Case Presentation: A 61-year-old woman presented to the Emergency Department (ED) with weakness. She had multiple falls over two months, including a presumed mechanical fall on the stairs that caused a nasal fracture two weeks prior to presentation. The patient had difficulty getting out of her car and climbing the stairs in her home and felt her symptoms were worsening over the prior four months. She had no pain. Medical history was otherwise notable for hyperlipidemia.In the ED, the patient was afebrile with heart rate 96 beats per minute, blood pressure 138/75 mmHg, respiratory rate 18 breaths per minute, and oxygen saturation 97% on room air. Physical exam showed mild weakness with hip flexion and shoulder abduction bilaterally but was otherwise unremarkable. Initial laboratory data showed normal complete blood count, creatinine 0.66 mg/dL, potassium 4.3 mmol/L, aspartate transferase (AST) 134 IU/L, alanine transaminase (ALT) 150 IU/L, alkaline phosphatase 51 IU/L, total bilirubin 0.3 mg/dL, creatine kinase (CK) 9,825 IU/L, and aldolase 49 U/L. She was given IV fluids and admitted to Medicine.Atorvastatin was discontinued, and Rheumatology was consulted. Rheumatology recommended obtaining myositis panel, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies, and left thigh MRI. MRI showed nonspecific myositis most conspicuous in the rectus femoris and sartorius muscle bellies. Rheumatology suspected an inflammatory myositis and recommended muscle biopsy. The patient was started on prednisone 40 mg daily and discharged with plans for outpatient biopsy. After discharge, Surgery performed a left thigh muscle biopsy. Pathologic examination showed necrotic and regenerating fibers indicative of active myopathy and most suspicious for immune-mediated necrotizing myopathy. Extended myositis panel showed a high titer of HMGCR autoantibodies (182 CU) confirming the diagnosis of anti-HMGCR-positive immune-mediated necrotizing myopathy (IMNM). She was started on azathioprine with plans to taper prednisone. Five months after the hospitalization, CK had improved to 1,348 IU/L and aldolase had improved to 15 U/L.
Discussion: Statins can cause mild musculoskeletal problems such as myalgias and in some cases can also lead to the more serious rhabdomyolysis with active muscle damage with elevation in CK. Statin-induced anti-HMGCR-positive IMNM is a very rare complication of statin therapy, estimated to occur in approximately 2 or 3 of every 100,000 patients treated with a statin (1). Despite its rarity, it is important that hospitalists recognize the possibility IMNM when CK does not improve with discontinuation of the statin, as therapy for IMNM requires immunosuppression to prevent disease progression. Particularly in patients with pharyngeal or respiratory muscle weakness, hospitalists should have a high index of suspicion for IMNM as delays in therapy could prove life-threatening. Clinical presentation is characterized by subacute, progressive proximal muscle weakness and elevations in CK in the absence of skin findings characteristic of dermatomyositis, features of connective tissue disease, or improvement in CK despite discontinuation of statin therapy.
Conclusions: IMNM is a complication of statin therapy. Given the high proportion of patients admitted to Hospital Medicine services on statin therapy, hospitalists should recognize the characteristic clinical presentation to ensure timely diagnosis, discontinuation of statin therapy, and initiation of immunosuppression.