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Name of Journal: World Journal of Clinical CasesManuscript NO: 65453Manuscript Type: CASE REPORTrole of ranulas in early diagnosis of Sj?gren’s syndrome: a case reportChen N et al. Ranulas and Sj?gren’s syndromeNa Chen, Da-shun Zeng, Yu-tong SuNa Chen, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDa-shun Zeng, Department of oral surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, Zhejiang Province, ChinaYu-tong Su, Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaAuthor contributions: Chen N and Su YT managed the case, and prepared and revised the manuscript; Zeng DS assisted with the preparation and revision of the manuscript; all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work; all authors take full responsibility for the integrity of the study and the final manuscript.Supported by the National Natural Science Foundation of China, No. 81801600.Corresponding author: Yu-tong Su, MD, PhD, Doctor, Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai 200025, China. suyt2015@Received: March 9, 2021Revised: April 13, 2021Accepted: May 24, 2021Published online: AbstractBACKGROUNDAlthough the presentations of Sj?gren’s syndrome (SS) are variable, ranging from mild dryness to wider systemic involvement, ranulas as early clinical signs were scarcely reported. Here, we present an adult patient with SS, who developed a unilateral simple ranula and was diagnosed primary SS 3 years later. We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARYA 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago, without obvious trauma or inducement. The diagnosis of a unilateral (left) simple ranula was made, and the ranula was surgically treated. Within 3 years after the ranula surgery, she developed acute lymphadenectasis in unilateral parotid twice without inducement, and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands, which strongly suggested SS. Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSIONOur study underlines that ranulas are early clinical signs of SS. As early diagnosis and early intervention of SS are important to obtain better outcomes, our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas. Key Words: Sj?gren’s syndrome; Ranulas; Early diagnosis; Parotitis; Case reportChen N, Zeng DS, Su YT. role of ranulas in early diagnosis of Sj?gren’s syndrome: a case report. World J Clin Cases 2021; In pressCore Tip: Although the presentations of Sj?gren’s syndrome (SS) are variable, ranulas as early clinical signs were scarcely reported. Here, we present an adult patient with SS, who developed a unilateral simple ranula and was diagnosed with primary SS 3 years later. We also provide a review of cases of SS and ranulas from 1980 to 2020. By analyzing the symptoms, treatment, and prognosis of these patients, we propose that ranulas could be early clinical signs and manifestations of SS, which may raise the awareness of clinicians and lead to early interventions for SS in order to obtain better outcomes.INTRODUCTIONSj?gren’s syndrome (SS) is a chronic systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands with a greater predilection in females ADDIN EN.CITE <EndNote><Cite><Author>Thorne</Author><Year>2017</Year><RecNum>1</RecNum><DisplayText><style face="superscript">[1]</style></DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608272915">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Thorne, Iona</style></author><author>Sutcliffe, Nurhan</author></authors></contributors><titles><title>Sj?gren's syndrome</title><secondary-title>British Journal of Hospital Medicine</secondary-title></titles><periodical><full-title>British Journal of Hospital Medicine</full-title></periodical><pages>438-442</pages><volume>78</volume><number>8</number><dates><year>2017</year></dates><isbn>1750-8460</isbn><accession-num>28783408</accession-num><urls></urls><electronic-resource-num>10.12968/hmed.2017.78.8.438</electronic-resource-num></record></Cite></EndNote>[1]. The reported prevalence ranges from 0.01% to 0.09% in the general population ADDIN EN.CITE <EndNote><Cite><Author>Qin</Author><Year>2015</Year><RecNum>2</RecNum><DisplayText><style face="superscript">[2]</style></DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608273024">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Qin, Baodong</style></author><author>Wang, Jiaqi</author><author>Yang, Zaixing</author><author>Yang, Min</author><author>Ma, Ning</author><author>Huang, Fenglou</author><author>Zhong, Renqian</author></authors></contributors><titles><title>Epidemiology of primary Sj?gren's syndrome: a systematic review and meta-analysis</title><secondary-title>Annals of the rheumatic diseases</secondary-title></titles><periodical><full-title>Annals of the rheumatic diseases</full-title></periodical><pages>1983-1989</pages><volume>74</volume><number>11</number><dates><year>2015</year></dates><isbn>0003-4967</isbn><accession-num>24938285</accession-num><urls></urls><electronic-resource-num>10.1136/annrheumdis-2014-205375</electronic-resource-num></record></Cite></EndNote>[2]. The symptoms are various and can involve the whole body, beyond sicca syndromes, and systemic manifestations include inflammatory arthritis, renal involvement, lung lesion, central nervous system involvement, etc. ADDIN EN.CITE <EndNote><Cite><Author>Ramos-Casals</Author><Year>2008</Year><RecNum>4</RecNum><DisplayText><style face="superscript">[3, 4]</style></DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608273830">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Ramos-Casals, Manuel</style></author><author>Solans, Roser</author><author>Rosas, Jose</author><author>Camps, María Teresa</author><author>Gil, Antonio</author><author>del Pino-Montes, Javier</author><author>Calvo-Alen, Jaime</author><author>Jiménez-Alonso, Juan</author><author>Micó, Maria-Luisa</author><author>Beltrán, Juan</author></authors></contributors><titles><title>Primary Sj?gren syndrome in Spain: clinical and immunologic expression in 1010 patients</title><secondary-title>Medicine</secondary-title></titles><periodical><full-title>Medicine</full-title></periodical><pages>210-219</pages><volume>87</volume><number>4</number><dates><year>2008</year></dates><isbn>0025-7974</isbn><accession-num>18626304</accession-num><urls></urls><electronic-resource-num>10.1097/MD.0b013e318181e6af</electronic-resource-num></record></Cite><Cite><Author>Mavragani</Author><Year>2014</Year><RecNum>3</RecNum><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608273828">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Mavragani, Clio P</style></author><author>Moutsopoulos, Haralampos M</author></authors></contributors><titles><title>Sj?gren