RDS | Rheumatologic Dermatology Society



LUPUSUltraviolet B generates Type 1 Interferon and induces autoantibody-mediated disease in a mouse model of cutaneous lupus. Sontheimer , Clayton, Elkon ,?Keith.Background/Purpose: Photosensitivity is a common symptom in patients with systemic lupus erythematosus (SLE) and lupus skin lesions often contain plasmacytoid dendritic cells (pDC). The mechanisms linking ultraviolet (UV) light to inflammation and cutaneous flares is not well understood. While in vitro experiments have suggested that UV-induced apoptosis exposes lupus-specific nuclear antigens and immune complex mediated inflammation, this has not been shown in vivo. Here, we asked whether, and under what conditions, UVB-induced inflammation could induce Type I interferon (IFN-I) and the roles of pDCs and also autoantibodies in cutaneous lupus. Methods: Shaved C57BL/6 (B6), IFNAR KO, BDCA2 DTR, and huFcgR2a transgenic mice were irradiated with narrowband UVB at 100 mJ/cm2/day for 5 consecutive days. To induce interface dermatitis, shaved and depilated mice were subject to 15 strokes of tape stripping using medical tape (3M). Serial punch biopsies (6 mm) were obtained at 3, 24, and 72 hrs following UVB exposure or tape stripping. PDCs were detected in enzyme digested skin samples by flow cytometry (CD45+, Ly6C+, PDCA1+, CD11c+, Siglec H+). Skin samples were examined for mRNA expression by QPCR of pro-inflammatory cytokines and Interferon Stimulated Genes (ISG). mRNA fold change was calculated by comparison with non-irradiated control mice. In experiments with huFcgR2a Tg mice, mice were irradiated as above but injected i.p. at the time of the final UVB exposure with purified immunoglobulin pooled from human lupus patients and the skin was examined by immunofluorescence for the presence of human IgG. Results: Whereas tape stripping induced a robust ISG response associated with the presence of pDC in the skin, repeated UVB exposure induced a more modest IFN-I skin response with bimodal peaks at 3 and 72 hrs when compared to control mice (p<0.05, n=20). UVB-irradiated IFNAR KO mice had increased levels of pro-inflammatory cytokines TNFα and IL-6 at (p<0.01 at 3 and 24 hr time points, n=12-13) and had increased levels of inflammation by visual scoring suggesting a protective role for IFN-I. Interestingly, pDCs did not appear to be the source of IFN following UVB as pDC-depleted BDCA2 DTR mice maintained moderate expression of ISGs. Immunoglobulin from human lupus patients, but not IVIG, localized to the skin at the dermal/epidermal junction following UVB of FcgR2A transgenic and wild-type mice, but FcγR2a signaling was required for cellular uptake and enhanced Type 1 IFN signaling (p<0.05, n=5-9).Conclusion: In the normal host, repeated doses of UVB induce a protective, pDC-independent Type1 IFN response in the skin that attenuates pro-inflammatory signals and limits tissue damage. In contrast, in situations associated with the presence of autoantibodies as occurs in lupus, the antibodies bind to UVB-exposed antigen, deposit in the skin and require Fcgr2a-mediated uptake to produce enhanced expression of IFN-I. This novel FcgR2a mouse model of cutaneous lupus establishes the role of UVB in exposing otherwise sequestered nuclear antigens and in facilitating immune-complex mediated skin disease in lupus.Unmet need for mental health care in skin-predominant lupus erythematosus and dermatomyositisJordan C. Achtman and Victoria P. WerthThe Perelman School of Medicine at the University of PennsylvaniaBackground: Patients with CLE and DM suffer from decreased quality of life compared to the healthy population and patients with other chronic conditions. While psychiatric comorbidities such as depression and anxiety have been thoroughly documented in other chronic dermatological and rheumatological conditions, these mental health issues remain less well described in skin-predominant lupus erythematosus and dermatomyositis. To date, the literature does suggest increased rates of mood and anxiety disorders in these diseases in the context of decreased quality of life; however, little is known about access and barriers to and utilization of mental health care in this population. The aim of this study is to characterize these aspects of mental health care in skin-predominant LE and DM and to determine the unmet need for mental health care.Methods: Patients recruited for this study were administered three questionnaires: PHQ-9, GAD-7, and MHCAQ. The PHQ-9 and GAD-7 are questionnaires validated for the screening, diagnosis, and severity determination of depression and anxiety, respectively. Based on validation studies, a PHQ-9 score ≥10 and a GAD-7 score ≥8 were used to determine the need for further evaluation and/or treatment. The MHCAQ is a novel questionnaire developed for this study that determines use of and barriers to mental health care. Rates for depression or anxiety with need for mental health care were calculated by the addition of all subjects who met PHQ-9/GAD-7 thresholds and all subjects below threshold who were being treated for depression or anxiety. A total of 44 skin-predominant LE and 31 dermatomyositis patients were enrolled.Results: For skin-predominant LE, 14 out of 44 (31.8%) subjects met criteria for depression, with a need for mental health care. 5 out of the 14 (35.7%) subjects were receiving no treatment giving a rate of 11.4% (5/44) untreated depression for all subjects. 14 out of 44 (31.8%) subjects met criteria for anxiety with need. 6 out of the 14 (42.9%) subjects were receiving no treatment giving a rate of 13.6% (6/44) untreated anxiety for all subjects. Overall, 7 out of 44 (15.9) subjects met criteria for depression and/or anxiety with need but without treatment. For dermatomyositis, 8 out of 31 (25.8%) subjects met criteria for depression with need. 5 out the 8 (62.5%) subjects were receiving no treatment giving a rate of 16.1% (5/31) untreated depression for all subjects. 12 out of 31 (38.7%) subjects met criteria for anxiety with need. 4 out of the 12 (33.3%) subjects were receiving no treatment giving a rate of 12.9% (4/31) untreated anxiety for all subjects. Overall, 5 out of 31 (16.1%) subjects met criteria for depression and/or anxiety with need but without treatment.Conclusion: Given the significant unmet need for mental health care in these populations and the lack of guidelines for dermatologists treating these autoimmune skin conditions, these findings suggest a need for improvement in awareness, screening, and referral of patients to appropriate psychiatric support services.Quality of life in discoid lupus patientsNoelle M. Teske, BA, MSc1, Zachary Cardon, BS1, Xilong Li, PhD, MBA2, Benjamin F. Chong, MD, MSCS1Department of Dermatology1, Department of Clinical Sciences2University of Texas Southwestern Medical Center, Dallas, TXBackground: Previous studies have demonstrated impairment of quality of life (QoL) in cutaneous lupus (CLE) patients. However, no studies have examined QoL in discoid lupus (DLE), whose unique clinical features may impact QoL distinctly.Objective: To identify characteristics that correlate with worse QoL in DLE patients.Methods: A cross-sectional study of DLE patients seen at University of Texas Southwestern Medical Center and Parkland Memorial Hospital between April 2010 and April 2014 was performed. 