To characterize necrotizing autoimmune myopathy (NAM) patients with atypical clinical or histological features leading to diagnostic uncertainty and delays.

NAM is an immune-mediated myopathy typically presenting with progressive subacute weakness and characteristic myopathological findings. Atypical cases however can mimic other inherited or acquired myopathies, depriving patients of treatment.

We searched the medical records of Mayo Clinic in Rochester, MN for NAM patients evaluated between 2004 and 2019 and who either (a) previously carried a diagnosis of an inherited myopathy established on clinicopathological grounds or (b) whose muscle biopsies displayed atypical features suggestive of a different histologically-defined myopathy.

Seven of 131 patients (5%) met inclusion criteria. One patient was previously reported. Of the remaining 6 patients, 2 were diagnosed with limb-girdle muscular dystrophy on the basis of a chronic progressive course of weakness and family history of myopathy or cardiomyopathy. The other 4 patients displayed atypical histological features (2 prominent mitochondrial abnormalities, 1 myofibrillar pathology and 1 granulomatous inflammation). Immunostaining of biopsies from 12 additional NAM patients did not identify myofibrillar pathology. The patient with granulomatous inflammation had a history of pulmonary sarcoidosis. In all patients with clinicopathological features suggestive of an inherited etiology, genetic testing was unrevealing. Antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle were identified in 4 and 1 patients, respectively. A seronegative patient developed subacute weakness in the context of a newly diagnosed pancreatic neuroendocrine tumor. Four patients presented with slowly progressive weakness over 2-13 years, while weakness was subacute in 2 patients. All patients responded to immunomodulatory therapy.