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.

Keywords

acquired myopathy - idiopathic inflammatory myopathies - chronic - myopathy - immune-mediated necrotizing myopathy

• References

• 1 Mammen AL. Autoimmune myopathies: autoantibodies, phenotypes and pathogenesis. Nat Rev Neurol 2011; 7 (06) 343-354
• 2 Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M. Clinical features and treatment outcomes of necrotizing autoimmune myopathy. JAMA Neurol 2015; 72 (09) 996-1003
• 3 Hoogendijk JE, Amato AA, Lecky BR. , et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands. Neuromuscul Disord 2004; 14 (05) 337-345
• 4 Allenbach Y, Drouot L, Rigolet A. , et al; French Myositis Network. Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Medicine (Baltimore) 2014; 93 (03) 150-157
• 5 Drouot L, Allenbach Y, Jouen F. , et al; French Myositis Network [CN]. Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies. Arthritis Res Ther 2014; 16 (01) R39
• 6 Musset L, Allenbach Y, Benveniste O. , et al. Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study. Autoimmun Rev 2016; 15 (10) 983-993
• 7 Mohassel P, Foley AR, Donkervoort S. , et al. Anti-HMGCR necrotizing myopathy masquerading as a muscular dystrophy in a child. Muscle Nerve 2017;
• 8 Suzuki S, Hayashi YK, Kuwana M, Tsuburaya R, Suzuki N, Nishino I. Myopathy associated with antibodies to signal recognition particle: disease progression and neurological outcome. Arch Neurol 2012; 69 (06) 728-732
• 9 Kishi T, Rider LG, Pak K. , et al; Childhood Myositis Heterogeneity Study Group. Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A reductase autoantibodies are associated with DRB1*07:01 and severe myositis in pediatric myositis patients. Arthritis Care Res (Hoboken) 2017; 69 (07) 1088-1094
• 10 Ikeda K, Mori-Yoshimura M, Yamamoto T. , et al. Chronic myopathy associated with anti-signal recognition particle antibodies can be misdiagnosed as facioscapulohumeral muscular dystrophy. J Clin Neuromuscul Dis 2016; 17 (04) 197-206
• 11 Liang WC, Uruha A, Suzuki S. , et al. Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies. Rheumatology (Oxford) 2017; 56 (02) 287-293
• 12 Vattemi G, Mirabella M, Guglielmi V. , et al. Muscle biopsy features of idiopathic inflammatory myopathies and differential diagnosis. Auto Immun Highlights 2014; 5 (03) 77-85
• 13 Dalakas MC. Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol 2010; 10 (03) 346-352