Immune-mediated necrotising myopathy linked to statin use

In December, 2013, a 59-year-old man presented to the Neurology Department with progressive pelvic girdle myalgia and proximal weakness so severe that he needed help walking. His myalgia had started in March, 2012, 4 months after starting atorvastatin, and had persisted despite discontinuation of the statin in September, 2013. On examination we noted severe proximal paraparesis. Laboratory tests revealed substantially raised serum creatine kinase concentration (3453 U/L, normal range <171 U/L) but no sign of systemic infl ammation. Electromyography showed widespread acute myopathic changes. T1-weighted pelvic MRI (fi gure) showed widespread muscle atrophy. Biopsy sample from the right glutaeus maximus showed prominent necrosis without signifi cant infl ammation, a cytoplasmic pattern with perinuclear reinforcement of indirect immunofl uorescence on human HEp-2 cells, and strong positivity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) auto-antibody (256 AU/mL, normal range <14 AU/mL; fi gure). These fi ndings were consistent with statin-associated immune-mediated necrotising myopathy. After 6 months of treatment with high dose oral corticosteroids, subcutaneous methotrexate, and intravenous immunoglobulins, the patient’s symptoms resolved, creatinine kinase concentrations returned to normal, and HMGCRantibody level dropped substantially (to 70 AU/mL). Statins are HMGCR inhibitors that show a good safety profi le despite frequent occurrence of benign myalgia that usually resolves after discontinuation of therapy. Nevertheless, severe side-eff ects such as myopathy (0·4 cases per 10 000 person-years) can occur. As in our patient, immune-mediated myopathy linked to statin use arises from an autoimmune mechanism that involves production of anti-HMGCR auto-antibodies. Thereafter myopathy is progressive, even after discontinuation of the the statin. Randomised controlled trials provide little evidence on the benefi ts of immunosuppressive therapy in such cases, but, as in our patient, some studies suggest immediate introduction of high-dose corticosteroids associated with other immunosuppressive agents and plasma exchange might be helpful (appendix).