2013 Annual Meeting Abstracts
Rheumatologic Dermatology Society
October 26, 2013
San Diego, California
LUPUS
Drug-Induced Subacute Cutaneous Lupus Erythematosus Isolated to the Hands Due
to Topical Terbinafine Cream.
Adnan Mir, Jonathan Leventhal, Sarika Ramachandran, Rishi Patel, David E. Cohen and Andrew G.
Franks, Jr.
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New
York, NY
Background: Drug-induced subacute cutaneous lupus erythematosus (SCLE) is the most common
form of drug-induced lupus erythematosus (DILE). It is comparable to idiopathic SCLE in terms of
clinical, histologic and serologic features. Anti-Ro/SS-A is as prevalent in both drug-induced and
idiopathic SCLE. Drugs associated with SCLE include calcium channel blockers, angiotensinconverting enzyme inhibitors, thiazide diuretics, terbinafine and tumor necrosis factor (TNF)-alpha
antagonists.
Methods: We describe the case of a 34-year-old female foot masseuse who presented with an
eruption isolated to the dorsal hands and interdigital spaces for 2 months while she was using
topical terbinafine on her clients. Ironically, the patient’s general physician treated this eruption
empirically with oral terbinafine for 16 days for a presumed diagnosis of dermatophytosis. The
patient did not improve but reported the development of a transient generalized urticarial reaction
in other parts of her body.
Results: Physical examination revealed scaly, erythematous plaques on the interdigital and dorsal
surfaces of the fingers. There were no lesions on the head or neck or other locations. The patient’s
ANA was positive at a titer of 1:40, in a speckled pattern, and SS-A antibody was positive at 1.4 (nl <
1.0). Histopathology was consistent with subacute cutaneous lupus erythematosus.
Conclusion: We propose that our patient developed localized SCLE due to topical terbinafine
cream from chronic topical exposure as a foot masseuse. In addition, when inadvertently challenged
with oral administration of terbinafine, she developed an urticarial reaction consistent with
systemic allergic sensitization. We believe that further investigation of the pharmacodynamics of
topical terbinafine and its potential to induce subacute cutaneous lupus erythematosus is
warranted.
Prognostic significance of anti-nuclear antibody titers in discoid lupus patients
Daniel Grabell, BA, MBA1, Christy Wang, MD1, Roselynn Nguyen1, MD, Jack O’Brien, BA1,
Beverley Adams-Huet, MS2 , Benjamin F. Chong, MD, MSCS1
1 Department of Dermatology, 2 Department of Clinical Sciences University of Texas Southwestern
Medical Center, Dallas, TX
Background: Anti-nuclear antibodies (ANAs) have been associated with generalized involvement
and systemic symptoms in discoid lupus erythematosus (DLE) patients, suggesting that ANA may
be a risk factor for systemic lupus erythematosus (SLE) development. However, these studies did
not longitudinally follow DLE patients with and without positive ANAs to assess ANA’s prognostic
value.
Objective: To determine ANA’s clinical significance at DLE diagnosis, we compared disease
courses of DLE-only patients (DLE patients without SLE) with and without positive ANAs
respectively, for at least two years.
Methods: A retrospective cohort study of 26 DLE-only patients seen at University of Texas
Southwestern Medical Center and Parkland Memorial Hospital between May 1987 and June
2013 was performed after local institutional review board approval. All were diagnosed with DLE
based on clinicopathological correlation and had ≥ two annual follow-ups. Patients who did not
have ANA drawn within the first year of DLE diagnosis, had concomitant SLE at DLE diagnosis, or
had a history of other autoimmune diseases were excluded. Indirect immunofluorescence tests
using Hep2 cells were used to measure ANA titers, with positive titers being ≥1:160. Clinical data at
initial visit (t=0) and subsequent annual follow-ups (t=one, two years, etc.) were collected for up to
six years. The number of body parts defined by Cutaneous Lupus Activity and Severity Index
(CLASI) was the primary outcome. Secondary outcomes included number of SLE criteria met and
oral medications. Results: 26 of 46 DLE-only patients passed initial screening. Nine had positive
ANA titers (ANA+), including one who developed SLE four years after DLE diagnosis. 17 had
negative ANA titers (ANA-) initially, including two who became ANA+ at year 3 and 5, respectively.
