" : "Hiroto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asashima", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takai", "given" : "Chinatsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiwara", "given" : "Shinya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiya", "given" : "Chihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosawa", "given" : "Masahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirota", "given" : "Tomoya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawakami", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sano", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsubota", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Yoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takamura", "given" : "Etsuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Ichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inoue", "given" : "Hiroko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Seiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moriyama", "given" : "Masafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Tsutomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yoshiya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirata", "given" : "Shintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mimori", "given" : "Tsuneyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshifuji", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohta", "given" : "Akiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsumoto", "given" : "Isao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sumida", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-24", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "464-70", "title" : "Primary and secondary surveys on epidemiology of Sj\u00f6gren's syndrome in Japan.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-25", "itemData" : { "abstract" : "There has been no previous prevalence study about of Sjogren's syndrome (SS) in Brazil. The aim was to evaluate the SS prevalence in a general population in Vitoria, ES, Brazil. This was an epidemiological, observational, and cross-sectional study conducted on 1,205 randomized people, aged 18-65 years, who lived in Vitoria. The subjects were screened for xerostomia and xerofphthalmia through home interviews. Those with sicca symptoms were asked to report to a hospital for further medical evaluation, unstimulated salivary flow, Schirmer I test, blood analysis and minor labial salivary biopsy. Sicca symptoms were found in 18% (217 subjects) of the sample. Of the 217 subjects with sicca symptoms, 127 (58%) were available for examination. In this sample, 61.7% were female and 46.8% were under medication. Sicca syndrome was confirmed in 12% by at least one examination (salivary flow or Schirmer I). Two patients (0.17%) matched four criteria according to American-European Criteria (95% CI = 0.020-0.5983)", "author" : [ { "dropping-particle" : "", "family" : "Valim", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zandonade", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira", "given" : "a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito", "given" : "O H", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Serrano", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musso", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giovelli", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciconelli", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista Brasileira de Reumatologia", "id" : "ITEM-25", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "24-34", "title" : "Primary Sjogren's syndrome prevalence in a major metropolitan area in Brazil", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-26", "itemData" : { "ISSN" : "0315-162X", "PMID" : "7791159", "abstract" : "OBJECTIVE: To determine the prevalence rate of primary Sj\u00f6gren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sj\u00f6gren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sj\u00f6gren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sj\u00f6gren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "N Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Q P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "G X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "L L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Z X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "X C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-26", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "659-61", "title" : "Prevalence of primary Sj\u00f6gren's syndrome in China.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^2\u201327", "plainTextFormattedCitation" : "2\u201327", "previouslyFormattedCitation" : "^2\u201327" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2–27Author (ref)YearCountryCriteriaSource of data(epidemiological bias)Incidence (cases per 100.00095% CIPillemer et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4065/76.6.593", "ISSN" : "0025-6196", "PMID" : "11393497", "abstract" : "OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sj\u00f6gren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients.\n\nPATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk.\n\nRESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia.\n\nCONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.", "author" : [ { "dropping-particle" : "", "family" : "Pillemer", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "E L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsson", "given" : "L T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martens", "given" : "P B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melton", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Fallon", "given" : "W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mayo Clinic proceedings", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001", "6" ] ] }, "page" : "593-9", "title" : "Incidence of physician-diagnosed primary Sj\u00f6gren syndrome in residents of Olmsted County, Minnesota.", "type" : "article-journal", "volume" : "76" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²", "plainTextFormattedCitation" : "2", "previouslyFormattedCitation" : "²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22001USPhysician-diagnosedPopulation-based6,905,01-8,79Plesivcnik et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2003.014027", "ISSN" : "0003-4967", "PMID" : "15194588", "abstract" : "OBJECTIVE: To determine the annual incidence of primary Sj\u00f6gren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.", "author" : [ { "dropping-particle" : "", "family" : "Plesivcnik Novljan", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rozman", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hocevar", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "874-876", "title" : "Incidence of primary Sjogren's syndrome in Slovenia.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³", "plainTextFormattedCitation" : "3", "previouslyFormattedCitation" : "³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32004Slovenia1996Hospital-based7,225,47-8,98Alamanos et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kei107", "ISSN" : "14620324", "PMID" : "16332955", "abstract" : "OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sj\u00f6gren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.", "author" : [ { "dropping-particle" : "", "family" : "Alamanos", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Voulgari", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venetsanopoulou", "given" : "a. I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siozos", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "a. a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "187-191", "title" : "Epidemiology of primary Sj??gren's syndrome in north-west Greece, 1982-2003", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴", "plainTextFormattedCitation" : "4", "previouslyFormattedCitation" : "⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }42006Greece2002Population-based10,109,11-11,08Weng et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.100883", "ISSN" : "0315-162X", "PMID" : "21239759", "abstract" : "To estimate the incidence and mortality of treated primary Sj\u00f6gren's syndrome (pSS) by sex and age group in Taiwan.", "author" : [ { "dropping-particle" : "", "family" : "Weng", "given" : "Meng-Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Yu-Tung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ming-Fei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Tsung-Hsueh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "706-708", "title" : "Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: a population-based study.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵", "plainTextFormattedCitation" : "5", "previouslyFormattedCitation" : "⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }52011Taiwan2002Insurance database11,0010,61-11,39Nannini et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmjopen-2013-003569", "ISSN" : "2044-6055", "PMID" : "24282246", "abstract" : "OBJECTIVE: A very few studies describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). METHODS: A population-based incidence cohort of patients diagnosed with pSS in 1976-2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. RESULTS: 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18-44 years: 2.1/100 000 vs \u226575 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (\u00b13%) at 1 year after diagnosis of pSS and increased to 20% (\u00b14%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). CONCLUSIONS: pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.", "author" : [ { "dropping-particle" : "", "family" : "Nannini", "given" : "Carlotta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jebakumar", "given" : "Adlene J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crowson", "given" : "Cynthia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryu", "given" : "Jay H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matteson", "given" : "Eric L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "e003569", "title" : "Primary Sjogren's syndrome 1976-2005 and associated interstitial lung disease: a population-based study of incidence and mortality.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸", "plainTextFormattedCitation" : "8", "previouslyFormattedCitation" : "⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82013US2002Population-based5,14,1-6,1Kvarnstrom et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/03009742.2014.931457 [doi]", "ISBN" : "0300-9742", "ISSN" : "1502-7732; 0300-9742", "PMID" : "25222653", "abstract" : "Objectives: To define the incidence rate of primary Sjogren's syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. Method: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. Results: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3-4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89-0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. Conclusions: The incidence rate of pSS is 3.1 (95% CI 2.3-4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.", "author" : [ { "dropping-particle" : "", "family" : "Kvarnstrom", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ottosson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordmark", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahren-Herlenius", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-8", "title" : "Incident cases of primary Sjogren's syndrome during a 5-year period in Stockholm County: a descriptive study of the patients and their characteristics", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹", "plainTextFormattedCitation" : "9", "previouslyFormattedCitation" : "⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92015Sweden2002Hospital-based3,12,3-4,3Yu et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.21820", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22899470", "abstract" : "OBJECTIVE: The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population-based database.\\n\\nMETHODS: We used the longitudinal health insurance database (comprising 1,000,000 beneficiaries) of the Taiwan National Health Insurance from 2000 to 2008 and the National Death Registry of Taiwan from 2000 to 2008.\\n\\nRESULTS: The overall prevalence of major ARDs was 101.3 (95% confidence interval [95% CI] 27.5-107.9) per 100,000 populations; the prevalence was 165.1 (95% CI 44.8-177.1) in women and 40.1 (95% CI 10.9-46.1) in men. The prevalences of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis, vasculitis, and Beh\u00e7et's disease were 52.4 (95% CI 14.2-57.2), 37.0 (95% CI 10.0-41.0), 16.0 (95% CI 4.3-18.7), 3.8 (95% CI 1.0-5.3), 2.9 (95% CI 0.8-4.2), 5.7 (95% CI 1.6-7.4), and 1.4 (95% CI 0.4-2.3) per 100,000 persons, respectively. Between 2001 and 2008, the incidence rates (per 100,000 person-years) for these diseases were 17.3, 8.4, 10.6, 1.5, 1.5, 1.2, and 0.8, respectively. The incident cases with ARDs had a higher risk of mortality, with the standardized mortality ratio (SMR) ranging from 1.3 to 3.7.\\n\\nCONCLUSION: In 2000, the prevalence of major ARDs was 1.4-52.4 per 100,000 persons in Taiwan. Between 2000 and 2008, the incidence rates of various ARDs were 0.8-17.3 per 100,000 person-years. The prevalence and incidence of RA were the highest, followed by SLE and Sj\u00f6gren's syndrome, and those of Beh\u00e7et's disease were the lowest. Patients with different types of ARDs had higher mortality and SMR than those of the general population.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "See", "given" : "Lai-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang-Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I-Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Meng-Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "244-50", "title" : "Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶", "plainTextFormattedCitation" : "6", "previouslyFormattedCitation" : "⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62013TaiwanICDInsurance database18,5017,16-19,84See et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.semarthrit.2013.06.001", "ISBN" : "0049-0172", "ISSN" : "00490172", "PMID" : "23916348", "abstract" : "Objectives: The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. Methods: A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. Results: Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sj\u00f6gren's syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Beh\u00e7et disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sj\u00f6gren's syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). Conclusions: ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sj\u00f6gren's syndrome and SLE, while the incidence of Beh\u00e7et disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases. \u00a9 2013 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "See", "given" : "Lai Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I. Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiou", "given" : "Meng Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "381-386", "title" : "Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷", "plainTextFormattedCitation" : "7", "previouslyFormattedCitation" : "⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72013TaiwanICDInsurance database20,0518,29-21,80Author (ref)YearCountryCriteriaSource of data(epidemiological bias)Prevalence (%)95% CIMiyasaka et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0047-1852", "PMID" : "8531339", "abstract" : "A nationwide epidemiological survey of Japanese Sj\u00f6gren's syndrome (SS) patients was conducted in 1994 by the Research Committee on Epidemiology of Intractable Diseases and the Research Committee of Autoimmune diseases, Ministry of Health and Welfare, Japan. The total number of patients treated for SS in 1993, in Japan, was estimated as 17,000 (95% confidence interval 15,000-20,000). The estimated crude prevalence rates were 1.9 and 25.6 per 100,000 population in males and females, respectively. The ratio of female to male patients was 13.7. The peak of age distribution was in their fifties. New research trends to explore the pathogenesis of SS are also discussed here.", "author" : [ { "dropping-particle" : "", "family" : "Miyasaka", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nihon rinsho. Japanese journal of clinical medicine", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "2367-70", "title" : "Epidemiology and pathogenesis of Sj\u00f6gren's syndrome", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰", "plainTextFormattedCitation" : "20", "previouslyFormattedCitation" : "²⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }201995JapanNSHospital-based0,01%0,0125-0,0167%Zhang et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0315-162X", "PMID" : "7791159", "abstract" : "OBJECTIVE: To determine the prevalence rate of primary Sj\u00f6gren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sj\u00f6gren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sj\u00f6gren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sj\u00f6gren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "N Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Q P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "G X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "L L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Z X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "X C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "659-61", "title" : "Prevalence of primary Sj\u00f6gren's syndrome in China.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁷", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "²⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }271995ChinaCopenhagenPopulation-based0,77%NSBjerrum et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1395-3907 (Print) 1395-3907 (Linking)", "ISSN" : "1395-3907", "PMID" : "9253975", "abstract" : "PURPOSE: To investigate the presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome a sample of 504 persons aged 30-60 years from Copenhagen was studied. METHODS: The presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome was estimated according to both the Copenhagen set of criteria and the preliminary European criteria. RESULTS: Symptoms of dry eye and oral dryness were very common and with no significant correlation to age or sex. Keratoconjuncitivis sicca was most frequent in persons aged 50-59 years and was equally common in men and women. Primary Sj\u00f6gren's syndrome could only be diagnosed in one person according to the Copenhagen criteria (cut-off the Schirmer-1 test < or = 5 mm/5 min), and in three persons according to the preliminary European criteria. CONCLUSION: The frequency of keratoconjunctivitis sicca in persons aged 30-60 years in Copenhagen may be estimated to be 11% according to the Copenhagen criteria and 8% according to the preliminary European criteria. The frequency of primary Sj\u00f6gren's syndrome in persons aged 30-60 years in Copenhagen may be estimated to be between 0.2% and 0.8% according to the Copenhagen criteria and between 0.6% and 2.1% according to the preliminary European criteria.", "author" : [ { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta ophthalmologica Scandinavica", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "281-286", "title" : "Keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome in a Danish population aged 30-60 years.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }121997DenmarkCopenhagenHospital-based (age 30-60 years)0,20%NSZhang et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0315-162X", "PMID" : "7791159", "abstract" : "OBJECTIVE: To determine the prevalence rate of primary Sj\u00f6gren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sj\u00f6gren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sj\u00f6gren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sj\u00f6gren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "N Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Q P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "G X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "L L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Z X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "X C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "659-61", "title" : "Prevalence of primary Sj\u00f6gren's syndrome in China.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁷", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "²⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }271995ChinaSan DiegoPopulation-based0,33%NSBjerrum et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1395-3907 (Print) 1395-3907 (Linking)", "ISSN" : "1395-3907", "PMID" : "9253975", "abstract" : "PURPOSE: To investigate the presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome a sample of 504 persons aged 30-60 years from Copenhagen was studied. METHODS: The presence of keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome was estimated according to both the Copenhagen set of criteria and the preliminary European criteria. RESULTS: Symptoms of dry eye and oral dryness were very common and with no significant correlation to age or sex. Keratoconjuncitivis sicca was most frequent in persons aged 50-59 years and was equally common in men and women. Primary Sj\u00f6gren's syndrome could only be diagnosed in one person according to the Copenhagen criteria (cut-off the Schirmer-1 test < or = 5 mm/5 min), and in three persons according to the preliminary European criteria. CONCLUSION: The frequency of keratoconjunctivitis sicca in persons aged 30-60 years in Copenhagen may be estimated to be 11% according to the Copenhagen criteria and 8% according to the preliminary European criteria. The frequency of primary Sj\u00f6gren's syndrome in persons aged 30-60 years in Copenhagen may be estimated to be between 0.2% and 0.8% according to the Copenhagen criteria and between 0.6% and 2.1% according to the preliminary European criteria.", "author" : [ { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta ophthalmologica Scandinavica", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "281-286", "title" : "Keratoconjunctivitis sicca and primary Sj\u00f6gren's syndrome in a Danish population aged 30-60 years.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }121997Denmark1993Hospital-based (age 30-60 years)0,60%NSDafni et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9370875", "abstract" : "OBJECTIVE: To define the prevalence of Sj\u00f6gren's syndrome (SS) through an epidemiological survey in a closed rural community. The classification of SS is based on the validated criteria reported by a multicentre study performed in Europe and supported by the Epidemiology Committee of the European Community (EEC-COMAC Epidemiology).\\n\\nMETHODS: The population under study consisted of 837 women aged 18 years or older, residing in the Astakos community of Aitoloakarnania, Greece. The study protocol was subdivided in two parts. In part I, an exhaustive epidemiological survey of these women was conducted in July and August of 1992. The validated questionnaire used in the survey assesses both ocular and oral involvement. In part II, 45 of the women reporting symptoms of both dry eye and dry mouth were approached for a full examination based on the validated set of classification criteria of SS. The full complement of the diagnostic tests was performed on 35 of these women. A subject is classified as a definite primary SS case if at least four of six items of the subject's test items are positive. If three of six items are positive the subject is classified as a probable primary SS case.\\n\\nRESULTS: The classification criteria for definite primary SS were satisfied by five women. This number corresponds to an estimated prevalence of 0.60% (exact 95% CI 0.19%, 1.39%). Probable primary SS was diagnosed for 25 women (prevalence = 2.99%).