syndrome</title><secondary-title>Cmaj</secondary-title></titles><periodical><full-title>Cmaj</full-title></periodical><pages>E579-E586</pages><volume>186</volume><number>15</number><dates><year>2014</year></dates><isbn>0820-3946</isbn><urls></urls></record></Cite></EndNote>[3,4]. Due to insidious onset in early stage, it is difficult to diagnose SS at an early stage in time and accurately.Ranulas are caused by extravasation of mucus from damage or obstruction of the sublingual gland or its duct ADDIN EN.CITE <EndNote><Cite><Author>Morton</Author><Year>2018</Year><RecNum>7</RecNum><DisplayText><style face="superscript">[5]</style></DisplayText><record><rec-number>7</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608275584">7</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Morton, RP</style></author></authors></contributors><titles><title>Surgical management of ranula revisited</title><secondary-title>World journal of surgery</secondary-title></titles><periodical><full-title>World journal of surgery</full-title></periodical><pages>3062-3063</pages><volume>42</volume><number>9</number><dates><year>2018</year></dates><isbn>0364-2313</isbn><accession-num>29750326</accession-num><urls></urls><electronic-resource-num>10.1007/s00268-018-4666-y</electronic-resource-num></record></Cite></EndNote>[5]. Eating and external blunt trauma could cause damage to the sublingual duct ADDIN EN.CITE <EndNote><Cite><Author>Harrison</Author><Year>2010</Year><RecNum>8</RecNum><DisplayText><style face="superscript">[6]</style></DisplayText><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608275911">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Harrison, John D</style></author></authors></contributors><titles><title>Modern management and pathophysiology of ranula: literature review</title><secondary-title>Head & neck</secondary-title></titles><periodical><full-title>Head & neck</full-title></periodical><pages>1310-1320</pages><volume>32</volume><number>10</number><dates><year>2010</year></dates><isbn>1043-3074</isbn><accession-num>20054853</accession-num><urls></urls><electronic-resource-num>10.1002/hed.21326</electronic-resource-num></record></Cite></EndNote>[6], meanwhile, anatomical variations and chronic disease of the sublingual glands could lead to the obstruction ADDIN EN.CITE <EndNote><Cite><Author>Carlini</Author><Year>2016</Year><RecNum>9</RecNum><DisplayText><style face="superscript">[7]</style></DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276047">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Carlini, Veronica</style></author><author>Calcaterra, Valeria</author><author>Pasqua, Noemi</author><author>Guazzotti, Marinella</author><author>Fusillo, Mario</author><author>Pelizzo, Gloria</author></authors></contributors><titles><title>Plunging ranula in children: case report and literature review</title><secondary-title>Pediatric reports</secondary-title></titles><periodical><full-title>Pediatric reports</full-title></periodical><volume>8</volume><number>4</number><dates><year>2016</year></dates><accession-num>28191301</accession-num><urls></urls><electronic-resource-num>10.4081/pr.2016.6576</electronic-resource-num></record></Cite></EndNote>[7]. 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ADDIN EN.CITE.DATA [10-13]. However, the association between ranulas and SS remains unknown.In the present review, we report a 22-year-old girl with a unilateral ranula who was diagnosed as having SS 3 years later. The clinical presentation, laboratory tests, and treatment are described. According to this case and literature review, we aim to draw the attention of early clinical signs "ranulas" for SS, which are easily neglected or inappropriately treated although they are the hints to early diagnosis of SS.CASE PRESENTATIONChief complaintsOn March 1, 2019, a 22-year-old girl came to our outpatient clinic asking for serologic testing for SS.History of present illnessThe patient denied having dry eyes, dry mouth, parotid enlargement, or other clinical manifestations.History of past illnessThe patient was referred to oral surgery department for evaluation of a left painless floor-of-mouth lesion 3 years ago. The lesion had been present for 1 mo and the patient showed no difficulty eating, drinking, or speaking. Before ranula presentation, there was no obvious trauma or inducement. A pink, fluctuant, dome-shaped bulge in the floor of the mouth on the left side of the patient's lingual frenulum was found in an oral examination (Figure 1). Palpation revealed that the bulge was confined to the soft tissue. Based on these manifestations, the diagnosis of a unilateral (left) simple ranula was made. Her oral surgeon at the time did not consider anything more than a ranula, and did not perform any further tests. The patient underwent a surgery to remove the entire unilateral sublingual gland with the ranula while the lingual nerve was preserved. The pathology showed a sublingual gland (left) with chronic inflammation, lymphocytic infiltration, and focal mucus extravasation (Figure 2). There was no ranula on her right sublingual gland so far. In 2017, 10 mo after the ranula surgery, the patient developed acute left submaxillary parotid lymphadenectasis without inducement. Ultrasonic (US) examination revealed patchy hypoechoic areas in the left parotid. Two years after the first parotid lymphadenectasis, she developed acute right parotid gland swelling without inducement as before. US examination revealed scattered, foveolate hypoechoic areas, and lymphadenectasis in bilateral parotids. Treatment with antibiotic and glucocorticoid were given. One month later, US reexamination still revealed diffuse lesion in bilateral parotids and submandibular glands, which strongly suggested SS. Personal and family historyThere was no family history of autoimmune disorders.Physical examinationNo abnormality was found on physical examination.Laboratory examinationsSerologic tests showed an antinuclear antibody (ANA) titer of 1:320, with antibody positivity for the extractable nuclear SS–related antigen A (SSA) as well as an elevated erythrocyte sedimentation rate of 33 mm/h (reference range 0-20 mm/h for females), rheumatoid factor (RF) of 441 IU/mL (reference range 0-20 IU/mL), and IgG of 20.10 g/L (reference range 8.6-17.4 g/L). The unstimulated whole saliva flow rate was 1.7 mL/min (reference range > 2 mL/min). Ophthalmologically, the Schirmer test results were 30 mm on both eyes in 5 min (reference range > 10 mm). The patient’s characteristics and laboratory data are shown in Table 1. FINAL DIAGNOSISAlong with the characteristic lesions in salivary glands, a diagnosis of primary SS was made. TREATMENTTreatment with hydroxychloroquine sulfate tables (400 mg/d) and total glycosides of paeony root capsule (1200 mg/d) was started.OUTCOME AND FOLLOW-UPThe parotitis did not relapse during the 2-year follow-up.DISCUSSIONSearch strategyA review of the literature for ranulas with SS was carried out based on the following databases: Web of Science, Scopus Database, and PubMed/MEDLINE up to December 2020. The search was performed with the following MESH terms: “Sj?gren’s syndrome” and “ranulas” or “floor-of-mouth mucocele”. The studies reported on children or adults diagnosed with SS with ranulas in the past 40 years (from 1980 to 2020) were included. Literature reviewFour seriesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaWViZXJtYW48L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFy
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ADDIN EN.CITE.DATA [8,13] have been published, which contain a total of 17 patients including our case (Table 2). Among the 17 patients described, 15 were women and two were men. The turnout is consistent with previous reports that pSS is a women dominant disease ADDIN EN.CITE <EndNote><Cite><Author>Pinheiro</Author><Year>2017</Year><RecNum>10</RecNum><DisplayText><style face="superscript">[13]</style></DisplayText><record><rec-number>10</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276096">10</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Pinheiro, Juliana </style><style face="normal" font="default" size="100%">Barchelli</style></author><author>Tirapelli, Camila</author><author>Silva, Claudia Helena Lovato da</author><author>Komesu, Marilena Chinali</author><author>Petean, Flávio Calil</author><author>Louzada Junior, Paulo</author><author>León, Jorge Esquiche</author><author>Motta, Ana Carolina Fragoso</author></authors></contributors><titles><title>Oral Nodular Lesions in Patients with Sj?gren’s Syndrome: Unusual Oral Implications of a Systemic Disorder</title><secondary-title>Brazilian Dental Journal</secondary-title></titles><periodical><full-title>Brazilian Dental Journal</full-title></periodical><pages>405-412</pages><volume>28</volume><number>3</number><dates><year>2017</year></dates><isbn>0103-6440</isbn><accession-num>29297564</accession-num><urls></urls><electronic-resource-num>10.1590/0103-6440201601013</electronic-resource-num></record></Cite></EndNote>[13]. Ranulas were detected before pSS diagnosis in nine patients , and ranulas were detected simultaneously with pSS diagnosis in six patients ADDIN EN.CITE <EndNote><Cite><Author>Delli</Author><Year>2014</Year><RecNum>22</RecNum><DisplayText><style face="superscript">[14]</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608280959">22</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Delli, Konstantina</style></author><author>Spijkervet, Fred KL</author><author>Vissink, Arjan</author></authors></contributors><titles><title>Salivary gland diseases: infections, sialolithiasis and mucoceles</title><secondary-title>Saliva: Secretion and Functions</secondary-title></titles><pages>135-148</pages><volume>24</volume><dates><year>2014</year></dates><publisher>Karger Publishers</publisher><accession-num>24862601</accession-num><urls></urls><electronic-resource-num>10.1159/000358794</electronic-resource-num></record></Cite></EndNote>[14]. Only three patients were detected with ranulas after pSS was diagnosed ADDIN EN.CITE <EndNote><Cite><Author>Beckman</Author><Year>2017</Year><RecNum>19</RecNum><DisplayText><style face="superscript">[15]</style></DisplayText><record><rec-number>19</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608279021">19</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Beckman, Kenneth A</style></author><author>Luchs, Jodi</author><author>Milner, Mark S</author><author>Ambrus, Julian L</author></authors></contributors><titles><title>The potential role for early biomarker testing as part of a modern, multidisciplinary approach to Sj?gren’s syndrome diagnosis</title><secondary-title>Advances in Therapy</secondary-title></titles><periodical><full-title>Advances in Therapy</full-title></periodical><pages>799-812</pages><volume>34</volume><number>4</number><dates><year>2017</year></dates><isbn>0741-238X</isbn><accession-num>28283891</accession-num><urls></urls><electronic-resource-num>10.1007/s12325-017-0501-3</electronic-resource-num></record></Cite></EndNote>[15]. This statistic suggests that ranulas may be the early clinical signs rather than the manifestations in the late period of pSS, according to the studies by Sato et al ADDIN EN.CITE <EndNote><Cite><Author>Sato</Author><Year>2019</Year><RecNum>14</RecNum><DisplayText><style face="superscript">[11]</style></DisplayText><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276110">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Sato, Kazumichi</style></author><author>Yoshida, Yoshifumi</author><author>Sakai, Katsuhiko</author><author>Shibui, Takeo</author><author>Hashimoto, Kazuhiko</author><author>Baba, Akira</author><author>Nomura, Takeshi</author></authors></contributors><titles><title>Sj?gren’s syndrome and ranula development</title><secondary-title>Oral Diseases</secondary-title></titles><periodical><full-title>Oral Diseases</full-title></periodical><pages>1664-1667</pages><volume>25</volume><number>6</number><dates><year>2019</year></dates><isbn>1354-523X
1601-0825</isbn><accession-num>31141241</accession-num><urls></urls><electronic-resource-num>10.1111/odi.13130</electronic-resource-num></record></Cite></EndNote>[11] and Takagi et al ADDIN EN.CITE <EndNote><Cite><Author>Delli</Author><Year>2014</Year><RecNum>22</RecNum><DisplayText><style face="superscript">[14]</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608280959">22</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Delli, Konstantina</style></author><author>Spijkervet, Fred KL</author><author>Vissink, Arjan</author></authors></contributors><titles><title>Salivary gland diseases: infections, sialolithiasis and mucoceles</title><secondary-title>Saliva: Secretion and Functions</secondary-title></titles><pages>135-148</pages><volume>24</volume><dates><year>2014</year></dates><publisher>Karger Publishers</publisher><accession-num>24862601</accession-num><urls></urls><electronic-resource-num>10.1159/000358794</electronic-resource-num></record></Cite></EndNote>[10]. The time interval from discovery of ranulas to the diagnosis of pSS is 0 to 7 years, which indicates that pSS occurs insidiously. In addition to presenting with unilateral or bilateral ranulas, six (6/17) patients were reported to have sicca symptoms including recurrent parotitis, dry eyes, dry mouth, and dental cariesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWFuczwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [8,9,12,13], and only one (1/17) patient was reported to have extra-glandular system involvement (joint pain) ADDIN EN.CITE <EndNote><Cite><Author>Lieberman</Author><Year>2018</Year><RecNum>12</RecNum><DisplayText><style face="superscript">[9]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276101">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Lieberman, Scott M.