Lower limb paralysis due to acute immune-mediated necrotizing myopathy: A very rare complication of statin therapy

Statins are the most commonly prescribed cholesterol-lowering drugs and the cornerstone of pharmacological LDL reduction. Although generally well tolerated, statins may cause self-limiting myalgias, myopathies and rhabdomyolysis.

Clinical Presentation:

A 70-year-old woman with previous long-term statin exposure presented with sudden onset of symmetrical proximal weakness of the lower extremities evolving to paraparesis with extreme difficulty standing up. Her past medical history included atrial fibrillation, hypertension, a moderate chronic kidney disease and hypercholesterolemia. Her laboratory findings were significant for markedly elevated creatinine kinase (CK) of 49291 U/l. Medication was discontinued and the patient was treated with aggressive intravenous fluid administration and urine alkalization along with continuous rhythm monitoring. After a further deterioration of her renal retention values, CK levels decreased and renal retention values declined. Despite the improvement in laboratory values, significant neurological improvement was not detectable. Thus, we conducted an MRI examination of the lumbar spine and lower extremities bilaterally revealing pronounced diffuse muscular edema/swelling in the legs. Subsequently, we opted for a muscle biopsy that revealed changes consistent with an autoimmune necrotizing myopathy. Anti-SRP and anti-HMGCR antibodies were not detected, leading us to the diagnosis of a seronegative immune-mediated necrotizing myopathy (IMNM). Intravenous high-dose corticosteroid therapy was empirically initiated. The patient received neurological rehabilitation over the coming weeks achieving a fast-complete disease remission. 

Discussion:

Immune-mediated necrotizing myopathy (IMNM) is a very rare (< 2/million/year) yet severe complication associated with statin medication. IMNM is based on the development of autoantibodies. The presence of anti-HMG CoA reductase or anti-SRP antibodies strongly supports the diagnosis but there is also a seronegative subtype, which is not accompanied by any known autoantibodies. Diagnosing IMNM promptly is frequently challenging due to its unpredictable development over time, with symptoms typically emerging many years after the initial exposure to statins. The symptoms persist even after discontinuing the medication, which is a distinctive characteristic in comparison to the statin-induced toxic myopathy. The basic treatment includes glucocorticosteroids for several weeks to months and often an additional immunosuppression by azathioprin or methotrexate. Treatment is largely based on expert opinion. Once strength recovers, immunosuppressive medications should be tapered.