Multiple drugs

Abstract

Immune-mediated necrotising myopathy, nausea, treatment failure and off-label use: case report A 61-year-old woman developed immune-mediated necrotising myopathy and nausea, during treatment with pravastatin and azathioprine, respectively. Additionally, she exhibited treatment failure during treatment with prednisone, and received off-label treatment with rituximab for immune-mediated necrotising myopathy [not all routes, dosages, duration of treatments to reactions onset and outcomes stated]. The woman, who had a history of primary hypercholesterolaemia, hypothyroidism and hypertension, presented with a rapidly progressing proximal upper and lower muscle extremity weakness for 7 days. Her symptoms were associated with muscle pain and slowly progressive dysphagia to both solids and liquids. Her medication history included taking pravastatin for 2 years. A physical examination showed a grade of 3/5 on the Medical Research Council (MRC) Scale for Muscle Strength in the proximal upper and lower extremities bilaterally. Laboratory tests were as follows: elevated level of creatinine kinase, myoglobin, aspartate aminotransferase and ALT. Differentials were included polymyositis, statin-induced myopathy, paraneoplastic myopathy and antisignal recognition particle-associated myopathy. Pravastatin-induced immune-mediated necrotising myopathy was suspected. The woman’s treatment with pravastatin was discontinued, and she was initiated on oral prednisone 60mg. An initial rheumatologic workup for autoimmune myopathies was found negative. A CT scan of the chest, abdomen and pelvis did not revealed evidence of any malignancy. An MRI of the right lower extremity showed a diffuse patchy muscular atrophy throughout the thigh with extensive patchy muscle oedema involving the anterior medial and posterior compartments. The right quadriceps was biopsied, an electromyogram and anti-HMGCR antibodies were tested. She was discharged on prednisone 60mg. During her 4-week follow up in the rheumatology clinic, she still reported weakness, and treatment failure secondary to prednisone was considered. Her upper arms and bilateral hip flexors were MHC grade 4/5. Her repeat creatine kinase level was still found to be elevated. The quadriceps biopsy showed a scattered myofiber atrophy, degeneration, regeneration, necrosis, and myophagocytosis suggestive of necrotising myopathy. Electromyography showed a myositis, and anti-HMG CoA reductase antibodies were found to be positive, with an elevated titer suggestive of anti-HMGCR-induced myopathy. Subsequently, she was initiated on azathioprine 50mg daily. However, after 15 days, she developed nausea secondary to azathioprine, and did not wanted to continue taking azathioprine. She still persisted weakness in her upper extremities. Her AST level, ALT level and creatinine Kinase remained elevated. Prednisone dose was decreased to 30mg, azathioprine was discontinued, and a plan was formulated to initiate him on offlabel rituximab. She received IV infusion of rituximab 1,000 mg/m2 with a second dose repeated 2 weeks later. Four weeks later, her strength improved in her shoulders, fingers and toes, and proximal hip flexors. Her rituximab dosage was then decreased to 375 mg/ m2, and given once in every 3 months. Remission was deemed to have been achieved after six doses of rituximab and her laboratory values remained normal as well as she remained asymptomatic. She also received alirocumab for hyperlipidaemia. She went into complete remission within 3 months of initiation of rituximab. She subsequently tolerated her maintenance therapy for one year with no complications, and remained symptom-free.