Case Presentation: 66-year-old Caucasian male with history of type 2 diabetes mellitus and prostate cancer presented to the emergency department with 6-week history of progressive weakness. Initially, he noted difficulty arising from a chair signifying weakness in his proximal lower extremity musculature. It then progressed to involve bilateral proximal upper extremities causing difficulty with brushing his teeth. He denied any associated myalgia, arthralgia, oral ulcers, rashes, dysphagia, or reflux. Medication history was notable for atorvastatin use for the past twenty years. On admission, vital signs were within normal limits. Physical examination revealed bilateral hip flexion weakness, muscle strength graded 3/5 as well as motor weakness with shoulder abduction, muscle strength graded 4/5. Labs were significant for elevated creatinine phosphokinase (CPK) of 22,255 Units/L, elevated aldolase of 71.8 U/L, transaminitis with elevated alanine transaminase (ALT) of 434 U/L, aspartate transaminase (AST) of 521 U/L. Renal function was normal. Atorvastatin was discontinued and he was aggressively hydrated with intravenous fluid, with initial improvement of his CPK to 9299 U/L. However, his CPK worsened again on hospital day 4 with CPK increased up to 12000 U/L. Tests for antinuclear antibody, anti-Jo 1, anti-PL-7, anti-PL-12, anti-MI-2, anti-KU, anti-EJ, anti-OJ and anti-SRP were all negative. Electromyogram (EMG) showed evidence of patchy myopathic process with electrical features of muscle inflammation, necrosis, or membrane irritability. His muscle biopsy done subsequently is consistent with necrotizing myopathy. His anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies eventually came back positive with a level of 103 (normal <20), thus providing a diagnosis of statin-induced necrotizing autoimmune myopathy (SINAM). The patient was started on pulse-dose steroid. His strength improved on steroid and CPK also eventually decreased to 4100 U/L. He was eventually discharged on oral prednisone.
Discussion: SINAM is an exceptionally rare and potentially life-threatening complication of statin therapy characterized by acute, severe onset of progressive proximal muscle weakness. The onset of muscle symptoms is highly variable, ranging from weeks to years, usually seen within weeks to six months but may occur at any time during treatment. Our case is unique as the timeline is over 20 years. Diagnosis of SINAM is often difficult due to its variable time course and requires a high index of suspicion. Its pathophysiology remains poorly understood. Muscle biopsy of SINAM is characterized by myonecrosis and thus serum CPK levels are usually markedly elevated (> 10,000 U/L). Unlike the self-limiting statin-induced myopathy, symptoms of SINAM persist and its CPK levels remain elevated even after discontinuation of statin therapy. Diagnosis is confirmed by positive anti-HMGCR antibodies. Management of SINAM involves discontinuation of statin therapy and initiation of high dose corticosteroid. Other immunosuppressants such as methotrexate, azathioprine are used as adjunctive therapy.
Conclusions: Although being a rare side effect of statin therapy, SINAM is a potentially life-threatening complication characterized by proximal muscle weakness and markedly elevated CPK levels that can occur anytime during treatment. Diagnosis requires a high index of suspicion as it requires prompt clinical evaluation and discontinuation of statin.