2012 Annual Meeting Abstracts
Rheumatologic Dermatology Society
November 10, 2012
Washington, D.C.
LUPUS
Cutaneous Manifestations Associated with Systemic Lupus Erythematosus
Disease Activity
Laura Sowerby1, Elizabeth O’Brien1, Lawrence Joseph2, Sasha Bernatsky2, 3, Emil
Nashi4, Évelyne Vinet2,3, Ann E Clarke2,4, Christian A Pineau3
1McGill
University Health Centre, Division of Dermatology, Montreal, Quebec, Canada;
University Health Centre, Division of Clinical Epidemiology; 3McGill University
Health Centre, Division of Rheumatology, Montreal, Quebec, Canada; 4McGill University
Health Centre, Division of Allergy and Clinical Immunology, Montreal, Quebec, Canada
2McGill
Background and Objective: This study examined the pattern of cutaneous
manifestations in a cohort of patients with Systemic Lupus Erythematous (SLE) and
evaluated their association with disease activity as measured by the SLE Disease
Activity Index 2000 (SLEDAI-2K). Lupus related cutaneous findings were recorded
based on Gilliam’s classification.
Methods: Consecutive patients meeting ACR criteria for SLE were recruited from a
multispecialty SLE clinic. All patients underwent a total body skin examination by a
dermatologist. SLE disease activity was assessed at the same visit using the SLEDAI2K which was modified by eliminating all muco-cutaneous items.
Patients reported on sun exposure, medications, and smoking. Multiple linear
regression models were run to estimate the effects of cutaneous manifestations on the
SLEDAI-2K while adjusting for potential confounding variables.
Results: Eighty subjects were recruited, of which 75 (93.8%) were women. The mean
SLEDAI-2K was 5.85 (SD 5.64). Of these patients, 24 (30%) had one or more lupusspecific cutaneous manifestations, of which 9 patients (11.3%) had ACLE, 6 (7.5%) had
SCLE and 10 (12.5%) had CCLE. No association could be demonstrated between the
presence of lupus-specific skin findings and modified SLEDAI-2K scores. There were
59 patients (73.8%) who had lupus-non-specific cutaneous manifestations, the 3 most
frequent ones being periungual telangiectasias (37 patients, 46.3%), Raynaud’s (34,
42.5%) and livedo reticularis (27, 33.8%). Multivariate analyses estimated that the
presence of any lupus-non-specific finding is associated with a higher modified SLEDAI2K (difference of 4.11 points on the SLEDAI-2K scale, 95% CI 1.39-6.84). Among
individual lupus-non-specific findings, livedo reticularis and periungual telangiectasias
were associated with increased SLE disease activity (differences of 3.67, 0.96-6.38 and
2.61, 0.14-5.07 respectively).
Conclusions: Lupus-non-specific cutaneous findings as a whole, and individual
manifestations such as livedo reticularis and periungual telangiectasias, are associated
with increased SLE disease activity. No association was demonstrated between lupusspecific cutaneous manifestations and SLEDAI-2K. Careful examination of SLE
patients for lupus-non-specific manifestations may aid clinicians in assessing global
disease activity.
Disease Progression in CLE: A Longitudinal Study of CLE
Authors: Chang YC, Propert K, Sirignano S, Chong B, Werth VP
1Dept
of Derm U Penn Phil PA, 2Dept of Derm, PVAMC, Phil, PA, 3Biostatistics, U Penn,
Phil, PA, 3 University of Texas Southwestern Medical Center, Dallas, TX
The CLASI is a validated clinical tool that measures CLE activity and responsiveness.
Clinically significant “flare” in CLE disease activity has not yet been determined, which
may be important when looking at changes in disease activity over time. Our study had
two aims: 1) to determine how to best use the CLASI to define clinical “flare,” and 2) to
objectively evaluate CLE disease course in terms of average disease activity (area
under the curve/year), overall progression (slope, or change in CLASI over time), and
variability (flares/year). Using ROC analysis to optimize specificity and sensitivity,
clinical “flare” between visits was defined as mean signed and percentage increase in
CLASI of 4 and 40%, respectively. We studied 96 patients in a longitudinal retrospective
analysis with at least 2 years follow-up. A majority of patients had mild disease activity
[CLASI 0-9] (74%) and stable disease course (67%), defined by slope <2, over an
average of 3.3 years. Those with mild disease activity tended to have stable disease,
fewer flares per year, and better quality of life on average than those with moderatesevere disease. Higher percentage of those with moderate-severe disease (64% vs
33%), especially those who remained stable or worsened, were current smokers. A
higher percentage of patients who worsened in disease activity were male (58%)
compared to improved or stable disease. Longitudinal studies of CLE have been difficult
in the past due to lack of validated clinical tools and databases, and this serves as a first
step to objectively analyzing longitudinal data.
