Mamatha Pasnoor1, Richard J Barohn1,2, Mazen M Dimachkie1. 1. Neuromuscular Division, Department of Neurology. 2. Research Institute, Heartland Institute for Clinical and Translational Research, University of Kansas Medical Center, Kansas City, USA.
Abstract
PURPOSE OF REVIEW: Our aim is to highlight major advances reported in the last few years in drug-induced muscle toxicity. RECENT FINDINGS: Our focus is on myopathies induced by statins and immune checkpoint inhibitors with a brief overview of rare steroid myopathies. Statin muscle injury is frequently because of direct toxicity rather than an autoimmune mechanism. Laboratory testing and muscle pathologic features distinguish these two conditions. Statin-associated necrotizing autoimmune myopathy (SANAM) is associated with an autoantibody in 66% of cases targeting the HMGCR enzyme. The later autoantibody is a marker for necrotizing autoimmune myopathy, regardless of statin exposure. In SANAM, MHC-I antigens are expressed on the surface of intact muscle fibers. Genetic HLA loci predispose patients exposed to statins to immunologic toxicity. SANAM requires long-term therapy with multiple immunosuppressive therapies. Immune checkpoint inhibitors are powerful emerging therapies for advanced cancer that pause a novel therapeutic challenge. SUMMARY: This review is focused on statins, the most prevalent myotoxic drug class. In addition, we examine the accumulating body of evidence of muscle injury and its management with immune checkpoint inhibitors. We anticipate the reader to become more knowledgeable in recent discoveries related to these myotoxic drugs, and their mechanisms of action and management.
PURPOSE OF REVIEW: Our aim is to highlight major advances reported in the last few years in drug-induced muscle toxicity. RECENT FINDINGS: Our focus is on myopathies induced by statins and immune checkpoint inhibitors with a brief overview of rare steroidmyopathies. Statin muscle injury is frequently because of direct toxicity rather than an autoimmune mechanism. Laboratory testing and muscle pathologic features distinguish these two conditions. Statin-associated necrotizing autoimmune myopathy (SANAM) is associated with an autoantibody in 66% of cases targeting the HMGCR enzyme. The later autoantibody is a marker for necrotizing autoimmune myopathy, regardless of statin exposure. In SANAM, MHC-I antigens are expressed on the surface of intact muscle fibers. Genetic HLA loci predispose patients exposed to statins to immunologic toxicity. SANAM requires long-term therapy with multiple immunosuppressive therapies. Immune checkpoint inhibitors are powerful emerging therapies for advanced cancer that pause a novel therapeutic challenge. SUMMARY: This review is focused on statins, the most prevalent myotoxic drug class. In addition, we examine the accumulating body of evidence of muscle injury and its management with immune checkpoint inhibitors. We anticipate the reader to become more knowledgeable in recent discoveries related to these myotoxic drugs, and their mechanisms of action and management.
Authors: George D Bittner; Jared S Bushman; Cameron L Ghergherehchi; Kelly C S Roballo; Jaimie T Shores; Tyler A Smith Journal: J Neuroinflammation Date: 2022-02-28 Impact factor: 8.322