Immune-Mediated Necrotizing Myopathy
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Purpose of Review
Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by relatively severe proximal weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy, and infrequent extra-muscular involvement. Here, we will review the characteristics of patients with IMNM.
Anti-signal recognition particle (SRP) and anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies are closely associated with IMNM and define unique subtypes of patients. Importantly, the new European Neuromuscular Centre criteria recognize anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM as three distinct subtypes of IMNM. Anti-SRP myopathy patients have more severe muscle involvement, have more common extra-muscular features, and may respond best to immunosuppressive regimens that include rituximab. In contrast, anti-HMGCR myopathy is often associated with statin exposure and intravenous immunoglobulin treatment may be an effective treatment, even as monotherapy. Both anti-SRP and anti-HMGCR myopathy tend to be most severe in younger patients. Furthermore, children with these forms of IMNM may present with dystrophy-like features which are potentially reversible with immunosuppressant treatment. IMNM patients with either autoantibody may experience fatty replacement of muscle soon after disease onset, suggesting that intense and early immunosuppressant therapy may provide the best chance to avoid long-term disability.
IMNM is composed of anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM. Both anti-SRP and anti-HMGCR myopathy can cause severe weakness, especially in younger patients. Anti-SRP myopathy patients tend to have the most severe weakness and most prevalent extra-muscular features. Autoantibody-negative IMNM remains poorly described.
KeywordsMyositis Autoantibodies Signal recognition particle HMGCR protein, human Necrotizing myositis Polymyositis
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Conflict of Interest
The authors declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 2.Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, 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(5):337–45.CrossRefPubMedGoogle Scholar
- 3.•• Allenbach Y, Mammen AL, Stenzel W, Benveniste O, Immune-mediated necrotizing myopathies working G. 224th ENMC International Workshop:: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14–16 October 2016. Neuromuscul Disord 2017. Most recent classification criteria in IMNM. It includes consensus treatment recommendations for the different IMNM subsets. Google Scholar
- 16.•• Pinal-Fernandez I, Parks C, Werner JL, et al. Longitudinal course of disease in a large cohort of myositis patients with autoantibodies recognizing the signal recognition particle. Arthritis care res (Hoboken). 2017;69(2):263–70. Longitudinal cohort study of anti-SRP patients. CrossRefGoogle Scholar
- 17.•• Kishi T, Rider LG, Pak K, et al. Association of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies with DRB1*07:01 and severe myositis in juvenile myositis patients. Arthritis Care Res (Hoboken). 2017;69(7):1088–94. Report of juvenile anti-HMGCR cases from the USA. CrossRefGoogle Scholar
- 21.•• Tiniakou E, Pinal-Fernandez I, Lloyd TE, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017;56(5):787–94. Comprehensive longitudinal cohort study of patients with anti-HMGCR myositis. Google Scholar
- 24.Pinal-Fernandez I, Casal-Dominguez M, Huapaya JA, Albayda J, Paik JJ, Johnson C, et al. A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies. Rheumatology (Oxford). 2017;56(6):999–1007.CrossRefGoogle Scholar
- 32.• Limaye V, Bundell C, Hollingsworth P, et al. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve. 2015;52(2):196–203. Report of the clinical features of anti-HMGCR patients from Australia. CrossRefPubMedGoogle Scholar
- 37.• Alvarado-Cardenas M, Marin-Sanchez A, Martinez MA, et al. Statin-associated autoimmune myopathy: a distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories. Autoimmun Rev. 2016;15(12):1161–6. New IFL pattern in anti-HMGCR myositis. CrossRefPubMedGoogle Scholar
- 38.Rider LG, Werth VP, Huber AM, et al. Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF-36), Child Health Questionnaire (CHQ), physician global damage, Myositis Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-2 (FI-2), Myositis Activities Profile (MAP), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI). Arthritis Care Res (Hoboken) 2011;63 Suppl 11:S118–57.Google Scholar
- 39.Compston A. Aids to the investigation of peripheral nerve injuries. Medical Research Council: nerve injuries research committee. His Majesty’s stationery office: 1942; pp. 48 (iii) and 74 figures and 7 diagrams; with aids to the examination of the peripheral nervous system. By Michael O'Brien for the Guarantors of Brain. Saunders Elsevier: 2010; pp.  64 and 94 figures. Brain 2010;133(10):2838–44.Google Scholar
- 40.•• Pinal-Fernandez I, Casal-Dominguez M, Carrino JA, et al. Thigh muscle MRI in immune-mediated necrotising myopathy: extensive oedema, early muscle damage and role of anti-SRP autoantibodies as a marker of severity. Ann Rheum Dis. 2017;76(4):681–7. Comprehensive MRI study in patients with immune-mediated necrotizing myositis compared to other myositis subtypes. CrossRefPubMedGoogle Scholar
- 47.Mammen AL, Gaudet D, Brisson D, Christopher-Stine L, Lloyd TE, Leffell MS, et al. Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Care Res (Hoboken). 2012;64(8):1233–7.Google Scholar
- 54.Pinal-Fernandez I, Ferrer-Fabregas B, Trallero-Araguas E, et al. Tumour TIF1 mutations and loss of heterozygosity related to cancer-associated myositis. Rheumatology (Oxford) 2017.Google Scholar
- 57.•• Arouche-Delaperche L, Allenbach Y, Amelin D, et al. Pathogenic role of anti-signal recognition protein and anti-3-hydroxy-3-methylglutaryl-CoA reductase antibodies in necrotizing myopathies: Myofiber atrophy and impairment of muscle regeneration in necrotizing autoimmune myopathies. Ann Neurol. 2017;81(4):538–48. Manuscript suggesting that in vitro, anti-SRP, and anti-HMGCCR autoantibodies are pathogenic. CrossRefPubMedGoogle Scholar