Photoprotective habits of cutaneous lupus erythematosus patients
Shirley Y. Yang, BS1, Ira Bernstein, PhD2, Benjamin F. Chong, MD1, Departments of
Dermatology1 and Clinical Science2, University of Texas Southwestern Medical Center,
Dallas, TX
Background: Previous studies have suggested that cutaneous lupus erythematosus
(CLE) patients are deficient in sunscreen use. CLE patients’ usage of other
photoprotective methods has not been assessed.
Objectives: We sought to identify demographic and clinical characteristics of CLE
patients who have the lowest overall sun protection habits (SPH) scores, and who are
least likely to practice five individual photoprotective methods (i.e. shade, sunscreen,
long sleeves, hat, and sunglasses).
Methods: 105 CLE patients at the University of Texas Southwestern (UTSW) Medical
Center at Dallas completed a survey to evaluate their photoprotective practices.
Additional information including demographics and clinical indicators related to CLE was
collected from the patients.
Results: Darker-skinned patients (i.e. skin type V-VI) and patients aged 31-50 were the
least likely CLE subgroups to practice overall photoprotection, as indicated by a low
SPH score (p=0.001 and 0.01, respectively). In terms of individual photoprotective
methods, CLE male patients were deficient in sunscreen use, but were more likely to
wear hats than females. Sunscreen and sunglasses use were also significantly
infrequent in darker-skinned patients than lighter-skinned patients. CLE patients
between ages of 41 and 50 were least likely to wear hats.
Conclusions: As similar findings have been shown in normal and skin cancer patients,
cultural customs and misconceptions shared by those from the general population have
a significant influence on the photoprotective habits of this CLE population. These need
to be addressed to improve photoprotection rates in these at-risk individuals.
A comparison of the disease course of subacute cutaneous lupus patients with
and without systemic lupus
Kim A, Song E, Chong BF, Departments of Dermatology1 University of Texas
Southwestern Medical Center, Dallas, TX
Background: In systemic lupus erythematosus (SLE), autoantibodies such as antidsDNA have already demonstrated clinical utility in depicting and predicting disease
activity. However, no similar studies to date have been performed for discoid lupus
erythematosus (DLE). Identifying autoantibody biomarkers in DLE could help guide
treatment and possibly lead to novel therapeutic targets.
Objective: We sought to compare the association of autoantibodies against nuclear
antigens with various disease activity markers in DLE patients.
Methods: A cross-sectional analysis was conducted on 90 DLE patients in the
University of Texas Southwestern Cutaneous Lupus Registry. ANA, dsDNA, ssDNA,
and RNP autoantibodies and additional ENA autoantibodies were measured on DLE
patient sera using ELISAs or multiplex-beaded array assays. Results were compared to
complement levels, CLASI activity and damage scores, SLEDAI scores, number of ACR
SLE criteria, and number of oral lupus medications.
Results: There were significantly positive correlations of ANA and anti-RNP antibodies
with CLASI activity (Spearman r=0.2905, p=0.0081 [ANA] and r=0.3310, p=0.0019 [antiRNP]) and SLEDAI scores (r=0.4143, p=0.0001 [ANA] and r=0.3344, p=0.0017 [antiRNP]). Negative correlations were observed in both C3 (r=-0.5021, p=0.0029 [ANA]
and r=-0.4613, p=0.0046 [anti-RNP]) and C4 levels (r=-0.5015, p=0.0029 [ANA] and r=0.5793, p=0.0002 [anti-RNP]). Other autoantibodies and disease activity markers did
not correlate significantly.
Conclusions: We found significant correlations of ANAs and autoantibodies against a
specific nuclear antigen, RNP, with various disease activity markers in DLE patients.
Longitudinal studies of these autoantibodies and disease activity need to be performed
to assess the biomarker potential of anti-RNP antibodies in DLE.
Characterization of clinical photosensitivity in cutaneous lupus erythematosus.
Authors. Kristen Foering, MD1,2,3 , Chang A, MD1,2, Piette E, MD1,2, Joyce Okawa,
RN1,2, and Victoria P. Werth, MD1,2. 1Philadelphia VA Medical Center, Philadelphia, PA;
2University of Pennsylvania, Department of Dermatology, Philadelphia, PA; 3Institute for
Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia,PA;
Background: The definition of photosensitivity (PS) in systemic lupus erythematosus
(SLE) is vague and its pathophysiology is not well understood. The objective of this
study was to characterize self-reported PS phenotypes among a cutaneous lupus (CLE)
population.
Methods: A novel PS survey was developed from LE subject interviews regarding sun
exposure and sensitivity. Subject responses were classified into one of five PS
phenotypes: sun-induced CLE exacerbation (directCLE); general worsening of CLE in
summer (genCLE); PMLE-like reactions (genSkin); general pruritus/paresthesia
(genRxn); and systemic symptoms, e.g. headache, arthralgia (genSys). 100 subjects
with CLE or both CLE and SLE were interviewed.
Results: 83% of subjects ascribed to any and 66% reported more than one PS
phenotype. 47% cited direct examples of sun-induced CLE [directCLE]. Other PS
phenotypes were reported as follows: 22% genCLE, 38% genSkin, 36% genRxn, and
37% genSys. Sun-induced systemic symptoms were reported by fewer discoid and
subacute cutaneous LE compared with acute and tumid LE subjects, X2=13.0, p<0.05.
Subjects with both CLE and SLE reported more paresthesias/pruritus (51% vs 23%)
and systemic symptoms (50% vs 26%) compared to those without SLE, p<0.05.
Subjects with PMLE-like reactions had lower CLE Disease Area and Severity Index
(CLASI) activity scores (6.4±5.4 vs 11.5±11.11, p=0.02).
Conclusions: Self-reported photosensitivity in lupus ranges from CLE-specific
reactions to general cutaneous eruptions to systemic symptoms. Recognition of various
PS phenotypes in CLE will permit improved definitions of clinical photosensitivity and
allow for more precise investigation into the pathophysiology of photosensitivity in lupus.
The Impact of Dyspigmentation and Scarring in Cutaneous Lupus on Quality of
Life
Authors: Verma SM,1,2 Okawa J,1,2 Propert K,3 Werth VP,1,2.
1Dept
of Derm U Penn Phil PA, 2Dept of Derm, PVAMC, Phil, PA, 3Biostatistics, U Penn,
Phil, PA
Patients with more severe CLE activity have poorer QoL. The main objective of the
current study was to evaluate the impact of lupus-related skin damage on skin-specific
QoL, as well as differences stratified by ethnic backgrounds. Data collected included
sex, race, diagnosis, CLASI scores, and Skindex-29. These parameters were analyzed
at the initial and last visits. CLASI damage scores (dyspigmentation and scarring) and
CLASI activity scores were collected, grouped by ethnicity, and correlated with Skindex29. 223 patients were analyzed at baseline, with 141 of these patients completing more
than one study visit. The majority were Caucasians (63.7%), followed by African
Americans (29.1%) and Asian Americans (4.0%). African American patients accounted
for a disproportionate percentage of both localized (50% of cases) and generalized
(48.9% of cases) DLE. Median CLASI damage scores significantly differed between our
African American, Caucasian, and Asian American patients, at both first (8.5, 4.0, 7.0)
(Kruskal-Wallis p<0.0001) and last visit (10.0, 6.0, 8.5) (Kruskal-Wallis p<0.01) (Dunn’s
Multiple Comparison p<0.0001, p<0.01). CLASI damage scores in African Americans
correlated with CLASI activity scores (Spearman’s r=0.4480, p=0.0003). There was no
significant correlation between CLASI damage scores and Skindex domains overall.
Individually, dyspigmentation and scarring also did not have a significant effect on QoL.
In conclusion, disease damage does not affect QoL, as measured by the Skindex-29.
Ethnic differences in CLE patients were found: African American patients with CLE, do
exhibit a high rate of DLE, experience damage early in their disease course, frequently
in conjunction with disease activity.
DERMATOMYOSITIS
Novel autoantibodies and clinical phenotypes in adult dermatomyositis
David Fiorentino, MD, PhD, Lorinda Chung, MD, MS, Lisa Zaba, MD, PhD, Bharathi
Lingala, PhD, Lisa Christopher-Stine, MD, MPH, Antony Rosen, MD, Livia CasciolaRosen, PhD
Background: Dermatomyositis (DM) is a heterogeneous disease in terms of
presentation, associated co-morbidities, and disease course. Myositis-specific
autoantibodies (MSA) are mutually exclusive and associated with clinical phenotypes.