</style></author><author>Lu, Annamaria</author><author>McGill, Monica M.</author></authors></contributors><titles><title>Oral lesions as presenting feature of childhood Sj?gren syndrome</title><secondary-title>International Journal of Pediatric Otorhinolaryngology</secondary-title></titles><periodical><full-title>International Journal of Pediatric Otorhinolaryngology</full-title></periodical><pages>303-304</pages><volume>113</volume><dates><year>2018</year></dates><isbn>01655876</isbn><accession-num>29764682</accession-num><urls></urls><electronic-resource-num>10.1016/j.ijporl.2018.05.007</electronic-resource-num></record></Cite></EndNote>[9]. Six surgical pathological specimens showed the lymphocytic infiltration. Anti-ANA and anti-SSA were detected in all patients. With regard to the treatment of ranulas, ten (10/17) patients were surgically treated, one (1/17) naturally resolved, and six (6/17) were uncertain. The detailed treatment of pSS was not described in most patients. It may be because that the cases were from oral surgeons or otolaryngologists. SS is a complex and multisystem disorder. The SS patients with both glandular and extra-glandular features suffer a poor prognosis. The advanced stage symptoms of tooth loss, severe fatigue, and joint and muscle pain impair the quality of life. Moreover, the development of lymphomas increases the mortality ADDIN EN.CITE <EndNote><Cite><Author>Brito-Zerón</Author><Year>2016</Year><RecNum>16</RecNum><DisplayText><style face="superscript">[16]</style></DisplayText><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608278479">16</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Brito-Zerón, Pilar</style></author><author>Baldini, Chiara</author><author>Bootsma, Hendrika</author><author>Bowman, Simon J.</author><author>Jonsson, Roland</author><author>Mariette, Xavier</author><author>Sivils, Kathy</author><author>Theander, Elke</author><author>Tzioufas, Athanasios</author><author>Ramos-Casals, Manuel</author></authors></contributors><titles><title>Sj?gren syndrome</title><secondary-title>Nature Reviews Disease Primers</secondary-title></titles><periodical><full-title>Nature Reviews Disease Primers</full-title></periodical><volume>2</volume><number>1</number><dates><year>2016</year></dates><isbn>2056-676X</isbn><accession-num>27383445</accession-num><urls></urls><electronic-resource-num>10.1038/nrdp.2016.47</electronic-resource-num></record></Cite></EndNote>[16]. In clinical practice, dryness such as dry eyes and dry mouth often indicates that glandular secretion has been disrupted by chronic soakage of inflammatory cells, which may be too late for treatment and would impair the effect of intervention.There are several diagnostic criteria for SS in the past two decades, including the 1999 revised Japanese Ministry of Health criteria for diagnosis of SS (JPN), 2002 American-European Consensus Group classification criteria for SS, 2012 ACR classification criteria for SS, and 2016 ACR-European League Against Rheumatism Classification Criteria ADDIN EN.CITE <EndNote><Cite><Author>Tsuboi</Author><Year>2017</Year><RecNum>5</RecNum><DisplayText><style face="superscript">[17]</style></DisplayText><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608274009">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Tsuboi, Hiroto</style></author><author>Hagiwara, Shinya</author><author>Asashima, Hiromitsu</author><author>Takahashi, Hiroyuki</author><author>Hirota, Tomoya</author><author>Noma, Hisashi</author><author>Umehara, Hisanori</author><author>Kawakami, Atsushi</author><author>Nakamura, Hideki</author><author>Sano, Hajime</author></authors></contributors><titles><title>Comparison of performance of the 2016 ACR-EULAR classification criteria for primary Sj?gren's syndrome with other sets of criteria in Japanese patients</title><secondary-title>Annals of the rheumatic diseases</secondary-title></titles><periodical><full-title>Annals of the rheumatic diseases</full-title></periodical><pages>1980-1985</pages><volume>76</volume><number>12</number><dates><year>2017</year></dates><isbn>0003-4967</isbn><accession-num>28330998</accession-num><urls></urls><electronic-resource-num>10.1136/annrheumdis-2016-210758</electronic-resource-num></record></Cite></EndNote>[17]. However, these criteria are mainly to confirm the diagnosis of SS when symptoms have progressed to a certain level, but not to identify the early symptoms. Several valuable biomarkers have been recently identified for early auxiliary diagnosis/stratification of SS ADDIN EN.CITE <EndNote><Cite><Author>Baldini</Author><Year>2018</Year><RecNum>17</RecNum><DisplayText><style face="superscript">[18]</style></DisplayText><record><rec-number>17</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608278737">17</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Baldini, Chiara</style></author><author>Ferro, Francesco</author><author>Elefante, Elena</author><author>Bombardieri, Stefano</author></authors></contributors><titles><title>Biomarkers for Sj?gren’s syndrome</title><secondary-title>Biomarkers in medicine</secondary-title></titles><periodical><full-title>Biomarkers in medicine</full-title></periodical><pages>275-286</pages><volume>12</volume><number>3</number><dates><year>2018</year></dates><isbn>1752-0363</isbn><accession-num>29460647</accession-num><urls></urls><electronic-resource-num>10.2217/bmm-2017-0297</electronic-resource-num></record></Cite></EndNote>[18]. 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ADDIN EN.CITE.DATA [15,19]. However, in the absence of the typical clinical symptoms of SS (such as dry eyes, dry mouth, or recurrent parotitis), these tests are not routinely performed. Besides, the diversity of symptoms also makes early diagnosis and intervention of SS difficult. Therefore, it is vital to detect early clinical signs in order to treat SS properly in its early stage and to achieve better clinical outcomes.Ranulas were detected before or at the same time of SS diagnosis in 82.35% (14/17) of patients, which is much higher than the incidence of ranulas after SS diagnosis as a complication (3/17). Ranulas are rare diseases, which have a predominance among teenagers and young adults, and the incidence is 2 per 1000 ADDIN EN.CITE <EndNote><Cite><Author>Huzaifa</Author><Year>2020</Year><RecNum>23</RecNum><DisplayText><style face="superscript">[20]</style></DisplayText><record><rec-number>23</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608778634">23</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Huzaifa, Muhammad</style></author><author>Soni, Abhinandan</author></authors></contributors><titles><title>Mucocele And Ranula</title><secondary-title>StatPearls [Internet]</secondary-title></titles><periodical><full-title>StatPearls [Internet]</full-title></periodical><dates><year>2020</year></dates><accession-num>32809690</accession-num><urls></urls></record></Cite></EndNote>[20]. Recently, Takagi et al ADDIN EN.CITE <EndNote><Cite><Author>Takagi</Author><Year>2020</Year><RecNum>15</RecNum><DisplayText><style face="superscript">[10]</style></DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276115">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Takagi, Yukinori</style></author><author>Hashimoto, Kunio</author><author>Katayama, Ikuo</author><author>Eida, Sato</author><author>Sumi, Misa</author></authors></contributors><titles><title>Juvenile primary Sj?gren’s syndrome with ranula: is ranula a clinical sign that leads to early detection of Sj?gren’s syndrome?