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. 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.

Keywords: Autoantibodies; HMGCR protein, human; Myositis; Necrotizing myositis; Polymyositis; Signal recognition particle.

Fig. 1

Association of creatine kinase (CK) levels with anti-HMGCR titers (a and b) and examples of the evolution of strength and CK over time in a patient with immune-mediated necrotizing myopathy (c and d). Expressing the CK levels in a logarithmic scale (a and c) correlates better with the activity of the disease (autoantibody levels and strength) than when using it in a linear scale (b and d)

Fig. 2

Examples of T1-weighted (T1W) turbo spin echo (TSE) and short tau inversion recovery (STIR) sequences showing edema (red arrow), atrophy (red arrow head), and fatty replacement (blue arrow) in a patient with immune-mediated necrotizing myositis (IMNM)

Fig. 3

Representative muscle biopsy of a patient with immune-mediated necrotizing myopathy, showing degenerating fibers (arrow head), myophagocytosis (arrow), and many atrophic fibers