\\n\\nCONCLUSION: Because of the loss of follow up (10 of 45) and the use of slightly stricter criteria for inclusion of possible SS cases in part II of the study, we consider our estimate of the prevalence of SS to be conservative. This study concurring with other recent reports, suggests that SS is more prevalent than previously thought.", "author" : [ { "dropping-particle" : "", "family" : "Dafni", "given" : "U G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzioufas", "given" : "A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staikos", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skopouli", "given" : "F N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "521-5", "title" : "Prevalence of Sj\u00f6gren's syndrome in a closed rural community.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "¹⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }141997Greece1993Population-based(only women, age > 18 years)0,60%0,19-1,39%Thomas et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "PMID" : "9825745", "abstract" : "OBJECTIVE: Using the European Community (EC) criteria for classification\\nVitali et al. Arthritis Rheum 1993;36:340 7, we report the prevalence\\nestimates of Sjogren's syndrome (SS) from a general population and\\npresent the first population data to assess the impact of the syndrome.\\nMETHODS: A cross-sectional population-based survey performed on 1000\\nadults, aged 18-75 yr, randomly selected from a population register.\\nResponders to the initial postal phase were invited for an interview.\\nThe five criteria measured at interview were: (1) the reporting of\\nsubjective oral symptoms lasting for > 3 months; (2) the reporting\\nof subjective ocular symptoms lasting for >3 months; (3) Schirmer-I\\ntest; (4) unstimulated salivary flow; (5) autoantibodies [Ro (SS-A),\\nLa (SS-B), rheumatoid factor (RF), antinuclear antibodies (ANA)].\\nSS was diagnosed if at least four of these five criteria were positive.\\nThe MOS Short-form 36 (SF-36), General Health Questionnaire (GHQ)\\nand the Health and Fatigue Questionnaire (HFQ) were completed by\\nsubjects after the interview, and scores were compared between those\\nwith and without a diagnosis of SS. RESULTS: A total of 341 subjects\\ncompleted both the postal questionnaire and home visit. A diagnosis\\nof SS could be given to 13 subjects. After adjusting for the presence\\nof possible bias due to non-response, our best estimate of the prevalence\\nof SS in the study population was 33 per 1000 subjects (95% CI 22\\n44). The prevalence of the disorder was higher in females (38; 95%\\nCI 27-52) and for those subjects aged > or = 55 yr (46; 95% CI 34-61).\\nThose subjects diagnosed positively were more impaired for each of\\nthe eight dimensions of the SF-36 than those without a diagnosis,\\nand also suffered from higher levels of depression and fatigue. CONCLUSIONS:\\nSS affects approximately 3-4% of adults and in the general population\\nappears to be associated with a clinically significant impairment\\nof a subject's health and well-being.", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajeer", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silman", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Br J Rheumatol", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "1069-1076", "title" : "Sj\ufffdgren's syndrome: a community-based study of prevalence and impact.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }221998UK1993Primary healthcare(age 18-75 years)3,30%2,2-4,4%Kabasakal et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/03009740600759704", "ISSN" : "0300-9742", "PMID" : "17062438", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sj\u00f6gren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey.\\n\\nMATERIALS AND METHOD: The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive.\\n\\nRESULTS: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria.\\n\\nCONCLUSION: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.", "author" : [ { "dropping-particle" : "", "family" : "Kabasakal", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turk", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oder", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durusoy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mete", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egrilmez", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akalin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "379-83", "title" : "The prevalence of Sj\u00f6gren's syndrome in adult women.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸", "plainTextFormattedCitation" : "18", "previouslyFormattedCitation" : "¹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182006Turkey1993Population-based(only adult Caucasian women)1,56%0,92-2,66%Haugen et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷", "plainTextFormattedCitation" : "17", "previouslyFormattedCitation" : "¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }17 2008Norway1993Population-based (born in 1925-27)3,39%2,77-4,14%Haugen et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷", "plainTextFormattedCitation" : "17", "previouslyFormattedCitation" : "¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }172008Norway1993Population-based (born in 1953-57)0,44%0,34-0,57%Birlik et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1742-1241.2008.01749.x", "ISSN" : "1742-1241", "PMID" : "18422594", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.", "author" : [ { "dropping-particle" : "", "family" : "Birlik", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gurler", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sari", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birlik", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarioglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oktem", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Can", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayahan", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akkoc", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onen", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of clinical practice", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "954-61", "title" : "Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112009Turkey1993Population-based(age > 20 years)0,28%0,13-0,51%Tomsic et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/38.2.164", "ISSN" : "14602172", "abstract" : "Objective. The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia., Methods. A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results. Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions. The estimated prevalence of definite SS in Slovenia is 0.60%", "author" : [ { "dropping-particle" : "", "family" : "Tomsic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Logar", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grmek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perkovic", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kveder", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "164-170", "title" : "Prevalence of Sjogren's syndrome in Slovenia", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³", "plainTextFormattedCitation" : "23", "previouslyFormattedCitation" : "²³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }231999Slovenia1996Population-based0,60%0,07-2,16%Haugen et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷", "plainTextFormattedCitation" : "17", "previouslyFormattedCitation" : "¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }172008Norway1996Population-based (born in 1925-27)1,40%1,02-1,92%Haugen et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/03009740701678712", "ISSN" : "0300-9742", "PMID" : "18189192", "abstract" : "OBJECTIVE: To estimate the point prevalence of primary Sj\u00f6gren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria.\\n\\nMETHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996.\\n\\nRESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27.\\n\\nCONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.", "author" : [ { "dropping-particle" : "", "family" : "Haugen", "given" : "a J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peen", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hult\u00e9n", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johannessen", "given" : "a C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halse", "given" : "a K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haga", "given" : "H-J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "30-4", "title" : "Estimation of the prevalence of primary Sj\u00f6gren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷", "plainTextFormattedCitation" : "17", "previouslyFormattedCitation" : "¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }172008Norway1996Population-based (born in 1953-57)0,22%0,15-0,32%Bowman et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0300-9742", "PMID" : "15124941", "abstract" : "To establish the prevalence among women of primary Sj\u00f6gren's syndrome (PSS) in Birmingham, UK.", "author" : [ { "dropping-particle" : "", "family" : "Bowman", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ibrahim", "given" : "G H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmes", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamburger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ainsworth", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "39-43", "title" : "Estimating the prevalence among Caucasian women of primary Sj\u00f6gren's syndrome in two general practices in Birmingham, UK.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "¹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }132004UK2002Primary healthcare(only Caucasian women, age 35-74 years)0,14%0,017-0,51%Trontzas et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0315-162X", "PMID" : "12858464", "abstract" : "OBJECTIVE:To assess the prevalence of rheumatic diseases in Greek urban, suburban, and rural adult general populations.METHODS:This cross-sectional population based epidemiological study of rheumatic diseases in Greece (the ESORDIG Study) was conducted on the total adult population of 2 urban, one suburban, and 4 rural communities (8547 subjects), as well as on 2100 out of 5686 randomly selected subjects in one suburban and one rural community. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Either established classification criteria or criteria set for the purposes of the study were used for diagnosis.RESULTS:A total of 8740 subjects participated in the study (response rate 82.1%). The overall age and sex adjusted prevalence (prevalence(asa)) of rheumatic diseases in the total target adult population was 26.9% (95% CI 26.2-27.6), being significantly higher among women (33.7%) than men (19.9%) (p &lt; 0.0005). Disease prevalence(asa) increased significantly with age (p &lt; 0.0005). The most common disease group was low back pain, with a prevalence(asa) of 11.0%, followed by symptomatic peripheral osteoarthritis (7.9%), neck pain (4.8%), miscellaneous rheumatic disorders (4.4%), soft tissue rheumatism disorders (4.3%), and inflammatory rheumatic disease (2.1%). Logistic regression analysis showed a significant positive association of female or male sex, age &gt;or= 50 years, high body mass index, low level of education, moderate or heavy alcohol consumption, and high socioeconomic level with particular diseases or disease groups.CONCLUSION:These findings indicate rheumatic diseases are very common in the general adult population of Greece; 26.9% of adults currently have active or chronic rheumatic disease in remission.", "author" : [ { "dropping-particle" : "", "family" : "Andrianakos", "given" : "Alexandros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trontzas", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christoyannis", "given" : "Fotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dantis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voudouris", "given" : "Costas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgountzos", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaziolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vafiadou", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pantelidou", "given" : "Kyriaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karamitsos", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontelis", "given" : "Leonidas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krachtis", "given" : "Petros", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nikolia", "given" : "Zouboulio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaskani", "given" : "Evaggelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavaniotou", "given" : "Elpiniki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antoniades", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karanikolas", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kontoyanni", "given" : "Anastasia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Study", "given" : "ESORDIG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Rheumatology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "1589-1601", "title" : "Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴", "plainTextFormattedCitation" : "24", "previouslyFormattedCitation" : "²⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }242005Greece2002Population-based(only Caucasian)0,15%0,09-0,21%Alamanos et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kei107", "ISSN" : "14620324", "PMID" : "16332955", "abstract" : "OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sj\u00f6gren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.", "author" : [ { "dropping-particle" : "", "family" : "Alamanos", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Voulgari", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venetsanopoulou", "given" : "a. I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siozos", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "a. a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "187-191", "title" : "Epidemiology of primary Sj??gren's syndrome in north-west Greece, 1982-2003", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴", "plainTextFormattedCitation" : "4", "previouslyFormattedCitation" : "⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }42006Greece2002Hospital-based0,09%0,08-0,10%Kabasakal et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/03009740600759704", "ISSN" : "0300-9742", "PMID" : "17062438", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sj\u00f6gren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey.\\n\\nMATERIALS AND METHOD: The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive.\\n\\nRESULTS: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria.\\n\\nCONCLUSION: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.", "author" : [ { "dropping-particle" : "", "family" : "Kabasakal", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitapcioglu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turk", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oder", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durusoy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mete", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egrilmez", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akalin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "379-83", "title" : "The prevalence of Sj\u00f6gren's syndrome in adult women.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸", "plainTextFormattedCitation" : "18", "previouslyFormattedCitation" : "¹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182006Turkey2002Population-based(only adult Caucasian women)0,72%0,33-1,57%Birlik et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1742-1241.2008.01749.x", "ISSN" : "1742-1241", "PMID" : "18422594", "abstract" : "OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.", "author" : [ { "dropping-particle" : "", "family" : "Birlik", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gurler", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sari", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birlik", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarioglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oktem", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Can", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayahan", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akkoc", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onen", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of clinical practice", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "954-61", "title" : "Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112009Turkey2002Population-based(age > 20 years)0,16%0,06-0,35%Anagnostopoulos et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2474-11-98", "ISBN" : "1471-2474 (Electronic) 1471-2474 (Linking)", "ISSN" : "1471-2474", "PMID" : "20504294", "abstract" : "BACKGROUND: Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece.\\n\\nMETHODS: In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases.\\n\\nRESULTS: The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sj\u00f6gren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension.\\n\\nCONCLUSIONS: Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.", "author" : [ { "dropping-particle" : "", "family" : "Anagnostopoulos", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinzaras", "given" : "Elias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexiou", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papathanasiou", "given" : "Aphrodite a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davas", "given" : "Evangelos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koutroumpas", "given" : "Athanasios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barouta", "given" : "Georgia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakkas", "given" : "Lazaros I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC musculoskeletal disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "98", "title" : "The prevalence of rheumatic diseases in central Greece: a population survey.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }102010Greece2002Population-based(only adults)0,23%0,22-0,75Goransson et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/03009742.2010.536164", "ISSN" : "1502-7732", "PMID" : "21231797", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (PSS) is a chronic autoimmune inflammatory disease characterized by exocrine gland inflammation producing clinical symptoms such as dryness of the mouth and eyes. The reported prevalence of PSS is variable, probably because of different classification criteria used and selection bias. The aim of this study was to determine the prevalence of PSS in a well-defined Norwegian Caucasian population using the revised American-European Consensus Group (AECG) criteria.\\n\\nMETHODS: Three hospitals and three private rheumatology practices provide all of the rheumatology services to the local population in Hordaland and Rogaland counties, which included 852 342 Caucasian inhabitants as of 1 January 2009. Patients on file fulfilling the new revised AECG criteria for PSS were included, and patients with incomplete data were invited to a screening visit.\\n\\nRESULTS: A total of 424 PSS patients were identified. Their mean age was 61.6 \u00b1 13.2 years; 28 (7%) were men and 396 (93%) were women. The point estimate for the proportion of PSS was 0.050% [95% confidence interval (CI) 0.048-0.052].\\n\\nCONCLUSION: The prevalence of PSS in this Norwegian population of Caucasians is lower than previously reported when less stringent criteria for identifying PSS were used, but is in line with more recent studies using the same criteria and methods as in this study.", "author" : [ { "dropping-particle" : "", "family" : "G\u00f8ransson", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haldorsen", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brun", "given" : "J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harboe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jonsson", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skarstein", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Time", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omdal", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "221-4", "title" : "The point prevalence of clinically relevant primary Sj\u00f6gren's syndrome in two Norwegian counties.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "¹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }162011Norway2002Hospital-based0,05%0,048-0,052%Maldini et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.22115", "ISSN" : "2151-4658", "PMID" : "23983119", "abstract" : "Purpose: To describe the epidemiology of primary Sj\u00f6gren's syndrome (pSS) in a multi-racial/ethnic population. Methods: A cross-sectional study, with 5 case-retrieval sources, identified adults with pSS living in the Greater Paris area (population 1,172,482 adults) in 2007. Diagnoses were verified by the American-European Consensus Group (AECG) criteria and study-specific enlarged criteria based on the presence of \u22653/4 AECG items among subjective oral or ocular dryness, anti-SSA/SSB positivity and positive minor salivary-gland biopsy results. Prevalence estimates were standardized to those for the world population and 5-source capture-recapture analysis (CRA) was used. Racial/ethnic differences in pSS features were evaluated. Results: In all, 133 subjects met the AECG criteria and 203 the enlarged criteria. The 2007 prevalence of pSS was 1.02 per 10,000 adults (95% confidence interval 0.85-1.22) for AECG criteria and 1.52 per 10,000 adults (1.30-1.76) for enlarged criteria. CRA indicated completeness of case findings of ~90%. Compared to subjects with European background, those with non-European background had 2.1-2.3 times higher pSS prevalence and were younger (P < 0.0001) and more likely to have polyclonal hypergammaglobulinemia (P < 0.0001) and SSA/SSB-antibodies (P = 0.0005 and < 0.0001 for AECG and enlarged criteria, respectively). Conclusion: The figure of 1.02-1.52 per 10,000 adults we found and estimates from the few other population-based census surveys support that the prevalence of diagnosed pSS is between 1 and 10 per 10,000 (0.01-0.1%) of the general population. Non-European race/ethnicity may be associated with increased pSS risk and a distinct disease profile. \u00a9 2013 American College of Rheumatology.", "author" : [ { "dropping-particle" : "", "family" : "Maldini", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seror", "given" : "Rapha\u00e8le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fain", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhote", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amoura", "given" : "Zahir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandt", "given" : "Michel", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delassus", "given" : "Jean-Luc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falgarone", "given" : "G\u00e9raldine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guillevin", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guern", "given" : "V\u00e9ronique", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lhote", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanoelina", "given" : "Jacky", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacr\u00e9", "given" : "Karim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uzunhan", "given" : "Yurdagul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leroux", "given" : "Jean-Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariette", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahr", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Epidemiology of primary Sj\u00f6gren's syndrome in a French Multi-Racial/Ethnic area.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "¹⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }192013France2002Population-based(age > 15 years)0,01%0,0085-0,0122%Valim et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "There has been no previous prevalence study about of Sjogren's syndrome (SS) in Brazil. The aim was to evaluate the SS prevalence in a general population in Vitoria, ES, Brazil. This was an epidemiological, observational, and cross-sectional study conducted on 1,205 randomized people, aged 18-65 years, who lived in Vitoria. The subjects were screened for xerostomia and xerofphthalmia through home interviews. Those with sicca symptoms were asked to report to a hospital for further medical evaluation, unstimulated salivary flow, Schirmer I test, blood analysis and minor labial salivary biopsy. Sicca symptoms were found in 18% (217 subjects) of the sample. Of the 217 subjects with sicca symptoms, 127 (58%) were available for examination. In this sample, 61.7% were female and 46.8% were under medication. Sicca syndrome was confirmed in 12% by at least one examination (salivary flow or Schirmer I). Two patients (0.17%) matched four criteria according to American-European Criteria (95% CI = 0.020-0.5983)", "author" : [ { "dropping-particle" : "", "family" : "Valim", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zandonade", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira", "given" : "a M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brito", "given" : "O H", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Serrano", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musso", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giovelli", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciconelli", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista Brasileira de Reumatologia", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "24-34", "title" : "Primary Sjogren's syndrome prevalence in a major metropolitan area in Brazil", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁶", "plainTextFormattedCitation" : "26", "previouslyFormattedCitation" : "²⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }262013Brazil2002Population-based)(age 18-65 years)0,17%0,02-0,59%Sardu et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0032487", "ISBN" : "1932-6203", "ISSN" : "1932-6203", "PMID" : "22396771", "abstract" : "BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases.\\n\\nMETHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals.\\n\\nRESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted.\\n\\nCONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases.", "author" : [ { "dropping-particle" : "", "family" : "Sardu", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cocco", "given" : "Eleonora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mereu", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massa", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuccu", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marrosu", "given" : "Maria Giovanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Contu", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e32487", "title" : "Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence and comorbidity.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "²¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212012ItalyICDPrimary healthcare(age 15-89)0,03%0,013-0,061%See et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.semarthrit.2013.06.001", "ISBN" : "0049-0172", "ISSN" : "00490172", "PMID" : "23916348", "abstract" : "Objectives: The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. Methods: A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. Results: Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sj\u00f6gren's syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Beh\u00e7et disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sj\u00f6gren's syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). Conclusions: ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sj\u00f6gren's syndrome and SLE, while the incidence of Beh\u00e7et disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases. \u00a9 2013 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "See", "given" : "Lai Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I. Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiou", "given" : "Meng Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "381-386", "title" : "Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷", "plainTextFormattedCitation" : "7", "previouslyFormattedCitation" : "⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72013TaiwanICDInsurance database0,06%0,0536-0,063%Eaton et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12026-009-8153-2", "ISBN" : "0257-277X", "ISSN" : "0257277X", "PMID" : "20066507", "abstract" : "Epidemiologic studies of autoimmune diseases have not considered them in the aggregate. The objective was to estimate the prevalence of 30 autoimmune diseases separately and in aggregate according to ICD-10 classification. The lifetime prevalence of the entire population of 5,506,574 persons alive in Denmark on October 31, 2006, was estimated by linking records of all visitors to hospitals and specialty clinics via National Patient Registers from January 1, 1977 through October 31, 2006. The prevalences vary from 0.06/1,000 for Pemphigus to 8.94/1,000 for Type 1 diabetes. Nearly 4% of the population had one or more autoimmune disease. The general conclusion is that autoimmune diseases as an aggregate are common.", "author" : [ { "dropping-particle" : "", "family" : "Eaton", "given" : "William W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Marianne G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atlad\u00f3ttir", "given" : "Hj\u00f6rd\u00eds \u00d3sk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregory", "given" : "Patricia E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Noel R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mortensen", "given" : "Preben Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Immunologic Research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "228-231", "title" : "The prevalence of 30 ICD-10 autoimmune diseases in Denmark", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "¹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }152011DenmarkICDHospital-based0,59%NSYu et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.21820", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22899470", "abstract" : "OBJECTIVE: The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population-based database.\\n\\nMETHODS: We used the longitudinal health insurance database (comprising 1,000,000 beneficiaries) of the Taiwan National Health Insurance from 2000 to 2008 and the National Death Registry of Taiwan from 2000 to 2008.\\n\\nRESULTS: The overall prevalence of major ARDs was 101.3 (95% confidence interval [95% CI] 27.5-107.9) per 100,000 populations; the prevalence was 165.1 (95% CI 44.8-177.1) in women and 40.1 (95% CI 10.9-46.1) in men. The prevalences of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis, vasculitis, and Beh\u00e7et's disease were 52.4 (95% CI 14.2-57.2), 37.0 (95% CI 10.0-41.0), 16.0 (95% CI 4.3-18.7), 3.8 (95% CI 1.0-5.3), 2.9 (95% CI 0.8-4.2), 5.7 (95% CI 1.6-7.4), and 1.4 (95% CI 0.4-2.3) per 100,000 persons, respectively. Between 2001 and 2008, the incidence rates (per 100,000 person-years) for these diseases were 17.3, 8.4, 10.6, 1.5, 1.5, 1.2, and 0.8, respectively. The incident cases with ARDs had a higher risk of mortality, with the standardized mortality ratio (SMR) ranging from 1.3 to 3.7.\\n\\nCONCLUSION: In 2000, the prevalence of major ARDs was 1.4-52.4 per 100,000 persons in Taiwan. Between 2000 and 2008, the incidence rates of various ARDs were 0.8-17.3 per 100,000 person-years. The prevalence and incidence of RA were the highest, followed by SLE and Sj\u00f6gren's syndrome, and those of Beh\u00e7et's disease were the lowest. Patients with different types of ARDs had higher mortality and SMR than those of the general population.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Kuang-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "See", "given" : "Lai-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chang-Fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "I-Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Meng-Jiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "244-50", "title" : "Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶", "plainTextFormattedCitation" : "6", "previouslyFormattedCitation" : "⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62013TaiwanICDInsurance database0,02%0,0043-0,0187%Tsuboi et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/14397595.2013.843765", "ISSN" : "1439-7609", "PMID" : "24252039", "abstract" : "Abstract Objective. To characterize the epidemiology of Sj\u00f6gren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan. Methods. The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments. Results. The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 \u00b1 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%). Conclusion. The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.", "author" : [ { "dropping-particle" : "", "family" : "Tsuboi", "given" : "Hiroto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asashima", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takai", "given" : "Chinatsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiwara", "given" : "Shinya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagiya", "given" : "Chihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosawa", "given" : "Masahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirota", "given" : "Tomoya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umehara", "given" : "Hisanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawakami", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sano", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsubota", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Yoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takamura", "given" : "Etsuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Ichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inoue", "given" : "Hiroko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Seiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moriyama", "given" : "Masafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Tsutomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yoshiya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirata", "given" : "Shintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mimori", "given" : "Tsuneyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshifuji", "given" : "Hajime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohta", "given" : "Akiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsumoto", "given" : "Isao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sumida", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "464-70", "title" : "Primary and secondary surveys on epidemiology of Sj\u00f6gren's syndrome in Japan.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "²⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }252014JapanJapan/ACR/2002Hospital-based0,05%NSNS: not specified; CI: confidence intervalTable 2. Clinical expression of Sj?gren syndrome in men in comparison with women: statistically-significant differences in the main studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajo.2015.06.004", "ISBN" : "0002-9394", "ISSN" : "1879-1891", "PMID" : "26093285", "abstract" : "PURPOSE: To report the ocular complications of primary Sj\u00f6gren's Syndrome (SS) in men.\\n\\nDESIGN: Retrospective cohort study.\\n\\nMETHODS: Setting: Tertiary-care SS center.\\n\\nPATIENT POPULATION: 163 consecutive primary Sj\u00f6gren's Syndrome patients evaluated between January 2007 and March 2013.\\n\\nMAIN OUTCOME MEASURE: Frequency of extraglandular ocular and systemic manifestations and serological results in men compared to women.\\n\\nRESULTS: 14 (9%) of the 163 primary Sj\u00f6gren's Syndrome patients were men. On initial presentation, men were a decade older (61 vs 50 years, p<0.01) and less likely than women to have a prior diagnosis of SS (43% vs 65%, p=0.09). A majority of men reported dry eye on presentation (92%), albeit less chronic compared to women (5.9 vs 10.8 years, p=0.07). Men were more likely to present with serious ocular complications than women (43% vs 11%, p=0.001). Extraglandular systemic complications of SS (i.e. vasculitis, interstitial nephritis) were also more common in men (64% vs 40%, p=0.07). Further, men were more likely to be negative for anti-SSA/Ro, anti-SSB/La, and antinuclear antibodies than women (36% men vs 11% women, p=0.01).\\n\\nCONCLUSION: Men with primary SS have a higher frequency of serious ocular and systemic manifestations. Although primary Sj\u00f6gren's Syndrome is typically considered a disease of middle-aged women, it may be underdiagnosed and consequentially more severe in men. Physicians should have a lower threshold to test for SS in men with dry eye.", "author" : [ { "dropping-particle" : "", "family" : "Mathews", "given" : "Priya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hessen", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grader-Beck", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birnbaum", "given" : "Julius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akpek", "given" : "Esen K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of ophthalmology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Ocular Complications of Primary Sj\u00f6gren's Syndrome in Men.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/ard.54.9.748", "ISSN" : "0003-4967", "PMID" : "7495348", "abstract" : "To describe the clinical expression of primary Sj\u00f6gren's syndrome (SS) in men, focusing on extraglandular manifestations (EGM) and serological markers of disease.", "author" : [ { "dropping-particle" : "", "family" : "Anaya", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "G T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Souza", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "748-51", "title" : "Primary Sj\u00f6gren's syndrome in men.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9175937", "abstract" : "OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sj\u00f6gren's syndrome (SS) patients.\n\nPATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.\n\nRESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.\n\nCONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.", "author" : [ { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsiakou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Politi", "given" : "E N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siamopoulou-Mavridou", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "page" : "333-5", "title" : "Subgroups of primary Sj\u00f6gren's syndrome. Sj\u00f6gren's syndrome in male and paediatric Greek patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0315-162X", "PMID" : "10555894", "abstract" : "To examine the clinical and serologic characteristics of 14 men compared to 28 women with primary Sj\u00f6gren's syndrome (SS) and contrast these findings with studies evaluating sex differences in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Brennan", "given" : "M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-4", "issue" : "11", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "2373-6", "title" : "Sex differences in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0961-2033", "PMID" : "10713648", "abstract" : "To determine the clinical and immunological characteristics of primary Sj\u00f6gren's syndrome (SS) in men from a large series of unselected patients with this condition.", "author" : [ { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morl\u00e0", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mu\u00f1oz", "given" : "F J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Artigues", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lupus", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "61-4", "title" : "Primary Sj\u00f6gren's syndrome in men: clinical and immunological characteristics.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "PMID" : "15229956", "abstract" : "OBJECTIVE: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease. It can be primary (pSS) or secondary (sSS) and is observed 90% more in women than in men, mainly in the fourth and fifth decades of life. We investigated the prevalence of serological and clinical manifestations in male and female patients with primary SS. METHODS: We analyzed 521 female and 28 male patients with pSS between 1993 and 2001. All patients fulfilled > or = 4 of the 1993 European Community Study Group criteria. RESULTS: Men presented higher concentrations of IgA, rheumatoid factor, and antinuclear antibodies than women. A higher percentage of women than men reported fibromyalgia, thyroidal manifestations, and carpal tunnel syndrome. There were no statistical differences between the 2 groups in relation to the presence of Raynaud's phenomenon, arthritis, erosive osteoarthritis, liver disease, or other visceral manifestations. CONCLUSION: The pattern of SS in our cohort of patients reveals a difference between male and female patients, in contrast with earlier studies.", "author" : [ { "dropping-particle" : "", "family" : "Diaz-Lopez", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geli", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corominas", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malat", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Torner", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Llobet", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Serna", "given" : "A R", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laiz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vazquez", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-6", "issue" : "7", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1352-1355", "title" : "Are there clinical or serological differences between male and female patients with primary Sjogren's syndrome?", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "ISSN" : "0300-9742", "abstract" : "OBJECTIVE: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient., METHODS: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study., RESULTS: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04)., CONCLUSION: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.", "author" : [ { "dropping-particle" : "", "family" : "Gondran", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauchais", "given" : "Al", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lambert", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ly", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launay", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Queyrel", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benazahari", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liozon", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loustaud-Ratti", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jauberteau", "given" : "Mo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Py", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "300-305", "title" : "Primary Sjogren's syndrome in men.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "", "ISBN" : "0770-3198", "ISSN" : "1434-9949", "PMID" : "2008546267", "abstract" : "The aim of the study was to define main symptoms of clinical appearance and immunoserological profile of male patients with primary Sjogren's syndrome (pSS). Four hundred and ninety-two patients fulfilling the European-American Consensus Criteria for pSS were involved in this study. The mean age of the patients was 55.93 years (55.67 years in women and 56.18 years in men). The female-male ratio was 7:1 (432 and 60 patients, respectively). At the time of the diagnosis of pSS, glandular, extraglandular manifestations (EGMs), and immunoserological parameters were assessed. The major EGMs differ between genders. Arthritis was frequently presented as EGM in both genders, but the ratio was higher in men (68% vs. 42%). Various vasculitis symptoms and lymphadenopathy were more frequent in men than in women, in contrast to Raynaud's phenomenon or autoimmune thyroiditis. Anti-SS-A and anti-SS-B were the most frequent autoantibodies in both genders, although autoantibodies against anti-nuclear factor and extractable nuclear antigens also presented in some patients. In a few cases, there were other specific autoantibodies correlated with EGMs, such as double-stranded DNA, anti-neutrophilic-cytoplasmic antibody, cyclic-citrullinated peptide, anti-thyreoglobuline antibodies, and anti-thyreoid-peroxidase antibodies. Based upon our large cohort of patients with pSS, we conclude that, although the disease is more frequent in women usually about climax, it develops also in men with the predominant symptoms of vasculitis or arthritis besides keratoconjunctivitis sicca or xerostomy. Clinical Rheumatology 2008.", "author" : [ { "dropping-particle" : "", "family" : "Horvath", "given" : "I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szodoray", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeher", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Rheumatology", "id" : "ITEM-8", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1479-1483", "title" : "Primary Sjogren's syndrome in men: Clinical and immunological characteristic based on a large cohort of Hungarian patients", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1097/MD.0b013e318181e6af", "ISBN" : "0025-7974 (Print)\\r0025-7974 (Linking)", "ISSN" : "0025-7974", "PMID" : "18626304", "abstract" : "We conducted the current study to characterize the clinical presentation of primary Sj\u00f6gren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gil", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pino-Montes", "given" : "Javier", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvo-Alen", "given" : "Jaime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Alonso", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mic\u00f3", "given" : "Maria-Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beltr\u00e1n", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belenguer", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "Lucio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "210-219", "title" : "Primary Sj\u00f6gren syndrome in Spain: clinical and immunologic expression in 1010 patients.", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^29\u201337", "plainTextFormattedCitation" : "29\u201337", "previouslyFormattedCitation" : "^29\u201337" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29–37Author (ref)YearCountryCriteriaIncreased frequencyDecreased frequencyAnaya et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.54.9.748", "ISSN" : "0003-4967", "PMID" : "7495348", "abstract" : "To describe the clinical expression of primary Sj\u00f6gren's syndrome (SS) in men, focusing on extraglandular manifestations (EGM) and serological markers of disease.", "author" : [ { "dropping-particle" : "", "family" : "Anaya", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "G T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Souza", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "748-51", "title" : "Primary Sj\u00f6gren's syndrome in men.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁰", "plainTextFormattedCitation" : "30", "previouslyFormattedCitation" : "³⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }301995US1995Systemic features-Drosos et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9175937", "abstract" : "OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sj\u00f6gren's syndrome (SS) patients.