</title><secondary-title>Oral Radiology</secondary-title></titles><periodical><full-title>Oral Radiology</full-title></periodical><dates><year>2020</year></dates><isbn>0911-6028
1613-9674</isbn><accession-num>32803681</accession-num><urls></urls><electronic-resource-num>10.1007/s11282-020-00473-8</electronic-resource-num></record></Cite></EndNote>[10] examined 50 patients with ranulas undergoing magnetic resonance imaging (MRI). Eleven patients were suspected to have SS, and seven of them were then confirmed by the rheumatologist according to the Japanese Ministry of Health criteria (1999) ADDIN EN.CITE <EndNote><Cite><Author>Takagi</Author><Year>2020</Year><RecNum>15</RecNum><DisplayText><style face="superscript">[10]</style></DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276115">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Takagi, Yukinori</style></author><author>Hashimoto, Kunio</author><author>Katayama, Ikuo</author><author>Eida, Sato</author><author>Sumi, Misa</author></authors></contributors><titles><title>Juvenile primary Sj?gren’s syndrome with ranula: is ranula a clinical sign that leads to early detection of Sj?gren’s syndrome?</title><secondary-title>Oral Radiology</secondary-title></titles><periodical><full-title>Oral Radiology</full-title></periodical><dates><year>2020</year></dates><isbn>0911-6028
1613-9674</isbn><accession-num>32803681</accession-num><urls></urls><electronic-resource-num>10.1007/s11282-020-00473-8</electronic-resource-num></record></Cite></EndNote>[10]. It is worth noting that the incidence of SS patients was significantly increased among patients with ranulas. The combination of these patients and ours suggests that ranulas may be the early clinical signs of SS.SS is characterized by lymphocytic infiltration of exocrine glands including the sublingual gland. Among patients with SS in early stage, ranulas usually appear without obvious trauma or cause. Sato et al ADDIN EN.CITE <EndNote><Cite><Author>Delli</Author><Year>2014</Year><RecNum>22</RecNum><DisplayText><style face="superscript">[14]</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608280959">22</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Delli, Konstantina</style></author><author>Spijkervet, Fred KL</author><author>Vissink, Arjan</author></authors></contributors><titles><title>Salivary gland diseases: infections, sialolithiasis and mucoceles</title><secondary-title>Saliva: Secretion and Functions</secondary-title></titles><pages>135-148</pages><volume>24</volume><dates><year>2014</year></dates><publisher>Karger Publishers</publisher><accession-num>24862601</accession-num><urls></urls><electronic-resource-num>10.1159/000358794</electronic-resource-num></record></Cite></EndNote>[11] hypothesized that ranulas could be caused by the constriction of ducts in the early stage of SS, especially when the obstruction is close to the opening. Considering that acinar atrophy and loss occur in the advanced stage, ranulas are rarely due to the decrease of saliva levels ADDIN EN.CITE <EndNote><Cite><Author>Bayetto</Author><Year>2010</Year><RecNum>20</RecNum><DisplayText><style face="superscript">[21]</style></DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608279257">20</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Bayetto, K</style></author><author>Logan, RM</author></authors></contributors><titles><title>Sj?gren’s syndrome: a review of aetiology, pathogenesis, diagnosis and management</title><secondary-title>Australian dental journal</secondary-title></titles><periodical><full-title>Australian dental journal</full-title></periodical><pages>39-47</pages><volume>55</volume><dates><year>2010</year></dates><isbn>0045-0421</isbn><accession-num>20553243</accession-num><urls></urls><electronic-resource-num>10.1111/j.1834-7819.2010.01197.x</electronic-resource-num></record></Cite></EndNote>[21]. Indeed, only three patients had a ranula after SS diagnosis in our review.Recurrent parotitis is a common symptom of SS, which is caused by an ascending ductal infection and the assistant of decreased salivary duct lavage ADDIN EN.CITE <EndNote><Cite><Author>Myers</Author><Year>2007</Year><RecNum>21</RecNum><DisplayText><style face="superscript">[22]</style></DisplayText><record><rec-number>21</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608280610">21</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Myers, Eugene N</style></author><author>Ferris, Robert L</author></authors></contributors><titles><title>Salivary gland disorders</title></titles><dates><year>2007</year></dates><publisher>Springer Science & Business Media</publisher><isbn>3540470727</isbn><urls></urls></record></Cite></EndNote>[22], whereas ranulas usually happen when saliva production is unaffected. This suggests that ranulas occur earlier than parotitis. In our case, the first manifestation of parotitis developed 10 mo after the unilateral ranula. Besides, the patient reported by Takagi et al ADDIN EN.CITE <EndNote><Cite><Author>Takagi</Author><Year>2020</Year><RecNum>15</RecNum><DisplayText><style face="superscript">[10]</style></DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276115">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Takagi, Yukinori</style></author><author>Hashimoto, Kunio</author><author>Katayama, Ikuo</author><author>Eida, Sato</author><author>Sumi, Misa</author></authors></contributors><titles><title>Juvenile primary Sj?gren’s syndrome with ranula: is ranula a clinical sign that leads to early detection of Sj?gren’s syndrome?</title><secondary-title>Oral Radiology</secondary-title></titles><periodical><full-title>Oral Radiology</full-title></periodical><dates><year>2020</year></dates><isbn>0911-6028
