Original article
The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): A retrospective study

https://doi.org/10.1016/j.jaad.2010.09.016Get rights and content

Background

Dermatomyositis (DM) is a multisystem autoimmune disease, in which serologic evidence of immune responses to disease-specific antigenic targets is found in approximately 50% to 70% of patients. Recently, melanoma differentiation-associated gene 5 (MDA5) has been identified as a DM-specific autoantigen that appears to be targeted in patients with DM and mild or absent muscle inflammation and with an increased risk of interstitial lung disease.

Objective

We wished to understand the role of MDA5 in DM skin inflammation by testing it to determine if a specific cutaneous phenotype is associated with MDA5 reactivity.

Methods

We retrospectively screened plasma from 77 patients with DM in the outpatient clinics at the Stanford University Department of Dermatology in California.

Results

We found that 10 (13%) patients had circulating anti-MDA5 antibodies, and had a characteristic cutaneous phenotype consisting of skin ulceration, tender palmar papules, or both. Typical areas of skin ulceration included the lateral nailfolds, Gottron papules, and elbows. Biopsy specimens of the palmar papules showed a vasculopathy characterized by vascular fibrin deposition with variable perivascular inflammation. Patients with anti-MDA5 antibodies also had an increased risk of oral pain and/or ulceration, hand swelling, arthritis/arthralgia, and diffuse hair loss. Consistent with previous reports, these patients had little or no myositis and had increased risk of interstitial lung disease.

Limitations

This study was conducted at a tertiary referral center. Multiple associations with MDA5 antibodies were tested retrospectively on a relatively small cohort of 10 anti-MDA5-positive patients.

Conclusion

We suggest that MDA5 reactivity in DM characterizes a patient population with severe vasculopathy.

Section snippets

Patients

All patients were seen in the outpatient clinics at the Stanford University Department of Dermatology in California between July 2004 and April 2010. The collection of plasma from patients with DM for the purposes of proteomic and antibody analysis was approved by the Stanford Institutional Review Board. The population from which plasma was collected represented approximately 80% of the total number of patients with DM seen during this time period. Patients were only included if they had a

Patient population

We collected plasma from 77 patients with DM seen at the outpatient dermatology clinic at Stanford University School of Medicine. The characteristics of these patients are shown in Table I. At the time of plasma harvesting, patients had a median global skin and muscle disease activity of moderate and mild, respectively, on a Likert scoring system, and the median muscle strength score was 130 (maximum 150). The percentage of patients taking systemic corticosteroids (median prednisone dosage 6

Discussion

Antibodies to MDA5 have been recently described to be specifically associated with DM.10, 11, 13 Originally termed “CADM-140,” MDA5 reactivity initially was described as marking a population of patients with DM that was “clinically amyopathic.”10, 11, 13 However, the definition of “clinically amyopathic” is not universally agreed upon. This designation was intended to identify patients with strictly no evidence of myositis based only on what the clinician can see in the examination room (eg,

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    • Cited by (0)

    Supported by the Scleroderma Research Foundation (Dr Chung), National Institutes of Health (NIH) RO1 R37-DE-12354 (Dr Rosen), and NIH RO1 AR-44684 (Dr Casciola-Rosen). We thank the Johns Hopkins University Rheumatic Diseases Research Core Center (P30-AR-053503) for assays.

    Conflicts of interest: None declared.

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    Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.