Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies

Rheumatology (Oxford). 2017 Feb;56(2):287-293. doi: 10.1093/rheumatology/kew386. Epub 2016 Nov 6.

Abstract

Objective: Antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have recently been associated with immune-mediated necrotizing myopathy, especially in patients with statin exposure. As the data are very limited concerning phenotypes and treatment in paediatric patients, we aimed to identify the paediatric patients positive for anti-HMGCR antibodies and clarify their features and therapeutic strategies.

Methods: We screened 62 paediatric patients who were clinically and/or pathologically suspected to have inflammatory myopathy for anti-HMGCR antibodies. We further re-assessed the clinical and histological findings and the treatment of the patients positive for anti-HMGCR antibodies.

Results: We identified nine paediatric patients with anti-HMGCR antibodies (15%). This was more frequent than anti-signal recognition particle antibodies (four patients, 6%) in our cohort. The onset age ranged from infancy to 13 years. Five patients were initially diagnosed with muscular dystrophy, including congenital muscular dystrophy. Most patients responded to high-dose corticosteroid therapy first but often needed adjuvant immunosuppressants to become stably controlled.

Conclusion: Paediatric necrotizing myopathy associated with anti-HMGCR antibodies may not be very rare. Phenotypes are similar to those of adult patients, but a chronic slowly progressive course may be more frequent. Some patients share the clinicopathological features of muscular dystrophy indicating that recognizing inflammatory aetiology would be challenging without autoantibody information. On the other hand, most patients responded to treatment, especially those who were diagnosed early. Our results suggest the importance of early autoantibody testing in paediatric patients who have manifestations apparently compatible with muscular dystrophy in addition to those who have typical features of inflammatory myopathy.

Keywords: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR); immune-mediated necrotizing myopathy; major histocompatibility complex (MHC); membrane attack complex (MAC); muscular dystrophy; paediatrics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies / immunology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / immunology*
  • Infant
  • Male
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myositis / immunology*
  • Myositis / metabolism
  • Myositis / pathology

Substances

  • Autoantibodies
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases