Treatment of severe psoriasis and psoriatic arthritis with leflunomide

Sir, Psoriasis is a chronic inflammatory skin disease with T cells and neutrophils infiltrating both the dermis and epidermis, and excessive scaling related to epidermal hyperproliferation. Psoriatic arthritis, i.e. concurrent inflammation of joints, bones and ligaments, is present in up to 20% of affected patients. The psoriatic inflammatory process is associated with characteristic changes in the cytokine network that are believed to play a major part in disease pathophysiology. Over‐expression of proinflammatory T‐helper type 1 cytokines such as tumour necrosis factor‐α and interferon‐γ and a relative deficiency of anti‐inflammatory factors such as interleukin (IL)‐10 and the IL‐1 receptor antagonist (IL‐1Ra) are observed in lesional and lesion‐free skin, peripheral blood mononuclear cells and the synovium of inflamed joints.1, 2 Leflunomide is a novel immunomodulatory drug that has been licensed for the treatment of active rheumatoid arthritis in several countries including the U.S.A. and several in Europe. The active metabolite of leflunomide, A77 1726, inhibits proliferation of activated T and B cells mainly through inhibition of protein tyrosine kinases and the enzyme dihydroorotate dehydrogenase that is involved in the de novo synthesis of pyrimidine nucleotides.3 Other in vitro activities of A77 1726 include the modulation of cytokine production in T cells and neutrophils, suppression of immunoglobulin synthesis in B cells and reduction of mononuclear cell adhesion, suggesting a therapeutic potential in a broad range of inflammatory and autoimmune disorders. We report the successful treatment with leflunomide of a patient with severe recalcitrant pustular psoriasis and psoriatic arthritis.