No DLE ANA- patient developed SLE. DLE ANA+ patients had increased CLASI body parts, fulfilled
significantly more SLE criteria (even excluding positive ANA titers), and required higher numbers
and potency of medications at diagnosis than DLE ANA- patients. Over time, DLE ANA- patients had
significantly higher rates of increase in number of CLASI body parts (p=0.03), SLE criteria
(p<0.0001), oral medications (p=0.0007), and potency of medications (p=0.005) than DLE ANA+
patients
Conclusions: Although DLE ANA+ patients had worse baseline disease activity, over time,
DLE ANA- patients exhibited greater disease spread. Our findings may result from efficacy of
aggressive treatments in ANA+ patients or differences in disease evolution between the groups.
Larger prospective studies comparing disease courses in DLE ANA+ and ANA- patients using CLASI
scores and other disease activity markers will be conducted.
MISCELLANEOUS CONNECTIVE TISSUE DISEASE
Facial erythromelalgia: A rare entity to consider in the differential diagnosis of
connective tissue diseases
1Mital
Patel MD, 1Alisa N. Femia MD, 2A. Brooke Eastham MD, 1Janice Lin MD, 1Ruth Ann Vleugels
MD, MPH
1Department
of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston,
MA; 2Harvard Combined Dermatology Residency Program, Boston, MA
We present an interesting case of a 53-year-old male with four years of an erythematous facial rash
associated with significant burning and exacerbated by sun exposure. Given his predominant facial
involvement, he was initially diagnosed with rosacea and actinic damage. After a lack of clinical
response, he was then diagnosed with connective tissue disease based on a biopsy that revealed
vacuolar interface alteration with prominent perivascular and periadnexal lymphoid infiltration
and mucin deposition. Treatment with both systemic corticosteroids and hydroxychloroquine
provided minimal clinical response. He was subsequently referred to our connective tissue disease
clinic for additional therapy. On exam, the patient had prominent erythema and edema of both the
face and ears. Additional history, specifically relief with cooling measures, established a clinical
diagnosis of erythromelalgia. After initiating therapy with aspirin, pentoxifylline, and gabapentin
the patient experienced significant improvement of his condition.
Erythromelalgia is a rare condition characterized by episodic erythema, swelling, warmth, and
burning pain which primarily occurs on the extremities, though may rarely manifest on the ears
and face. Exposure to heat may trigger these episodes, and patients frequently report that cooling
alleviates their symptoms. This disorder can lead to significant long-term morbidity; therefore
timely recognition and initiation of therapy is essential. Given there is no confirmatory or
diagnostic test, the patient's history and physical examination during the episodes establishes the
diagnosis. Patients often receive numerous incorrect diagnoses prior to being recognized as having
erythromelalgia, and those with facial involvement can be misdiagnosed as having connective
tissue disease. Although biopsy findings are often non-specific in erythromelalgia, histopathologic
findings of connective tissue disease have been reported. This case illustrates the difficulty in
diagnosing atypical cases of erythromelalgia. Specifically, it highlights that patients with facial
involvement can be misdiagnosed as having connective tissue disease, particularly when skin
biopsy findings support this entity. This is the second reported case of clinically consistent
erythromelalgia with biopsy demonstrating vacuolar interface dermatitis and mucin deposition,
underscoring the need for physicians who follow patients with connective tissue disease to be
aware of the clinical presentation of facial erythromelalgia.
Calcinosis Cutis Occurring in Association with Autoimmune Connective Tissue
Disease
**David A. Wetter, M.D.
Objective: To describe characteristics and treatment of patients with calcinosis cutis in the clinical
setting of autoimmune connective tissue disease.
Design: Retrospective study.
Setting: Tertiary referral center (Mayo Clinic, Rochester, Minnesota).
Patients: Seventy-eight patients with calcinosis cutis and autoimmune connective tissue disease
between 1996 and 2009.
Main Outcome Measures: Clinical features, treatments, and outcomes of patients with calcinosis
cutis in the clinical setting of autoimmune connective tissue disease.
Results: Of 78 patients (mean age at onset of calcinosis cutis, 40.1 years), 64 (82%) were female.
