ORAL RETINOIDS - EFFICACY AND TOXICITY IN PSORIASIS

Psoriasis is a disease of unknown aetiology, affecting approximately 1 - 3% of the population. In most cases involving relatively localized disease. patients are best managed with either topical therapy alone o r topical therapy in combination with UV-phototherapy. However, approx imately 35% of patients do not respond well to these conventional trea tments or have moderate-to-severe disease requiring more aggressive fo rms of therapy. The second-generation retinoids, etretinate and its me tabolite acitretin, are important additions to the armamentarium of ag ents used to treat these recalcitrant or severe forms of the disease. Generalized pustular psoriasis generally responds well to high-dose (0 .7-1 mg/kg/day) oral retinoid monotherapy. In contrast, increasing sma ll doses of the retinoid are recommended initially in erythrodermic ps oriasis in order not to provoke the disease. Long-term clinical experi ence favours a combination treatment of the retinoid with either topic al and/or UV irradiation in chronic plaque-like psoriasis. Both oral r etinoids have comparable efficacy and tolerability profiles, and the r elapse rates for both drugs are similar, The toxicities associated wit h both short- and long-term treatment with oral retinoids are signific ant and include mucocutaneous effects, adverse modulation of serum lip id chemistries, elevation of liver enzymes, and after long-term chroni c dosing, skeletal and ligamentous calcification, and hyperostosis. Bo th etretinate and acitretin, like all retinoids, are known teratogens in animal models, and documented evidence exists for teratogenic activ ity in humans as well. Consequently, women of childbearing age are str ongly advised to avoid pregnancy during treatment and up to 5 years fo llowing cessation of therapy with both etretinate and the carboxylic a cid metabolite acitretin.