117 DLE patients completed demographic, medical history, and QoL questionnaires, including SKINDEX-29, and underwent clinical assessments (e.g. Cutaneous Lupus Erythematosus Disease Severity and Area Index (CLASI)). Univariate analyses were performed to assess relationships between predictor variables and primary outcome measures of SKINDEX-29 scores in emotions, functioning, and symptoms subdomains. Predictor variables with p<0.25 in the univariate analyses were included in multivariate logistic regression models. Results: DLE patients had significantly higher and worse SKINDEX-29 symptoms scores (40.58±21.19) than other CLE patients (33.21±22.13, n=47) (p=.0451). Univariate analyses showed that higher SKINDEX-29 emotions, functioning, and symptoms scores correlated with higher CLASI activity (p=0.0456 (emotions), p=0.0015 (functioning), p<0.0001 (symptoms)) and damage (p=0.0378 (emotions), p=0.0319 (functioning), p=0.0163 (symptoms)) scores, current smoking status (p=0.0002 (emotions), p=0.0011 (functioning), p=0.0129 (symptoms)), and income less than $10K/year (p=0.013 (emotions), p<0.0001 (functioning), and p=0.003). Multivariate analyses highlighted female gender as a significant factor associated with higher SKINDEX-29 emotions (p=0.0189) and symptoms scores (p=0.0077), and correlated current smoking status with poorer QoL in the SKINDEX-29 emotion (p=0.0013) and functioning subdomains (p=0.0173). Conclusions: DLE patients have greater symptom-related QoL impairment than other subtypes of CLE. Subsets of DLE patients, such as females and current smokers, may be particularly vulnerable to poorer QoL, and providers may consider these demographic factors in their overall management of these patients. Malar and discoid rash at diagnosis of SLE does not impact SLICC damage scores at 5- and 10-year follow-up Aaron M Drucker MD1, Farheen Mussani MD1, Jiandong Su BSc2, Dominique Ibanez MSc2, Sanjay K Siddha1 MD, Dafna D Gladman MD2 and Murray B Urowitz MD2From the Division of Dermatology (1) and Centre for Prognostic Studies in the Rheumatic Diseases (2), University Health Network, Toronto, Ontario, CanadaObjective: Previous studies have suggested that systemic lupus erythematosus (SLE) patients with cutaneous lupus erythematosus (CLE), in particular discoid lupus erythematosus (DLE), may have less severe systemic disease than SLE patients without CLE. We aimed to compare SLE patients without skin manifestations to SLE patients with DLE or malar rash at diagnosis with regards to eventual organ damage.Methods: The Toronto Lupus Clinic database has prospectively collected data on patients with SLE from 1970 to the present. Data collected includes clinical phenotype and organ damage as measured by the System Lupus International Collaborating Clinics/ACR Damage Index (SLICC). The SLICC evaluates irreversible damage in 12 organs, including the skin, with a maximum score of 46. We limited this study to an “inception cohort” of patients first assessed in the Lupus Clinic within one year of diagnosis of SLE. We compared SLICC scores and SLICC scores minus skin damage at 5 and 10 years post-inception between SLE patients who never developed CLE and patients who had DLE or the malar rash at their inception visit. Statistical significance was defined as a p-value ≤0.05 calculated using Wilcoxon or Chi-Square tests.Results: In a cohort of 764 SLE inception patients, 284 (37.1%) never developed CLE, 65 (8.5%) had DLE at inception and 175 (22.9%) had a malar rash at inception. At 5 years of follow-up, mean total SLICC scores were similar in the group that never developed CLE (0.75) compared to the DLE (0.73, p=0.57) and malar rash (0.67, p=0.84) groups. Additionally, there was no statistically significant difference between the percentage of patients with SLICC scores above 0 in the group without skin manifestations (35.9%), the DLE group (41.5%, p=0.4) and the malar rash group (36.0%, p=0.99). At 10 years, results were similar with no statistically significant differences seen between the groups with regards to mean total SLICC scores and percentage of patients with scores above 0. Additionally, there was no statistically significant difference in mean SLICC scores and the percentage of patients with scores above 0 between the groups at 5 and 10 years of follow-up when skin damage was subtracted from the total score.Conclusions: Malar and discoid rashes around the time of diagnosis of SLE do not have appear to have a significant prognostic impact on overall SLE damage. Supported by a grant from the Canadian Dermatology FoundationSunscreen use in cutaneous lupus erythematosus patientsElizabeth N. Le, MD*, Danielle Q. Lin, BA*, Ira Bernstein, PhD**, Steven Q. Wang, MD***, and Benjamin F. Chong, MD, MSCS**University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX**University of Texas Southwestern Medical Center, Department of Clinical Sciences, Dallas, TX***Memorial Sloan Kettering Cancer Center, Division of Dermatology, New York, NYBackground: Sunscreen use among cutaneous lupus erythematosus (CLE) patients has been suboptimal. Characteristics of non-sunscreen CLE users and reasons for CLE patients not wearing sunscreens are unknown. Objective: To determine the frequency and patterns of sunscreen use and identify barriers to sunscreen use in patients with CLE.Methods: A cross-sectional survey on sunscreen use was administered to patients enrolled in the University of Texas Southwestern CLE Registry. Demographics and patient history were obtained from the registry database and medical charts. Additional information including disease severity and quality of life scores were collected from patients seen in person. Results: 100 CLE patients completed the survey. 32 patients reported daily sunscreen use, and 40 patients noted that they did not use sunscreen. 