The following diseases were associated with calcinosis cutis: dermatomyositis (n=30) with classic
(n=15), juvenile (n=14), and amyopathic (n=1) subtypes; systemic sclerosis with limited cutaneous
scleroderma (n=24); lupus panniculitis (n=4); systemic lupus erythematosus (n=2); mixed
connective tissue disease (n=4); overlap connective tissue disease (n=6); undifferentiated
connective tissue disease (n=6); polymyositis (n=1); and rheumatoid arthritis (n=1). Therapy for
calcinosis cutis consisted of medical treatment alone (n=19; 24%), surgical therapy alone (n=11;
14%), combined medical and surgical treatment (n=17; 22%), and no treatment (n=30; 38%).
Diltiazem was the most commonly used medical therapy, with 9 of 17 patients having a partial
response. Twenty-eight patients had surgical excision of 1 or more lesions of calcinosis cutis; 22
had a complete response and 5 had a partial response.
Conclusions: Dermatomyositis and systemic sclerosis were the most common autoimmune
connective tissue diseases associated with calcinosis cutis. Although no treatment was uniformly
effective, surgical excision of symptomatic lesions and medical treatment with a calcium channel
blocker (diltiazem) provided benefit for some patients.
**From Arch Dermatol. 2012;148(4):455-462 (Balin SJ, Wetter DA, Andersen LK, Davis MDP)
DERMATOMYOSITIS
Identification of clinical features and risk factors associated with calcinosis in adult
patients with dermatomyositis
Antonia Valenzuela1, Lorinda Chung1,3, Livia Casciola-Rosen2, Antony Rosen2, David Fiorentino1,3
1Stanford
University School of Medicine, Division of Immunology and Rheumatology
Hopkins University School of Medicine, Department of Rheumatology
3Stanford University School of Medicine, Department of Dermatology
2Johns
Background: Prior studies have estimated that up to 20% of adult dermatomyositis (DM) patients
suffer from calcinosis. Although calcinosis is related to persistent disease activity, poor treatment
adherence, and therapy refractoriness in juvenile DM (JDM) patients, risk factors for calcinosis in
the adult DM population have not been extensively studied. Antibodies to nuclear matrix protein 2
(NXP-2) have been associated with calcinosis in JDM patients but only one study has shown a trend
for this association in adult DM. We aimed to determine the prevalence of calcinosis and to identify
associated clinical features in our cohort of extensively phenotyped adult DM patients.
Methods: This is a cross-sectional study of 126 patients diagnosed with DM at Stanford University
Medical Center between 01/2006 and 01/2013. 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: 94% of patients had DM-specific or myositis-specific autoantibodies (against NXP-2,
transcription intermediary factor-gamma (TIF-), melanoma differentiation antigen 5 (MDA-5),
sumoyl activating enzyme (SAE1/2), Mi-2, or Jo-1). A total of 14 (11%) patients had calcinosis. The
association between the autoantibodies to NXP-2 and to TIF- and calcinosis reached statistical
significance in separate multivariate analyses adjusting for digital ulcers, disease duration,
interstitial lung disease and the autoantibody to Ro52 (OR=15.5, 95%CI 2.01-119.9, p=0.008 and
OR= 0.2, 95%CI 0.01-0.99, p=0.04), while MDA-5 was no longer significantly associated with
calcinosis. Digital ulcers and disease duration were strongly associated with calcinosis in all
multivariate models, independent of the underlying autoantibody present (Table 1).
Conclusion: Calcinosis was a relatively uncommon clinical feature in our cohort of DM patients.
Our data support an association with NXP-2 autoantibodies as well as digital ulcers. A common
vascular mechanism may underlie the development of both calcinosis and digital ulcers in patients
with DM.