1613-9674</isbn><accession-num>32803681</accession-num><urls></urls><electronic-resource-num>10.1007/s11282-020-00473-8</electronic-resource-num></record></Cite></EndNote>[10] developed parotitis 9 mo after SS diagnosis, and the patient reported by Lieberman et al ADDIN EN.CITE <EndNote><Cite><Author>Lieberman</Author><Year>2018</Year><RecNum>12</RecNum><DisplayText><style face="superscript">[9]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276101">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Lieberman, Scott M.</style></author><author>Lu, Annamaria</author><author>McGill, Monica M.</author></authors></contributors><titles><title>Oral lesions as presenting feature of childhood Sj?gren syndrome</title><secondary-title>International Journal of Pediatric Otorhinolaryngology</secondary-title></titles><periodical><full-title>International Journal of Pediatric Otorhinolaryngology</full-title></periodical><pages>303-304</pages><volume>113</volume><dates><year>2018</year></dates><isbn>01655876</isbn><accession-num>29764682</accession-num><urls></urls><electronic-resource-num>10.1016/j.ijporl.2018.05.007</electronic-resource-num></record></Cite></EndNote>[9] had no parotitis or parotid gland swelling throughout. Oral lesions are characteristics of Sj?gren syndrome in childhood. No parotid mucocele or submandibular gland mucocele has been reported in SS. We hypothesized that this might be the structure of the glands themselves. The duct of the parotid or submandibular gland is covered with thicker glandular tissue and muscle; however, the sublingual gland is exposed at the base of the mouth. The ranulas are routinely treated by marsupialization or sublingual gland surgical removal ADDIN EN.CITE <EndNote><Cite><Author>Delli</Author><Year>2014</Year><RecNum>22</RecNum><DisplayText><style face="superscript">[14]</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608280959">22</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Delli, Konstantina</style></author><author>Spijkervet, Fred KL</author><author>Vissink, Arjan</author></authors></contributors><titles><title>Salivary gland diseases: infections, sialolithiasis and mucoceles</title><secondary-title>Saliva: Secretion and Functions</secondary-title></titles><pages>135-148</pages><volume>24</volume><dates><year>2014</year></dates><publisher>Karger Publishers</publisher><accession-num>24862601</accession-num><urls></urls><electronic-resource-num>10.1159/000358794</electronic-resource-num></record></Cite></EndNote>[14]. Patients with new-onset ranulas usually visited stomatology or otolaryngology department, and the doctors would not routinely perform serological examinations or detailed glandular tests, unless patients show other symptoms of autoimmune diseases. Therefore, SS was easily neglected even with the discovery of ranulas. In the five patients diagnosed with ranulas and SS simultaneously, the results of MRI examinations in four patients revealed chronic sialadenitisPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWFuczwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [8,11], and the surgical pathological specimen of one patient showed lymphocytic infiltration, which prompted the imaging detection of exocrine glands and serological examinations of SS in patients who had not yet developed symptoms such as dry mouth, dry eyes, or parotitis. Thus, we recommend ranula patients to undergo postoperative pathological examination and imaging detection, which can be helpful for early detection of SS. Besides, US is a convenient and inexpensive procedure and should be considered a suitable tool for diagnosing juvenile SS ADDIN EN.CITE <EndNote><Cite><Author>Takagi</Author><Year>2020</Year><RecNum>15</RecNum><DisplayText><style face="superscript">[10]</style></DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276115">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Takagi, Yukinori</style></author><author>Hashimoto, Kunio</author><author>Katayama, Ikuo</author><author>Eida, Sato</author><author>Sumi, Misa</author></authors></contributors><titles><title>Juvenile primary Sj?gren’s syndrome with ranula: is ranula a clinical sign that leads to early detection of Sj?gren’s syndrome?</title><secondary-title>Oral Radiology</secondary-title></titles><periodical><full-title>Oral Radiology</full-title></periodical><dates><year>2020</year></dates><isbn>0911-6028
1613-9674</isbn><accession-num>32803681</accession-num><urls></urls><electronic-resource-num>10.1007/s11282-020-00473-8</electronic-resource-num></record></Cite></EndNote>[10]. CONCLUSIONIn the present review, we summarize all published papers on SS and ranulas. We hope that these cases will raise the awareness of clinicians that ranulas are early clinical signs of SS. As early diagnosis and early intervention of SS are important to obtain better outcomes, we recommend histopathological test after sublingual adenectomy and imaging detection of exocrine gland for the patients with ranulas. ACKNOWLEDGEMENTSWe thank the Innovative Research Team of High-level Local Universities in Shanghai.REFERENCES1 Thorne I, Sutcliffe N. Sj?gren's syndrome. Br J Hosp Med (Lond) 2017; 78: 438-442 [PMID: 28783408 DOI: 10.12968/hmed.2017.78.8.438]2 Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F, Zhong R. Epidemiology of primary Sj?gren's syndrome: a systematic review and meta-analysis. Ann Rheum Dis 2015; 74: 1983-1989 [PMID: 24938285 DOI: 10.1136/annrheumdis-2014-205375]3 Ramos-Casals M, Solans R, Rosas J, Camps MT, Gil A, Del Pino-Montes J, Calvo-Alen J, Jiménez-Alonso J, Micó ML, Beltrán J, Belenguer R, Pallarés L; GEMESS Study Group. Primary Sj?gren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 2008; 87: 210-219 [PMID: 18626304 DOI: 10.1097/MD.0b013e318181e6af]4 Mavragani CP, Moutsopoulos HM. Sj?gren syndrome. Cmaj 2014; 186: E579-E586 [PMID: 24566651 DOI: 10.1503/cmaj.122037]5 Morton RP. Surgical Management of Ranula Revisited. World J Surg 2018; 42: 3062-3063 [PMID: 29750326 DOI: 10.1007/s00268-018-4666-y]6 Harrison JD. Modern management and pathophysiology of ranula: literature review. Head Neck 2010; 32: 1310-1320 [PMID: 20054853 DOI: 10.1002/hed.21326]7 Carlini V, Calcaterra V, Pasqua N, Guazzotti M, Fusillo M, Pelizzo G. Plunging Ranula in Children: Case Report and Literature Review. Pediatr Rep 2016; 8: 6576 [PMID: 28191301 DOI: 10.4081/pr.2016.6576]8 Means C, Aldape MA, King E. Pediatric primary Sj?gren syndrome presenting with bilateral ranulas: A case report and systematic review of the literature. Int J Pediatr Otorhinolaryngol 2017; 101: 11-19 [PMID: 28964279 DOI: 10.1016/j.ijporl.2017.07.019]9 Lieberman SM, Lu A, McGill MM. Oral lesions as presenting feature of childhood Sj?gren syndrome. Int J Pediatr Otorhinolaryngol 2018; 113: 303-304 [PMID: 29764682 DOI: 10.1016/j.ijporl.2018.05.007]10 Takagi Y, Hashimoto K, Katayama I, Eida S, Sumi M. Juvenile primary Sj?gren's syndrome with ranula: is ranula a clinical sign that leads to early detection of Sj?gren's syndrome? Oral