Anti–Melanoma Differentiation–Associated Protein 5–Associated Dermatomyositis: Expanding the Clinical Spectrum

OBJECTIVE: Autoantibodies against melanoma differentiation-associated protein 5 (MDA-5) have been described in several Asian dermatomyositis (DM) cohorts, often associated with amyopathic DM and rapidly progressive interstitial lung disease (ILD). A recent study of a DM cohort seen at a US dermatology clinic reports that MDA-5 autoantibodies are associated with a unique cutaneous phenotype. Given the widening spectrum of clinical findings, we evaluated the clinical features of anti-MDA-5-positive patients seen at a US myositis referral center. METHODS: One hundred sixty DM patients were screened for MDA-5 autoantibodies by immunoprecipitation and antibody titers were analyzed in longitudinal serum samples. Anti-MDA-5-positive patients were evaluated for the presence of additional myositis autoantibodies. Patient clinical characteristics were compared by retrospective chart review. RESULTS: MDA-5 was targeted in 11 (6.9%) of 160 patients with DM. Of these, 9 presented with a symmetric polyarthropathy, 6 demonstrated overt clinical myopathy, and 8 had ILD. Eight anti-MDA-5-positive patients exhibited the clinical attributes of the antisynthetase syndrome in the absence of Jo-1 or other antisynthetase autoantibodies. MDA-5 autoantibody titers did not correlate with clinical course. CONCLUSION: MDA-5 autoantibodies are found in DM patients presenting with a symmetric polyarthritis, clinically similar to rheumatoid arthritis. These patients often have features of the antisynthetase syndrome, but in the absence of antisynthetase autoantibodies. Most anti-MDA-5-positive patients had overt clinical myopathy and ILD. The latter, while occasionally severe, typically resolved with immunosuppressive therapy. In this cohort, the MDA-5 phenotype is frequently a clinical mimic of the antisynthetase syndrome and is not associated with rapidly progressive ILD.