50% and 63% of all CLE patients re-apply sunscreen daily or while outside for a prolonged time, respectively. Univariate analyses revealed that non-married status (p=0.007) and low income (p=0.01) were associated with non-sunscreen use. Multivariate analyses identified non-married status (p=0.04) as significant factors seen in non-sunscreen users. When comparing daily and non-sunscreen users, significant barriers to regular sunscreen use included forgetfulness (p=0.0002), inconvenience (p=0.006) and perception that sunscreen did not prevent lupus flares (p=0.03). Conclusions: A large proportion of CLE patients do not wear sunscreen. Non-sunscreen users, who tend to be not married, would benefit from education on the virtues of sunscreen application. Providers are encouraged to counsel CLE patients on appropriate timing and frequency of sunscreen use throughout the day and protection from future lupus flares. Furthermore, educational programs geared towards improving sunscreen use in this population will be developed and implemented in future pilot studies.The incidence of zoster in patients with cutaneous lupus erythematosus and dermatomyositis is increased compared to the average U.S. populationES Robinson,1,2 J Okawa,1,2 R Feng,3 AS Payne,2 VP Werth1,2 1 Veteran Affairs Medical Center, Philadelphia, PA2 Department of Dermatology, University of Pennsylvania, Philadelphia, PA3 Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PABackground: Herpes zoster is a common condition that causes significant pain and, often, post-herpetic neuralgia. In the United States the incidence of zoster per 1,000 person-years is 6 for people 60 years old and increases with age to nearly 11 for people above 80 years old. The incidence of zoster may be increased in autoimmune diseases, but few studies have looked specifically at cutaneous autoimmune diseases. Prior studies have found that the incidence of zoster in systemic lupus erythematosus is up to 32.5 per 1,000 person-years (n=303). Methods: This retrospective chart review examined the incidence of zoster in patients with cutaneous lupus erythematosus (CLE) (n=105), dermatomyositis (DM) (n=66) and pemphigus vulgaris (PV) (n=55) seen in the practices of two dermatologists between April 1, 2013 and September 31, 2013. An incidence of zoster was determined according to a matched text search for “zoster” or “shingles” in all available electronic medical records. The date of the zoster episode, if known, and the medications that the patient was taking at the time of the episode were recorded. The date of each patient's earliest visit with his dermatologist recorded in the electronic medical record until the most recent visit through September 31, 2013 or an episode of zoster, whichever was earlier, was used to estimate the time that the person had been at risk. The total number of incidences of zoster divided by the total number of person-years at risk was used to determine the incidence rate. Patients with a known history of zoster prior to the start of their electronic medical records and patients whose date of zoster was unknown were excluded from the incidence rate calculations.Results: The incidence rate of zoster per 1,000 person-years was 23 for CLE, 54 for DM, and 7 for PV. The incidence rates were based on 6 episodes of zoster per 257.9 person-years for CLE, 8 episodes of zoster per 149.5 person-years for DM and 1 episode of zoster per 145.4 person-years for PV. Six CLE, 7 DM and 3 PV subjects had an unknown date of zoster. One CLE, 5 DM and 2 PV patients had zoster prior to the start of their electronic medical records. The mean (SD) duration of follow-up was 2.7 (1.7) years for CLE, 2.8 (1.7) years for DM and 3.0 (1.8) years for PV. The mean age (standard deviation) of each group was: 46.2 (14.1) for CLE, 55.9 (14.2) for DM and 56.1 (13.8) for PV. Fourteen of the 16 patients who had zoster were on immunosuppressive medications at the time of the zoster episode. Some patients were on more than one immunosuppressive therapy at the time of their zoster episode. The immunosuppressive medications were: mycophenolate mofetil (n=7), prednisone (n=6), methotrexate (n=1) and azathioprine (n=1). The majority of patients in each disease group were Caucasian women. Conclusions: The incidence rate of zoster in CLE and DM is higher than in the average U.S. population at or above 80 years old. The incidence of zoster in PV is close to that of the average U.S. population of a similar age. The use of immunosuppressive therapies may play a role in the increased incidence of zoster in CLE and DM.Treatment of Scarring Alopecia in Chronic Cutaneous Lupus Erythematosus with Tacrolimus 0.3% SolutionEmily Milam1, BA; Sarika Ramachandran1, MD; Jerry Shapiro1, MD, Andrew G. Franks, Jr.1, MD1The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NYAbstract: Topical and intralesional steroids and antimalarials have been the mainstay of treatment for chronic cutaneous lupus, e.g. discoid lupus erythematosus (DLE). For recalcitrant cases, systemic immunosuppressants are sometimes used. Calcineurin inhibitors have been used to treat psoriasis and eczema and have also shown some success in the treatment of DLE lesions, namely in the form of tacrolimus ointment.1,2 We used a custom formulated tacrolimus 0.3% (not 0.03%) in an alcohol base as adjunct therapy in three patients with recalcitrant alopecia secondary to discoid lupus. All three patients had significant improvement in disease activity consistent with CLASI criteria, including a reduction in erythema, scale, and surface area of the lesions, and increased hair growth after using the solution for many months. The results of these cases support the use of topical tacrolimus 0.3% in an alcohol solution as an adjunct therapeutic option in resistant cases of DLE-associated alopecia. ReferencesSugano M. Shintani Y. Kobayashi K. et al. Successful treatment with topical tacrolimus in four cases of discoid lupus erythematosus. J Dermatol. 2006 Dec; 33(12): 887-91. Heffernan MP. Nelson MM. Smith DI et al. 0.1% Tacrolimus Ointment in the Treatment of Discoid Lupus Erythematosus. Arch Dermatol. 2005;141(9):1170-1171.Lampropoulos CE, Sangle S, Harrison P. et al. Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus: a possible alternative.Rheumatology.2004 Nov;43(11):1383-5.DERMATOMYOSITISAdequacy of Skin Variables in the New Classification Criteria for Adult and Juvenile IdiopathicInflammatory Myopathies for the Diagnosis of Amyopathic Dermatomyositis Neelam Khan, MS1, 2, Victoria P. Werth, MD1 1 Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 2 Georgetown University School of Medicine, Washington, DC Background: There have been numerous classification systems set forth for the diagnosis of adult dermatomyositis (DM) that have varied in their inclusion of clinical criteria, diagnostic technologies, and DM subtypes. As an international, multidisciplinary collaboration, the International Myositis Classification Criteria Project (IMCCP) has sought to develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM). The purpose of this study is to evaluate the adequacy of the skin variables included within the IMCCP classification criteria for the diagnosis of amyopathic dermatomyositis (ADM). Those with ADM have a higher likelihood of misdiagnosis and are particularly at risk for rapidly progressive interstitial lung disease. It is essential that any new classification scheme for DM include criteria to appropriately classify those with ADM as well as those with other subtypes of DM.Methods: This retrospective study was conducted at the University of Pennsylvania Health System. Patients included were 18 years or older with a clinical and/or histological diagnosis of dermatomyositis and enrolled in a prospective database study for dermatomyositis between July 2008-?‐2014. A total of 135 patients were evaluated for their skin findings at time of enrollment using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), a validated outcome measure quantifying disease activity in fifteen anatomic locations.Results: The 135 patients evaluated included 51.85% with classic DM (CDM) and 48.15% with clinically amyopathic DM (CADM). Of those with CADM, 41.48% had ADM and 6.67% had hypomyopathic DM. There was no significant difference in the cutaneous presentation of CDM vs. CADM. In patients with ADM, 91.07% had at least one of the three skin variables included in the IMCCP criteria (heliotrope rash, Gottron’s sign, Gottron’s papules), with 26.79% presenting only with one skin variable, 41.07% with two skin variables, and 23.21% with all three. Five patients with ADM presented with none of the three skin variables at time of enrollment.Conclusions: Most patients with ADM had at least one of the three skin variables included inthe new IMCCP classification criteria for diagnosis of adult dermatomyositis. Because the IMCCP criteria uses a minimum probability cutoff and assigns a distinct score for each skin variable, a patient with ADM must have at least two out of the three skin criteria for diagnosis. Of theADM patients analyzed in this study, approximately ? would not meet such criteria. As these patients with ADM all presented with cutaneous manifestations of disease, it is important to consider the possibility of additional skin variables within the new classification criteria or in a separate criteria for clinically amyopathic DM to allow for the inclusion of such patients. Furthermore, as five patients with ADM did not present with any of the three skin variables at enrollment, it is important for practitioners to consider the full history of a patient’s cutaneous manifestations of DM and the impact medication use may have on skin findings.Disease Progression and Flare in Cutaneous Dermatomyositis: A Longitudinal Study Using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)Jeannette M. Olazagasti, Rui Feng, Victoria P. WerthBackground/Purpose: To characterize disease course in cutaneous dermatomyositis (DM) by conducting a longitudinal analysis using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score.Methods: Patients 18 years or older with clinical or histologic evidence of DM who had the CDASI activity scores recorded for at least 2 years from time of initial visit were included. For each patient, time from initial visit (in years) was plotted on the x-axis and CDASI activity score for each visit was plotted on the y-axis. The plots were then used to determine 3 features of disease course over time: average disease activity, overall progression, and variability. The average disease activity over time was estimated by calculating the Area under the Curve per number of years of follow-up. The overall progression of disease activity over time was assessed by conducting a linear regression analysis and calculating the slope to determine average change in CDASI per year. Disease progression in each patient was classified as “improved,” “worsened,” or “stable” over time by the slopes of m < -4, m > +4, and -4 < m < +4, respectively. The variability in disease activity over time was evaluated by calculating the number of flares; with “flare” defined as a 4-point increase in the CDASI, divided by the number of years of follow-up. Study patients were divided into two groups based on disease severity at baseline (mild versus moderate-severe disease activity). The above-mentioned parameters were analyzed in both groups and statistical significance was evaluated using Mann-Whitney tests. Graphpad 5.0 software was used for all descriptive statistics, AUC calculations, slope estimates, and group comparisons.Results: A total of 40 DM patients fulfilled inclusion criteria. The majority of the patients were female (90%) and Caucasian (95%), with a mean age of 52.9 years at the time of initial visit. Disease subtype was classified as classic in 52.5% of patients and skin predominant in 47.5%. The mean follow-up time was 3.50 years. Patients with moderate-severe disease activity at baseline made up a majority of the patients (N=23, 58%). The average disease activity over time, calculated by AUC/yr, was statistically significantly different for mild and moderate-severe disease patients (9.39 versus 15.08; P<0.002). Patients with mild disease activity at baseline had stable disease activity over time (m = +0.36) while those with moderate-severe disease activity tended to improve (m = -3.36; P<0.004).Variability in disease activity over time was similar for the mild and moderate-severe patients (0.32 versus 0.33 flares/yr; P=0.86). Conclusion: Cutaneous DM disease course over time can be characterized by 3 features: average disease activity, overall progression, and variability. The definition of cutaneous DM “flare” can be used to describe variability in disease activity. This longitudinal study provides a framework for using CDASI to monitor disease course over time.Anti-MDA5 Dermatomyositis: A Longitudinal Analysis Matt Lewis, Shufeng Li, Lorinda Chung, David FiorentinoStanford University, Department of DermatologyBackground: Dermatomyositis patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are at increased risk of developing interstitial lung disease (ILD). The natural history of ILD among this subset of dermatomyositis patients is poorly understood. Objective: We sought to characterize the temporal trends in ILD severity, cutaneous ulceration and calcinosis in MDA5 dermatomyositis patients. Methods: We retrospectively reviewed the cohort of 23 MDA5 dermatomyositis patients seen at Stanford University Dermatology in California between July 2004 and July 2014.Results: Of the 23 MDA5 dermatomyositis patients seen, 14 patients (60%) had at least 2, serial pulmonary function tests available for analysis. Among the 14 patients followed, we found a statistically significant increase in diffusion capacity (DLCO) over time using repeated measures model. The regression trend line estimated an average increase of 0.36% in DLCO per month, (95% CI .05-0.66%, p=.02). Of the 12 MDA5 dermatomyositis patients with abnormal lung function tests, 8 of those patients (67%) showed a greater than 15% absolute increase in DLCO (average=24%). Among the 6 patients in whom both serial pulmonary function tests and cutaneous dermatomyositis disease area and severity index (CDASI) scores were available, 5 of the patients (83%) had nadirs in DLCO at their time-matched peak CDASI scores, although this relationship did not reach statistical significance. The median times to onset of cutaneous ulceration, ulcer healing and calcinosis were 6, 22 and 28 months, respectively. 