Radiol 2021; 37: 328-335 [PMID: 32803681 DOI: 10.1007/s11282-020-00473-8]11 Sato K, Yoshida Y, Sakai K, Shibui T, Hashimoto K, Baba A, Nomura T. Sj?gren's syndrome and ranula development. Oral Dis 2019; 25: 1664-1667 [PMID: 31141241 DOI: 10.1111/odi.13130]12 Katayama I, Yamazaki S, Nishioka K. Giant mucocele of oral cavity as a mucocutaneous manifestation of Sj?gren syndrome. J Dermatol 1993; 20: 238-241 [PMID: 8315114 DOI: 10.1111/j.1346-8138.1993.tb03868.x]13 Pinheiro JB, Tirapelli C, Silva CHLD, Komesu MC, Petean FC, Louzada Junior P, León JE, Motta ACF. Oral Nodular Lesions in Patients with Sj?gren's Syndrome: Unusual Oral Implications of a Systemic Disorder. Braz Dent J 2017; 28: 405-412 [PMID: 29297564 DOI: 10.1590/0103-6440201601013]14 Delli K, Spijkervet FK, Vissink A. Salivary gland diseases: infections, sialolithiasis and mucoceles. Monogr Oral Sci 2014; 24: 135-148 [PMID: 24862601 DOI: 10.1159/000358794]15 Beckman KA, Luchs J, Milner MS, Ambrus JL Jr. The Potential Role for Early Biomarker Testing as Part of a Modern, Multidisciplinary Approach to Sj?gren's Syndrome Diagnosis. Adv Ther 2017; 34: 799-812 [PMID: 28283891 DOI: 10.1007/s12325-017-0501-3]16 Brito-Zerón P, Baldini C, Bootsma H, Bowman SJ, Jonsson R, Mariette X, Sivils K, Theander E, Tzioufas A, Ramos-Casals M. Sj?gren syndrome. Nat Rev Dis Primers 2016; 2: 16047 [PMID: 27383445 DOI: 10.1038/nrdp.2016.47]17 Tsuboi H, Hagiwara S, Asashima H, Takahashi H, Hirota T, Noma H, Umehara H, Kawakami A, Nakamura H, Sano H, Tsubota K, Ogawa Y, Takamura E, Saito I, Inoue H, Nakamura S, Moriyama M, Takeuchi T, Tanaka Y, Hirata S, Mimori T, Matsumoto I, Sumida T. Comparison of performance of the 2016 ACR-EULAR classification criteria for primary Sj?gren's syndrome with other sets of criteria in Japanese patients. Ann Rheum Dis 2017; 76: 1980-1985 [PMID: 28330998 DOI: 10.1136/annrheumdis-2016-210758]18 Baldini C, Ferro F, Elefante E, Bombardieri S. Biomarkers for Sj?gren's syndrome. Biomark Med 2018; 12: 275-286 [PMID: 29460647 DOI: 10.2217/bmm-2017-0297]19 Shen L, Suresh L, Lindemann M, Xuan J, Kowal P, Malyavantham K, Ambrus JL Jr. Novel autoantibodies in Sjogren's syndrome. Clin Immunol 2012; 145: 251-255 [PMID: 23123440 DOI: 10.1016/j.clim.2012.09.013]20 Huzaifa M, Soni A. Mucocele And Ranula 2021 [PMID: 32809690]21 Bayetto K, Logan RM. Sj?gren's syndrome: a review of aetiology, pathogenesis, diagnosis and management. Aust Dent J 2010; 55 Suppl 1: 39-47 [PMID: 20553243 DOI: 10.1111/j.1834-7819.2010.01197.x]22 Myers EN, Ferris RL. Salivary gland disorders. Springer Science & Business Media, 2007FootnotesInformed consent statement: Informed consent was obtained from the patient for her inclusion in this report.Conflict-of-interest statement: The authors declare no potential con?icts of interest with respect to the research, authorship, and/or publication of this article.CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: source: Unsolicited manuscriptPeer-review started: March 9, 2021First decision: April 4, 2021Article in press: Specialty type: RheumatologyCountry/Territory of origin: ChinaPeer-review report’s scientific quality classificationGrade A (Excellent): 0Grade B (Very good): B, B, B, BGrade C (Good): 0Grade D (Fair): 0Grade E (Poor): 0P-Reviewer: Erkut B, Kai K, Liakina V S-Editor: Gong ZM L-Editor: Wang TQ P-Editor: Figure LegendsFigure 1 Clinical picture of the unilateral (left) simple ranula. Figure 2 Histopathological findings of the sublingual gland. Chronic multifocal lymphocytic infiltration and ductal epithelial destruction are visible in the sublingual gland. Hematoxylin and eosin staining; magnification: × 40 (A) and × 100 (B). Table 1 Laboratory parameters of the patient with primary Sj?gren’s syndrome who had a ranula beforeLaboratory parameters Day 1 (March 1 on outpatient service)After 2 wk of treatmentAfter 3 mo of treatmentAfter 6 mo of treatmentAfter one year and three mo of treatmentWBC (× 109/L)3.42↓3.974.254.794.25Neutrophils, %49.1↓55.855.660.255.6Lymphocytes, %43.3↑35.736.631.936.6ESR (mm/h)33↑1710177ALT (U/L)2318171324AST (U/L)3123272429Creatinine (μmol/L)6766867668EGFR (ml/min)110.5112.581.794.2107.8ANA1:320--1:3201:320Anti-dsDNA antibodyNegative--NegativeNegativeAnti-RNP/Sm antibodyNegative--NegativeNegativeAnti-Sm antibodyNegative--NegativeNegativeAnti-SSA antibodyPositive--PositivePositiveAnti-SSB antibodyPositive--PositivePositiveIgA (g/L)1.60--1.661.57IgG (g/L)20.10↑--15.9↑14.47IgM (g/L)1.15--1.001.08C3 (g/L)0.69↓--0.75↓1.05C4 (g/L)0.18--0.190.26RF (IU/ml)441↑--165↑46.86↑WBC: white blood cells; ESR: erythrocyte sedimentation rate; ALT: alanine aminotransferase; AST: aspartate aminotransferase; EGFR: estimate glomerular filtration rate; ANA: anti-nuclear antibody; dsDNA: double-stranded DNA; RNP: ribonucleoprotein; SSA: Sj?gren’s syndrome–related antigen A; SSB: Sj?gren’s syndrome–related antigen B; Ig: immunoglobulin; C3: complement component 3; C4: complement component 4; RF: rheumatoid factor.Table 2 Review of primary Sj?gren’s syndrome patients associated with ranulasRef.CountryNo. of casesAge/genderFirst visit departmentType of ranulaSicca symptomsExtra-landular symp-tomsTime interval between pSS diagnosis and detection of ranula Antibody positivityTreatment of ranulaTreatment of pSSOutcomeKatayama et al ADDIN EN.CITE <EndNote><Cite><Author>Ichiro</Author><Year>1993</Year><RecNum>11</RecNum><DisplayText><style face="superscript">[12]</style></DisplayText><record><rec-number>11</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276096">11</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Ichiro,Katayama</style></author><author>Sayuri,Yamazaki</author><author>Kiyoshi,Nishioka</author></authors></contributors><titles><title>Giant Mucocele of Oral Cavity as a Mucocutaneous Manifestation ofSjogren Syndrome</title><secondary-title>The journal of Dennatology</secondary-title></titles><periodical><full-title>The journal of Dennatology</full-title></periodical><pages>238-241</pages><volume>20</volume><dates><year>1993</year></dates><accession-num>8315114</accession-num><urls></urls><electronic-resource-num>10.1111/j.1346-8138.1993.tb03868.x</electronic-resource-num></record></Cite></EndNote>[12], 1993Japan233, F34, FPatient 1: dermato-logy departmentPatient 2: NAUnilateralPatient 1: oral dryness, caries, alopecia, and pruritic skin rashPatient 2: oral drynessNAPatient 1: after SSPatient 2: 7 yr after SSANA, SSASurgically treatedNANAPinheiro et al ADDIN EN.CITE <EndNote><Cite><Author>Pinheiro</Author><Year>2017</Year><RecNum>10</RecNum><DisplayText><style face="superscript">[13]</style></DisplayText><record><rec-number>10</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276096">10</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Pinheiro, Juliana </style><style