\n\nPATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.\n\nRESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.\n\nCONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.", "author" : [ { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsiakou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Politi", "given" : "E N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siamopoulou-Mavridou", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "page" : "333-5", "title" : "Subgroups of primary Sj\u00f6gren's syndrome. Sj\u00f6gren's syndrome in male and paediatric Greek patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³¹", "plainTextFormattedCitation" : "31", "previouslyFormattedCitation" : "³¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }311997Greece1993-ArthritisRaynaudANARoBrennan et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0315-162X", "PMID" : "10555894", "abstract" : "To examine the clinical and serologic characteristics of 14 men compared to 28 women with primary Sj\u00f6gren's syndrome (SS) and contrast these findings with studies evaluating sex differences in primary SS.", "author" : [ { "dropping-particle" : "", "family" : "Brennan", "given" : "M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "P C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "2373-6", "title" : "Sex differences in primary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³²", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }321999US1993-ANAFatigueRaised ESRCervera et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0961-2033", "PMID" : "10713648", "abstract" : "To determine the clinical and immunological characteristics of primary Sj\u00f6gren's syndrome (SS) in men from a large series of unselected patients with this condition.", "author" : [ { "dropping-particle" : "", "family" : "Cervera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Font", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Carrasco", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morl\u00e0", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mu\u00f1oz", "given" : "F J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Artigues", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelmo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lupus", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "61-4", "title" : "Primary Sj\u00f6gren's syndrome in men: clinical and immunological characteristics.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³³", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "³³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }332000Spain1993-ArticularDiaz-Lopez et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "PMID" : "15229956", "abstract" : "OBJECTIVE: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease. It can be primary (pSS) or secondary (sSS) and is observed 90% more in women than in men, mainly in the fourth and fifth decades of life. We investigated the prevalence of serological and clinical manifestations in male and female patients with primary SS. METHODS: We analyzed 521 female and 28 male patients with pSS between 1993 and 2001. All patients fulfilled > or = 4 of the 1993 European Community Study Group criteria. RESULTS: Men presented higher concentrations of IgA, rheumatoid factor, and antinuclear antibodies than women. A higher percentage of women than men reported fibromyalgia, thyroidal manifestations, and carpal tunnel syndrome. There were no statistical differences between the 2 groups in relation to the presence of Raynaud's phenomenon, arthritis, erosive osteoarthritis, liver disease, or other visceral manifestations. CONCLUSION: The pattern of SS in our cohort of patients reveals a difference between male and female patients, in contrast with earlier studies.", "author" : [ { "dropping-particle" : "", "family" : "Diaz-Lopez", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geli", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corominas", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malat", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Torner", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Llobet", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Serna", "given" : "A R", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laiz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vazquez", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1352-1355", "title" : "Are there clinical or serological differences between male and female patients with primary Sjogren's syndrome?", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁴", "plainTextFormattedCitation" : "34", "previouslyFormattedCitation" : "³⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }342004Spain1993RFANAFMThyroiditisCarpal tunnelGondran et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0300-9742", "abstract" : "OBJECTIVE: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient., METHODS: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study., RESULTS: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04)., CONCLUSION: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.", "author" : [ { "dropping-particle" : "", "family" : "Gondran", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauchais", "given" : "Al", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lambert", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ly", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launay", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Queyrel", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benazahari", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liozon", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loustaud-Ratti", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hachulla", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jauberteau", "given" : "Mo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatron", "given" : "Py", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of rheumatology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "300-305", "title" : "Primary Sjogren's syndrome in men.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁵", "plainTextFormattedCitation" : "35", "previouslyFormattedCitation" : "³⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }352008France2002ThrombocytopeniaLymphomaLymphopeniaLeukopeniaHorvath et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "", "ISBN" : "0770-3198", "ISSN" : "1434-9949", "PMID" : "2008546267", "abstract" : "The aim of the study was to define main symptoms of clinical appearance and immunoserological profile of male patients with primary Sjogren's syndrome (pSS). Four hundred and ninety-two patients fulfilling the European-American Consensus Criteria for pSS were involved in this study. The mean age of the patients was 55.93 years (55.67 years in women and 56.18 years in men). The female-male ratio was 7:1 (432 and 60 patients, respectively). At the time of the diagnosis of pSS, glandular, extraglandular manifestations (EGMs), and immunoserological parameters were assessed. The major EGMs differ between genders. Arthritis was frequently presented as EGM in both genders, but the ratio was higher in men (68% vs. 42%). Various vasculitis symptoms and lymphadenopathy were more frequent in men than in women, in contrast to Raynaud's phenomenon or autoimmune thyroiditis. Anti-SS-A and anti-SS-B were the most frequent autoantibodies in both genders, although autoantibodies against anti-nuclear factor and extractable nuclear antigens also presented in some patients. In a few cases, there were other specific autoantibodies correlated with EGMs, such as double-stranded DNA, anti-neutrophilic-cytoplasmic antibody, cyclic-citrullinated peptide, anti-thyreoglobuline antibodies, and anti-thyreoid-peroxidase antibodies. Based upon our large cohort of patients with pSS, we conclude that, although the disease is more frequent in women usually about climax, it develops also in men with the predominant symptoms of vasculitis or arthritis besides keratoconjunctivitis sicca or xerostomy. Clinical Rheumatology 2008.", "author" : [ { "dropping-particle" : "", "family" : "Horvath", "given" : "I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szodoray", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeher", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Rheumatology", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1479-1483", "title" : "Primary Sjogren's syndrome in men: Clinical and immunological characteristic based on a large cohort of Hungarian patients", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁶", "plainTextFormattedCitation" : "36", "previouslyFormattedCitation" : "³⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }362008Hungary2002VasculitisLymphadenopathyRaynaudThyroiditisRamos-Casals et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MD.0b013e318181e6af", "ISBN" : "0025-7974 (Print)\\r0025-7974 (Linking)", "ISSN" : "0025-7974", "PMID" : "18626304", "abstract" : "We conducted the current study to characterize the clinical presentation of primary Sj\u00f6gren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.", "author" : [ { "dropping-particle" : "", "family" : "Ramos-Casals", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solans", "given" : "Roser", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosas", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camps", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gil", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pino-Montes", "given" : "Javier", "non-dropping-particle" : "Del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvo-Alen", "given" : "Jaime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Alonso", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mic\u00f3", "given" : "Maria-Luisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beltr\u00e1n", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belenguer", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallar\u00e9s", "given" : "Lucio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "210-219", "title" : "Primary Sj\u00f6gren syndrome in Spain: clinical and immunologic expression in 1010 patients.", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }372008Spain2002-Altered ocular testsRaynaudThyroiditisANAMathews et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajo.2015.06.004", "ISBN" : "0002-9394", "ISSN" : "1879-1891", "PMID" : "26093285", "abstract" : "PURPOSE: To report the ocular complications of primary Sj\u00f6gren's Syndrome (SS) in men.\\n\\nDESIGN: Retrospective cohort study.\\n\\nMETHODS: Setting: Tertiary-care SS center.\\n\\nPATIENT POPULATION: 163 consecutive primary Sj\u00f6gren's Syndrome patients evaluated between January 2007 and March 2013.\\n\\nMAIN OUTCOME MEASURE: Frequency of extraglandular ocular and systemic manifestations and serological results in men compared to women.\\n\\nRESULTS: 14 (9%) of the 163 primary Sj\u00f6gren's Syndrome patients were men. On initial presentation, men were a decade older (61 vs 50 years, p<0.01) and less likely than women to have a prior diagnosis of SS (43% vs 65%, p=0.09). A majority of men reported dry eye on presentation (92%), albeit less chronic compared to women (5.9 vs 10.8 years, p=0.07). Men were more likely to present with serious ocular complications than women (43% vs 11%, p=0.001). Extraglandular systemic complications of SS (i.e. vasculitis, interstitial nephritis) were also more common in men (64% vs 40%, p=0.07). Further, men were more likely to be negative for anti-SSA/Ro, anti-SSB/La, and antinuclear antibodies than women (36% men vs 11% women, p=0.01).\\n\\nCONCLUSION: Men with primary SS have a higher frequency of serious ocular and systemic manifestations. Although primary Sj\u00f6gren's Syndrome is typically considered a disease of middle-aged women, it may be underdiagnosed and consequentially more severe in men. Physicians should have a lower threshold to test for SS in men with dry eye.", "author" : [ { "dropping-particle" : "", "family" : "Mathews", "given" : "Priya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hessen", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grader-Beck", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birnbaum", "given" : "Julius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akpek", "given" : "Esen K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of ophthalmology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "Ocular Complications of Primary Sj\u00f6gren's Syndrome in Men.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁹", "plainTextFormattedCitation" : "29", "previouslyFormattedCitation" : "²⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }292015US2002Older onset of the diseaseSevere ocular featuresSystemic featuresANA/Ro/LaANA, anti-nuclear antibodies; FM, Fibromyalgia; RF, rheumatoid factor.Table 3. Reported cases of primary Sj?gren syndrome in children (age < 14 years) since 1994ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9175937", "abstract" : "OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sj\u00f6gren's syndrome (SS) patients.\n\nPATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.\n\nRESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.\n\nCONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.", "author" : [ { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsiakou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Politi", "given" : "E N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siamopoulou-Mavridou", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "page" : "333-5", "title" : "Subgroups of primary Sj\u00f6gren's syndrome. Sj\u00f6gren's syndrome in male and paediatric Greek patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0008-4182", "PMID" : "7859177", "author" : [ { "dropping-particle" : "", "family" : "Rocha", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kavalec", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian journal of ophthalmology. Journal canadien d'ophtalmologie", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1994", "10" ] ] }, "page" : "234-7", "title" : "Sj\u00f6gren's syndrome in a child.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0315-162X VN - ", "abstract" : "To describe the clinical characteristics of juvenile Sj&#xF6;gren's syndrome (JSS) and report 5 new primary cases.", "author" : [ { "dropping-particle" : "", "family" : "Anaya", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "1152-1158", "title" : "Sj\u00f6gren's syndrome in childhood.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0022-3476", "PMID" : "8523198", "abstract" : "A 9-year-old girl had hemiparesis, and a diagnosis of primary Sj\u00f6gren syndrome was made. The neurologic dysfunction was multifocal, involving both the brain and spinal cord, and was recurrent; the findings mimicked multiple sclerosis. Corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial.", "author" : [ { "dropping-particle" : "", "family" : "Ohtsuka", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasegawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tatsuno", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takita", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arita", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okuyama", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of pediatrics", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "1995", "12" ] ] }, "page" : "961-3", "title" : "Central nervous system disease in a child with primary Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0960-7439", "PMID" : "9601239", "abstract" : "A 5-year-old boy of Pakistani parents first presented with rampant dental caries and later developed bilateral parotid gland enlargement accompanied by intermittent nocturnal fever, anorexia, lethargy and weight loss. Investigations revealed anaemia, hypergammaglobulinaemia, elevated non-specific indices of inflammation, a reduced Schirmer's test value, lymphocytic infiltration and some atrophy of the parotid gland. The parotid gland enlargement, low Schirmer's test value and salivary gland biopsy showing non-focal lymphocytic infiltration led to the diagnosis of primary Sjogren's syndrome. The present case report highlights the need for health professionals to be aware that Sjogren's syndrome is a possible, if rare, predisposing cause of rampant dental caries in children.", "author" : [ { "dropping-particle" : "", "family" : "Nathavitharana", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarlow", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bedi", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Southwood", "given" : "T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children", "id" : "ITEM-5", "issue" : "3", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "173-176", "title" : "Primary Sjogren's syndrome and rampant dental caries in a 5-year-old child.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "ISSN" : "0007-0963", "PMID" : "8555033", "abstract" : "We report four children with anti-Ro/SSA positive who presented with an annular erythema as a manifestation of Sj\u00f6gren's syndrome. One patient had an aseptic meningoencephalitis as well as cutaneous lesions. Children with annular erythema should be carefully followed for features of Sj\u00f6gren's syndrome, which is believed to be a rare condition in children.", "author" : [ { "dropping-particle" : "", "family" : "Miyagawa", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iida", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukumoto", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsunaga", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshioka", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shirai", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British journal of dermatology", "id" : "ITEM-6", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "page" : "779-82", "title" : "Anti-Ro/SSA-associated annular erythema in childhood.", "type" : "article-journal", "volume" : "133" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "ISSN" : "0392-856X", "abstract" : "OBJECTIVE: Ten new cases with primary Sjogren's syndrome (pSS) whose disease began before age 16 are described. Special attention is paid both to the follow-up and treatment of this condition., METHODS: Cases with juvenile pSS were retrospectively identified from our series of 180 pSS patients. Ocular, salivary, and extraglandular manifestations as well as a full laboratory evaluation including HLA-DR typing were retrieved., RESULTS: A disease prevalence of 5.5% (10 cases, 8 female and 2 male) was found in our series. The mean age at onset was 11.0 years, but the disease started at the age of 4 in 2 patients. At onset, parotid swelling was found in 6 cases and extraglandular manifestations in 3. Throughout the follow-up period (mean 48.6 months from the time of diagnosis), the clinical picture was similar to that of pSS in adults, but oral involvement was generally milder. Extraglandular manifestations were always present but never severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB antibodies) were found in all patients. Specifically, ANA and anti-SSA were always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and DR 52 were closely associated with the disease. Clinical outcome was difficult to predict; however, no serious complications have been observed so far. We obtained good results with low-dose steroids and/or hydroxychloroquine, especially with regard to the extraglandular manifestations and laboratory abnormalities., CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely resembles pSS in adults except for the extremely high prevalence of recurrent parotitis and immunological findings.", "author" : [ { "dropping-particle" : "", "family" : "Ostuni", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ianniello", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sfriso", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzola", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andretta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gambari", "given" : "P F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-7", "issue" : "6", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "689-693", "title" : "Juvenile onset of primary Sjogren's syndrome: report of 10 cases.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "ISBN" : "0374-5600 (Print)\\r0374-5600 (Linking)", "ISSN" : "0374-5600", "PMID" : "8942017", "abstract" : "A case of Sj\u00f6gren's syndrome with glomerulonephritis is presented. The patient was a 13 year old male with hematuria and proteinuria discovered by urine screening of school children. Evaluation showed no evidence of any associated connective tissue disease. Kidney biopsy was consistent with membranous glomerulonephritis. Sj\u00f6gren's syndrome with membranous glomerulonephritis is rare and the patient was the youngest case in the literature.", "author" : [ { "dropping-particle" : "", "family" : "Yoshida", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kume", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isome", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta paediatrica Japonica; Overseas edition", "id" : "ITEM-8", "issue" : "5", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "533-6", "title" : "Sj\u00f6gren's syndrome with membranous glomerulonephritis detected by urine screening of schoolchildren.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "ISSN" : "0340-6199", "PMID" : "8891560", "abstract" : "Sj\u00f6gren syndrome (SS) is a common disorder in adults and involves both glandular and extraglandular systems. We report here four cases of childhood SS complicated by chronic thyroiditis, interstitial nephritis or sweat gland inflammation. Additionally, in one of these cases, the central nervous system was involved. All of these complications are common in adult cases. CONCLUSION: Childhood SS is a systemic \"ductilitis\" or \"exocrinopathy\" with complications which are commonly observed in adult cases.", "author" : [ { "dropping-particle" : "", "family" : "Kobayashi", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furuta", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tame", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawamura", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kojima", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Endoh", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okano", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakiyama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pediatrics", "id" : "ITEM-9", "issue" : "10", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "890-4", "title" : "Complications of childhood Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "ISBN" : "0374-5600 (Print)", "abstract" : "An 8-year-old girl with hypergammaglobulinemia showed an abnormal 67gallium accumulation in the orbits and parotid glands. Although she did not have any subjective siccant complaints, reported typical histopathological and sialographic changes suggesting Sjogren's syndrome (SjS) were observed in the salivary glands. Gallium scintigram might be a valuable and non-invasive diagnostic tool in the diagnosis of children with SjS without sicca symptoms.", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onodera", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ito", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higuchi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monma", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waga", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Paediatr Jpn", "id" : "ITEM-10", "issue" : "6", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "621-623", "title" : "Subclinical Sjogren's syndrome: a significant 67gallium accumulation in the orbits and parotid glands", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "ISSN" : "0392-856X", "PMID" : "10410277", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (pSS) in childhood is a rare disease. Diagnostic criteria are available for adult patients only. In order to establish diagnostic criteria for juvenile pSS an analysis of 7 girls and one boy suffering from pSS with early onset is reported. Due to the rarity of the disease, data on patients with pSS reported in the literature are included in the proposal for modified diagnostic criteria.