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 or topical therapy in combination with UV-phototherapy. However, approximately 35% of patients do not respond well to these conventional treatments or have moderate-to-severe disease requiring more aggressive forms of therapy. The second-generation retinoids, etretinate and its metabolite acitretin, are important additions to the armamentarium of agents 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 small doses of the retinoid are recommended initially in erythrodermic psoriasis in order not to provoke the disease. Long-term clinical experience favours a combination treatment of the retinoid with either topical and/or UV irradiation in chronic plaque-like psoriasis. Both oral retinoids have comparable efficacy and tolerability profiles, and the relapse rates for both drugs are similar. The toxicities associated with both short- and long-term treatment with oral retinoids are significant and include mucocutaneous effects, adverse modulation of serum lipid chemistries, elevation of liver enzymes, and after long-term chronic dosing, skeletal and ligamentous calcification, and hyperostosis. Both etretinate and acitretin, like all retinoids, are known teratogens in animal models, and documented evidence exists for teratogenic activity in humans as well. Consequently, women of childbearing age are strongly advised to avoid pregnancy during treatment and up to 5 years following cessation of therapy with both etretinate and the carboxylic acid metabolite acitretin.