Immune-Mediated Necrotizing Myopathy

Abstract

Purpose of Review Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by relatively severe proximal weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy, and infrequent extra-muscular involvement. Here, we will review the characteristics of patients with IMNM. Recent Findings Anti-signal recognition particle (SRP) and anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies are closely associated with IMNM and define unique subtypes of patients. Importantly, the new European Neuromuscular Centre criteria recognize anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM as three distinct subtypes of IMNM. Anti-SRP myopathy patients have more severe muscle involvement, have more common extra-muscular features, and may respond best to immunosuppressive regimens that include rituximab. In contrast, anti-HMGCR myopathy is often associated with statin exposure and intravenous immunoglobulin treatment may be an effective treatment, even as monotherapy. Both anti-SRP and anti-HMGCR myopathy tend to be most severe in younger patients. Furthermore, children with these forms of IMNM may present with dystrophy-like features which are potentially reversible with immunosuppressant treatment. IMNM patients with either autoantibody may experience fatty replacement of muscle soon after disease onset, suggesting that intense and early immunosuppressant therapy may provide the best chance to avoid long-term disability. Summary IMNM is composed of anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM. Both anti-SRP and anti-HMGCR myopathy can cause severe weakness, especially in younger patients. Anti-SRP myopathy patients tend to have the most severe weakness and most prevalent extra-muscular features. Autoantibody-negative IMNM remains poorly described.

Juvenile Dermatomyositis and the Inflammatory Myopathies

“…Patients present with severely pronounced proximal muscle weakness similar to JDM, DM, and PM, with a biopsy that demonstrates prominent necrotic changes with minimal or no cellular infiltrate. 60 This necrosis distinguishes it from the previously described myopathies. Laboratory evaluation reveals elevated muscle enzymes (CK, LDH, ALT, AST), and anti-SRP and anti-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR) autoantibodies are highly associated with the disease.…”

“…Laboratory evaluation reveals elevated muscle enzymes (CK, LDH, ALT, AST), and anti-SRP and anti-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR) autoantibodies are highly associated with the disease. 60 The presence of specific antibodies helps delineate clinical course and treatment. Anti-SRP-positive patients resemble those of JDM and DM without the skin findings.…”

Secondary cardiac involvement in anti-SRP-antibody-positive myopathy: an 87-year-old woman with heart failure symptoms as the first clinical presentation

“…Anti-SRP-antibody-positive myopathy, which usually leads to severe proximal muscle weakness, is also known to involve extramuscular symptoms such as dysphagia, respiratory disorders, and cardiac disorders [1,14].…”

“…Necrotizing myopathy (NM) is defined by the dominant pathological feature of necrosis of muscle fibers without substantial lymphocytic inflammatory infiltration. Currently, anti-signal recognition particle (SRP) and anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies are reported to have a close association with NM [1].…”

Statin-associated immune-mediated necrotizing myopathy: a retrospective analysis of individual case safety reports from VigiBase

“…Nowadays new diagnostic tests have been established to confirm the diagnosis of anti-HMG-CoA positive IMNM, which are now commercially available [32]. Therefor a biopsy is no more required to confirm the diagnosis of IMNM in case of a positive HMG-CoA antibody result, but remains necessary to establish diagnosis of antibody-negative IMNM [33].…”