4 patients (17%) died during follow-up: 1 patient died from rapidly progressive ILD at 2 weeks, 1 patient died following a bilateral lung transplant, and 2 patients died at 7 and 18 months from progressive ILD.Limitations: The trends and associations identified are limited by the small sample size, location at a tertiary referral center, varied treatments and retrospective nature of the investigation. We also may not capture dermatomyositis patients with rapidly progressive ILD who present in critical condition. Conclusion: There is a large subset of MDA5 dermatomyositis patients who have interstitial lung disease that improves over time with treatment. Among MDA5 dermatomyositis patients with ILD, their skin disease activity may be an indicator of their ILD severity. The onset of calcinosis in MDA5 dermatomyositis patients temporally occurs around healing of cutaneous ulcerations. Histopathologic findings?in dermatomyositis of the scalp Santos, Leopoldo; Martinka, Magdalena; Shapiro, Jerry; Dutz, JanUniversity of British Columbia, 835 West 10th avenue, Vancouver, BC, V5Z4E8, Canada?Background: Cutaneous features of dermatomyositis (DM) often begin and continue to involve the scalp. While there are clinical descriptions of scalp dermatomyositis, there are no published descriptions of the histopathology of this disorder?affecting the?scalp.?Objective: To describe the histopathologic features of dermatomyositis of the scalp.?Methodology: Scalp biopsies of two patients with typical cutaneous features of dermatomyositis were examined and compared to scalp biopsies of patients with cutaneous forms of lupus erythematosus (LE). Horizontal and transverse sections stained with hematoxylin and eosin and transverse sections stained with PAS and mucin stains were examined.?Results: DM histopathology showed the following features within the epidermis; follicular plugging and mild vacuolar interface changes. Within the dermis, superficial and deep perivascular and peri-adnexial lymphocytic infiltrates were noted that extended to the subcutis in one case. Both cases showed basement membrane thickening on PAS stain and increased mucin. The control case (LE) showed within epidermis; mild atrophy, subtle vacuolar interface change and follicular plugging. Within the dermis, dense superficial and deep perivascular, perifollicular and perieccrine lymphocytic infiltrates which extended to the superficial subcutis. However, basement membrane thickening and increased mucin were absent features. Conclusion: The dermatopathological features of scalp dermatomyositis include superficial and deep perivascular lymphocytic infiltrates, the presence of lichenoid interface changes, colloid bodies, a thickened basement membrane and mucin deposition. Clinicians and dermatopathologists should be aware that scalp dermatomyositis may mimic cutaneous lupus erythematosus of the scalp and that a pathological distinction between these two entities affecting the scalp may not be possible. Double Trouble: Psoriasis-like Eruptions in Dermatomyositis Patients Allison Truong BS, David Fiorentino MD, PhDDepartment of Dermatology, Stanford University School of Medicine, Redwood City, CABackground: Dermatomyositis (DM) and psoriasis are inflammatory skin disorders that have heterogeneous clinical presentations, co-morbidities, and disease courses. Skin lesions in DM patients manifest as atrophic scaly violaceous eruption on the eyelids, knuckles, shoulders, and hips. Classic psoriatic lesions demonstrate well-demarcated, erythematous plaques with underlying silvery, micaceous scales. Histopathologically, DM demonstrates interface dermatitis with superficial perivascular infiltrate and dermal mucin deposition whereas psoriasis displays epidermal acanthosis, hypogranulosis, confluent parakeratosis, increased vascularity, subcorneal neutrophils, and thinning of the suprapapillary plate. However, when DM patients present with erythematous scaly plaques in the scalp and extremities, this poses a diagnostic dilemma for clinicians.Objective: We aimed to describe three cases of psoriasis-like eruptions in DM patients and discuss clinical and histopathological findings to identify whether these patients have two distinct clinical phenomenon (DM and psoriasis) or rather atypical DM with psoriasis-like eruption. Methods: Our first case is a 32-year old female who presented with violaceous rash on the eyelids, discolored fingernail beds, and scalp erythema. Our second case is a 38-year-old female who presented with well-demarcated violaceous erythematous, scaly plaques on her elbows, extensor forearms, dorsal hands, lateral thighs, knees, and lower legs along with diffuse scalp and periungual erythema. Our third case is a 67-year-old female who presented with well-demarcated erythematous scaly slightly atrophic plaques with surrounding ill-defined erythema on scalp, face, trunk, and bilateral upper and lower extremities along with scalp alopecia. Results: All three patients initially presented with skin manifestations prior to meeting clinical criteria for DM. Skin biopsies were performed on psoriatic-appearing plaques at time of diagnosis or during acute flares. Our first patient’s skin biopsy revealed epidermal acanthosis with mounded parakeratosis favoring psoriasis. Patient’s skin lesions remain stable on Stelara, prednisone taper, IVIG, and MTX. Our second patient had epidermal acanthosis, parakeratosis, mild superficial perivascular infiltrate, and dilated papillary dermal vessels, without interface dermatitis consistent with psoriasis. However, a colloidal iron stain revealed abundant mucin throughout the dermis, which is unusual in psoriasis and more consistent with DM. Her skin lesions progressed