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

J Am Acad Dermatol. 2011 Jul;65(1):25-34. doi: 10.1016/j.jaad.2010.09.016. Epub 2011 Apr 29.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / genetics
  • Autoantibodies / immunology
  • Biopsy, Needle
  • Cohort Studies
  • DEAD-box RNA Helicases / genetics*
  • Dermatomyositis / blood
  • Dermatomyositis / genetics*
  • Dermatomyositis / pathology
  • Disease Progression
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease / epidemiology*
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins
  • Interferon-Induced Helicase, IFIH1
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Peptides / genetics*
  • Phenotype
  • Prognosis
  • Retrospective Studies

Substances

  • Autoantibodies
  • CADM-140 peptide, human
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1