Anti-HMGCR Immune-Mediated Myopathy: Literature Review Based in a Case Report
DOI:
https://doi.org/10.24950/rspmi/Revisao/5/19/4/2019Keywords:
Autoantibodies, Autoimmune Diseases, Hydroxymethylglutaryl CoA Reductases;, Muscular Diseases; MyositisAbstract
Statins are amongst the most prescribed drugs worldwide and they are generally safe. A rare but potentially serious adverse effect of statins’ therapy has been described
– anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (anti-HMGCR) immune-mediated necrotizing myopathy (IMNM) – that can occur years after the drug has been
started. We conducted a literature review after illustrating
a typical case of anti-HMGCR IMNM. A 67-year-old female
treated with simvastatin for the past 5 years presented with
proximal myalgias and tetraparesis, raised creatine kinase,
a myopathic pattern on electromyogram, a necrotizing myopathy on muscle biopsy and anti-HMGCR antibodies. The
statin was stopped, and immunosuppressive therapy was
commenced, leading to a complete remission. The distinction between anti-HMGCR IMNM and other myopathies is
crucial, so that the appropriate treatment can be started
promptly. Likewise, it is important that clinicians be aware
of this entity
Downloads
References
Selva-O’Callaghan A, Alvarado-Cardenas M, Pinal-Fernández I, Trallero-Araguás E, Milisenda JC, Martínez MÁ, et al. Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations. Expert Rev Clin Immunol. 2018;14:215–24. doi: 10.1080/1744666X.2018.1440206. Miopatia Imunomediada Por Anticorpos Anti-HMGCR: Revisão da Literatura com Base Num Caso Clínico 319 PUBLICAÇÃO TRIMESTRAL VOL.26 | N.º4 | OUT/DEZ 2019 ARTIGOS DE REVISÃO REVIEW ARTICLES
Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;62:2757–66. doi: 10.1002/art.27572.
Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63:713–21. doi: 10.1002/art.30156.
Arouche-Delaperche L, Allenbach Y, Amelin D, Preusse C, Mouly V, Mauhin W, 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: Anti-SRP and Anti-HMGCR. Ann Neurol. 2017;81:538–48. doi: 10.1002/ana.24902.
McGrath ER, Doughty CT, Amato AA. Autoimmune myopathies: updates on evaluation and treatment. Neurotherapeutics. 2018;15:976-94. doi: 10.1007/s13311-018-00676-2.
Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Immune-mediated necrotizing myopathy. Curr Rheumatol Rep. 2018;20:21. doi: 10.1007/ s11926-018-0732-6.
Allenbach Y, Mammen AL, Benveniste O, Stenzel W, Allenbach Y, Amato A, et al. 224th ENMC International Workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016. Neuromuscul Disord. 2018;28:87–99. doi: 10.1016/j.nmd.2017.09.016.
Lim J, Rietveld A, De Bleecker JL, Badrising UA, Saris CGJ, van der Kooi AJ, et al. Seronegative patients form a distinctive subgroup of immune-mediated necrotizing myopathy. Neurol - Neuroimmunol Neuroinflammation. 2019;6:e513. doi: 10.1212/NXI.0000000000000513.
Mammen AL. Necrotizing myopathies: beyond statins. Curr Opin Rheumatol. 2014;26:679–83. doi: 10.1097/BOR.0000000000000106
Mammen AL. Autoimmune myopathies: autoantibodies, phenotypes and pathogenesis. Nat Rev Neurol. 2011;7:343–54. doi: 10.1038/nrneurol.2011.63.
Nazir S, Lohani S, Tachamo N, Poudel D, Donato A. Statin-associated autoimmune myopathy: a systematic review of 100 cases. J Clin Rheumatol. 2017;23:149–54. doi: 10.1097/RHU.0000000000000497.
Allenbach Y, Drouot L, Rigolet A, Charuel JL, Jouen F, Romero NB, et al. Anti-HMGCR autoantibodies in european patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Medicine. 2014;93:150–7. doi: 10.1097/MD.0000000000000028.
Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, et al. More severe disease and slower recovery in younger patients with anti-3- -hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology. 2017;56:787-94. doi: 10.1093/rheumatology/ kew470.
Waters MJ, Limaye V. Clinico-serologic features of statin-induced necrotising autoimmune myopathy in a single-centre cohort. Clin Rheumatol. 2018;37:543–7. doi: 10.1007/s10067-017-3831-2.
Musset L, Allenbach Y, Benveniste O, Boyer O, Bossuyt X, Bentow C, 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;15:983–93. doi: 10.1016/j.autrev.2016.07.023.
Limaye V, Bundell C, Hollingsworth P, Rojana-Udomsart A, Mastaglia F, Blumbergs 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: Anti-HMGCR antibodies in myositis. Muscle Nerve. 2015;52:196–203. doi: 10.1002/mus.24541.