to neck and chest on prednisone taper and azathioprine. Our third patient’s biopsy revealed vacuolar interface dermatitis and vascular ectasia without eosinophils, favoring DM. Her skin disease remains stable with MTX and topical steroids.Conclusion: Although rare, patients with DM and psoriasis-like skin eruptions represent therapeutic challenges to clinicians. Histopathologically, our first patient appeared to have both DM and psoriasis whereas our third patient appeared to have atypical DM with psoriasis-like eruption. Our second patient initially appeared to have psoriasis but additional stains clenched the diagnosis of DM. It remains unclear if there are patients with both distinct clinical entities DM and psoriasis, or if DM patients develop psoriasis-like eruption. Interestingly, there are common pathways to inducing both inflammatory skin disorders as they share similar interferon-induced responses and dysregulation of cytokines. Further research into ways to distinguish these two clinical entities where histopathologic criteria may be inconclusive would facilitate therapeutic challenges seen in caring for these patients with two concurrent autoimmune or inflammatory skin diseases. Currently, therapies for one may exacerbate symptoms of the other requiring multi-tier therapeutic approach to avoid flaring of coexisting conditions. In cases where diagnosis is unclear, we recommend requesting additional stains to evaluate for atypical DM.Venous Thromoboembolism and Cutaneous Autoimmune Disease:Case Report of Amyopathic Dermatomyositis related Thrombophilia and Review of LiteratureMark G Kirchhof1,2 and Jan P Dutz1,31Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada; 2Division of Dermatology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada; 3Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.Abstract:Autoimmune diseases, and in particular cutaneous autoimmune disease, increase the risk of venous thromboembolism (VTE). Biochemical markers of hypercoagulability, such as D-dimer levels, correlate with disease activity and may provide a method of screening patients for thromboembolic events. We report a case of amyopathic dermatomyositis in which D-dimer levels and disease activity were followed. The patient developed an elevated D-dimer level that correlated with active cutaneous disease. One month after an elevated D-dimer level value was noted, the patient suffered deep vein thrombosis (DVT) and bilateral pulmonary emboli (PE). Anticoagulant therapy and changes to treatment of the dermatomyositis resulted in clinical improvement with no recurrence of these thromboembolic events.Dermatologists should be aware of the increased risk of VTE in patients with DM and that this increased risk may include patients with clinically amyopathic DM. The clinical value of screening DM patients and other autoimmune patients for thromboembolism in order to prevent potentially fatal PEs and DVTs should be explored.Contact information for MGK:835 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 4E8Phone: (604) 875-4747Fax: (604) 873-9919Email: kirchhof.mark@Conflicts of Interest: None to declare. A Predictive Model of Disease Outcome in Rituximab-treated Myositis Patients Using Clinical Features, Autoantibodies, and Serum Biomarkers Jeannette M. Olazagasti, Cynthia S. Crowson, Molly S. Hein, Consuelo M. Lopez De Padilla, Rohit Aggarwal, Chester V. Oddis, Ann M. ReedBackground/Purpose: Develop predictive models of early (8 week) and late (24 week) disease outcomes using clinical features, autoantibodies, and serum biomarkers in patients with refractory myositis treated with rituximab.Methods: In the Rituximab in Myositis (RIM) trial, all subjects (76 with adult dermatomyositis, 76 with adult polymyositis and 48 with juvenile dermatomyositis) received rituximab (2 doses on consecutive weeks) with half the patients receiving drug at baseline and half receiving drug 8 weeks later. Using start of treatment as baseline, serum samples (n=177) were analyzed at baseline and after 8 and 24 weeks after rituximab. Potential predictors included the following baseline factors: clinical features, serum muscle enzymes, interferon gene score, autoantibodies (anti-synthetase n=28, TIF1- n=19, Mi-2 n=25, SRP n=21, NXP2 n=18, non-myositis associated n=24, undefined autoantibody n=9), and cytokines/chemokines measured by multiplexed sandwich immunoassays (Meso Scale Discovery) (type-1 IFN-inducible [IP-10, I-TAC, MCP1], Th1 [IFNγ, TNFα, IL2], Th2 [IL4, IL5, IL10, IL12, IL13], Th17 [IL6, IL17, IL1β] and regulatory cytokines [IL10, TNF, MIP-1α, MIP-1β]). Our primary definition of response to treatment was based on absolute change from baseline to 8 weeks and 24 weeks in physician global visual analog scale (VAS), muscle VAS, and extramuscular VAS. Multivariable linear regression models were developed using stepwise variable selection methods. Results: Preliminary models were built with good predictive ability both for change in physician global assessment and muscle disease activity at 24 weeks (R-square=0.41 and 0.40, respectively). The model for change in physician global assessment included the following baseline clinical and lab features: muscle disease activity, physician global assessment, and I-TAC (Table). The model for change in muscle disease activity included baseline physician global assessment, skeletal disease activity, I-TAC and IFNγ. Similarly, a predictive model was built with excellent predictive ability (R-square=0.67) for change in extramuscular disease activity at 24 weeks. This model included the following baseline clinical and lab features: constitutional, skeletal and extramuscular disease activity by VAS, and MIP-1β and Mi-2. We also built models from baseline to 8 weeks but their predictive ability was inferior compared to those for 24 weeks (R-square<0.3).Conclusion: Changes in disease activity over time following treatment with rituximab in patients with refractory myositis can be predicted. These models could be clinically useful to optimize treatment selection in these patients.Outcomes ->Change in Physician Global VASChange in Muscle VASChange in Extramuscular VASPredictors (baseline)CoefficientP-valueCoefficientP-valueCoefficientP-valuePhysician Global Assessment-0.800.0007-0.330.002----Muscle Disease Activity0.510.0008--------Extramuscular Global Assessment--------0.600.0002Skeletal Disease Activity----0.380.020.260.04Constitutional Disease Activity--------0.230.02Mi-2---------15.470.002I-TAC-0.010.025-0.020.01----IFNγ-----0.350.01----MIP-1β--------0.008<0.0001SYSTEMIC SCLEROSISCalcinosis is associated with digital ulcers and osteoporosis in patients with Systemic Sclerosis: A Scleroderma Clinical Trials Consortium StudyAntonia Valenzuela1, Murray Baron2, Ariane Herrick3, Susanna Proudman4, Wendy Stevens5, Tatiana S. Rodriguez-Reyna6, Alessandra Vacca7, Thomas A. Medsger Jr.8, David Fiorentino9, Lorinda Chung1. 