An Unusual Case of Statin-Induced Myopathy: Anti-HMGCoA Necrotizing Autoimmune Myopathy

Abstract

Statins are some of the most widely prescribed medications, and though generally well tolerated, can lead to a self-limited myopathy in a minority of patients. Recently, these medications have been associated with a necrotizing autoimmune myopathy (NAM). Statin-associated NAM is characterized by irritable myopathy on electromyography (EMG) and muscle necrosis with minimal inflammation on muscle biopsy. The case presented is a 63-year-old woman who has continued elevation of creatine kinase (CK) after discontinuation of statin therapy. She has irritable myopathy on EMG and NAM is confirmed by muscle biopsy. She subsequently tests positive for an experimental anti-3-hydroxy-3-methylglutaryl-coenzyme A (anti-HMGCoA) antibody that is found to be present in patients with statin-associated NAM. Though statin-associated NAM is a relatively rare entity, it is an important consideration for the general internist in patients who continue to have CK elevation and weakness after discontinuation of statin therapy. Continued research is necessary to better define statin-specific and dose-dependent risk, as well as optimal treatment for this condition.

Keywords: anti-HMGCR antibody; idiopathic inflammatory myopathy; necrotizing autoimmune myopathy; statin.

Figure 1.

Creatine kinase (U/L) fluctuation from previously normal levels to levels at diagnosis and after treatment.

Figure 2.

Pathological findings in skeletal muscle (bar = 50 μm). a H&E stain showing a myopathic process with muscle fiber size variability with regenerative and degenerative fibers, the latter indicative of attempts at healing. Prominent necrotic fibers (arrows) and non-necrotic fibers undergoing immune-mediated attack (arrowheads) are noted. The paucity of inflammation (T cells, B cells, Dendritic cells and macrophages) is consistent with statin-induced myopathy compared to PM or DM. b C5b9 (complement membrane attack complex; MAC) immunofluorescence staining showing diffuse (involving sarcolemma and myofiber) upregulation within the necrotic fibers (arrows) and only sarcolemmal upregulation in non-necrotic fibers (arrowheads), a finding seen in antibody-mediated myopathies. c Major histocompatibility complex class I (MHC-I) staining showing upregulation within necrotic (arrow) and non-necrotic (arrowheads) fibers, also indicative of an immune-mediated process. d Spectrin (a protein found on the sarcolemma) immunofluorescence highlights the abnormal pattern of staining in necrotic fibers (arrows) while showing normal pattern of staining in non-necrotic fibers (arrowheads). This confirms that during the early antibody-mediated phase of the disease, the membrane is relatively intact, but in later phases, the membrane integrity is compromised.