Mammen AL. Statin-associated autoimmune myopathy. N Engl J Med. 2016 ;374:664–9.
Mohassel P, Mammen AL. Statin-associated autoimmune myopathy and anti-HMGCR autoantibodies: Anti-HMGCR-Associated Myopathy. Muscle Nerve. 2013;48:477–83. doi: 10.1002/mus.23854.
Mammen AL, Gaudet D, Brisson D, Christopher-Stine L, Lloyd TE, Leffell MS, et al. Increased frequency of DRB1*11:01 in anti-HMG-CoA reductase- -associated autoimmune myopathy. Arthritis Care Res. 2012;64:1233-7. doi: 10.1002/acr.21671.
Watanabe Y, Suzuki S, Nishimura H, Murata K, Kurashige T, Ikawa M, et al. Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan. Medicine. 2015;94:e416. doi: 10.1097/MD.0000000000000416.
Ge Y, Lu X, Peng Q, Shu X, Wang G. Clinical characteristics of anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies in chinese patients with idiopathic inflammatory myopathies. Kuwana M, editor. PLoS One. 2015;10:e0141616. doi: 10.1371/journal.pone.0141616.
Werner JL, Christopher-Stine L, Ghazarian SR, Pak KS, Kus JE, Daya NR, et al. Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Rheum. 2012;64:4087–93. doi: 10.1002/ art.34673.
Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, et al. Neurological complications associated with anti–programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74:1216-22. doi: 10.1001/jamaneurol.2017.1912.
Liewluck T, Kao JC, Mauermann ML. PD-1 Inhibitor-associated myopathies: emerging immune-mediated myopathies. J Immunother. 2018;41:208–11. doi: 10.1097/CJI.0000000000000196.
Allenbach Y, Keraen J, Bouvier A-M, Jooste V, Champtiaux N, Hervier B, et al. High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody. Brain J Neurol.2016;139:2131–5. doi: 10.1093/ brain/aww054.
Kadoya M, Hida A, Hashimoto Maeda M, Taira K, Ikenaga C, Uchio N, et al. Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy. Neurol Neuroimmunol Neuroinflammation. 2016;3:e290.
Mohassel P, Mammen AL. Anti-HMGCR myopathy. J Neuromuscul Dis. 2018;5:11–20. doi: 10.3233/JND-170282.
Mammen AL. Which nonautoimmune myopathies are most frequently misdiagnosed as myositis? Curr Opin Rheumatol. 2017;29:618–22. doi: 10.1097/BOR.0000000000000441.
Parikh P, Tavee J, Soltanzadeh P, Mammen AL, McKeever P, Li Y. Anti-3- -hydroxy-3-methylglutaryl-coenzyme a reductase autoantibody-positive necrotizing autoimmune myopathy with dermatomyositis-like eruption. Muscle Nerve. 2018;57:E135–6. doi: 10.1136/jnnp-2016-313166.
Watanabe Y, Uruha A, Suzuki S, Nakahara J, Hamanaka K, Takayama K, et al. Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry. 2016;87:1038–44.
Ashton C, Junckerstorff R, Bundell C, Hollingsworth P, Needham M. Treatment and outcomes in necrotising autoimmune myopathy: An Australian perspective. Neuromuscul Disord. 2016;26:734–40. doi: 10.1016/j. nmd.2016.08.013.
McHugh NJ, Tansley SL. Autoantibodies in myositis. Nat Rev Rheumatol. 2018 ;14:290–302. doi: 10.1038/nrrheum.2018.56.
Mammen AL, Pak K, Williams EK, Brisson D, Coresh J, Selvin E, et al. Rarity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in statin users, including those with self-limited musculoskeletal side effects. Arthritis Care Res. 2012;64:269–72. doi: 10.1002/acr.20662.
Meira Dias O, Guedes Baldi B, Nathan Costa A, Katsuyuki Shinjo S, Miossi R, Adib Kairalla R. Interstitial lung disease with statin-associated necrotizing autoimmune myopathy responding to rituximab. Arch Bronconeumol. 2016;52:395–7. doi: 10.1016/j.arbres.2015.10.011.
Ramanathan S, Langguth D, Hardy TA, Garg N, Bundell C, Rojana- -Udomsart A, et al. Clinical course and treatment of anti-HMGCR antibody-associated necrotizing autoimmune myopathy. Neurol Neuroimmunol Neuroinflammation. 2015 ;2:e96. doi: 10.1212/NXI.0000000000000096.
Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M. clinical features and treatment outcomes of necrotizing autoimmune myopathy. JAMA Neurol. 2015;72:996–1003. doi: 10.1001/jamaneurol.2015.1207.
Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med. 2015;373:1680–2. doi: 10.1056/ NEJMc1506163.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2023 Medicina Interna
Open Access