\n\nMETHODS: The diagnosis of pSS was established according to the criteria for adulthood pSS, duly modified, which include clinical symptoms and laboratory immunological evaluation.\n\nRESULTS: The average age of our patients at clinical onset was 13.5 years (range: 10-17 yrs.). Clinical signs included systemic (fever, fatigue) as well as local (parotitis, vulvovaginitis, conjunctivitis) symptoms. Paralysis due to hypokalemia linked to renal tubular acidosis and central nervous system (CNS) involvement was seen in one patient. Asymptomatic renal tubular acidosis was diagnosed in another 2 patients. Autoimmune hepatitis was present in 2 patients. All patients had laboratory abnormalities: hyperimmunoglobulinemia IgG, high titers of antinuclear antibodies (anti-SS-A and/or anti-SS-B) and elevated serum amylases. Sicca syndrome was never seen during childhood, although it developed later in 3 patients, after 7 to 10 years of follow-up.\n\nCONCLUSIONS: It has been stressed that the classical diagnostic criteria for adult Sj\u00f6gren's syndrome, especially sicca syndrome, are not applicable to a pediatric onset of the disease. On the other hand, the presence of typical laboratory abnormalities can allow the diagnosis of these patients in the early stages. Both laboratory and clinical symptoms typical for childhood are included in our proposal for diagnostic criteria applicable to juvenile pSS. Life-threatening conditions such as hypokalemic paralysis, CNS involvement and hepatitis may also occur in children. Sicca syndrome tends to develop much later in pediatric patients.", "author" : [ { "dropping-particle" : "", "family" : "Bart\u016fnkov\u00e1", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediv\u00e1", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vencovsk\u00fd", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tesar", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-11", "issue" : "3", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "381-6", "title" : "Primary Sj\u00f6gren's syndrome in children and adolescents: proposal for diagnostic criteria.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "ISSN" : "1079-2104", "PMID" : "10556760", "abstract" : "OBJECTIVE: The application of anamnestic data on siccative symptoms required for classifying adult Sj\u00f6gren's syndrome is limited in childhood. Instrumental test procedures are therefore necessary for objectively recording the oral and ophthalmologic manifestations of the disease. The aim of this study was to clarify the sialographic changes that occur in Sj\u00f6gren's syndrome in children.\n\nSTUDY DESIGN: A total of 23 sialograms were obtained with both conventional and digital subtraction techniques in 21 children with primary (10 girls and 1 boy) or secondary Sj\u00f6gren's syndrome (10 girls). The films were assessed by 3 physicians and submitted for a consensus analysis if necessary.\n\nRESULTS: The pathologic features observed in the children varied from a slightly narrowed ductal system to multiple peripheral ductal ectasias and completely destroyed parenchyma. Sialographic examinations demonstrate that, with progressing disease, regression of acinar dilatations and rarification of the ductal system occur.\n\nCONCLUSION: The results show that the spectrum of sialographically recordable lesions in Sj\u00f6gren's syndrome in children is greater than is described thus far in the literature.", "author" : [ { "dropping-particle" : "", "family" : "Stiller", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golder", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6ring", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kliem", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics", "id" : "ITEM-12", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "11" ] ] }, "page" : "620-7", "title" : "Diagnostic value of sialography with both the conventional and digital subtraction techniques in children with primary and secondary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-13", "itemData" : { "ISSN" : "0340-6199", "PMID" : "10968247", "abstract" : "Complications observed in adulthood Sj\u00f6gren syndrome also occur in the childhood disease and suggest that Sj\u00f6gren syndrome should be considered as a cause of neuropathy in children. Treatment with corticosteroid is a choice for such cases.", "author" : [ { "dropping-particle" : "", "family" : "Kumon", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satake", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mizumoto", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishikawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pediatrics", "id" : "ITEM-13", "issue" : "8", "issued" : { "date-parts" : [ [ "2000", "8" ] ] }, "page" : "630-1", "title" : "A case of sensory neuropathy associated with childhood Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "159" }, "uris" : [ "" ] }, { "id" : "ITEM-14", "itemData" : { "DOI" : "10.1177/088307380101600911", "ISSN" : "0883-0738", "abstract" : "We describe a case of pediatric Sjogren's syndrome with progressive neurologic involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal syndrome. After being stable with facial diplegia and swelling for 5 years, she acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic findings confirmed primary Sjogren's syndrome. She responded well to intravenous methylprednisolone, with subsequent clinical improvement and MRI resolution. This report reviews the pediatric literature and underscores the importance of considering Sjogren's syndrome in a child with unexplained facial weakness and in the differential diagnosis of pediatric stroke.", "author" : [ { "dropping-particle" : "", "family" : "Gottfried", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Hunter", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentieri", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "R S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of child neurology", "id" : "ITEM-14", "issue" : "9", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "683-685", "title" : "Central nervous system Sjogren's syndrome in a child: case report and review of the literature.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-15", "itemData" : { "DOI" : "10.1016/S1079-2104(03)00159-8", "ISSN" : "10792104", "PMID" : "12847443", "abstract" : "Sj??gren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition. The purpose of this study is to report a case of primary SS (PSS) in a 4-year-old Venezuelan girl and to review the pertinent literature. The patient presented with bilateral recurrent parotid enlargement, predominantly on the right side. She did not complain of dry mouth or eyes; however, decreased stimulated salivary flow rate and positive Schirmer and rose bengal tests were obtained. Sialography, sonograms, and a computed tomography scan of the parotid glands revealed pathologic changes consistent with SS. Anti-SS-A and anti-SS-B antibodies were present. Evaluation for antibodies against cytomegalovirus, Epstein-Barr virus, and HIV rendered negative results. Histopathologic examination of incisional biopsies of the right parotid and labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. Taken together, these findings are consistent with the diagnosis of juvenile PSS. The salient features of this rare disease are summarized on the basis of a comprehensive review of the epidemiologic, clinical, and serologic findings of the previously reported cases of PSS in children.", "author" : [ { "dropping-particle" : "", "family" : "Nikitakis", "given" : "Nikolaos G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lariccia", "given" : "Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papadimitriou", "given" : "John C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sauk", "given" : "John J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics", "id" : "ITEM-15", "issue" : "1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "42-47", "title" : "Primary Sjogren syndrome in childhood: Report of a case and review of the literature", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] }, { "id" : "ITEM-16", "itemData" : { "ISBN" : "0315-162X (Print)\\n0315-162X (Linking)", "PMID" : "11327263", "abstract" : "OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific for adult Sjogren's syndrome (SS) in patients with juvenile onset SS. METHODS: Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11 cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha-fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis. In contrast, reactivity was found in only 2 of the 16 patients with SLE. The clinical features of the 15 patients with juvenile onset SS were very specific; only 4 patients complained of dryness, while 6 had abnormal excretion ability. Salivary gland enlargement was the most common clinical manifestation. Characteristic laboratory findings in juvenile onset SS included a higher prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid factor, as well as increased erythrocyte sedimentation rate and hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be the same as that of adult SS, although subjective symptoms of dryness are less frequent in juvenile cases. This discrepancy may indicate that SS is a slowly progressive disease with a long time span. The anti-alpha-fodrin antibody is likely to be a reliable diagnostic marker for juvenile SS.", "author" : [ { "dropping-particle" : "", "family" : "Maeno", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imanaka", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayashi", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyata", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-16", "issue" : "4", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "860-864", "title" : "Anti-alpha-fodrin antibodies in Sjogren's syndrome in children", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] }, { "id" : "ITEM-17", "itemData" : { "ISSN" : "0886-4470", "PMID" : "12431170", "abstract" : "OBJECTIVES: To describe our experience with primary and secondary Sj\u00f6gren syndrome (SS) in the pediatric population and to evaluate the effectiveness of parotid gland biopsy in the diagnosis of pediatric SS.\n\nDESIGN: Case series review of 6 pediatric patients evaluated during a 4-year period with varied head and neck manifestations of SS.\n\nSETTING: Tertiary care children's hospital.\n\nPATIENTS: Six children (4 boys and 2 girls) ranging in age from 6 to 12 years, who were diagnosed as having primary or secondary SS.\n\nINTERVENTION: Six minor salivary gland and 4 parotid gland biopsies for pathologic examination.\n\nMAIN OUTCOME MEASURES: Pathologic examination of salivary tissue consistent with SS.\n\nRESULTS: All 6 patients underwent minor salivary gland biopsy, 2 (33%) were consistent with SS, while the remaining 4 (67%) were nondiagnostic. The 4 patients with nondiagnostic minor salivary gland biopsy results went on to have parotid biopsies, of which all 4 had histologic findings consistent with SS. No complications were encountered.\n\nCONCLUSION: Parotid gland biopsy is an effective and safe means of obtaining salivary gland tissue for histologic evaluation of SS in the pediatric population.", "author" : [ { "dropping-particle" : "", "family" : "McGuirt", "given" : "William F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whang", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreland", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-17", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "11" ] ] }, "page" : "1279-81", "title" : "The role of parotid biopsy in the diagnosis of pediatric Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] }, { "id" : "ITEM-18", "itemData" : { "DOI" : "10.1007/s00431-003-1277-9", "ISSN" : "1432-1076", "PMID" : "12898241", "abstract" : "Primary Sj\u00f6gren syndrome (SS) is very rare in childhood. We collected a series of primary paediatric SS cases from different centres. A data collection form was prepared and sent to rheumatologists who were willing to participate. Data on 40 cases of primary SS with onset before the 16th birthday were collected. Almost all patients (35/40) were females, age at onset varied from 9.3 to 12.4 years (mean 10.7 years). Signs and symptoms at disease onset were mainly recurrent parotid swelling followed by sicca symptoms. Abnormal laboratory tests were found in the majority of cases. Regarding treatment, 22 patients were treated at some time with oral corticosteroids, seven with non-steroidal anti-inflammatory drugs, and five with hydroxychloroquine; two patients needed cyclosporine and one cyclophosphamide. Follow-up varied from 0 to 7.5 years from onset, without major complications in the majority of patients. CONCLUSION: recurrent parotid swelling is a common feature of primary Sj\u00f6gren syndrome in childhood and often occurs as a presenting feature. Sicca symptoms may be rarer.", "author" : [ { "dropping-particle" : "", "family" : "Cimaz", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadei", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartunkova", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediva", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falcini", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picco", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taglietti", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zulian", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cate", "given" : "R", "non-dropping-particle" : "Ten", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sztajnbok", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voulgari", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Pediatrics", "id" : "ITEM-18", "issue" : "10", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "661-665", "title" : "Primary Sj\u00f6gren syndrome in the paediatric age: a multicentre survey", "type" : "article-journal", "volume" : "162" }, "uris" : [ "" ] }, { "id" : "ITEM-19", "itemData" : { "ISBN" : "1110-4902 (Print)", "PMID" : "15724389", "abstract" : "Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P < 0.05). There was no statistically significant difference of levels of ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine screening of alpha fodrin antibodies is a valuable tool for the diagnosis of SS.", "author" : [ { "dropping-particle" : "", "family" : "Lawind", "given" : "M F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alyasky", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elwan", "given" : "N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mourad", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Bendary", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Egypt J Immunol", "id" : "ITEM-19", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "75-81", "title" : "Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-20", "itemData" : { "DOI" : "0315162X-32-1603 [pii]", "ISBN" : "0315-162X", "PMID" : "16078341", "abstract" : "Primary Sjogren's syndrome (pSS) is uncommonly recognized in childhood, and familial cases are rare. Pulmonary involvement in pediatric pSS is infrequently reported. In adults, asymptomatic pulmonary involvement is increasingly recognized, manifest by pulmonary function test abnormalities and changes on high resolution computerized tomographic scan. We describe a case of pSS in a 14-year-old Vietnamese-Canadian girt who presented with pulmonary symptoms, radiologic changes, and biopsy confirmation of lymphocytic interstitial pneumonia. Her dizygotic twin sister has primary SS without extraglandular manifestations. To our knowledge this is the first report of pediatric pSS with lymphocytic interstitial pneumonia and multiple pulmonary nodules on chest radiograph, We review the literature on pulmonary involvement and familial cases of pSS in childhood", "author" : [ { "dropping-particle" : "", "family" : "Houghton", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabral", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petty", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "L B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Rheumatology", "id" : "ITEM-20", "issue" : "8", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1603-1606", "title" : "Primary Sjogren's syndrome in dizygotic adolescent twins: One case with lymphocytic interstitial pneumonia", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-21", "itemData" : { "DOI" : "0315162X-32-2225 [pii]", "ISBN" : "0315-162X (Print)\\r0315-162X (Linking)", "PMID" : "16265707", "abstract" : "OBJECTIVE: To compare the proposed criteria for the diagnosis of primary Sjogren's syndrome (pSS) in childhood to the validated American-European Consensus Group (AECG) classification criteria for pSS in adults. METHODS: Charts of 7 children with pSS seen at British Columbia's Children's Hospital (BCCH) and data on 128 children identified through Medline in the English language literature between 1963 and 2003 were reviewed for pediatric and AECG criteria for pSS. The presence of > or = 4 criteria was required to satisfy the respective classification criteria. The expert clinical opinion of pediatric rheumatologists was considered the gold standard for diagnosis. RESULTS: A total of 24/62 (39%) cases satisfied the AECG criteria; 47/62 (76%) satisfied the proposed pediatric criteria. Inclusion of recurrent parotitis increased the sensitivity of the pediatric clinical criteria. From the cases, 78/133 (59%) satisfied the pediatric oral symptom criteria; only 6/78 (8%) had xerostomia in the absence of recurrent parotitis. There was no reported case of recurrent conjunctivitis in the absence of keratoconjunctivitis sicca. We found 101/130 (78%) cases had at least one positive autoantibody test result [antinuclear antibodies (ANA), rheumatoid factor (RF), SSA, SSB]; 78/123 (63%) had autoantibodies to SSA or SSB. CONCLUSION: The AECG adult criteria for pSS should not be applied to children as the sensitivity is unacceptably low. The inclusion of recurrent parotitis increases the sensitivity of the pediatric criteria, and recurrent parotitis should alert the clinician to the possibility of pSS. The inclusion of recurrent conjunctivitis did not improve the sensitivity over the AECG ocular criteria. The addition of ANA and RF to the AECG criteria did not change the number of patients satisfying the criteria for pediatric pSS.", "author" : [ { "dropping-particle" : "", "family" : "Houghton", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malleson", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabral", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petty", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-21", "issue" : "11", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2225-2232", "title" : "Primary Sjogren's syndrome in children and adolescents: are proposed diagnostic criteria applicable?", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-22", "itemData" : { "DOI" : "10.1093/rheumatology/kei175", "ISSN" : "1462-0324", "PMID" : "16352643", "author" : [ { "dropping-particle" : "", "family" : "Ohlsson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strike", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James-Ellison", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tizard", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Ramanan", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-22", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "2" ] ] }, "page" : "238-40", "title" : "Renal tubular acidosis, arthritis and autoantibodies: primary Sj\u00f6gren's syndrome in childhood.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-23", "itemData" : { "DOI" : "10.1007/s10067-005-0042-z", "ISSN" : "0770-3198", "PMID" : "16391885", "abstract" : "Tumor necrosis factor alpha (TNFalpha) blockade has recently been found to be ineffective in treating glandular and extraglandular manifestations of adult Sj\u00f6gren syndrome (SS), including arthralgia and arthritis. We report a girl who developed purpura, polyarthritis, uveitis, and severe dental caries in the first year of life and optic neuritis by age three. SS was diagnosed at 11 years of age, when severe hypokalemic renal tubular acidosis developed during infliximab treatment for arthritis. In contrast to her other disease manifestations, the arthritis responded remarkably well to TNFalpha blockade, suggesting that TNFalpha blockers may have a role in the treatment of arthritis with pediatric SS.", "author" : [ { "dropping-particle" : "", "family" : "Pessler", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monash", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rettig", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forbes", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreiger", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cron", "given" : "R Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical rheumatology", "id" : "ITEM-23", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "9" ] ] }, "page" : "746-8", "title" : "Sj\u00f6gren syndrome in a child: favorable response of the arthritis to TNFalpha blockade.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-24", "itemData" : { "abstract" : "Primary Sjogren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjogren syndrome antigen A, and anti-Sjogren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of PSS", "author" : [ { "dropping-particle" : "", "family" : "Civilibal", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canpolat", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yurt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurugoglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdamar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagci", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sever", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasapcopur", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caliskan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arisoy", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Pediatrics", "id" : "ITEM-24", "issue" : "8", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "738-742", "title" : "A child with primary Sjogren syndrome and a review of the literature", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-25", "itemData" : { "DOI" : "10.1007/s10165-010-0313-7", "ISBN" : "1439-7609 (Electronic)\\r1439-7595 (Linking)", "ISSN" : "1439-7609", "PMID" : "20517630", "abstract" : "The number of patients with juvenile-onset Sj\u00f6gren's syndrome (SS) has recently increased. However, there is no drug that is safe and effective for the xerostomia that occurs in patients of this age group. We evaluated the efficacy and safety of orally administered pilocarpine hydrochloride for juvenile-onset SS patients. Five female patients, aged from 9 to 16 years, received 5-10 mg/day for 4 weeks. On days 1 and 28, salivary production was measured by the Saxon test, and patients completed subjective self-evaluations of xerostomia symptoms and were asked about changes in water intake and overall improvement of dry mouth on day 28. After 4 weeks of pilocarpine administration, salivary production increased significantly in all patients, and overall status was assessed as \"improved\" in all patients. One patient had excessive sweating. No serious adverse events or laboratory examination abnormalities correlated with pilocarpine administration were found. In conclusion, the results of this study suggest that orally administered pilocarpine is safe and effective for treating xerostomia in juvenile-onset SS patients. This is the first report of the efficacy of pilocarpine for juvenile SS patients; further evaluations are needed to confirm our result.", "author" : [ { "dropping-particle" : "", "family" : "Tomiita", "given" : "Minako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "Syuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuwada", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nonaka", "given" : "Yukiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Kimiyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimojo", "given" : "Naoki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Yoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-25", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "486-90", "title" : "Efficacy and safety of orally administered pilocarpine hydrochloride for patients with juvenile-onset Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-26", "itemData" : { "DOI" : "10.1007/s00467-009-1358-8", "ISSN" : "1432-198X", "PMID" : "19902265", "author" : [ { "dropping-particle" : "", "family" : "Jung", "given" : "Seong Kwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyu Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yim", "given" : "Hyung Eun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoo", "given" : "Kee Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Young Sook", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Joo Won", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Won", "given" : "Nam Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric nephrology (Berlin, Germany)", "id" : "ITEM-26", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "567-8", "title" : "Primary Sj\u00f6gren's syndrome with mesangial proliferative glomerulonephritis and IgA deposits in a child.