title: The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  We suggest that MDA5 reactivity in DM characterizes a patient population with severe vasculopathy.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA. fiorentino@stanford.edu
authors.forename: David
authors.initials: D
authors.lastname: Fiorentino
authors.forename: Lorinda
authors.initials: L
authors.lastname: Chung
authors.forename: Jeff
authors.initials: J
authors.lastname: Zwerner
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001707:Biopsy, Needle; D015331:Cohort Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D003882:Dermatomyositis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D010455:Peptides / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; C501597:CADM-140 peptide, human; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1