Statin Associated Autoimmune Myopathy
Approximately 2 of every 100, 000 patients taking statin medications develop an autoimmune myopathy that is characterized by muscle weakness, muscle-cell necrosis, and autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Onset of muscle weakness may occur very soon after initiation of statin therapy or many years later. The myopathy usually persists or worsens even if statin therapy is discontinued.
Plasma creatine kinase levels are persistently elevated to more than ten times the upper limit of the reference range in persons with active disease. Muscle biopsy demonstrates myocyte necrosis, myocyte regeneration and endomysial and perivascular inflammation with macrophages and T cells.
Autoantibodies against HMG-CoA reductase, the pharmacologic target of statins, are found predominantly in biopsy specimens from patients with necrotizing myopathy and much less frequently in specimens from patients with other types of myopathy. Anti–HMG-CoA reductase autoantibodies have not been detected in statin-treated patients who do not have muscle disease. Therefore, a positive test for anti–HMG-CoA reductase autoantibodies in patients who develop muscle weakness after stain therapy strongly supports the diagnosis of an autoimmune disorder. In antibody-negative patients, alternative diagnoses should be considered.
Class II HLA allele DRB1*11:01 is strongly associated with the development of anti–HMG-CoA reductase autoantibodies, even in patients without known exposure to statins. Expression of HMG-CoA reductase is low in most tissues, but it is markedly increased when muscle and other types of cells are exposed to statins. Regenerating myocytes express even higher levels of HMG-CoA reductase. Binding of statin to HMG-CoA reductase may alter protein conformation, exposing cryptic epitopes to which the immune system is not tolerant, leading to autoimmunity.
Initial therapy usually includes oral prednisone at a dose of 1 mg per kilogram of body weight per day. Unless the patient has only mild weakness, another immunosuppressive drug, such as methotrexate, azathioprine, or mycophenolate mofetil, should be included at the outset.
Mammen AL, Statin-Associated Autoimmune Myopathy, N ENgl J Med 2016;374:664-9.
