Case Presentation:

A 90 year old woman presented with weakness for one month. Atorvastatin 80mg was newly prescribed for a myocardial infarction. On exam proximal muscle strength on all extremities was 3/5. Creatine phosphokinase (CPK) was 4,515U/L with a normal creatinine. The statin was discontinued and intravenous hydration was given. One week later, CPK rose to 30,000U/L and strength declined to 1/5. Autoimmune serologies were negative. An electromyogram (EMG) showed an acute noninflammatory myopathy. Prednisone 60mg daily was started to treat immune mediated necrotizing myopathy (IMNM). CPK decreased but relapsed when prednisone was held for psychosis. Prednisone was tapered over 7 days with normalization of CPK, however, symptoms persisted and the patient was discharged to a rehabilitation center.

A 58 year old man with hyperlipidemia presented to his PCP with weakness three weeks after switching from brand name atorvastatin to the generic. On exam proximal muscle strength of the lower extremities was 4/5. CPK was 7,700U/L with a normal creatinine. The statin was discontinued but CPK remained elevated at two weeks. The patient was admitted for intravenous hydration but CPK did not improve. Autoimmune serologies were negative. EMG showed a mild myopathic disorder. MRI of the right thigh showed a mild generalized nonspecific myositis. A biopsy of the right quadriceps showed an active necrotizing myopathy. Prednisone 60mg daily was started to treat IMNM. The patient was discharged to outpatient rheumatology where methotrexate was started but with minimal serological or clinical response over 4 months. Monthly intravenous immunoglobulin therapy led to normalization of CPK with clinical improvement to near baseline.

Discussion:

While statins are a largely well‐tolerated medication class, occasionally patients are hospitalized for hepatotoxicity, myositis, and rhabdomyolysis. These events are self‐limited and resolve with hydration and cessation of therapy. If symptoms persist, IMNM should be considered. Risk factors for myopathy include: age >80, females, petite habitus, high statin doses, multiple comorbidities, and polypharmacy. Symptom onset can range from weeks to several years and usually present as proximal muscle weakness. Laboratory studies show a persistently elevated CPK and negative autoimmune inflammatory myopathy serologies. EMG reveals a noninflammatory myopathic disorder. Muscle biopsy is sensitive but not specific and reveals scattered necrotic regenerating fibers without inflammatory infiltrate. Anti‐HMGCR is a novel serology that is 94% sensitive and 99.3% specific but not yet commercially available. IMNM responds to immunosuppressants but symptoms can relapse when therapy is tapered and may require multi‐suppressant therapy. Complete resolution of weakness may be difficult to achieve.

Conclusions:

When discontinuation of statin therapy does not lead to resolution of weakness or elevated CPK, hospitalists should consider IMNM. Initiation of immunosuppression and rheumatology consultation is recommended.