Table 1. Multivariate analyses
Multivariate model OR
95% CI
NXP-2 analysis
p-value
Disease duration
Digital ulcers
ILD
Ro52
NXP-2
MDA-5 analysis
1.2
1.03–1.42
12.3 2.24–67.9
4.7
0.91–24.2
4.3 0.78–23.07
15.5 2.01–119.9
0.018
0.003
0.06
0.09
0.008
Disease duration
Digital ulcers
ILD
Ro52
MDA-5
TIF- analysis
1.2
11.5
3.5
2.2
0.7
0.01
0.03
0.13
0.30
0.80
1.03–1.37
1.21–109
0.67–17.8
0.49– 10.2
0.06 –9.20
Disease duration
1.2 1.02 – 1.39
0.02
Digital ulcers
12.2 2.17 – 69.3 0.004
ILD
1.7 0.34 – 9.11
0.4
Ro52
3.7 0.75 – 18.9
0.10
TIF0.2 0.01 – 0.99
0.04
ILD= Interstitial lung disease, OR=Odds ratios, CI=Confidence intervals
Dermatomyositis Associated with Hematologic Malignancies: Report of Two Cases
and Discussion
Maria Aleshin, BA, David Geffen School of Medicine at UCLA
Scott Worswick, MD, UCLA Department of Medicine, Division of Dermatology
Dermatomyositis (DM) is an idiopathic inflammatory myopathy which is characterized clinically by
symmetric proximal muscle weakness and unique cutaneous findings. While dermatomyositis
primarily affects the skin and muscle, it can also have systemic manifestations including arthralgias,
dysphagia and interstitial pneumonitis. Furthermore, 20 to 25% of cases of dermatomyositis have
been linked to an internal malignancy, most commonly carcinomas of ovarian, pancreatic and
colorectal origin. Some cases of dermatomyositis resolve following cancer treatment suggesting a
paraneoplastic disease origin, while others follow an independent course suggesting an alternative
disease mechanism. To date, few studies have associated dermatomyositis with hematologic
malignancies. Here we report two cases of dermatomyositis in patients with myelodysplastic
syndrome (MDS) and monoclonal gammopathy of undetermined significance (MGUS) and propose
a common immune mediated mechanism possibly contributing to these disease processes. DM is a
truly systemic disease with broad implications for a patient’s health. In addition to the classical
teaching of the overlap of DM and solid malignancies, the above reports present further evidence
for the association between DM and hematological disorders.
The Use of Static and Dynamic Diffusion-Weighted Magnetic Resonance Imaging in
the Diagnosis and Treatment of Dermatomyositis
1Sarika
Ramachandran, MD; 1Alisa Femia, MD; 2Eric Sigmund, PhD; 1Andrew Franks, MD
New York University School of Medicine, New York, NY, The Ronald O. Perelman Department of
Dermatology1 and the Department of Radiology2
Dermatomyositis (DM) is an inflammatory disorder that primarily affects skin and skeletal muscle
and can result in destruction of muscle function and structure and impaired quality-oflife. Although skin histopathology and muscle enzymes may provide diagnostic assistance,
diagnosis is often delayed. In addition, therapeutic benefit and optimal dosing regimens may be
difficult to determine due to difficulty distinguishing between muscle disease activity and damage.
Therefore, it would be highly desirable to find an objective and non-invasive measure that would
improve and expedite diagnosis, help monitor therapeutic benefit, and help distinguish between
disease activity and damage. Magnetic resonance imaging (MRI) is a non-invasive tool that may
accomplish these objectives, and we propose using static and dynamic diffusion-weighted MRI for
this purpose, specifically employing state-of-the-art compressed sensing strategies to accelerate
dynamic multiple echo diffusion tensor acquisition technique (MEDITATE) in skeletal muscle. We
plan to perform proximal muscle diffusion-weighted MRI (DWI) in forty normal controls and forty
DM patients identified through clinical and laboratory data and/or skin biopsy, and to perform
structure and vascular-sensitive DWI at rest and during and after physical exertion. We plan to
compare this data with clinical markers of DM, and patients with DM will be followed during the
course of immunosuppressive treatment with repeated imaging after 6 weeks. We hypothesize
that the results of this study will show that these novel compressed sensing strategies will increase
sensitivity of the MEDITATE technique to detect kinematic changes in muscle, that these imaging
techniques will provide further evidence that DM pathology includes reduction in microvascular
flow and myofiber disruption and degradation, that dynamic imaging before and after exercise will
correlate with analogous measures such as electromyography, and that static and dynamic diffusion
MRI can help predict response to immunosuppressive therapy. This data and development of this
imaging technique is hoped to aid in earlier detection of DM, to provide further insight into the
pathophysiology of DM, and to help monitor disease activity, thereby providing an objective
measure to aid in the adjustment of therapeutic regimens.
Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index:
characterizing severity and assessing responsiveness to clinical change
Cynthia O. Anyanwu, 1,2 BS, David Fiorentino,3 MD, PhD, Lorinda Chung,3 MD, Yanli Wang,4 MS, Joyce
Okawa,2 RN, Kasey Carr,2 RN, Kathleen Joy Propert,4 ScD, Victoria P. Werth,1,2 MD.
1Philadelphia
Veterans Affairs Medical Center, Philadelphia, PA,
of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA
3Department of Dermatology, Stanford University School of Medicine, Stanford, CA
4Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA
2Department
Background/Purpose: Translational research and clinical trials necessitate validated outcome
measures to reliably assess disease progression and treatment efficacy. The Cutaneous
Dermatomyositis Disease Area and Severity Index (CDASI), a disease-specific and skin-based
outcome measure, was developed for use in clinical trials and longitudinal patient assessment. The
reliability and validity of this instrument have been established.1 The goal of this study is to assess
responsiveness of this tool and characterize severity and clinical response of cutaneous
dermatomyositis (DM) using the CDASI.
Methods: In this two-center prospective database study the skin of patients with clinical or
histologic evidence of DM was evaluated. Patients were evaluated using clinical instruments
including the CDASI, a physician global assessment (PGA) 5-point Likert scale measuring disease
severity (none, mild, moderate, severe, extremely severe), a PGA 0 – 10 cm visual analog scale
(VAS) of disease severity and a PGA 3-point Likert scale that captured change in disease severity
since the last visit (improved, worse, no change). The severity analysis compared CDASI scores for
patients with mild disease to those with moderate and severe disease according to the PGA 5-point
Likert. The PGA 3-point Likert and PGA VAS were used to evaluate responsiveness. Clinical
response was defined as a rating of “improved” on the PGA 3-point Likert or a change in VAS scores
of at least 2 cm. Statistical analysis included logistic regression models using generalized estimating
equations to account for correlation among patients. A receiver operating characteristic curve was
used with each model to determine cutoffs.
Results: A total of 199 patients from two sites completed up to 12 study visits each. Study
participants were 79% female and 78% Caucasian. Disease subtype was classified as classic in 65%
of patients and skin predominant in 35%. Separate site-specific analyses were performed due to
interactions between study site and score in both the severity and responsiveness analyses.
Baseline CDASI scores at the two sites range from 0 to 47 (median 17) and 0 to 48 (median 21).
Data collected at one site resulted in a cutoff of 19 to differentiate mild from moderate and severe
disease while at the second site CDASI scores of 14 or less characterized mild disease. Compared to
the PGA VAS, the PGA 3-point Likert may be a less reliable measure of clinical response. Using a PGA
VAS to assess responsiveness we found that improvement in CDASI scores of 4 or 5 indicates a
clinically significant change.
Conclusion: Inter-rater variations in the use of the external PGA Likert and VAS gold measures may
account for the differences between sites. The above results suggest that the CDASI is a valid and
responsive tool for the evaluation of cutaneous dermatomyositis but randomized controlled trials
are needed to confirm these results.
Reference:
1. Goreshi R, Okawa J, Rose M et al. Evaluation of reliability, validity, and responsiveness of the
CDASI and the CAT-BM. J Invest Dermatol2012; 132:1117-24.
Management of cutaneous dermatomyositis: results of a stepwise therapeutic
strategy
Cynthia O. Anyanwu, 1,2 BS, Rui Feng,3 ScD, Kasey Carr,2 RN, Joyce Okawa,2 RN, Victoria P. Werth,1,2
MD
1Philadelphia
Veterans Affairs Medical Center, Philadelphia, PA
of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA
3Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA
2Department
Background: Dermatomyositis requires a multifaceted approach to treatment that considers the
involved organs, potential adverse effects of medications, patient preference, and comorbidities.
Treatment of dermatomyositis (DM) is conventionally approached in a stepwise manner but the
literature is lacking strong evidence to support use of this therapeutic strategy.
Methods: Using a prospective, longitudinal cohort study of 102 (DM) patients, we describe the
result of a stepwise therapeutic strategy in the management of DM. DM was managed using a
stepwise algorithm wherein patients with primarily skin disease initially received antimalarials.
