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.