Objective Autoantibodies against melanoma differentiation-associated protein 5 (MDA5) 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 MDA5 autoantibodies are associated with a unique cutaneous phenotype. Given the widening spectrum of clinical findings, we evaluated the clinical features of anti-MDA5-positive patients seen at a US myositis referral center. Methods 160 DM patients were screened for MDA5 autoantibodies by immunoprecipitation and antibody titers were analyzed in longitudinal serum samples. Anti-MDA5 positive patients were evaluated for the presence of additional myositis autoantibodies. Patient clinical characteristics were compared by retrospective chart review. Results MDA5 was targeted in 11/160 (6.9%) patients with DM. Of these, nine presented with a symmetric polyarthropathy, six demonstrated overt clinical myopathy and eight had ILD. Eight anti-MDA5-positive patients exhibited the clinical attributes of the antisynthetase syndrome in the absence of Jo-1 or other anti-synthetase autoantibodies. MDA5 autoantibody titers did not correlate with clinical course. Conclusions MDA5 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-MDA5 positive patients had overt clinical myopathy and ILD. The latter, while occasionally severe, typically resolved with immunosuppressive therapy. In this cohort, the MDA5 phenotype is frequently a clinical mimic of the antisynthetase syndrome and is not associated with rapidly progressive ILD.

Anti-HMGCR myositis is usually a chronic disease requiring long-term immunosuppression. Although younger patients had more severe disease and a worse prognosis than older patients, they did not have evidence of a known co-existing muscular dystrophy to explain their persistent, and sometimes progressive, muscle weakness.

Objective Anti-HMGCR antibodies are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed subjects with autoimmune myopathy. The main objective of this study is to define the association of anti-HMGCR antibody levels with disease activity. Methods Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR positive subjects. Associations of antibody level with CK and strength at visit 1 were analyzed in 55 subjects, 40 of whom were statin-exposed. In 12 statin-exposed and 5 statin-unexposed subjects with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated. Results Antibody levels were associated with CK levels (p < 0.001), arm strength (p < 0.05), and leg strength (p < 0.05) at visit 1 but these associations were only significant amongst statin-exposed patients in stratified analyses. With treatment over 26.2 +/− 12.6 months, antibody levels declined (p < 0.05) and arm abduction strength improved (p < 0.05) in 17 subjects followed longitudinally. When analyzed separately, statin-exposed subjects developed decreased antibody levels (p < 0.01), decreased CK levels (p < 0.001), improved arm strength (p < 0.05), and improved hip flexion strength (p < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any subject. Conclusion In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with treatment, antibody levels declined and arm strength improved. Statin-exposed but not statin-unexposed subjects had significant improvements in CK and strength, suggesting a phenotypic difference between statin-exposed and -unexposed anti-HMGCR patients.