8. Myositis as an idiosyncratic drug reaction to leflunomide

Abstract

Introduction: Myositis is a broad diagnosis with a number of potential causes. There are numerous drugs that can lead to myotoxicity.We discuss a case of a patient with known rheumatoid arthritis who developed myositis with no evidence of an additional autoimmune condition and wherethemost likelycauseseemstobeleflunomide. Case description: A 46-year-old Asian lady with a background of seropositive rheumatoid arthritis and overactive bladder developed increasing muscle weakness. Disease activity was well-controlled on leflunomide which had been started four years ago after an initial trial of methotrexate proved ineffective. Other regular medications include tolterodine and rigevidon (combined oral contraceptive pill), paracetamol and co-codamol. She presented to her GP in February with generalised muscleweakness,fatigue, drymouth, hair lossandoccasionalshortness of breath on exertion. Blood tests showed elevated CK at 1132 u/l, ALT 57 u/l(ASTnormal),LDH302 u/L,CRP4 mg/landESR25mm/h. Further tests were subsequently arranged following rheumatology review including ANA and ENA (both negative), an extended myositis panel and HMGCoAR antibodies (also negative). MRI of her lower limbs showed bilateral oedemawithin the anterior and lateral muscle compartments of her thighs, worse on the left, and in keeping with myositis. Given the possibility of leflunomide being the cause of her symptoms it was stopped.HerCKonemonthafter stopping leflunomidehaddecreasedto 819 u/l and then 389 u/l after four months. The patient reported improvementin hermuscleweakness,CKis currentlybeing monitored,andsheis awaiting an EMG. A muscle biopsy has been discussed with her previously and although shehad refused initially, in view of persistent mild elevation inCK,the biopsy andleflunomidewashout willbediscussed again with her again. As she is clinically asymptomatic and not keen to try new medications,furtherimmunosuppressionhasnotbeenstarted. Discussion: Myositis isseeninawiderangeof conditions withnumerous possible causes. It can be drug-induced, secondary to viral infections or causedbyautoimmuneconditionsincluding overlap conditionsandidiopathic inflammatory myopathies. Drug-induced myositis is most commonly associated with statins, but has been seen with many different medications. Leflunomideisadisease-modifying anti rheumatic drugusedparticularly in the treatment of inflammatory arthritis but has also been used in treatment resistant dermatomyositis. It inhibits the mitochondrial enzyme, dihydroorotate dehydrogenase to reduce the reproduction of rapidly dividing cells. A rise in CK is considered a common side effect. We have only found one other case report where leflunomide was suspected to have induced polymyositis, also in a patient with rheumatoid arthritis. Both biochemical and clinical improvement following cessation of leflunomide, with no other inventions raises the likelihood of this being a leflunomide-inducedmyositis. Keylearning points:Whenfaced with a patient with rheumatoid arthritis presentingwithsymptomssuggestiveofmyositis, whilstanoverlapautoimmunecondition isapossibility, it isimportanttoconsiderpotentialdrug causes.Numerousdrugshavebeenimplicated through both directmyotoxicityandimmunologicallymediated myotoxicity. Importantly forrheumatologists these can include glucocorticoids, antimalarial drugs, colchicine and tumour necrosis factor inhibitors. According to the summary of product characteristics a rise inCK is commonly seenwith leflunomidebutclinicalmyositishasonlybeenreportedrarely. Conflicts of interest: The authors have declared no conflicts of interest.