Case Presentation: A 54-year-old man with history of type II diabetes mellitus and hyperlipidemia presented to the Emergency Department with 6 weeks of generalized weakness. On arrival, he was mildly tachycardic but otherwise stable. Physical examination was most notable for diffuse proximal muscle weakness in the bilateral upper and lower extremities. Pertinent laboratory studies showed erythrocyte sedimentation rate 89 mm/h (2 – 20 mm/h), alanine aminotransferase 1046 (ALT) U/L (4 – 55 U/L), aspartate aminotransferase (AST) 1365 U/L (8 – 48 U/L), alkaline phosphatase 138 U/L (40-129 U/L), creatinine 0.46 mg/dL (0.74 – 1.35 mg/dL), creatinine kinase (CK) 30802 U/L (39 – 308 U/L). Urinalysis revealed a large amount of myoglobin. Hepatitis and acetaminophen screenings were negative. CT abdomen and pelvis showed no acute findings. He was admitted to the hospital for rhabdomyolysis.After admission, he received intravenous fluids and his urine output was closely monitored. Despite this, severe proximal muscle weakness persisted. Further testing revealed HMG-CoA reductase antibody greater than 550 CU (< 20 CU). Electromyography showed proximal myopathy with features of myonecrosis, inflammation and vacuolization. He was diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM) and treatment with intravenous methylprednisolone, intravenous immunoglobulin (IVIG) and mycophenolate mofetil was initiated. His rhabdomyolysis improved over the coming weeks as evidenced by reduction in his CK, AST, and ALT. However, significant strength deficits persisted and rituximab was added. He required a lengthy hospital stay and was ultimately discharged to a skilled facility for ongoing therapy needs.
Discussion: SINAM is an exceedingly rare complication of statin use with an estimated incidence of two cases per 100,000 people. At presentation, laboratory findings are often consistent with rhabdomyolysis (1). The pathogenesis of SINAM is poorly understood but one hypothesis is statin-mediated modification of the HMG-CoA reductase enzyme which results in antibody formation against this enzyme. It is thought that this antibody then directly targets myocytes (2). However, in-vitro studies have demonstrated that these antibodies may activate the complement pathway rather than targeting myocytes themselves (3). Patients can develop symptoms as early as two months after beginning a statin and as late as 10 years after initiation. Unlike the more common statin-induced myalgias, SINAM does not resolve with discontinuation of the offending medication and immunosuppressants are required for treatment (4). Even after the medication is stopped and the appropriate immunosuppressants are employed, time to remission is approximately eight months with fewer than 50% of patients ever returning to their pre-disease baseline (1).
Conclusions: SINAM is a rare entity that can result in debilitating and possibly life-threatening effects. Generalized weakness is the most common presenting feature and labs will show evidence of muscle damage. Following discontinuation of the statin, patients still require immediate management with immunosuppressants. Even with prompt diagnosis, patients have prolonged recovery and the majority of patients do not return to their previous baseline. Because SINAM has been shown to occur up to a decade after statin initiation, it must be on a Hospitalist’s differential for a patient who presents with myopathy and statin use of any duration.