Anti-HMGCR Antibody–Related Necrotizing Autoimmune Myopathy Mimicking Muscular Dystrophy

Abstract

Introduction Necrotizing autoimmune myopathies (NAMs) are acquired myopathies with myofibrillar necrosis and weak or absent inflammatory component, sometimes associated with anti-signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. Observation The patient, a girl now aged 20 years, was first assessed at the age of 5 years for abnormal gait revealing frank pelvic deficit. Creatine kinase (CK) levels were as high as 7,500 IU/L. Subsequent muscle biopsy showed some necrosis, fiber regeneration, and fibrosis consistent with muscular dystrophy (MD). Protein immunohistochemistry was normal. The disease course was progressive until wheelchair use at the age of 9 years. At 12 years of age, a second muscle biopsy found an advanced MD with some perivascular inflammatory mononuclear cells. All molecular analyses done through 14 years of follow-up were negative till anti-HMGCR antibodies were detected at a significant amount when she was 19 years old. Discussion NAMs begin at a pediatric age and may have a chronic course mimicking MDs. Muscular biopsy can be misleading with a predominantly dystrophic pattern without inflammation. Conclusion This observation should prompt the assessment of NAMs in all MDs, even pediatric, without molecular solutions.

Myopathy due to HMGCR antibodies in adult mimicking muscular dystrophy associated with cancer and statin exposure – narrative review of the literature – case report

“…According to a previous report, weakness in NAM anti-HMGCR in some cases presents an acute onset (within ≤4 weeks), and in a few cases, weakness could evolve slowly (from months to several years), occasionally mimicking MD, the most common and representative myopathy, being part of hereditary or sporadic progressive diseases and characterized by several phenotypic and genetic features. 2 , 6 , 9 …”

Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy

“…4 Yet, young adults and children without statin exposure may also develop anti-HMGCR myopathy, some of whom are anecdotally reported to present with a chronic, LGMD-like phenotype. 5–11 Thus, we hypothesized that some patients with presumed LGMD, specifically those in whom genetic testing has failed to elucidate causative mutations (i.e., “unrevealing genetic testing”), may actually have anti-HMGCR myopathy. We use the term “anti-HMGCR myopathy” to refer to a myopathy associated with anti-HMGCR autoantibodies.…”

Pediatric immune-mediated necrotizing myopathy

“…The typical muscle pathologies associated with IMNM are as follows: necrosis and regeneration of muscle fibers; elevated expression levels of MHC-I, but not MHC-II, on the sarcolemma; frequent deposition of MAC on the sarcolemma ( 14 , 66 ); infiltration of lymphocytes to the endomysium but rare invasion of healthy myofibers; and fine granular patterns of p62 (autophagy marker) over the sarcolemma ( 14 , 66–69 ). In some pediatric patients with a prolonged disease duration, increased endomysial fibrosis, increased fiber size variability, and internal nuclei have been observed ( 34 , 35 , 37 ). Because of the pathological similarity between IMNM and muscular dystrophy, initial misdiagnosis is common.…”