Background Hydroxy-methyl-glutaryl Coenzyme-A reductase (HMGCR) inhibitors or statins are a well-acknowledged cause of a spectrum of myopathic consequences including an asymptomatic increase of creatine kinase (CK), myalgias, myositis and rhabdomyolysis. A unique autoantibody with specificity against 200-kd and 100-kd proteins has been recently associated with statin induced myositis (1) based on identification of cases with features of necrotizing myopathy. The 100kd autoantigen has been identified as HMGCR (2). We sought to further characterize cases of clinically suspected statin-induced myositis using clinical, serological and pathological data.
Objectives The aim was to characterize statin induced myositis patients in a clinical setting and test the utility of the newly identified anti-200/100 autoantibody.
Methods Patients with a statin induced myositis were identified from a large tertiary myositis referral centre in Salford, UK. Case records of all patients were reviewed with selected patients’ blood samples tested for anti-200/100 autoantibody. Clinical features, concomitant medications, co-morbidities, immunology, electromyography (EMG), magnetic resonance imaging (MRI) and muscle biopsies for each patient were reviewed.
Results 10 patients were identified with a clinical diagnosis of statin induced myositis. Mean age of diagnosis was 59 years (70% male). Median CK level detected at onset was 1,750 IU/litre (range 28-11,984). 9/10 patients were on a lipophilic statin (simvastatin/atorvastatin) with 1 patient on a hydrophilic statin (rosuvastatin); mean daily dose of 39mg/day prior to symptom onset. 5/10 patients were on a concomitant medication known to interact with a statin (amiodarone, proton pump inhibitors, high dose vitamin D). 3/10 patients were anti-nuclear-antibody positive (2 had low titres, 1/100; 1 positive 1/1000), whilst 2 patients were anti-Ro antibody positive. 6 patients demonstrated some evidence of myositis on MRI, of which 3 patients exhibited myopathic changes on EMG. 8 patients had evidence of myopathic muscle on biopsy, 2 patients with type II fibre atrophy. Of the 7 patients tested for anti-HMGCR by Western blotting using a recombinant source, 6 tested positive. 2 patients who tested strongly 200/100 positive required immunosuppression and had biopsy features of necrosis, phagocytosis and regeneration. 2 further 200/100 positive patients (1 strong and 1 weak positive) had occasional necrotic fibres with little regenerative activity on biopsy and did not require further treatment. The remaining 2 200/100 positive patients had no features of necrosis on biopsy, one of whom required immunosuppression without corticosteroids.
Conclusions EMG and MRI were non-specific in identifying patients with a statin induced myositis, whilst CK levels varied significantly in this group. A strongly positive anti-200/100 antibody in combination with a necrotizing myopathy on muscle biopsy could be useful clinically to identify which patients have an autoimmune element to their disease, hence may potentially benefit from immunosuppression.
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Mammen AL et al. Arthritis Rheum. 2011 Mar;63(3):713-21.
Acknowledgements MJ is a MRC Clinical Training Fellow funded by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics.
Disclosure of Interest None Declared
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