P039 Diagnostic challenges and monitoring strategies in statin-induced immune mediated necrotising myopathy with co-existing cerebrovascular disease: a case report

Abstract Introduction Statin-induced immune-mediated necrotising myopathy (IMNM), although rare, can be a serious condition. It is linked to exposure to statins and is characterised by positive 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) antibodies. It is becoming more recognised as the use of statins increases. Interestingly, the subset of patients who may potentially be at risk of developing this condition tend to have other co-morbidities that could present similarly to statin-Induced IMNM, thus making diagnosis and monitoring challenging. This case describes the management of a patient with statin-induced IMNM but also highlights the challenges of monitoring in the presence of a co-existing cerebrovascular disease. Case description A 72-year-old woman with a medical history of hypothyroidism, atrial fibrillation, and prior stroke with right-sided weakness presented with generalised muscle weakness. She had been on atorvastatin since her stroke a year earlier. Upon examination, muscle strength was generally reduced, with a more pronounced deficit on the right side and in the proximal muscles. Laboratory investigations revealed a significantly elevated creatine kinase (CK) level of 8,500 U/L (normal range: 25–200 U/L), with negative myositis autoantibodies. Given her statin use, an HMG-CoA reductase antibody test was performed and returned positive. She was diagnosed with statin-induced immune-mediated necrotising myopathy (IMNM). Atorvastatin was discontinued, and treatment was initiated with tapering prednisolone and methotrexate. After prednisolone discontinuation, she remained on methotrexate for four years with clinical and biochemical remission. Methotrexate was eventually weaned off, and she was discharged. Two years later, she suffered another stroke, this time presenting with left arm ataxia and visual symptoms. The stroke team managed her and then referred to rheumatology on account of progressive muscle weakness and a rising CK level of 1,023 U/L, leading to diagnostic uncertainty, whether this was stroke-related weakness or a recurrence of her statin-induced IMNM. Examination again showed generalised weakness, predominant in proximal muscles, and on the right side of the body. Further investigations were required. MRI of the thighs showed muscle oedema in vastus lateralis, vastus medialis and right adductor group muscles consistent with myositis, while CT imaging ruled out malignancy. Electromyogram (EMG) revealed a patchy myopathic process, and muscle biopsy confirmed necrotising myopathy, in keeping with a recurrence of statin-associated IMNM. She was restarted on oral prednisolone at 40 mg/day, leading to normalisation of CK levels and improvement in muscle strength. Plans are in place to escalate to a disease-modifying antirheumatic drug (DMARD) if her condition deteriorates. Discussion Immune-mediated necrotising myopathy (IMNM) is a rare and challenging condition to diagnose due to its clinical overlap with other idiopathic inflammatory myopathies. Statin-induced IMNM is an increasingly recognised subset, especially with the widespread use of statins for the prevention of cardiovascular and cerebrovascular disease. Although rare, clinicians should consider this diagnosis in patients presenting with muscle pain and proximal muscle weakness, with a history of statin use. Diagnosis can be complex, especially when comorbidities requiring statins present with similar symptoms. A thorough history and physical examination are critical. Statin-induced IMNM typically involves progressive bilateral proximal limb weakness that persists even after stopping statins, due to the ongoing expression of HMG-CoA reductase in regenerating muscle fibres. Initial investigations should include creatine kinase (CK), antinuclear antibodies (ANA), anti-myositis antibodies, and HMG-CoA reductase antibodies. A typical pattern involves elevated creatine kinase (CK), negative antinuclear antibody (ANA) and anti-myositis antibodies, and positive HMG-CoA reductase antibodies. EMG, MRI, and muscle biopsy may be considered in diagnosis. In patients with prior cerebrovascular accidents, where statins are commonly prescribed, distinguishing between stroke-related weakness and IMNM is crucial. Important factors to consider for differentiation include the pattern of muscle weakness, persistently elevated CK, aldolase, and lactate dehydrogenase, a positive HMG-CoA reductase antibody, and further evaluation with electromyography (EMG), magnetic resonance imaging (MRI), and a muscle biopsy as appropriate. The first step in management is discontinuation of statins. There are no standardised guidelines, so treatment is guided by expert opinion and case reports. Immunosuppressive therapy is the mainstay. Corticosteroids are used first to induce remission. DMARDs such as methotrexate, azathioprine, mycophenolate mofetil, or ciclosporin may be added. IVIG may be used alone or with steroids. In refractory cases, biologics like rituximab or abatacept are options. It requires close monitoring of disease activity and response to treatment in Rheumatology clinics. Key learning points • Statin-induced IMNM should be considered early in patients presenting with progressive muscle weakness and a history of statin use, even after discontinuing the statins. • Anti-HMG CoA reductase antibodies should be tested promptly when suspected to facilitate early diagnosis. • Other conditions that may also justify the use of statins can present similarly, such as cerebrovascular disease, which could complicate diagnosis and monitoring. • Key factors to consider when differentiating Statin-induced IMNM for diagnosis and ongoing monitoring during follow-up appointments include weakness involving proximal muscles, persistently elevated muscle-specific enzymes such as creatine kinase (CK), aldolase, and LDH, a positive HMG-CoA reductase antibody, as well as distinctive EMG, MRI, and muscle biopsy findings. • Immunosuppressive therapy is the mainstay of treatment, and prompt initiation is crucial to prevent progressive muscle damage and disability in the patient. • There may be instances that require the escalation of immunosuppressants to induce remission. • Further research will be necessary, as we may encounter more cases of this, given the continued popularity of statin use.