Leflunomide-induced skin necrosis

BACKGROUND: Leflunomide is prescribed in inflammatory rheumatisms. Cutaneous side effects have rarely been described. We report the case of a patient presenting skin necrosis attributed to this drug. PATIENTS AND METHODS: A 73-year-old woman had been taking leflunomide for psoriatic arthritis for one year and subsequently, developed three abdominal ulcerations and necrosis of one hallux. No immunological, vascular or neoplastic aetiology was found. Corticotherapy was started, based on a hypothesis of vasculitis, but lesions progressed, leading to amputation of the hallux. Leflunomide was stopped and the ulcerations healed completely within 12 weeks, whereas prolonged local treatment had failed to yield any improvement. DISCUSSION: Skin necrosis due to leflunomide is rare; we found seven cases in the literature. Ulcerations may occur anywhere. Potentially life-threatening glomerulonephritis with mesangial deposits may be associated. Discontinuation of leflunomide followed by wash-out with cholestyramine allows healing. Corticosteroids or cyclophosphamide are sometimes necessary. The ulcerations appear to be result from excessive immunomodulation in the skin or from an inhibiting role of leflunomide on the epidermal growth factor receptor. CONCLUSION: In the absence of any demonstrated aetiology in patients presenting ulcerations or skin necrosis, a contributory role of leflunomide must be considered, even in cases of prolonged use.