In the past 5 years 4 new DM-specific autoantibodies have been described. To date, no
study has examined the frequency of all of these antibodies in a single cohort. In
addition, suboptimal assays using crude extracts as antigen sources have been
employed. Thus, the true frequency and clinical phenotypes associated with these
serotypes is at present unclear.
Methods: We designed, optimized and validated novel, sensitive, and highly specific
assays to detect antibodies against TIF-g, NXP-2, MDA5, SAE 1/2, and Jo-1. Assays
were based on immunoprecipitation using 35S-methionine labeled antigens generated
by in vitro transcription-translation as source material. Patient sera from a DM cohort at
the Stanford University Dermatology Outpatient Clinic (n = 111) or Johns Hopkins
University (n=201) were tested. Odds ratios and p values were calculated using
univariate logistic regression.
Results: 81% of DM patients had at least one of the myositis-specific antibodies. TIF-g
and NXP-2 antibodies were significantly associated with cancer (OR=3.4, p=0.0046 for
cancer if either antibody is positive). Various cutaneous and systemic features were
associated with particular antibodies (results to be presented).
Conclusion: Most DM patients can be identified using novel autoantibody assays, and
each of these subtypes has characteristic clinical features that will aid the clinician is
diagnosing and stratifying risk for their DM patients.
MORPHEA
Clinical features of generalized morphea patients with the pansclerotic subtype: a
prospective study from the Morphea in Adults and Children (MAC) cohort.
Kim A1, Marinkovich N2, Jacobe HJ1. Department of Dermatology1, University of Texas
Southwestern Medical Center, Dallas, TX; Department of Dermatology2, Washington
Hospital Center, Washington, DC.
Introduction: Pansclerotic morphea is a poorly described form of generalized
morphea. Our experience with this particular subgroup from the Morphea in Adults and
Children (MAC) cohort led us to hypothesize that it constitutes a distinct clinical
phenotype of increased severity and recalcitrantance to treatment compared to other
generalized morphea patients. The objective of this study was to identify the
prevalence of pansclerotic morphea in the MAC cohort, describe the demographic and
clinical features, and determine how this group differs from generalized morphea.
Methods: 113 patients in our registry identified with generalized morphea at enrollment
were segregated into 2 groups according to their noted subtype (13 for the pansclerotic
subtype and 100 for other generalized subtypes). Baseline demographic and clinical
features of all generalized patients were first compiled before the 2 groups were
analyzed for differences in demographic and clinical characteristics.
Results: Pansclerotic patients had a higher predominance of males (54% vs. 6%,
p<0.0001), shorter time to diagnosis (1.2±0.4 years vs. 5.1±0.9 years, p<0.0001), higher
rates of functional impairment (54% vs. 16%, p=0.0046), and higher average modified
Rodnan Skin Scores (MRSS) (15.3±2.0 vs. 7.0±0.5, p=0.0017).
Conclusions: Subgroup comparison lends supports for the possibility that pansclerotic
morphea is a distinct phenotype. A more severe disease course was suggested by
objective measure with the MRSS, but other clinical indicators point toward a more rapid
and extensive course with higher rates of functional impairment from joint deformities or
loss of range of motion and a shorter time interval between symptom onset and
diagnosis.
Title: Road map to consensus treatment plans for adults with morphea:
Establishing current practice trends
Authors: Amanda Strickland, Nicole Fett, Christopher Hansen, Kari Connolly, Heidi
Jacobe
Background: Therapeutic clinical trials are challenging in rare disorders like morphea,
but needed given recent reports documenting wide variation treatment among
providers. One solution is to determine comparative efficacy of common treatments by
comparing patients treated with a consensus treatment plan (CTP) with a universally
accepted outcome measure. The first step in creating a CTP is gathering data on
current practice. This study characterizes treatment regimens offered to adult patients
with morphea by members of the Medical Dermatology Society (MDS) as the first step
in developing a CTP for adults with morphea.
Objective: To determine current approach to treatment among dermatologists with
experience in the treatment of morphea(MDS members).
Design: Cross-sectional survey of MDS members.
Setting: Web-based survey (Survey Monkey)
Main Outcome Measures: Frequency count analysis of responses for severity, activity,
and treatment of 6 subtypes of morphea: plaque, linear, generalized, mixed, deep, and
lichen sclerosus
Results: MDS respondents vary treatment according to morphea subtype. More severe
forms of morphea were treated with systemic agents, while less severe forms were
treated with topicals. The choice of systemic agents, duration, dose, and combination
treatments varied widely. Phototherapy was used relatively infrequently. MDS members
used systemic immunosuppressives in generalized and linear morphea less frequently
and for shorter time periods compared with prior reports in rheumatology.
