Progressive myopathy with up-regulation of MHC-I associated with statin therapy

Merrilee Needham; Victoria Fabian; Wally Knezevic; Peter Panegyres; Paul Zilko; Frank L Mastaglia

doi:10.1016/j.nmd.2006.10.007

Progressive myopathy with up-regulation of MHC-I associated with statin therapy

Neuromuscul Disord. 2007 Feb;17(2):194-200. doi: 10.1016/j.nmd.2006.10.007. Epub 2007 Jan 22.

Authors

Merrilee Needham¹, Victoria Fabian, Wally Knezevic, Peter Panegyres, Paul Zilko, Frank L Mastaglia

Affiliation

¹ Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre, University of Western Australia, Australia. needhm01@uwa.edu.au

PMID: 17241784
DOI: 10.1016/j.nmd.2006.10.007

Abstract

Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Anti-Inflammatory Agents / therapeutic use
Atorvastatin
Creatine Kinase / blood
Female
Folic Acid Antagonists / therapeutic use
Genes, MHC Class I / genetics*
Heptanoic Acids / adverse effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
Immunohistochemistry
Male
Methotrexate / therapeutic use
Middle Aged
Mitochondria, Muscle / enzymology
Mitochondria, Muscle / pathology
Muscle Weakness / chemically induced
Muscle Weakness / pathology
Muscular Diseases / chemically induced*
Muscular Diseases / genetics*
Muscular Diseases / pathology
Prednisolone / therapeutic use
Pyrroles / adverse effects
Sarcolemma / metabolism
Simvastatin / adverse effects
Up-Regulation / drug effects

Substances

Anti-Inflammatory Agents
Folic Acid Antagonists
Heptanoic Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pyrroles
Prednisolone
Atorvastatin
Simvastatin
Creatine Kinase
Methotrexate