face="normal" font="default" size="100%">Barchelli</style></author><author>Tirapelli, Camila</author><author>Silva, Claudia Helena Lovato da</author><author>Komesu, Marilena Chinali</author><author>Petean, Flávio Calil</author><author>Louzada Junior, Paulo</author><author>León, Jorge Esquiche</author><author>Motta, Ana Carolina Fragoso</author></authors></contributors><titles><title>Oral Nodular Lesions in Patients with Sj?gren’s Syndrome: Unusual Oral Implications of a Systemic Disorder</title><secondary-title>Brazilian Dental Journal</secondary-title></titles><periodical><full-title>Brazilian Dental Journal</full-title></periodical><pages>405-412</pages><volume>28</volume><number>3</number><dates><year>2017</year></dates><isbn>0103-6440</isbn><accession-num>29297564</accession-num><urls></urls><electronic-resource-num>10.1590/0103-6440201601013</electronic-resource-num></record></Cite></EndNote>[13], 2017Brazil137, FClinic of the Dental SchoolUnilateralIrritation of the eyes, enlargement of the parotid glands, and dry mouthNA1 yr after SSANA, SSA and SSBSurgically treatedPrednisone, methotrexate, chloroquine diphosphate, and artificial tears and salivaImproving all signs and symptomsMeans et al ADDIN EN.CITE <EndNote><Cite><Author>Means</Author><Year>2017</Year><RecNum>13</RecNum><DisplayText><style face="superscript">[8]</style></DisplayText><record><rec-number>13</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276106">13</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Means, Casey</style></author><author>Aldape, Mark A.</author><author>King, Ericka</author></authors></contributors><titles><title>Pediatric primary Sj?gren syndrome presenting with bilateral ranulas: A case report and systematic review of the literature</title><secondary-title>International Journal of Pediatric Otorhinolaryngology</secondary-title></titles><periodical><full-title>International Journal of Pediatric Otorhinolaryngology</full-title></periodical><pages>11-19</pages><volume>101</volume><dates><year>2017</year></dates><isbn>01655876</isbn><accession-num>28964279</accession-num><urls></urls><electronic-resource-num>10.1016/j.ijporl.2017.07.019</electronic-resource-num></record></Cite></EndNote>[8], 2017United States110, MPediatric Otolaryngo-logy clinicBilateralBilateral recurrent parotitis, dry eyes, dental cariesNA4 yr before SSANA, SSA and SSBTransoral excision and marsupial-zationRoutine follow-upNALieberman et al ADDIN EN.CITE <EndNote><Cite><Author>Lieberman</Author><Year>2018</Year><RecNum>12</RecNum><DisplayText><style face="superscript">[9]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276101">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Lieberman, Scott M.</style></author><author>Lu, Annamaria</author><author>McGill, Monica M.</author></authors></contributors><titles><title>Oral lesions as presenting feature of childhood Sj?gren syndrome</title><secondary-title>International Journal of Pediatric Otorhinolaryngology</secondary-title></titles><periodical><full-title>International Journal of Pediatric Otorhinolaryngology</full-title></periodical><pages>303-304</pages><volume>113</volume><dates><year>2018</year></dates><isbn>01655876</isbn><accession-num>29764682</accession-num><urls></urls><electronic-resource-num>10.1016/j.ijporl.2018.05.007</electronic-resource-num></record></Cite></EndNote>[9], 2018United States212, F 8, FPatient 1: Dental Department; Patient 2: Otolaryngo-logyPatient 1: Bilateral; Patient 2: UnilateralPatient 1: Recurrent parotid gland discomfort; Patient 2: NoPatient 1: Severe joint pain; Patient 2: noPatient 1: 7 yr before SS; Patient 2: simultaneousPatient 1: SS-APatient 2: ANA, SSA, SSB and RFPatient 1: surgically treated; Patient 2: Surgically treatedNAPatient 1: NAPatient 2: Developed significant dry eyesSato et al ADDIN EN.CITE <EndNote><Cite><Author>Sato</Author><Year>2019</Year><RecNum>14</RecNum><DisplayText><style face="superscript">[11]</style></DisplayText><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276110">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Sato, Kazumichi</style></author><author>Yoshida, Yoshifumi</author><author>Sakai, Katsuhiko</author><author>Shibui, Takeo</author><author>Hashimoto, Kazuhiko</author><author>Baba, Akira</author><author>Nomura, Takeshi</author></authors></contributors><titles><title>Sj?gren’s syndrome and ranula development</title><secondary-title>Oral Diseases</secondary-title></titles><periodical><full-title>Oral Diseases</full-title></periodical><pages>1664-1667</pages><volume>25</volume><number>6</number><dates><year>2019</year></dates><isbn>1354-523X
1601-0825</isbn><accession-num>31141241</accession-num><urls></urls><electronic-resource-num>10.1111/odi.13130</electronic-resource-num></record></Cite></EndNote>[11], 2019Japan366, F 30, F26, FDepartment of Oral MedicineNANANASimultaneousSSA, SSBPatients 1 and 2: Surgically treated; Patient 3: Naturally resolved NANATakagi et al ADDIN EN.CITE <EndNote><Cite><Author>Takagi</Author><Year>2020</Year><RecNum>15</RecNum><DisplayText><style face="superscript">[10]</style></DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="vxt2axet520vvfevdf1px298ax2zpprp0arf" timestamp="1608276115">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Takagi, Yukinori</style></author><author>Hashimoto, Kunio</author><author>Katayama, Ikuo</author><author>Eida, Sato</author><author>Sumi, Misa</author></authors></contributors><titles><title>Juvenile primary Sj?gren’s syndrome with ranula: is ranula a clinical sign that leads to early detection of Sj?gren’s syndrome?</title><secondary-title>Oral Radiology</secondary-title></titles><periodical><full-title>Oral Radiology</full-title></periodical><dates><year>2020</year></dates><isbn>0911-6028
1613-9674</isbn><accession-num>32803681</accession-num><urls></urls><electronic-resource-num>10.1007/s11282-020-00473-8</electronic-resource-num></record></Cite></EndNote>[10], 2020Japan712, M33, F41, F43, F46, F48, F51, FNAPatient 1: Bilateral, plunging; Patients 2-7: NA, simpleNANAPatient 1: simultaneous; Patients 2-7: NA, but before SSPatient 1: ANA, SSA, SSB and RF; Patients 2-7: NAPatient 1: Open fenestration; Patients 2-7: NAPatient 1: Mizoribine and cortices-teroid medication; Patients 2-7: NAPatient 1: Developed parotitis after 9 mo; Patients 2-7: NAPresent caseChina125, FOral surgeryUnilateral, simpleRanula and recurrent parotitisNo3 yr before SSANA, SSA and RFSurgically treatedHydroxychloroquine sulfate and total glycosides of paeony root capsule No symptomsM: male; F: female; pSS: primary Sj?gren’s syndrome; ANA: antinuclear antibodies; SSA: Sj?gren’s syndrome–related antigen A; SSB: Sj?gren’s syndrome–related antigen B; RF: rheumatoid factor; NA: not available. ................
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