Conclusions: Dermatologists have more variation in their approach to treatment of
morphea patients than rheumatologists. Accounting for this variation will be crucial in
the development of CTP for morphea if they are to be adapted by dermatologists.
PITYRIASIS RUBRA PILARIS
Clinical presentation and management of Pityriasis Rubra Pilaris: An academic
medical center experience
1A.
Brooke Eastham MD, 2Alisa N. Femia MD, 2,3Abrar Qureshi MD, MPH, 2Ruth Ann
Vleugels MD, MPH
1Harvard
Combined Dermatology Residency Program, Boston, MA; 2Department of
Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston,
MA; 3Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital,
Boston, MA
Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous disorder characterized
by folliculocentric hyperkeratotic papules, palmoplantar keratoderma, and widespread
orange-red erythema with islands of sparing. Treatment is challenging and a standard
therapeutic protocol does not exist. We retrospectively reviewed medical records of 40
patients with PRP seen from 2000 to 2011. We extracted data on disease presentation,
treatment, and clinical response (CR). Of the 40 cases, 36 were adult type I (of which 3
had associated polyarthritis), 3 were juvenile type IV, and 1 was juvenile type V. Partial
to marked CR was noted in 14 patients given topical corticosteroid monotherapy.
Narrow band UVB, UVA1, and bath PUVA provided partial CR in three. Twenty-five
received acitretin, methotrexate (MTX), MTX plus acitretin, mycophenolate mofetil
(MMF), or cyclosporine. Of these patients, marked CR resulting in clearance was noted
in four on acitretin, two on MTX, two on MTX plus acitretin, and one on MMF. Ten
patients received biologic agents (infliximab, etanercept, or alefecept), having failed
systemic agents, light therapy, and/or topicals. Seven had marked CR, two had partial
CR, and one had no CR. Of those with polyarthritis, one had marked CR to acitretin,
whereas two required TNF antagonists. Each had a prolonged disease course. These
data indicate that therapeutic response in PRP varies greatly, with some patients
responding to topical therapy and others requiring systemic immunosuppression.
Furthermore, polyarthritis may portend chronic disease and the necessity for systemic
agents. Additional systematic investigation is necessary to determine which patients
with PRP may respond to individual therapeutic options.
SARCOIDOSIS
Title: Reliability and convergent validity of outcome instruments for cutaneous
sarcoidosis
Authors: Howa Yeung, BS; Emily Y. Chu, MD, PhD; Joel M. Gelfand, MD, MSCE; Ellen
J. Kim, MD; Aimee S. Payne, MD, PhD; Junko Takeshita, MD, PhD; Carmela C. Vittorio,
MD; Karolyn A. Wanat, MD; Victoria P. Werth, MD; Misha Rosenbach, MD
Abstract
A reliable and valid instrument is necessary for the assessment of disease severity in
cutaneous sarcoidosis. The objectives of this study are to assess reliability and
convergent validity of two cutaneous sarcoidosis outcome instruments: Cutaneous
Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and
Severity Index (SASI), compared to Physician’s Global Assessment (PGA) as
reference. Eight dermatologists evaluated 11 patients with cutaneous sarcoidosis using
CSAMI, SASI, and PGA. All instruments demonstrated good to excellent intra-rater
reliability. Inter-rater reliability was excellent for CSAMI Activity scores (intraclass
correlation coefficient, 0.82; 95% confidence interval, 0.66-0.94), fair for CSAMI
Damage (0.42; 0.21-0.72) and SASI components scores (0.54-0.57; 0.42-0.69), and
poor for modified Facial SASI (0.395; 0.17-0.72) and PGA scores (0.399; 0.18-0.70).
CSAMI Activity, Damage, and modified Facial SASI scores were all significant linear
predictors of PGA scores. Exploratory analysis revealed significant correlations between
CSAMI Activity scores and Skindex-29 Emotions domain (Pearson’s r = 0.744) and
between CSAMI Damage scores and Skindex-29 Functioning domain (r = 0.677). While
CSAMI on average required 1.8 minutes longer to complete than SASI, a majority of
investigators believed that CSAMI was better for grading skin severity. Generalizability
of these findings may be limited by our small sample size. CSAMI appears to be a
reliable and valid outcome instrument to measure cutaneous sarcoidosis and may
capture a wide range of body surface and cutaneous morphologies. Future research is
necessary to demonstrate its sensitivity to change and to confirm its correlation with
quality of life measures.