Immunosuppressive agents such as mycophenolate, methotrexate and azathioprine were added
when antimalarials were not sufficient. Intravenous immunoglobulins were administered when
dermatomyositis was refractory to antimalarials and immunosuppressives. Systemic
corticosteroids were used with any combination of treatment agents to manage myositis or severe
cutaneous disease activity. The Cutaneous Dermatomyositis Disease Area and Severity Index
(CDASI) was used to assess disease severity at each visit.
Results: Of 102 dermatomyositis patients, 30% were managed with antimalarials, 64% required
the use of immunosuppressive agents and 7% did not receive systemic therapy during the study
period. When patients presented with only skin disease 48% received antimalarials alone, 44%
received immunosuppressive or immunomodulatory agents and 8% did not require systemic
therapy. Prednisone was included in the treatment regimen for 46% of all patients and 23% of skinonly patients. For 14% of all study patients the current treatment regimen was not sufficient so
therapy was escalated at the last study visit. After a median follow-up of 21 months (range 1 - 56)
the median final CDASI activity score for all patients was 11 (range 0 - 52) and 13.5 (0 - 52) for
patients with skin-only disease. Median duration of treatment for all patients was 21 months (range
1 - 192). In 13% of patients exposed to antimalarials a cutaneous eruption attributable to
antimalarial use was noted.
Conclusions: These results indicate that antimalarials alone are frequently insufficient for skinpredominant patients and management of DM often requires the use of second-line agents. Patients
continue to have mild disease activity despite long periods of therapy. Our data supports the use of
the above-mentioned treatment algorithm and highlights the need for clinical trials to determine
the efficacy of these treatment regimens.
SYSTEMIC SCLEROSIS
Adult and juvenile systemic sclerosis: two cases illustrating differences in disease
presentation and potential treatment options
1Alisa
N. Femia, MD; 1Janice Lin, MD, MPH; 1Christina Lam, MD; 1Mital Patel, MD;
Eastham, MD; 2Fatma Dedeoglu, MD; 1Ruth Ann Vleugels, MD, MPH
1
A. Brooke
1Brigham
and Women’s Hospital and Harvard Medical School, Department of Dermatology, Boston,
MA; 2Boston Children’s Hospital, Division of Allergy and Immunology, Boston, MA
Systemic sclerosis is an inflammatory and fibrotic disorder that can affect multiple organs and may
lead to significant functional limitation, morbidity and mortality. The disorder presents a unique
challenge to physicians, as data regarding therapy is limited, and no treatment has been proven to
modify overall disease course. Systemic corticosteroids may be included in therapeutic regimens,
especially for patients with severe skin or internal organ involvement. However, use of
corticosteroids is controversial due to some data linking them to scleroderma renal crisis, although
no causal relationship has been established. Mycophenolate mofetil has emerged as a therapy
capable of decreasing modified Rodnan skin scores in patients with diffuse systemic sclerosis,
particularly in patients with early-onset disease; however, although this is supported by recent
prospective data, no randomized controlled trials have confirmed this benefit. Evidence regarding
treatment for juvenile-onset systemic sclerosis is even more limited, partially due to the fact that
the disease is exceptionally rare, with an estimated incidence of 0.05 per 100,000 persons. In this
presentation, we discuss two cases: a 28 year-old woman who presented with Raynaud’s
phenomenon and sclerosis of the digits, face, trunk, and extremities after being admitted with
severe cardiac, pulmonary, and renal involvement, and an 8 year-old girl who presented with
sclerosis of the digits, trunk, and extremities without substantial internal organ involvement. Both
patients were managed successfully with a combination of systemic corticosteroids and
mycophenolate mofetil. To our knowledge, this constitutes the first reported case of mycophenolate
mofetil for the treatment of systemic sclerosis during childhood. We use these cases to help define
clinical characteristics of juvenile-onset systemic sclerosis, and to illustrate the clinical differences
between juvenile and adult-onset disease. In addition, we discuss the controversy regarding
systemic corticosteroids and scleroderma renal crisis, consider the existing data for treating adults
with systemic sclerosis with mycophenolate mofetil and emphasize that prolonged treatment with
this agent may be necessary prior to appreciating clinical benefit, and propose mycophenolate
mofetil as a treatment option for juvenile-onset systemic sclerosis.