1Department of Immunology and Rheumatology, Stanford University School of Medicine, 2Department of Rheumatology, Jewish General Hospital McGill University, 3Department of Rheumatology, University of Manchester, 4Rheumatology Unit, Royal Adelaide Hospital North Terrace, 5Department of Rheumatology, St. Vincent’s Hospital Melbourne, 6Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, 7II Chair of Rheumatology, University of Cagliari-Policlinico Universitario, 8Department of Medicine/Rheumatology, University of Pittsburg School of Medicine, 9Department of Dermatology, Stanford University School of MedicineBackground: Calcinosis is a debilitating cutaneous complication of systemic sclerosis (SSc) with no effective treatments. We sought to determine the clinical factors associated with calcinosis in an international multi-center collaborative effort with the Scleroderma Clinical Trials Consortium (SCTC). Methods: This is a retrospective cohort study of 5162 patients with SSc from 7 centers within the US, Australia, Canada, United Kingdom, Italy, and Mexico. Calcinosis was defined as the presence of calcium deposition in the skin and/or subcutaneous tissues as determined by physical examination and/or radiography. Logistic regression was used to obtain odds ratios (OR) relating calcinosis to various clinical features in multivariate analyses.Results: The cohort was 84.8% female, 81.6% Caucasian, mean age at first non-RP symptom was 45±14.4 years, and median follow-up was 2 years (range 0 -19). 38.3% had diffuse cutaneous SSc, 60.6% had limited cutaneous SSc, and 0.8% had SSc sine sclerosis. A total of 1225 patients (24%) had calcinosis. Patients with calcinosis were older than patients without calcinosis (59.5 ± 12.7 vs. 56.8±13.4), more likely to be female (88.9% vs. 83.6%), had higher modified Rodnan skin score at baseline (10.9 ± 9.9 vs. 10± 10.6), and had longer disease duration from first non-Raynaud’s phenomenon symptom to baseline (13± 10.4 vs. 8.3±9.2) (p-value <.0001). They were more likely to have digital ulcers (65.8% vs. 34.4%) and telangiectasias (89.9% vs. 64.9%). Regarding SSc-associated internal organ involvement, patients with calcinosis were more likely to have cardiac disease (17.5% vs. 12.5%), pulmonary hypertension (16% vs. 13.7%), gastrointestinal involvement (73.7% vs. 63%), and arthritis (30% vs. 26.7%), but less likely to have myositis (8.2% vs. 12.3%). Osteoporosis was much more common in patients who had calcinosis (11.8% vs. 2.7%). Autoantibodies independently associated with the presence of calcinosis included anticentromere (ACA), PM-1, and anticardiolipin antibodies. In multivariate analysis also inclusive of female gender, ACA, arthritis, cardiac and gastrointestinal disease, the strongest associations with calcinosis were digital ulcers (OR 3.4, 95%CI 2.4-4.9, p=<.0001), and osteoporosis (OR 4.4, 95%CI 2.3-8.5, p=<.0001) (Table 1).Conclusion: Almost one quarter of patients with SSc have calcinosis. Our data support a strong association of calcinosis with digital ulcers as well as osteoporosis, which may shed light on the pathogenesis of calcinosis and guide the development of future therapies. MORPHEAClassification of morphea severityTina Michelle S. Vinoya, MD and Heidi T. Jacobe, MD, MSCSUniversity of Texas Southwestern Medical Center Department of Dermatology, Dallas, TexasBackground: Morphea, or localized scleroderma, is an inflammatory condition that affects the dermis and extends into the subcutaneous fat and fascia. This produces thickening and hardening of the skin. Recently-validated skin scoring tools in morphea are the Localized Skin Severity Index (LoSSI), which describes activity and the Localized Scleroderma Disease Severity (LoSSDI), which describes damage and extent of cutaneous lesions. To date, the LoSSI and the LoSSDI have not been examined with regards to the clinical significance of individual scores. This makes it difficult to put any given score in context clinically in terms of what constitutes mild, moderate and severe disease.Objective: We aim to develop an index of severity of disease for morphea. Design: The Morphea Adult and Children (MAC) Cohort cross sectional studySetting: The morphea clinic at the University of Texas Southwestern Medical Center at DallasInterventions: NoneMain Outcome Measures: The LoSSI, LoSSDI, and the Physicians’ Subjective Assessment of Activity and Damage were completed at every visit.Results: Disease severity was assessed in one clinic visit of 51 patients enrolled in the MAC Cohort from June 2007 to September 2014. Mean and standard deviation of the LoSSI showed no significant difference in classifying disease activity into mild and moderate. Analysis of the LoSDI showed that disease damage could be categorized into mild, moderate and severe.Limitations: Due to the rarity of the disease, a small sample size was used. Conclusion: The LoSSI, LoSSDI and Physician’s Subjective Assessment of Severity can be used as indices of morphea severity. For future studies, we recommend that more patients be included and a wider range of assessment of activity and damage scores be used.Key words:Morphea, Localized Scleroderma, LoSSI, LoSSDI, Physician’s Subjective Assessment of Activity and DamageA Longitudinal Study of the Impact of Morphea on Quality of Life Over TimeNoelle Teske, BA, MSc, Simer Grewal, BA, Heidi T. Jacobe, MD, MSCSDepartment of DermatologyUniversity of Texas Southwestern Medical Center, Dallas, TXBackground:?Cross-sectional studies have examined the effect of morphea on health-related quality of life (HRQOL). However, little is known about the effect of disease duration on HRQOL in morphea.Objective:?Describe longitudinal changes in HRQOL in morphea over time and baseline demographic and clinical features that are associated with impairment of HRQOL in morpheaMethods: Participants were selected from the prospective Morphea in Adults and Children (MAC) cohort. Inclusion criteria were: age ≥18 years and ≥ 2 visits with a recorded HRQOL measure: Dermatology Life Quality Indexes (DLQI), Skindex-29+3 (with Morphea-specific subscale), and Short Form-36 (SF-36). Demographic features including age at first visit, sex, and race, as well as clinical features of morphea subtype, disease activity and damage (measured by Physician Global Assessment of Disease (PGA) activity and damage scores, Localized Scleroderma Skin Severity Index (LOSSI) and damage correlate LOSDI scores) were assessed as predictors.Results:? 142 patients met inclusion criteria and had a range of 2-4 visits annually. The median DLQI score for participants was 4 at the initial visit (n=142), 2 at the second visit (n=142), 2 at the third visit (n=68), and 1 at the fourth visit (n=36), reflecting a significant improvement in HRQOL over time (p<.0001). At initial visit, DLQI scores did not differ significantly by any demographic features, (age, sex, or race). Clinical features of morphea subtype and disease damage (PGA Damage, LOSDI) did not show significant associations with HRQOL. However, skin disease activity was correlated with poorer HRQOL at initial visit as measured by the LOSSI (r=.2198, p=.0445). Skin disease activity decreased significantly over time as measured by PGA Activity (p<.0001) and LOSSI scores (p<.0001). Skin damage (PGA-Damage and LOSDI) remained stable over the study duration. The QoL for patients with morphea was shown to be worse than the general population, with median SF-36 PCS and MCS scores below 50 at initial visit (n=38), and median Skindex scores were comparable to those shown in other skin diseases such as alopecia and eczema. Limitations: Participants were enrolled at a tertiary referral center and small sample sizes for some measures, visits, and population subsets may limit analysis.Conclusions:? HRQOL was initially impaired in morphea patients as measured by the DLQI, but improved over time as disease activity subsided. Impairment in HRQOL was similar across age, gender, race, and morphea subtypes, but patients with increased disease activity had greater impairment. In contrast to studies in other diseases (acne, vitiligo), damage was not associated with greater impairment. This implies a potential role for adjustment to chronic disease over time.VASCULITISThree cases of macular arteritis: Separate entity or on the clinical spectrum of cutaneous polyarteritis nodosaCecilia Larocca MD, Deon Wolpowitz MD PhD, Christina Lam MDDepartment of Dermatology, Boston University School of Medicine, Boston, MABackground: Macular arteritis, also known as macular lymphocytic arteritis or lymphocytic thrombophilic arteritis, is a recently described clinical entity. It is characterized by hyperpigmented macules of the lower extremities and histologically by a lymphocytic arteritis. Given the histopathological overlap of this entity with the late stage findings of cutaneous polyarteritis nodosa (PAN), controversy exists as to whether this represents a latent or indolent form of cutaneous PAN or a separate entity. Methods: We conducted a retrospective chart review of three cases of macular arteritis seen at our institution in which we describe the demographic, clinical, histologic and laboratory findings of these cases. We compare these cases with the existing 15 cases described in the literature. We also compare and contrast macular arteritis with cutaneous polyarteritis nodosa and other lymphocytic vasculitides.Results: The median age of diagnosis is 37.5 years with a range of 6-73 years of age. The majority of patients are female (83%) and Black (50%). The median duration of the skin lesions is 12 months prior to presentation. Clinically, asymptomatic hyperpigmented macules on the lower extremities are noted. Other common features include erythematous macules and a livedoid pattern. The majority of lesions are asymptomatic but 22% of patients report a mild pruritus. There are no defining serologies. To date there are no reports of systemic involvement. Histopathologically all lesions have a lymphocytic arteritis. Commonly considered differential diagnoses include polyarteritis nodosa, Sneddon’s syndrome, or a thrombotic vasculopathy.Conclusion: Here we present three new cases of macular arteritis to help expand the clinical spectrum of this novel entity. Comparison of these patients with the known clinical history, histological pattern, and evolution of skin lesions in PAN provides support that macular arteritis is a distinct entity. PSORIASISTNF-α Inhibitor-Induced psoriasis: A decade of experience at the Cleveland ClinicSean Mazloom, Stephanie Saed, Anthony P. FernandezCleveland Clinic, Department of DermatologyBackground: Development of psoriasiform dermatitis precipitated by TNF-α inhibitor therapy is a poorly understood phenomenon. Objective: The goal of this study was to gain insight into this reaction by characterizing affected patients seen at our institution over the past ten years. Methods: A systematic retrospective chart review of all patients with TNF-α Inhibitor-induced psoriasis from 2003 to 2013 was performed. Results: 102 patients who developed TNF-α Inhibitor-induced psoriasis were identified. 73.5% of affected patients were females. Age at onset ranged from 8-80 years, with a mean of 40 years. Crohn’s disease (46%) and Rheumatoid arthritis (24.5%) were the most common primary conditions for which TNF-α Inhibitors were prescribed. Among inciting TNF-α Inhibitors, infliximab was most common (51%). The most common subtypes of psoriasis developing were plaque-type (49.5%), scalp (47.5%), and palmoplantar pustulosis (41%). Patients who developed psoriasiform dermatitis while taking infliximab had a higher percentage of scalp (58%) and inverse psoriasis (40%) compared with those taking other TNF-inhibitors. Fifty biopsy specimens from 41 patients were reviewed, and psoriasiform or spongiotic reaction patterns characterized the vast majority (>85%). Plasma cells (62%) and eosinophils (81%) were found in the majority of specimens. No trend was observed between histologic characteristics and medication type. Characteristics did not significantly differ depending on time period between rash onset and biopsy date. A variety of treatment interventions were attempted. Discontinuation of inciting TNF-α Inhibitor agent with or without other interventions improved or resolved the psoriatic lesions in 70% of cases. Methotrexate at doses >15mg/wk and cyclosporine also effectively controlled the reaction in the majority of patients treated with these. Conclusion: This study represents the largest single-institution cohort of patients with TNF-α Inhibitor-induced psoriasis to date. Our cohort displayed many features described in other published cohorts. The variability in onset, clinical presentation, and disease course suggests that an additional insult, either endogenous or exogenous, is required to precipitate this reaction. The presence of plasma cells and eosinophils suggests this reaction is distinct from psoriasis vulgaris. Future studies focusing on potential inciting factors may add further insight into the pathogenesis of this paradoxical reaction. ................
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