Necrotizing autoimmune myopathy (NAM) is a subgroup of idiopathic inflammatory myopathies (IIM) that presents with myalgias, weakness, and markedly elevated CPK levels (up to 50 times upper limit of normal). Most cases of NAM are seen in patients who have a history of statin use, the average duration of which is about 3 yr. Unlike typical statin-induced myopathy, the symptoms of NAM may present long after statins are initiated and can persist long after statins have been discontinued. In contrast with IIM, there is necrosis but sparse inflammation seen on muscle biopsy. Two specific autoantibodies associated with NAM are antisignal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR). Statins have been associated with developing anti-HMGCR in all populations; however, these autoantibodies can be present without statin exposure. Rarely, an individual with NAM can have both antibodies.
Immune-mediated necrotizing myopathy
Necrotizing autoimmune myositis
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Incidence of IIM in a homogenous population is 2.2 to 7.7 per million, and NAM, which is a rare disorder, accounts for 20% of IIM. Anti-SRP-associated NAM accounts for 3% to 6% of IIM, while anti-HMGCR accounts for 5% to 7% of IIM.
Primarily affects adults >18 yr, with mean age at onset around 50 to 60 yr, while younger ages of 47 to 49 have been reported in European studies. Also, statin- and cancer-related NAM patients are found to be older (60s). Anti-SRP-positive patients tend to be younger. There is a female predominance.
- Statin exposure: Atorvastatin and simvastatin more than others (although this may reflect prescribing patterns)
- Cancer: GI origin most common as well as lung, thymoma, ovarian, etc.
- CTD: Scleroderma, Sjögren, and less with systemic lupus erythematosus
- Infections: Rarely HIV
- Can occur in association with the antisynthetase syndrome
Acute (<4 wk) or subacute (<6 mo) onset of severe symmetrical proximal muscle weakness and atrophy that can involve both shoulder and pelvic girdle. Distal weakness may be present, along with myalgias and arthralgias. May be associated with interstitial lung disease, cardiac conduction abnormalities, mechanic hands, dysphagia or dyspnea, weight loss, and Raynaud. Case reports of isolated involvement of neck extensors have been reported.
The exact pathogenesis of NAM is not clear, but studies suggest that statin exposure upregulates HMGCR in muscle in genetically susceptible individuals. Variable durations of statin exposure suggest environmental triggers may initiate autoimmunity. Increased TH1 responses and increased INF-gamma production by macrophages have been described. The presence of an autoantibody to HMGCR suggests that statins may be pathogenic, and that the aberrant immune response is sustained due to high levels of HMGCR expression by regenerating muscle fibers. However, elevated levels of HMGCR are often seen after full remission, suggesting that HMGCR antibodies may have a less direct role in pathogenesis.