MORPHEA
The role of skin trauma in the distribution of morphea lesions: a cross sectional
survey of the Morphea in Adults and Children (MAC) cohort IV
Daniel Grabell, BA, MBA; Clifford Hsieh, BS; Rachel Andrew, MD; Kathryn Martires, MD;
Andrew Kim, MD; Rebecca Vasquez, MD; Heidi Jacobe, MD, MSCS
Background: Morphea is a sclerosing disorder of the skin and subcutaneous tissue. Distribution of
trauma-induced skin lesions have been described using “isotopic” and “isomorphic” terms in
chronic GVHD which has features in common with morphea. These distribution patterns have not
been well-examined in morphea patients.
Objective: To determine whether patients enrolled in the Morphea in Adults and Children
(MAC) cohort exhibit preferential distribution of skin lesions in areas of skin trauma in an
isotopic or isomorphic distribution. The “isotopic response” is defined as the development of a
second, unrelated disease in the same area as previous healed disease or injury whereas the
isomorphic response of Koebner is the manifestation of disease in an area predisposed to
developing it. In addition patient demographics, clinical characteristics, and impact on quality of life
in patients with trauma-induced morphea lesions will be evaluated.
Methods: A cross-sectional analysis of the MAC cohort at the University of Texas Southwestern
Medical Center in Dallas, Texas. Patients were included from those enrolled in the MAC cohort from
June 2007 through March 2012. Of the 329 patients in the cohort, 277 were excluded due to the
following: age <4 years (N=9), insufficient data on variables of interest (N=29), indeterminate
subtype (N=8), and lack of inciting event or isomorphic distribution of lesions (N=231). Patients
were evaluated using modified Rodnan skin scores (MRSS), the Dermatology Life Quality Index
(DLQI), and analysis of specific clinical variables using a standardized case report form. Fisher’s
exact test was used for comparisons of categorical variables, and unpaired t-test was used for
comparisons of continuous variables between groups. P values less than 0.05 were considered
significant.
Results: 52 (16%) of patients in the MAC cohort had skin trauma associated lesions, 21 (6%) in an
isotopic and 31 (9%) in an isomorphic distribution. There was a difference in the MRSS between
the groups, with the isotopic mean score of 13.8 and the isomorphic mean score of 5.3 (P = 0.004,
95% CI= 3.08 to 13.92). The DLQI has a mean of 8.4 in isotopic patients versus 4.1 in isomorphic
patients (P = 0.009, 95% CI= 1.18 to 7.50). The LoSSI and the LoSDI were 46 and 24 respectively for
the isotopic group and 25 and 20 for the isomorphic group. There was no significant difference in
MRSS and DLQI between those with skin trauma-induced morphea and the overall MAC cohort.
Conclusion: Some patients with morphea likely have a reaction in response to skin trauma
resulting in cutaneous sclerosis. This implies that patients with morphea may be at risk for
extension or reactivation of their disease in areas of skin trauma and procedures should be
undertaken with caution.
VASCULITIS
D-Dimer Levels as a Marker of Disease Activity in Skin Disease:
Case Reports of Cutaneous Polyarteritis Nodosa and Recurrent Urticaria with Case
Series
Mark G Kirchhof1, Agnes Y Y Lee2, and Jan P Dutz1,3
1Department
of Dermatology and Skin Science, University of British Columbia, Vancouver, BC,
Canada; 2Vancouver Coastal Health, Vancouver General Hospital and Associate Professor,
Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 3Child and Family
Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Biochemical markers of disease allow clinicians to monitor disease severity, progression and
response to treatment. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are
commonly used biochemical markers of inflammatory disease. D-dimers are small protein
fragments generated by fibrinolysis of a thrombus or blood clot. D-dimer assays are often used as
aids in the diagnosis venous thrombosis. Damage to blood vessel walls leads to activation of the
coagulation cascade, thrombus formation and D-dimer release into the blood stream. D-dimer
levels may be elevated in forms of vasculitis including Henoch-Schonlein purpura (HSP), Kawasaki
disease and Churg-Strauss syndrome.