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-27", "itemData" : { "ISSN" : "1980-5322", "PMID" : "22086534", "author" : [ { "dropping-particle" : "", "family" : "Longhi", "given" : "Barbara S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Appenzeller", "given" : "Simone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centeville", "given" : "Maraisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gusm\u00e3o", "given" : "Reinaldo J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marini", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinics (S\u00e3o Paulo, Brazil)", "id" : "ITEM-27", "issue" : "11", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "1991-3", "title" : "Primary Sj\u00f6gren's syndrome in children: is a family approach indicated?", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-28", "itemData" : { "ISSN" : "0392-856X", "PMID" : "24847722", "abstract" : "Primary Sj\u00f6gren's syndrome (pSS) is a systemic autoimmune disease uncommon in children, clinically characterized by recurrent parotitis at the onset, which is a common disorder in childhood, most of them of infectious origin. Juvenile pSS diagnosis is based on clinical symptoms and presence of autoantibodies, after exclusion of infectious or lymphoproliferative diseases. However, salivary gland ultrasound (SGU) shows typical features of pSS that can add useful information for the diagnosis of this disorder. We describe three patients who presented with recurrent parotitis in which characteristic autoantibodies and typical SGU pattern allow us to make the diagnosis of juvenile pSS. We suggest that in children with recurrent parotitis SGU and autoantibodies should be routinely performed.", "author" : [ { "dropping-particle" : "", "family" : "Nieto-Gonz\u00e1lez", "given" : "Juan Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monteagudo", "given" : "Indalecio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bello", "given" : "Natalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Estupi\u00f1an", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naredo", "given" : "Esperanza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carre\u00f1o", "given" : "Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-28", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Salivary gland ultrasound in children: a useful tool in the diagnosis of juvenile Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-29", "itemData" : { "DOI" : "10.3899/jrheum.131511", "ISSN" : "0315-162X", "PMID" : "24786923", "abstract" : "OBJECTIVE: To determine an appropriate focus score cutoff for childhood Sj\u00f6gren syndrome (SS).\\n\\nMETHODS: Labial salivary gland tissue from specimens from children with SS and age-matched controls was retrospectively identified and reviewed by a blinded oral pathologist.\\n\\nRESULTS: The presence of any focal sialadenitis (focus score > 0 foci/4 mm(2)) was common among childhood SS samples but present in only 1 of 8 control samples.\\n\\nCONCLUSION: The presence of any focal lymphocytic sialadenitis in minor labial salivary gland tissue is suggestive of childhood SS and should be included in future childhood SS-specific diagnostic or classification criteria.", "author" : [ { "dropping-particle" : "", "family" : "Yokogawa", "given" : "Naoto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieberman", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alawi", "given" : "Faizan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bout-Tabaku", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guttenberg", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherry", "given" : "David D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vivino", "given" : "Frederick B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-29", "issue" : "6", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1178-82", "title" : "Comparison of labial minor salivary gland biopsies from childhood Sj\u00f6gren syndrome and age-matched controls.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{31,40\u201367}", "plainTextFormattedCitation" : "31,40\u201367", "previouslyFormattedCitation" : "^{31,40\u201367}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,40–67Author (ref)YearNFemaleMean age (years)Parotid enlargem.(n)Oral dryness (n)Ocular dryness (n)ANA+ (n)RF+ (n)Ro/SS-A+ (n)La/SS-B+ (n)Rocha et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0008-4182", "PMID" : "7859177", "author" : [ { "dropping-particle" : "", "family" : "Rocha", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kavalec", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian journal of ophthalmology. Journal canadien d'ophtalmologie", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1994", "10" ] ] }, "page" : "234-7", "title" : "Sj\u00f6gren's syndrome in a child.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁰", "plainTextFormattedCitation" : "40", "previouslyFormattedCitation" : "⁴⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }40199411101111110Anaya et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0315-162X VN - ", "abstract" : "To describe the clinical characteristics of juvenile Sj&#xF6;gren's syndrome (JSS) and report 5 new primary cases.", "author" : [ { "dropping-particle" : "", "family" : "Anaya", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talal", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "1152-1158", "title" : "Sj\u00f6gren's syndrome in childhood.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴¹", "plainTextFormattedCitation" : "41", "previouslyFormattedCitation" : "⁴¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }41199539308,937262722201210Ohtsuka et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0022-3476", "PMID" : "8523198", "abstract" : "A 9-year-old girl had hemiparesis, and a diagnosis of primary Sj\u00f6gren syndrome was made. The neurologic dysfunction was multifocal, involving both the brain and spinal cord, and was recurrent; the findings mimicked multiple sclerosis. Corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial.", "author" : [ { "dropping-particle" : "", "family" : "Ohtsuka", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasegawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tatsuno", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takita", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arita", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okuyama", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of pediatrics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1995", "12" ] ] }, "page" : "961-3", "title" : "Central nervous system disease in a child with primary Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴²", "plainTextFormattedCitation" : "42", "previouslyFormattedCitation" : "⁴²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4219951191111111Nathavitharana et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0960-7439", "PMID" : "9601239", "abstract" : "A 5-year-old boy of Pakistani parents first presented with rampant dental caries and later developed bilateral parotid gland enlargement accompanied by intermittent nocturnal fever, anorexia, lethargy and weight loss. Investigations revealed anaemia, hypergammaglobulinaemia, elevated non-specific indices of inflammation, a reduced Schirmer's test value, lymphocytic infiltration and some atrophy of the parotid gland. The parotid gland enlargement, low Schirmer's test value and salivary gland biopsy showing non-focal lymphocytic infiltration led to the diagnosis of primary Sjogren's syndrome. The present case report highlights the need for health professionals to be aware that Sjogren's syndrome is a possible, if rare, predisposing cause of rampant dental caries in children.", "author" : [ { "dropping-particle" : "", "family" : "Nathavitharana", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarlow", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bedi", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Southwood", "given" : "T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "173-176", "title" : "Primary Sjogren's syndrome and rampant dental caries in a 5-year-old child.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴³", "plainTextFormattedCitation" : "43", "previouslyFormattedCitation" : "⁴³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4319951051010000Miyagawa et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0007-0963", "PMID" : "8555033", "abstract" : "We report four children with anti-Ro/SSA positive who presented with an annular erythema as a manifestation of Sj\u00f6gren's syndrome. One patient had an aseptic meningoencephalitis as well as cutaneous lesions. Children with annular erythema should be carefully followed for features of Sj\u00f6gren's syndrome, which is believed to be a rare condition in children.", "author" : [ { "dropping-particle" : "", "family" : "Miyagawa", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iida", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukumoto", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsunaga", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshioka", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shirai", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British journal of dermatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "page" : "779-82", "title" : "Anti-Ro/SSA-associated annular erythema in childhood.", "type" : "article-journal", "volume" : "133" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁴", "plainTextFormattedCitation" : "44", "previouslyFormattedCitation" : "⁴⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }44199544113134343Ostuni et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "abstract" : "OBJECTIVE: Ten new cases with primary Sjogren's syndrome (pSS) whose disease began before age 16 are described. Special attention is paid both to the follow-up and treatment of this condition., METHODS: Cases with juvenile pSS were retrospectively identified from our series of 180 pSS patients. Ocular, salivary, and extraglandular manifestations as well as a full laboratory evaluation including HLA-DR typing were retrieved., RESULTS: A disease prevalence of 5.5% (10 cases, 8 female and 2 male) was found in our series. The mean age at onset was 11.0 years, but the disease started at the age of 4 in 2 patients. At onset, parotid swelling was found in 6 cases and extraglandular manifestations in 3. Throughout the follow-up period (mean 48.6 months from the time of diagnosis), the clinical picture was similar to that of pSS in adults, but oral involvement was generally milder. Extraglandular manifestations were always present but never severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB antibodies) were found in all patients. Specifically, ANA and anti-SSA were always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and DR 52 were closely associated with the disease. Clinical outcome was difficult to predict; however, no serious complications have been observed so far. We obtained good results with low-dose steroids and/or hydroxychloroquine, especially with regard to the extraglandular manifestations and laboratory abnormalities., CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely resembles pSS in adults except for the extremely high prevalence of recurrent parotitis and immunological findings.", "author" : [ { "dropping-particle" : "", "family" : "Ostuni", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ianniello", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sfriso", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzola", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andretta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gambari", "given" : "P F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "689-693", "title" : "Juvenile onset of primary Sjogren's syndrome: report of 10 cases.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁵", "plainTextFormattedCitation" : "45", "previouslyFormattedCitation" : "⁴⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4519961081110310107109Yoshida et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0374-5600 (Print)\\r0374-5600 (Linking)", "ISSN" : "0374-5600", "PMID" : "8942017", "abstract" : "A case of Sj\u00f6gren's syndrome with glomerulonephritis is presented. The patient was a 13 year old male with hematuria and proteinuria discovered by urine screening of school children. Evaluation showed no evidence of any associated connective tissue disease. Kidney biopsy was consistent with membranous glomerulonephritis. Sj\u00f6gren's syndrome with membranous glomerulonephritis is rare and the patient was the youngest case in the literature.", "author" : [ { "dropping-particle" : "", "family" : "Yoshida", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kume", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isome", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta paediatrica Japonica; Overseas edition", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "533-6", "title" : "Sj\u00f6gren's syndrome with membranous glomerulonephritis detected by urine screening of schoolchildren.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁶", "plainTextFormattedCitation" : "46", "previouslyFormattedCitation" : "⁴⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46199610131001NA11Kobayashi et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0340-6199", "PMID" : "8891560", "abstract" : "Sj\u00f6gren syndrome (SS) is a common disorder in adults and involves both glandular and extraglandular systems. We report here four cases of childhood SS complicated by chronic thyroiditis, interstitial nephritis or sweat gland inflammation. Additionally, in one of these cases, the central nervous system was involved. All of these complications are common in adult cases. CONCLUSION: Childhood SS is a systemic \"ductilitis\" or \"exocrinopathy\" with complications which are commonly observed in adult cases.", "author" : [ { "dropping-particle" : "", "family" : "Kobayashi", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furuta", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tame", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawamura", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kojima", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Endoh", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okano", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakiyama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pediatrics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "890-4", "title" : "Complications of childhood Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁷", "plainTextFormattedCitation" : "47", "previouslyFormattedCitation" : "⁴⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4719962210,52NA11221Drosos et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4967", "PMID" : "9175937", "abstract" : "OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sj\u00f6gren's syndrome (SS) patients.\n\nPATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients.\n\nRESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.\n\nCONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.", "author" : [ { "dropping-particle" : "", "family" : "Drosos", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsiakou", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsifetaki", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Politi", "given" : "E N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siamopoulou-Mavridou", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "page" : "333-5", "title" : "Subgroups of primary Sj\u00f6gren's syndrome. Sj\u00f6gren's syndrome in male and paediatric Greek patients.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³¹", "plainTextFormattedCitation" : "31", "previouslyFormattedCitation" : "³¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31199713119,410NANA9674Tanaka et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0374-5600 (Print)", "abstract" : "An 8-year-old girl with hypergammaglobulinemia showed an abnormal 67gallium accumulation in the orbits and parotid glands. Although she did not have any subjective siccant complaints, reported typical histopathological and sialographic changes suggesting Sjogren's syndrome (SjS) were observed in the salivary glands. Gallium scintigram might be a valuable and non-invasive diagnostic tool in the diagnosis of children with SjS without sicca symptoms.", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onodera", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ito", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higuchi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monma", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waga", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Paediatr Jpn", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "621-623", "title" : "Subclinical Sjogren's syndrome: a significant 67gallium accumulation in the orbits and parotid glands", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁸", "plainTextFormattedCitation" : "48", "previouslyFormattedCitation" : "⁴⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4819981181001011Bartunkova et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "PMID" : "10410277", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (pSS) in childhood is a rare disease. Diagnostic criteria are available for adult patients only. In order to establish diagnostic criteria for juvenile pSS an analysis of 7 girls and one boy suffering from pSS with early onset is reported. Due to the rarity of the disease, data on patients with pSS reported in the literature are included in the proposal for modified diagnostic criteria.\n\nMETHODS: The diagnosis of pSS was established according to the criteria for adulthood pSS, duly modified, which include clinical symptoms and laboratory immunological evaluation.\n\nRESULTS: The average age of our patients at clinical onset was 13.5 years (range: 10-17 yrs.). Clinical signs included systemic (fever, fatigue) as well as local (parotitis, vulvovaginitis, conjunctivitis) symptoms. Paralysis due to hypokalemia linked to renal tubular acidosis and central nervous system (CNS) involvement was seen in one patient. Asymptomatic renal tubular acidosis was diagnosed in another 2 patients. Autoimmune hepatitis was present in 2 patients. All patients had laboratory abnormalities: hyperimmunoglobulinemia IgG, high titers of antinuclear antibodies (anti-SS-A and/or anti-SS-B) and elevated serum amylases. Sicca syndrome was never seen during childhood, although it developed later in 3 patients, after 7 to 10 years of follow-up.\n\nCONCLUSIONS: It has been stressed that the classical diagnostic criteria for adult Sj\u00f6gren's syndrome, especially sicca syndrome, are not applicable to a pediatric onset of the disease. On the other hand, the presence of typical laboratory abnormalities can allow the diagnosis of these patients in the early stages. Both laboratory and clinical symptoms typical for childhood are included in our proposal for diagnostic criteria applicable to juvenile pSS. Life-threatening conditions such as hypokalemic paralysis, CNS involvement and hepatitis may also occur in children. Sicca syndrome tends to develop much later in pediatric patients.", "author" : [ { "dropping-particle" : "", "family" : "Bart\u016fnkov\u00e1", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediv\u00e1", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vencovsk\u00fd", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tesar", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "381-6", "title" : "Primary Sj\u00f6gren's syndrome in children and adolescents: proposal for diagnostic criteria.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁹", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4919998713,53648786Stiller et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1079-2104", "PMID" : "10556760", "abstract" : "OBJECTIVE: The application of anamnestic data on siccative symptoms required for classifying adult Sj\u00f6gren's syndrome is limited in childhood. Instrumental test procedures are therefore necessary for objectively recording the oral and ophthalmologic manifestations of the disease. The aim of this study was to clarify the sialographic changes that occur in Sj\u00f6gren's syndrome in children.\n\nSTUDY DESIGN: A total of 23 sialograms were obtained with both conventional and digital subtraction techniques in 21 children with primary (10 girls and 1 boy) or secondary Sj\u00f6gren's syndrome (10 girls). The films were assessed by 3 physicians and submitted for a consensus analysis if necessary.\n\nRESULTS: The pathologic features observed in the children varied from a slightly narrowed ductal system to multiple peripheral ductal ectasias and completely destroyed parenchyma. Sialographic examinations demonstrate that, with progressing disease, regression of acinar dilatations and rarification of the ductal system occur.