Immune-mediated necrotizing myopathy: unusual presentations of a treatable disease.

INTRODUCTION/AIMS Immune-mediated necrotizing myopathy (IMNM) is an immune-mediated myopathy typically presenting with progressive subacute weakness and characteristic, but nonspecific, myopathological findings. Atypical cases however can mimic other inherited or acquired myopathies, depriving patients of treatment. We describe a cohort of such patients. METHODS We retrospectively identified IMNM patients who either previously carried a diagnosis of an inherited myopathy established on clinicopathological grounds or whose muscle biopsies displayed atypical features suggestive of a different myopathy. RESULTS Among 131 IMNM patients, 7 previously unreported patients (5%) met one of the above criteria. Three patients 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 IMNM patients did not identify myofibrillar pathology. The patient with granulomatous inflammation was known to have pulmonary sarcoidosis. Genetic testing for inherited myopathies was unrevealing. Antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle were identified in 5 and 1 patients, respectively. Four patients presented with slowly progressive weakness over 3-13 years, while weakness was subacute over ≤6 months in 3 patients. All patients responded to immunomodulatory therapy. DISCUSSION Atypical clinical and histological features can occur in IMNM patients, causing delays in diagnosis and treatment. Clinicians should therefore consider IMNM in the differential diagnosis of unexplained proximal myopathies in spite of atypical clinical and myopathological findings.