Here we report two cases where disease activity correlated with D-dimer levels. The first case is 51
year old female patient with a diagnosis of cutaneous polyarteritis nodosa. The second case is a 29
year old male with recurrent urticaria. We further present a case series of D-Dimer analysis in a
variety of inflammatory conditions including HSP, leukocytoclastic vasculitis, Behcet’s syndrome,
lupus, Still’s disease, graft versus host disease (GVHD), urticarial vasculitis and pyoderma
gangrenosum (n = 15). D-dimer levels were compared with CRP values and clinical assessment of
disease activity. The sensitivity of the D-dimer test was 0.91 and the specificity was 0.50, while the
sensitivity of the CRP test was 0.89 and the specificity was 0.38.
Our findings suggest that measuring D-dimer levels may be useful as a clinical marker of
vasculopathy in autoimmune and autoinflammatory disease. We show here the use of D-dimer
measurements as a marker of vasculocentric/vasculopathic inflammation and reveal the possibility
that vascular enodothelial damage may be ongoing in many inflammatory conditions.
PITYRIAIS RUBRA PILARIS
Pityriasis Rubra Pilaris: Evaluating Patient Quality of Life
1A.
Brooke Eastham MD, 2Alisa N. Femia MD, 3Lisa K. Pappas-Taffer MD, 3Misha A. Rosenbach MD,
Ann Vleugels MD, MPH
2Ruth
1Harvard
Combined Dermatology Residency Program, Boston, MA; 2Department of Dermatology,
Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 3Department of
Dermatology, University of Pennsylvania, Philadelphia, PA
Although pityriasis rubra pilaris (PRP) is often considered a debilitating skin condition that can
negatively impact patient quality of life (QoL), no formal studies of PRP and its impact on QoL exist.
We aimed to determine the impact of PRP on QoL and to elucidate which independent variables are
associated with poor QoL in patients with PRP. An online survey consisting of validated skinspecific QoL instruments, including Skindex-29 and Dermatology Life Quality Index (DLQI), as well
as the validated global medical QoL instrument Short Form-36 (SF-36) was administered to
members of the online PRP support group. Additionally, we collected information on demographic
characteristics and PRP-related sequelae including alopecia, photosensitivity, palmoplantar
keratoderma, ectropion, joint pain associated with PRP onset, and hospitalization. A total of 116
patients with dermatologist-diagnosed PRP completed all eligible surveys. Those with active
disease (n = 85) were asked to complete all surveys, while those with inactive disease (n = 31) were
asked to complete all except the DLQI and Skindex-29. Quality-of-life scores from patients with PRP
were compared to pre-existing data from the same QoL measures performed in patients with other
dermatologic or non-dermatologic conditions, and the level of statistical significance was set at P =
0.01. According to functioning scores from Skindex-29, patients with active PRP had significantly
worse QoL than all other dermatologic conditions to which it was compared (P = < 0.01) including
vulvodynia, dermatomyositis, cutaneous lupus erythematosus (CLE), epidermolysis bullosa,
eczema, pemphigus vulgaris, psoriasis, acne, and cutaneous T-cell lymphoma, amongst others. With
respect to Skindex-29 emotions scores, patients with active PRP demonstrated significantly worse
QoL than all of these same skin diseases (P = 0.01), except for vulvodynia (P = 0.011),
dermatomyositis (P = 0.193) and CLE (P = 0.033). With respect to Skindex-29 symptoms scores,
PRP was found to have significantly worse QoL than all these same skin diseases (P = < 0.01),
except for epidermolysis bullosa (P = 0.025). There was significant correlation between the DLQI
and Skindex-29 scores (all P values <0.001). With respect to SF-36, those with active PRP have
worse QoL in role physical and bodily pain domains than patients with recent myocardial infarction
(MI), hypertension, type 2 diabetes mellitus (T2DM), and the general population (all P values < .01).
Analysis of vitality, social functioning, and role emotional indicated worse QoL than those with
congestive heart failure, CLE, recent MI, hypertension, T2DM, and the general population (all P
values < .01). Factors related to poor QoL in patients with PRP include alopecia and joint pain. This
study indicates that active PRP profoundly impacts patient QoL. Additional systematic investigation
is necessary to further elucidate treatment options for PRP and to determine the ways in which
treatment may impact QoL over time.