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Review
. 2018 Mar;14(3):215-224.
doi: 10.1080/1744666X.2018.1440206. Epub 2018 Feb 23.

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations

Albert Selva-O'Callaghan  1 , Marcelo Alvarado-Cardenas  1 , Iago Pinal-Fernández  2   3 , Ernesto Trallero-Araguás  4 , José Cesar Milisenda  5 , María Ángeles Martínez  6 , Ana Marín  7 , Moisés Labrador-Horrillo  1   7 , Cándido Juárez  6 , Josep María Grau-Junyent  5
Affiliations
Review

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations

Albert Selva-O'Callaghan et al. Expert Rev Clin Immunol. 2018 Mar.

Abstract

Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms 'myositis', 'statin-induced autoimmune myopathy', 'immune-mediate necrotizing myopathy', 'statins', 'muscular manifestations', and 'anti-HMGCR antibodies' were used. Expert commentary: Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.

Keywords: Myositis; anti-HMGCR antibodies; muscular manifestations; statin-induced autoimmune myopathy: immune-mediate necrotizing myopathy; statins.

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Conflict of interest statement

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1
Figure 1
Immune-mediated necrotizing myopathy. Necrotic muscle fiber cells (arrows). (a) Hematoxylin-eosin, (b) Numerous regenerating fibers are seen (arrows). Masson Trichrome. (c) Universal sarcolemmal MHC class I positive (stronger in regenerating cells). (d) MHC class I negative control (positivity only in endothelial cells). All samples are frozen tissue. Published with permission of Elsevier. Original source: Alvarado Cárdenas et al. Med Clin (Barc) [63]. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.
Figure 2
Figure 2
HALIP indirect immunofluorescence pattern on rat liver cryostat section. Confocal microscope FV (Olympus × 200)27.
Figure 3
Figure 3
Clinical, functional, and biological evolution of a severe form of IMNM (see description in the text). GC: glucocorticoids, IVIG: intravenous immunoglobulin, MMT: manual muscle test, NGT: nasogastric tube, PMF: plasmapheresis, RTX: rituximab.
Figure 4
Figure 4
Etiopathogenesis of statin-induced immune-mediated necrotizing myopathy. EXPERT REVIEW OF CLINICAL IMMUNOLOGY 219
Figure 5
Figure 5
Diagnostic algorithm in statin-associated myopathy. CK: creatine kinase (values are intended to be approximate); EMG: electromyography; HMGCR: 3-hydroxy-3-methylglutaryl coenzyme A reductase; IMNM: immune-mediated necrotizing myopathy. Dotted line indicates that muscle biopsy is not always mandatory (see text).
See this image and copyright information in PMC

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