Immune-mediated necrotizing myopathy

Immune-mediated necrotizing myopathy (IMNM), also known as necrotizing autoimmune myopathy, is a subtype of idiopathic inflammatory myopathy characterized by severe proximal muscle weakness and markedly elevated serum creatine kinase (CK) levels. Unlike other inflammatory myopathies such as polymyositis or dermatomyositis, muscle biopsy in IMNM typically shows prominent myofiber necrosis and regeneration with minimal or absent inflammatory cell infiltration. The disease primarily affects skeletal muscle, leading to progressive weakness of the proximal limbs (shoulders, hips, and thighs), difficulty climbing stairs, rising from chairs, and lifting objects overhead. Some patients may also experience dysphagia (difficulty swallowing) and, less commonly, cardiac or pulmonary involvement. Two major autoantibodies are associated with IMNM: anti-signal recognition particle (anti-SRP) antibodies and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. The anti-HMGCR form is notably associated with prior statin exposure, though it can also occur in statin-naive individuals. Anti-SRP-associated IMNM tends to present with more severe weakness and may be more refractory to treatment. A subset of patients is seronegative for both antibodies. Treatment of IMNM typically requires aggressive immunosuppressive therapy. First-line treatment generally includes high-dose corticosteroids combined with steroid-sparing immunosuppressive agents such as methotrexate, azathioprine, or mycophenolate mofetil. Intravenous immunoglobulin (IVIG) is frequently used, particularly in refractory cases, and rituximab has shown benefit in patients who do not respond to conventional therapy. Early and sustained treatment is important, as delayed therapy can lead to significant irreversible muscle damage and disability. The disease follows a chronic course and often requires long-term immunosuppression to maintain remission.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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