LAUSR

Immune-mediated necrotizing myopathy (IMNM) is a group of inflammatory myopathies that was distinguished from polymyositis in 2004. Most IMNMs are associated with anti-signal recognition particle (anti-SRP) or anti-3-hydroxy-3-methylglutaryl-coA reductase (anti-HMGCR) myositis-specific autoantibodies, although ~20% of patients with IMNM remain seronegative. These associations have led to three subclasses of IMNM: anti-SRP-positive IMNM, anti-HMGCR-positive IMNM and seronegative IMNM. IMNMs are frequently rapidly progressive and severe, displaying high serum creatine kinase levels, and failure to treat IMNMs effectively may lead to severe muscle impairment. In patients with seronegative IMNM, disease can be concomitant with cancer. Research into IMNM pathogenesis has shown that anti-SRP and anti-HMGCR autoantibodies cause weakness and myofibre necrosis in mice, suggesting that, as well as being diagnostic biomarkers of IMNM, they may play a key role in disease pathogenesis. Therapeutically, treatments such as rituximab or intravenous immunoglobulins can now be discussed for IMNM, and targeted therapies, such as anticomplement therapeutics, may be a future option for patients with refractory disease. The association of immune-mediated necrotizing myopathy (IMNM) with myositis-specific autoantibodies has led to the classification of three subclasses of IMNM and provided insight into the pathogenesis of, and treatment options for, these inflammatory myopathies. Anti-3-hydroxy-3-methylglutaryl-coA reductase (anti-HMGCR) and anti-signal recognition particle (anti-SRP) myositis-specific autoantibodies are crucial for defining immune-mediated necrotizing myopathy (IMNM) when muscle biopsy is absent but required for diagnosis. IMNM can be considered a muscle-specific autoimmune disease; patients with anti-SRP-positive IMNM are at an increased risk of myocarditis and patients with seronegative IMNM are at a major risk of associated malignancy. Among treatable idiopathic inflammatory myopathies, IMNM is the most severe in terms of muscle-related morbidities such as muscle atrophy, muscle fat replacement and/or disability, and is of long duration. Anti-HMGCR and anti-SRP myositis-specific autoantibodies seem to play a key role in the pathophysiology of IMNM; autoantibody-induced muscle damage is complement dependent. A combination of corticosteroids, immunosuppressants and intravenous immunoglobulins is frequently required to control disease activity. No specific randomized clinical trial is available to define the best treatment strategy for keeping patients with IMNM in remission. Anti-3-hydroxy-3-methylglutaryl-coA reductase (anti-HMGCR) and anti-signal recognition particle (anti-SRP) myositis-specific autoantibodies are crucial for defining immune-mediated necrotizing myopathy (IMNM) when muscle biopsy is absent but required for diagnosis. IMNM can be considered a muscle-specific autoimmune disease; patients with anti-SRP-positive IMNM are at an increased risk of myocarditis and patients with seronegative IMNM are at a major risk of associated malignancy. Among treatable idiopathic inflammatory myopathies, IMNM is the most severe in terms of muscle-related morbidities such as muscle atrophy, muscle fat replacement and/or disability, and is of long duration. Anti-HMGCR and anti-SRP myositis-specific autoantibodies seem to play a key role in the pathophysiology of IMNM; autoantibody-induced muscle damage is complement dependent. A combination of corticosteroids, immunosuppressants and intravenous immunoglobulins is frequently required to control disease activity. No specific randomized clinical trial is available to define the best treatment strategy for keeping patients with IMNM in remission.