\n\nCONCLUSION: The results show that the spectrum of sialographically recordable lesions in Sj\u00f6gren's syndrome in children is greater than is described thus far in the literature.", "author" : [ { "dropping-particle" : "", "family" : "Stiller", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golder", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6ring", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kliem", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "11" ] ] }, "page" : "620-7", "title" : "Diagnostic value of sialography with both the conventional and digital subtraction techniques in children with primary and secondary Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁰", "plainTextFormattedCitation" : "50", "previouslyFormattedCitation" : "⁵⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }50200011109,56NA87343Kumon et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0340-6199", "PMID" : "10968247", "abstract" : "Complications observed in adulthood Sj\u00f6gren syndrome also occur in the childhood disease and suggest that Sj\u00f6gren syndrome should be considered as a cause of neuropathy in children. Treatment with corticosteroid is a choice for such cases.", "author" : [ { "dropping-particle" : "", "family" : "Kumon", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satake", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mizumoto", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishikawa", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pediatrics", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2000", "8" ] ] }, "page" : "630-1", "title" : "A case of sensory neuropathy associated with childhood Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "159" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵¹", "plainTextFormattedCitation" : "51", "previouslyFormattedCitation" : "⁵¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }51200011140011111Gottfried et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/088307380101600911", "ISSN" : "0883-0738", "abstract" : "We describe a case of pediatric Sjogren's syndrome with progressive neurologic involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal syndrome. After being stable with facial diplegia and swelling for 5 years, she acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic findings confirmed primary Sjogren's syndrome. She responded well to intravenous methylprednisolone, with subsequent clinical improvement and MRI resolution. This report reviews the pediatric literature and underscores the importance of considering Sjogren's syndrome in a child with unexplained facial weakness and in the differential diagnosis of pediatric stroke.", "author" : [ { "dropping-particle" : "", "family" : "Gottfried", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Hunter", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpentieri", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "R S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of child neurology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "683-685", "title" : "Central nervous system Sjogren's syndrome in a child: case report and review of the literature.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵²", "plainTextFormattedCitation" : "52", "previouslyFormattedCitation" : "⁵²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5220011141111010Maeno et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0315-162X (Print)\\n0315-162X (Linking)", "PMID" : "11327263", "abstract" : "OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific for adult Sjogren's syndrome (SS) in patients with juvenile onset SS. METHODS: Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11 cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha-fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis. In contrast, reactivity was found in only 2 of the 16 patients with SLE. The clinical features of the 15 patients with juvenile onset SS were very specific; only 4 patients complained of dryness, while 6 had abnormal excretion ability. Salivary gland enlargement was the most common clinical manifestation. Characteristic laboratory findings in juvenile onset SS included a higher prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid factor, as well as increased erythrocyte sedimentation rate and hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be the same as that of adult SS, although subjective symptoms of dryness are less frequent in juvenile cases. This discrepancy may indicate that SS is a slowly progressive disease with a long time span. The anti-alpha-fodrin antibody is likely to be a reliable diagnostic marker for juvenile SS.", "author" : [ { "dropping-particle" : "", "family" : "Maeno", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imanaka", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayashi", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyata", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "860-864", "title" : "Anti-alpha-fodrin antibodies in Sjogren's syndrome in children", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁴", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "⁵⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54200111NA11,6933111095Nikitakis et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S1079-2104(03)00159-8", "ISSN" : "10792104", "PMID" : "12847443", "abstract" : "Sj??gren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition. The purpose of this study is to report a case of primary SS (PSS) in a 4-year-old Venezuelan girl and to review the pertinent literature. The patient presented with bilateral recurrent parotid enlargement, predominantly on the right side. She did not complain of dry mouth or eyes; however, decreased stimulated salivary flow rate and positive Schirmer and rose bengal tests were obtained. Sialography, sonograms, and a computed tomography scan of the parotid glands revealed pathologic changes consistent with SS. Anti-SS-A and anti-SS-B antibodies were present. Evaluation for antibodies against cytomegalovirus, Epstein-Barr virus, and HIV rendered negative results. Histopathologic examination of incisional biopsies of the right parotid and labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. Taken together, these findings are consistent with the diagnosis of juvenile PSS. The salient features of this rare disease are summarized on the basis of a comprehensive review of the epidemiologic, clinical, and serologic findings of the previously reported cases of PSS in children.", "author" : [ { "dropping-particle" : "", "family" : "Nikitakis", "given" : "Nikolaos G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lariccia", "given" : "Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papadimitriou", "given" : "John C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sauk", "given" : "John J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "42-47", "title" : "Primary Sjogren syndrome in childhood: Report of a case and review of the literature", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵³", "plainTextFormattedCitation" : "53", "previouslyFormattedCitation" : "⁵³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5320021141010011McGuirt et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0886-4470", "PMID" : "12431170", "abstract" : "OBJECTIVES: To describe our experience with primary and secondary Sj\u00f6gren syndrome (SS) in the pediatric population and to evaluate the effectiveness of parotid gland biopsy in the diagnosis of pediatric SS.\n\nDESIGN: Case series review of 6 pediatric patients evaluated during a 4-year period with varied head and neck manifestations of SS.\n\nSETTING: Tertiary care children's hospital.\n\nPATIENTS: Six children (4 boys and 2 girls) ranging in age from 6 to 12 years, who were diagnosed as having primary or secondary SS.\n\nINTERVENTION: Six minor salivary gland and 4 parotid gland biopsies for pathologic examination.\n\nMAIN OUTCOME MEASURES: Pathologic examination of salivary tissue consistent with SS.\n\nRESULTS: All 6 patients underwent minor salivary gland biopsy, 2 (33%) were consistent with SS, while the remaining 4 (67%) were nondiagnostic. The 4 patients with nondiagnostic minor salivary gland biopsy results went on to have parotid biopsies, of which all 4 had histologic findings consistent with SS. No complications were encountered.\n\nCONCLUSION: Parotid gland biopsy is an effective and safe means of obtaining salivary gland tissue for histologic evaluation of SS in the pediatric population.", "author" : [ { "dropping-particle" : "", "family" : "McGuirt", "given" : "William F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whang", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreland", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "11" ] ] }, "page" : "1279-81", "title" : "The role of parotid biopsy in the diagnosis of pediatric Sj\u00f6gren syndrome.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁵", "plainTextFormattedCitation" : "55", "previouslyFormattedCitation" : "⁵⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5520026276324644Cimaz et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00431-003-1277-9", "ISSN" : "1432-1076", "PMID" : "12898241", "abstract" : "Primary Sj\u00f6gren syndrome (SS) is very rare in childhood. We collected a series of primary paediatric SS cases from different centres. A data collection form was prepared and sent to rheumatologists who were willing to participate. Data on 40 cases of primary SS with onset before the 16th birthday were collected. Almost all patients (35/40) were females, age at onset varied from 9.3 to 12.4 years (mean 10.7 years). Signs and symptoms at disease onset were mainly recurrent parotid swelling followed by sicca symptoms. Abnormal laboratory tests were found in the majority of cases. Regarding treatment, 22 patients were treated at some time with oral corticosteroids, seven with non-steroidal anti-inflammatory drugs, and five with hydroxychloroquine; two patients needed cyclosporine and one cyclophosphamide. Follow-up varied from 0 to 7.5 years from onset, without major complications in the majority of patients. CONCLUSION: recurrent parotid swelling is a common feature of primary Sj\u00f6gren syndrome in childhood and often occurs as a presenting feature. Sicca symptoms may be rarer.", "author" : [ { "dropping-particle" : "", "family" : "Cimaz", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadei", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartunkova", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediva", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falcini", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picco", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taglietti", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zulian", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cate", "given" : "R", "non-dropping-particle" : "Ten", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sztajnbok", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voulgari", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drosos", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Pediatrics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "661-665", "title" : "Primary Sj\u00f6gren syndrome in the paediatric age: a multicentre survey", "type" : "article-journal", "volume" : "162" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁶", "plainTextFormattedCitation" : "56", "previouslyFormattedCitation" : "⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }562003403512,42352734302930Lawind et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1110-4902 (Print)", "PMID" : "15724389", "abstract" : "Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P < 0.05). There was no statistically significant difference of levels of ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine screening of alpha fodrin antibodies is a valuable tool for the diagnosis of SS.", "author" : [ { "dropping-particle" : "", "family" : "Lawind", "given" : "M F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alyasky", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elwan", "given" : "N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mourad", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Bendary", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Egypt J Immunol", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "75-81", "title" : "Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁷", "plainTextFormattedCitation" : "57", "previouslyFormattedCitation" : "⁵⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }572004131010,1NANANANANA87Houghton et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "0315162X-32-1603 [pii]", "ISBN" : "0315-162X", "PMID" : "16078341", "abstract" : "Primary Sjogren's syndrome (pSS) is uncommonly recognized in childhood, and familial cases are rare. Pulmonary involvement in pediatric pSS is infrequently reported. In adults, asymptomatic pulmonary involvement is increasingly recognized, manifest by pulmonary function test abnormalities and changes on high resolution computerized tomographic scan. We describe a case of pSS in a 14-year-old Vietnamese-Canadian girt who presented with pulmonary symptoms, radiologic changes, and biopsy confirmation of lymphocytic interstitial pneumonia. Her dizygotic twin sister has primary SS without extraglandular manifestations. To our knowledge this is the first report of pediatric pSS with lymphocytic interstitial pneumonia and multiple pulmonary nodules on chest radiograph, We review the literature on pulmonary involvement and familial cases of pSS in childhood", "author" : [ { "dropping-particle" : "", "family" : "Houghton", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabral", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petty", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "L B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Rheumatology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1603-1606", "title" : "Primary Sjogren's syndrome in dizygotic adolescent twins: One case with lymphocytic interstitial pneumonia", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁸", "plainTextFormattedCitation" : "58", "previouslyFormattedCitation" : "⁵⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58200522142102222Houghton et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "0315162X-32-2225 [pii]", "ISBN" : "0315-162X (Print)\\r0315-162X (Linking)", "PMID" : "16265707", "abstract" : "OBJECTIVE: To compare the proposed criteria for the diagnosis of primary Sjogren's syndrome (pSS) in childhood to the validated American-European Consensus Group (AECG) classification criteria for pSS in adults. METHODS: Charts of 7 children with pSS seen at British Columbia's Children's Hospital (BCCH) and data on 128 children identified through Medline in the English language literature between 1963 and 2003 were reviewed for pediatric and AECG criteria for pSS. The presence of > or = 4 criteria was required to satisfy the respective classification criteria. The expert clinical opinion of pediatric rheumatologists was considered the gold standard for diagnosis. RESULTS: A total of 24/62 (39%) cases satisfied the AECG criteria; 47/62 (76%) satisfied the proposed pediatric criteria. Inclusion of recurrent parotitis increased the sensitivity of the pediatric clinical criteria. From the cases, 78/133 (59%) satisfied the pediatric oral symptom criteria; only 6/78 (8%) had xerostomia in the absence of recurrent parotitis. There was no reported case of recurrent conjunctivitis in the absence of keratoconjunctivitis sicca. We found 101/130 (78%) cases had at least one positive autoantibody test result [antinuclear antibodies (ANA), rheumatoid factor (RF), SSA, SSB]; 78/123 (63%) had autoantibodies to SSA or SSB. CONCLUSION: The AECG adult criteria for pSS should not be applied to children as the sensitivity is unacceptably low. The inclusion of recurrent parotitis increases the sensitivity of the pediatric criteria, and recurrent parotitis should alert the clinician to the possibility of pSS. The inclusion of recurrent conjunctivitis did not improve the sensitivity over the AECG ocular criteria. The addition of ANA and RF to the AECG criteria did not change the number of patients satisfying the criteria for pediatric pSS.", "author" : [ { "dropping-particle" : "", "family" : "Houghton", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malleson", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabral", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petty", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Rheumatol", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2225-2232", "title" : "Primary Sjogren's syndrome in children and adolescents: are proposed diagnostic criteria applicable?", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁹", "plainTextFormattedCitation" : "59", "previouslyFormattedCitation" : "⁵⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5920057611,75327477Ohlsson et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kei175", "ISSN" : "1462-0324", "PMID" : "16352643", "author" : [ { "dropping-particle" : "", "family" : "Ohlsson", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strike", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James-Ellison", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tizard", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Ramanan", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "2" ] ] }, "page" : "238-40", "title" : "Renal tubular acidosis, arthritis and autoantibodies: primary Sj\u00f6gren's syndrome in childhood.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁰", "plainTextFormattedCitation" : "60", "previouslyFormattedCitation" : "⁶⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6020061181001111Pessler et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10067-005-0042-z", "ISSN" : "0770-3198", "PMID" : "16391885", "abstract" : "Tumor necrosis factor alpha (TNFalpha) blockade has recently been found to be ineffective in treating glandular and extraglandular manifestations of adult Sj\u00f6gren syndrome (SS), including arthralgia and arthritis. We report a girl who developed purpura, polyarthritis, uveitis, and severe dental caries in the first year of life and optic neuritis by age three. SS was diagnosed at 11 years of age, when severe hypokalemic renal tubular acidosis developed during infliximab treatment for arthritis. In contrast to her other disease manifestations, the arthritis responded remarkably well to TNFalpha blockade, suggesting that TNFalpha blockers may have a role in the treatment of arthritis with pediatric SS.", "author" : [ { "dropping-particle" : "", "family" : "Pessler", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monash", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rettig", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forbes", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreiger", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cron", "given" : "R Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "9" ] ] }, "page" : "746-8", "title" : "Sj\u00f6gren syndrome in a child: favorable response of the arthritis to TNFalpha blockade.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶¹", "plainTextFormattedCitation" : "61", "previouslyFormattedCitation" : "⁶¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }61200611110101000Civilibal et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "Primary Sjogren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjogren syndrome antigen A, and anti-Sjogren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of PSS", "author" : [ { "dropping-particle" : "", "family" : "Civilibal", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canpolat", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yurt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurugoglu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdamar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagci", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sever", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasapcopur", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caliskan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arisoy", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Pediatrics", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "738-742", "title" : "A child with primary Sjogren syndrome and a review of the literature", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶²", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "⁶²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62200711131011111Bartunkova et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "PMID" : "10410277", "abstract" : "OBJECTIVE: Primary Sj\u00f6gren's syndrome (pSS) in childhood is a rare disease. Diagnostic criteria are available for adult patients only. In order to establish diagnostic criteria for juvenile pSS an analysis of 7 girls and one boy suffering from pSS with early onset is reported. Due to the rarity of the disease, data on patients with pSS reported in the literature are included in the proposal for modified diagnostic criteria.\n\nMETHODS: The diagnosis of pSS was established according to the criteria for adulthood pSS, duly modified, which include clinical symptoms and laboratory immunological evaluation.\n\nRESULTS: The average age of our patients at clinical onset was 13.5 years (range: 10-17 yrs.). Clinical signs included systemic (fever, fatigue) as well as local (parotitis, vulvovaginitis, conjunctivitis) symptoms. Paralysis due to hypokalemia linked to renal tubular acidosis and central nervous system (CNS) involvement was seen in one patient. Asymptomatic renal tubular acidosis was diagnosed in another 2 patients. Autoimmune hepatitis was present in 2 patients. All patients had laboratory abnormalities: hyperimmunoglobulinemia IgG, high titers of antinuclear antibodies (anti-SS-A and/or anti-SS-B) and elevated serum amylases. Sicca syndrome was never seen during childhood, although it developed later in 3 patients, after 7 to 10 years of follow-up.\n\nCONCLUSIONS: It has been stressed that the classical diagnostic criteria for adult Sj\u00f6gren's syndrome, especially sicca syndrome, are not applicable to a pediatric onset of the disease. On the other hand, the presence of typical laboratory abnormalities can allow the diagnosis of these patients in the early stages. Both laboratory and clinical symptoms typical for childhood are included in our proposal for diagnostic criteria applicable to juvenile pSS. Life-threatening conditions such as hypokalemic paralysis, CNS involvement and hepatitis may also occur in children. Sicca syndrome tends to develop much later in pediatric patients.", "author" : [ { "dropping-particle" : "", "family" : "Bart\u016fnkov\u00e1", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sediv\u00e1", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vencovsk\u00fd", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tesar", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "381-6", "title" : "Primary Sj\u00f6gren's syndrome in children and adolescents: proposal for diagnostic criteria.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁹", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4920098713,53648786Tomiita et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10165-010-0313-7", "ISBN" : "1439-7609 (Electronic)\\r1439-7595 (Linking)", "ISSN" : "1439-7609", "PMID" : "20517630", "abstract" : "The number of patients with juvenile-onset Sj\u00f6gren's syndrome (SS) has recently increased. However, there is no drug that is safe and effective for the xerostomia that occurs in patients of this age group. We evaluated the efficacy and safety of orally administered pilocarpine hydrochloride for juvenile-onset SS patients. Five female patients, aged from 9 to 16 years, received 5-10 mg/day for 4 weeks. On days 1 and 28, salivary production was measured by the Saxon test, and patients completed subjective self-evaluations of xerostomia symptoms and were asked about changes in water intake and overall improvement of dry mouth on day 28. After 4 weeks of pilocarpine administration, salivary production increased significantly in all patients, and overall status was assessed as \"improved\" in all patients. One patient had excessive sweating. No serious adverse events or laboratory examination abnormalities correlated with pilocarpine administration were found. In conclusion, the results of this study suggest that orally administered pilocarpine is safe and effective for treating xerostomia in juvenile-onset SS patients. This is the first report of the efficacy of pilocarpine for juvenile SS patients; further evaluations are needed to confirm our result.", "author" : [ { "dropping-particle" : "", "family" : "Tomiita", "given" : "Minako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "Syuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuwada", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nonaka", "given" : "Yukiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Kimiyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimojo", "given" : "Naoki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Yoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Modern rheumatology / the Japan Rheumatism Association", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "486-90", "title" : "Efficacy and safety of orally administered pilocarpine hydrochloride for patients with juvenile-onset Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶³", "plainTextFormattedCitation" : "63", "previouslyFormattedCitation" : "⁶³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6320102213,50002222Jung et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00467-009-1358-8", "ISSN" : "1432-198X", "PMID" : "19902265", "author" : [ { "dropping-particle" : "", "family" : "Jung", "given" : "Seong Kwan", "non-dropping-particle" : "", 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"2010", "3" ] ] }, "page" : "567-8", "title" : "Primary Sj\u00f6gren's syndrome with mesangial proliferative glomerulonephritis and IgA deposits in a child.