Necrotizing myopathies: beyond statins

This review discusses the spectrum of diseases associated with a necrotizing muscle biopsy. Although patients with toxic myopathies, endocrine dysfunction, and heritable myopathies may have prominent necrosis on muscle biopsy, immune-mediated myopathies are emphasized here.

A decade ago, immune-mediated necrotizing myopathy was recognized as a distinct form of myositis. Recent evidence now suggests that immune-mediated necrotizing myopathy is not one disease, but can be divided on the basis of the presence of distinct autoantibodies recognizing either the signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Anti-HMG-CoA reductase-positive patients can be further subdivided into those with and without statin exposure, the latter of which may be particularly refractory to immunosuppressive therapy.

A significant number of patients with autoimmune myopathy have a predominantly necrotizing muscle biopsy with minimal lymphocytic infiltration. This biopsy finding occurs in various forms myositis, including the antisynthetase syndrome, scleroderma-associated myopathy, antisignal recognition particle-associated myopathy, statin-associated anti-HMG-CoA reductase-positive autoimmune myopathy, and statin-naïve anti-HMG-CoA reductase-positive myopathy. Future progress in elucidating pathogenic mechanisms and defining optimal treatment strategies may depend upon recognizing these distinct forms of myositis and analyzing them as separate entities.