Medline ® Abstracts for References 32,33

We report patients from two neuromuscular centers who were evaluated between the years 2000 and 2008 and met the following criteria: (1) proximal muscle weakness occurring during or after treatment with statins; (2) elevated serum creatine kinase (CK); (3) persistence of weakness and elevated CK despite discontinuation of the statin; (4) improvement with immunosuppressive agents; and (5) muscle biopsy showing necrotizing myopathy without significant inflammation. Twenty-five patients fulfilled our inclusion criteria. Twenty-four patients required multiple immunosuppressive agents. Fifteen patients relapsed after being tapered off immunosuppressive therapy. Exposure to statins prior to onset was significantly higher in patients with necrotizing myopathy (82%) as compared to those with dermatomyositis (18%), polymyositis (24%), and inclusion-body myositis (38%) seen in the same time period. The lack of improvement following discontinuation of statins, the need for immunosuppressive therapy, and frequent relapse when treatment was tapered suggest an immune-mediated etiology for this rare, statin-associated necrotizing myopathy.

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.