The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): A retrospective study - 28/07/11

Doi : 10.1016/j.jaad.2010.09.016

David Fiorentino, MD, PhD ^a,^⁎ , Lorinda Chung, MD, MS ^b, Jeff Zwerner, MD, PhD ^c, Antony Rosen, MD ^d, Livia Casciola-Rosen, PhD ^d
^a Department of Dermatology, Stanford University School of Medicine, Stanford, California
^c Department of Pathology, Stanford University School of Medicine, Stanford, California
^b Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, California
^d Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland

Reprint requests: David Fiorentino, MD, PhD, 450 Broadway, C-234, Redwood City, CA 94063.

Abstract

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.

Le texte complet de cet article est disponible en PDF.

Key words : autoantibodies, clinically amyopathic dermatomyositis antibody, 140 kd (CADM-140) peptide, dermatomyositis, human, interferon-induced helicase 1 protein, interstitial, lung diseases, phenotype, ulcer

Abbreviations used : ANA, DM, ILD, MDA5

Plan

Methods

Patients

Assays to detect antibodies against MDA5, Mi-2, Ro60, Ro52, and Jo-1

Statistics

Results

Patient population

The anti-MDA5 phenotype

Extracutaneous disease

Palmar papules

Ulceration

Other mucocutaneous findings

Discussion

	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.