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁴", "plainTextFormattedCitation" : "64", "previouslyFormattedCitation" : "⁶⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6420101011111NANA11Longhi et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1980-5322", "PMID" : "22086534", "author" : [ { "dropping-particle" : "", "family" : "Longhi", "given" : "Barbara S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Appenzeller", "given" : "Simone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centeville", "given" : "Maraisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gusm\u00e3o", "given" : "Reinaldo J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marini", "given" : "Roberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinics (S\u00e3o Paulo, Brazil)", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "1991-3", "title" : "Primary Sj\u00f6gren's syndrome in children: is a family approach indicated?", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁵", "plainTextFormattedCitation" : "65", "previouslyFormattedCitation" : "⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }652011228,52001121Nieto-Gonzalez et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0392-856X", "PMID" : "24847722", "abstract" : "Primary Sj\u00f6gren's syndrome (pSS) is a systemic autoimmune disease uncommon in children, clinically characterized by recurrent parotitis at the onset, which is a common disorder in childhood, most of them of infectious origin. Juvenile pSS diagnosis is based on clinical symptoms and presence of autoantibodies, after exclusion of infectious or lymphoproliferative diseases. However, salivary gland ultrasound (SGU) shows typical features of pSS that can add useful information for the diagnosis of this disorder. We describe three patients who presented with recurrent parotitis in which characteristic autoantibodies and typical SGU pattern allow us to make the diagnosis of juvenile pSS. We suggest that in children with recurrent parotitis SGU and autoantibodies should be routinely performed.", "author" : [ { "dropping-particle" : "", "family" : "Nieto-Gonz\u00e1lez", "given" : "Juan Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monteagudo", "given" : "Indalecio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bello", "given" : "Natalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Estupi\u00f1an", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naredo", "given" : "Esperanza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carre\u00f1o", "given" : "Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and experimental rheumatology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Salivary gland ultrasound in children: a useful tool in the diagnosis of juvenile Sj\u00f6gren's syndrome.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁶", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }662014324,33003132Yokogawa et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3899/jrheum.131511", "ISSN" : "0315-162X", "PMID" : "24786923", "abstract" : "OBJECTIVE: To determine an appropriate focus score cutoff for childhood Sj\u00f6gren syndrome (SS).\\n\\nMETHODS: Labial salivary gland tissue from specimens from children with SS and age-matched controls was retrospectively identified and reviewed by a blinded oral pathologist.\\n\\nRESULTS: The presence of any focal sialadenitis (focus score > 0 foci/4 mm(2)) was common among childhood SS samples but present in only 1 of 8 control samples.\\n\\nCONCLUSION: The presence of any focal lymphocytic sialadenitis in minor labial salivary gland tissue is suggestive of childhood SS and should be included in future childhood SS-specific diagnostic or classification criteria.", "author" : [ { "dropping-particle" : "", "family" : "Yokogawa", "given" : "Naoto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieberman", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alawi", "given" : "Faizan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bout-Tabaku", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guttenberg", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherry", "given" : "David D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vivino", "given" : "Frederick B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of rheumatology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1178-82", "title" : "Comparison of labial minor salivary gland biopsies from childhood Sj\u00f6gren syndrome and age-matched controls.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁷", "plainTextFormattedCitation" : "67", "previouslyFormattedCitation" : "⁶⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6720148811,24238NA74TOTAL201157/190 (83%)10,1138/177 (78%)64/154 (42%)102/174 (59%)150/198 (75%)116/167 (69%)138/181 (76%)114/181 (63%)NA: not available; RF: rheumatoid factor.Table 4. Systemic and organ-specific autoimmune diseases associated with Sj?gren’s syndromeSystemic autoimmune diseasesSystemic lupus erythematosusRheumatoid arthritisSystemic sclerosisInflammatory myopathiesAntiphospholipid syndromeSarcoidosisANCA vasculitidesStill diseaseOrgan-specific autoimmune diseasesAutoimmune thyroiditisPrimary biliary cholangitisSclerosing cholangitisAutoimmune hepatitisMultiple sclerosisDiabetes mellitusInflammatory bowel diseaseCeliac diseaseTable 5. Main diagnostic tests for the study of salivary and lachrymal dysfunction in Sj?gren’s syndromeDiagnostic testTechnical equipmentAbnormal valuesPractical issuesUnstimulated salivary flow rates (UWF)Graduated test tube/preweighed tubeLess than 1.5 mL collected over a 15 min (< 0.1 mL/min)Results may be influenced by age, length of disease, comorbidities, temperature or medications.Stimulated salivary flow rates (SWF)Graduated test tube/preweighed tube Chewing gums or lemon juiceLess than 0.2-0.3 mL/min collected over a 15 minBetter correlation with histopathological results or structural glandular damage.Salivary scintigraphyRadioactive tracer, technetium 99 Gamma scintillation cameraSchall's categorical classification into 4 grades (from normal to very severe involvement),Severe involvement (grade IV) at diagnosis associated with higher systemic activity and poor outcomes.Schirmer’s test IFilter paper (no. 41 whatman)Anesthesic< 5 mm of the paper after 5 minutesEvaluates baseline secretionSchirmer’s test IIFilter paper (no. 41 whatman)< 10 mm of the paper after 5 minutesMeasures baseline plus reflex secretionCorneal stainingsDyes (fluorescein, rose Bengal and lissamine green)Slit lampBlue cobalt filtervan Bijsterveld score ≥ 4Oxford scale score ≥ IIIOSS score ≥ 3Rose begal (non-vital dye) has been substituted by lissamine green (vital dye)Studies in development are suggesting the increase of abnormal OSS score to 5Table 6. Sensitivity and specificity of the main features evaluated in the main sets of classification criteria. Features with % higher than 80% in all the studies are marked in boldADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.21591", "ISBN" : "2151-4658 (Electronic)\\r2151-464X (Linking)", "ISSN" : "2151-4658", "PMID" : "22563590", "abstract" : "OBJECTIVE: We propose new classification criteria for Sj\u00f6gren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.\\n\\nMETHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sj\u00f6gren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American\u2013European Consensus Group (AECG) criteria, a model-based \u201cgold standard\u201dobtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development.\\n\\nRESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications.\\n\\nCONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.", "author" : [ { "dropping-particle" : "", "family" : "Shiboski", "given" : "S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiboski", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Criswell", "given" : "L A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baer", "given" : "A N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Challacombe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanfranchi", "given" : "H", "non-dropping-particle" : "", 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"suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenspan", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis care & research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "475-87", "title" : "American College of Rheumatology classification criteria for Sj\u00f6gren's syndrome: a data-driven, expert consensus approach in the Sj\u00f6gren's International Collaborative Clinical Alliance cohort.", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/art.1780360309", "ISSN" : "0004-3591", "PMID" : "8452579", "abstract" : "Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.", "author" : [ { "dropping-particle" : "", "family" : "Vitali", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balestrieri", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bencivelli", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernstein", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjerrum", "given" : "K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braga", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coll", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vita", "given" : "S", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis and rheumatism", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "340-347", "title" : "Preliminary criteria for the classification of Sj\u00f6gren's syndrome. Results of a prospective concerted action supported by the European Community", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0003-4967", "PMID" : "7979575", "abstract" : "AIM: To establish a definitive set of diagnostic criteria in a multicentre European study a selected number of oral and ocular tests were performed on a large number of patients with Sj\u00f6grens Syndrome (SS) and controls. The diagnostic accuracy of each test for patients with primary and secondary SS and for controls at different ages, was studied. METHODS: Each centre received a clinical chart describing the series of tests to be conducted. The tests included: questionnaires for dry eye and dry mouth symptoms, Schirmer's-I-test (ScT), tear fluid lactoferrin level (TFLL), break-up time (BUT) and rose Bengal score (RBS) for the eye evaluation; unstimulated and stimulated whole saliva collection (UWSC and SWSC), salivary gland scintigraphy (SGS), parotid sialography (PS) and minor salivary gland biopsy (MSGB) for oral involvement. RESULTS: Data from 22 centres and 11 countries was collected on a total of 447 patients with SS (246 with primary SS and 201 with secondary SS) and 246 controls (of whom 113 had a connective tissue disease without SS). Among the ocular symptoms, the feeling of dry eye and 'sand in the eye' were the ones most commonly recorded in patients with SS. Similarly, the feeling of dry mouth, appearing either spontaneously or when the patient was eating or breathing, was the most frequent subjective oral symptom. Among the ocular tests, ScT showed the best balance between sensitivity and specificity (76.9% and 72.4% respectively), while RBS was the most specific test (81.7%). ScT and RBS gave also sufficiently concordant results. TFLL and BUT gave considerably less reliable results, which were not concordant with each other or with the other ocular tests. The quantitative lacrimal tests ScT and TFLL produced significantly different results in elderly controls, while RBS did not. Abnormal results for all of the ocular tests were less marked and less frequent in patients with secondary SS than in those with primary SS. The oral tests (except SWSC) were generally more reliable than the ocular tests in diagnosing SS. In particular, PS was the most specific diagnostic tools (100%), while MSGB (where the presence of at least one inflammatory focus was considered as indicative for the diagnosis) showed a good balance between sensitivity and specificity (82.4% and 86.2%, respectively). The tests showed a good degree of agreement, and, with the exception of UWSC, were not influenced by age. In the oral, as in the ocular tests, abnormal results were \u2026", "author" : [ { "dropping-particle" : "", "family" : "Vitali", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsopoulos", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bombardieri", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "637-647", "title" : "The European Community Study Group on diagnostic criteria for Sj\u00f6gren's syndrome. Sensitivity and specificity of tests for ocular and oral involvement in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "12", "14" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Vitali C, Bombardieri S, Moutsopoulos HM, Coll J, Gerli R, Hatron PY", "given" : "Kater L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konttinen YT, Manthorpe R, Meyer O, Mosca M, Ostuni P, Pellerito RA", "given" : "Pennec Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porter SR, Richards A, Sauvezie B, Schi\u00f8dt M, Sciuto M, Shoenfeld Y", "given" : "Skopouli FN", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smolen JS, Soromenho F, Tishler M, Wattiaux MJ", "given" : "et al.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Assessment of the European classification criteria for Sj\u00f6gren's syndrome in a series of clinically defined cases: results of a prospective multice... - PubMed - NCBI", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/sj.eye.6702204", "ISSN" : "0950-222X", "PMID" : "16397619", "abstract" : "OBJECTIVE: To evaluate the diagnostic performance of the tests included in primary Sjogren's syndrome (SS-I) diagnostic criteria (Schirmer I, break-up time, vital dye staining) and to compare them with other examinations related to the ocular surface status. METHODS: Clinical and cytological data were collected from 177 patients (62 SS-1, 56 non-SS autoimmune diseases, 59 Sicca syndrome). Tear tests included: a validated questionnaire on symptoms, Schirmer I, Jones test, Ferning test, BUT, corneal aesthesiometry, tear clearance test, lissamine green staining, impression conjunctival cytology. Data were statistically evaluated and sensitivity, specificity, likelihood ratio (LR+), receiver-operating characteristics (ROC) curves were calculated for each test. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (sensitivity 0.42; specificity 0.76; LR+1.75) and BUT (sensitivity 0.92; specificity 0.17; LR+1.11) (area under the curve in ROC analysis <0.58). Validated subjective symptoms questionnaire (sensitivity 0.89; specificity 0.72; LR+3.18), Jones test (sensitivity 0.60; specificity 0.88; LR+5), corneal aesthesiometry (sensitivity 0.80; specificity 0.67; LR+2.42), and tear clearance test (sensitivity 0.63; specificity 0.84; LR+3.93), all exhibited a high diagnostic performance (area under the curve in the ROC analysis always >0.70). Lissamine green staining exhibited the best performance (sensitivity 0.63; specificity 0.89; LR+5.72) but the result could be distorted by an incorporation bias. CONCLUSIONS: Our data suggest to implement the items for ocular signs and symptoms contained in many SS-I diagnostic criteria with the use of a validated questionnaire, performance of Jones test, corneal aesthesiometry measurement, and tear clearance rate evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Versura", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frigato", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cellini", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mul\u00e8", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malavolta", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campos", "given" : "E C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eye (London, England)", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "229-237", "title" : "Diagnostic performance of tear function tests in Sjogren's syndrome patients.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "ISSN" : "1790-5427", "PMID" : "25097897", "abstract" : "Our aim was to validate eight scintigraphic salivary gland (SG) parameters, as diagnostic parameters in patients with Sj\u00f6gren's syndrome (SS). We used the standardized stimulated dynamic salivary gland scintigraphy (DSGS) protocol and correlated this with the unstimulated whole sialometry (UWS) functions. The DSGS and UWS tests meeting the European and the USA diagnostic classification criteria for SS were applied in twenty patients and in ten normal controls. The DSGS tests were performed 60min after the intravenous (i.v.) injection of 370MBq of technetium-99m-pertechnetate ((99m)TcO(-)4) and after per os stimulation with a 0.5g tablet of ascorbic acid administered 40min after the injection. Using time-activity curves, eight different parameters were calculated for each parotid gland (PG) and each submandibular salivary gland (SMG): a) time at maximum counts (Tmax), b) time at minimum counts (Tmin), c) maximum accumulation (MA), d) accumulation velocity (AV), e) maximum secretion (MS), f) maximum stimulated secretion (MSS), g) stimulated secretion velocity (SSV), and h) uptake ratio (UR). Values of UWS below 2.5mL/15min, were considered abnormal. All these parameters, as for the PG, showed significant abnormality in SS patients (P<0.001), especially of the secretion function. All SMG parameters also showed a significant abnormality (P<0.001), but especially of the accumulation function. There was a greater impairment of the above parameters in SMG than in PG in the SS patients. Sensitivity of the standardized DSGS was 100%, specificity 80%, negative prognostic value 100%, and positive prognostic value 91%. Sensitivity of UWS was 75%. In conclusion, this paper suggested that the best diagnostic parameters for the SS patients were those of: a) the maximum secretion, b) the maximum stimulated secretion for both the parotid and the submandibular glands, c) maximum accumulation and d) accumulation velocity of submandibular glands. The times at maximum and at minimum counts were non diagnostic.", "author" : [ { "dropping-particle" : "", "family" : "Dugonji\u0107", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefanovi\u0107", "given" : "Du\u0161an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ethurovi\u0107", "given" : "Branka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spasi\u0107-Joki\u0107", "given" : "Vesna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajdinovi\u0107", "given" : "Boris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hellenic journal of nuclear medicine", "id" : "ITEM-6", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "116-22", "title" : "Evaluation of diagnostic parameters from parotid and submandibular dynamic salivary glands scintigraphy and unstimulated sialometry in Sj\u00f6gren's syndrome.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{133,157\u2013161}", "plainTextFormattedCitation" : "133,157\u2013161", "previouslyFormattedCitation" : "^{133,157\u2013161}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }133,157–161CriteriaSensitivity (%)Specificity (%)Dry eyes80%12%Dry mouth87%7%Abnormal BUT78-92%17-45%Abnormal Rose Bengal staining53-64%82-92%Abnormal Schirmer I43-86%71-76%Abnormal Schirmer II60%88%Abnormal UWS56-90%38-86%Abnormal SWS65-66%56-60%Abnormal Scintigraphy80-100%63-86%Abnormal Sialography72-79%92-100%ANA+69-73%59-80%RF+59-72%80-86%Ro/SS-A+46%89%La/SS-B+33%98%Ro and/or La+84%93%Focal lymphocytic sialadenitis (salivary gland biopsy)82-87%82-90%UWF: Unstimulated salivary flow rates; SWF Stimulated salivary flow rates; BUT: break-up time; ANA: antinuclear antibodies; RF: rheumatoid factorTABLE 7. Clinical, laboratory, immunological, histopathological and genetic findings associated with a higher risk of development of lymphoma in patients with primary Sj?gren’s syndrome.a) Clinical features- Persistent enlargement of parotid glands- Purpura- Moderate or high disease activity (ESSDAI)b) Laboratory abnormalities- CD4 lymphopeniac) Immunological findings- Low C3/C4 levels- Mixed cryoglobulinemia- Monoclonal gammopathy- Raised lymphocyte-related cytokine levels (BAFF, Fms-like tyrosine kinase 3 ligand, CXCL13, CCL11)- Raised beta2-microglobulin levels- Rheumatoid factord) Histopathological features- Germinal centers- Focus score >3e) Genetic polymorphisms- BAFF/BAFF-R- TNFAIP3 (A20)Table 8. Ongoing diagnostic and therapeutic studies in primary SjS (, accessed December 16, 2015) NCT IdentificationPatientsDiagnostic approachesType of studyStudy phaseFundingNCT00074373Congenital Heart BlockResearch RegistryObservationalNAOtherNCT02132585SjSSpeckle tracking echocardiographyObservationalNAOtherNCT01470638SjSFlt3-Ligand LevelsObservationalNAOtherNCT01807689SjSSalivary BiomarkersObservationalNAOtherNCT IdentificationPatientsNew drugsType of studyStudy phaseFundingNCT02503163Dry Eye With SjSKCT-0809 ophthalmic solutionInterventionalPhase 3IndustryNCT02503176Dry Eye With SjSKCT-0809 ophthalmic solutionInterventionalPhase 3IndustryNCT02503189Dry Eye With SjSKCT-0809 ophthalmic solutionInterventionalPhase 3IndustryNCT02004067Primary SjSOcular CyclosporineInterventionalPhase 4IndustryNCT01316770SjSDexamethasone irrigationInterventionalPhase 2NIHNCT01379573Congenital Heart BlockHydroxychloroquineInterventionalPhase 2OtherNCT00543166SjSDehydroepiandrosteroneInterventionalPhase 4OtherNCT01759108SjSRebamipideInterventionalNPOtherNCT01782235Primary SjSTocilizumabInterventionalPhase 2-3OtherNCT02067910SjSAbataceptInterventionalPhase 3IndustryNCT02464319Primary SjSHuman IL-2InterventionalPhase 2OtherNCT01552681SjSBaminerceptInterventionalPhase 2NIHNCT02610543Primary SjSUCB5857InterventionalPhase 2IndustryNCT02334306Primary SjSAMG 557/MEDI5872InterventionalPhase 2IndustryNCT02149420Primary SjSVAY736InterventionalPhase 2IndustryNCT02291029Primary SjSCFZ533InterventionalPhase 2IndustryNCT IdentificationPatientsOther therapeutic approachesType of studyStudy phaseFundingNCT02370225SjSAerobic exerciseInterventionalNPOtherNCT01501019Primary SjSExercise trainingInterventionalNPOtherNCT02031172SjSEffects of Sustained Reading on the Ocular SurfaceObservationalNPOtherNCT02110446SjSChinese Herbal Formula SS-1InterventionalPhase 2OtherNCT02153515Dry EyesFingerprick Autologous BloodInterventionalPhase 3OtherNCT02193490Dry EyeDnaseInterventionalPhase 1-2IndustryNCT00953485SjSAllogeneic Mesenchymal Stem CellsInterventionalPhase 1-2OtherNCT02148497Dry EyeMulti-colored Placido disk imagingInterventionalNPOtherNCT02066896Keratoconjunctivitis siccaLaser 3R 790nm infrared Ga AIAsInterventionalPhase 2OtherNCT02112019SjSSialoendoscopyInterventionalNPOtherNCT01174329SjSAutomatic neuro-electrostimulationInterventionalPhase 2-3OtherSjS: Sj?gren’s syndrome; NP: not provided; NA: not applicableREFERENCES ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1.Ramos-Casals, M., Brito-Zerón, P., Sisó-Almirall, A. & Bosch, X. 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