Management of psoriasis: the position of retinoid drugs

Oral synthetic retinoids have been established as effective systemic therapy for psoriasis since their introduction for clinical use in the 1970s; a compound for topical use, tazarotene has been recently marketed. Despite the demonstrated clinical success of retinoid therapy in psoriasis, its mechanism of action has not been fully elucidated, and investigators are confronted with two paradoxes. One is that the binding of retinoids to nuclear retinoic acid receptors (RARs) does not match their therapeutic efficacy: acitretin activates the three receptor subtypes, RAR-alpha, -beta and -gamma, without measurable receptor binding, whereas tazarotene preferentially binds to and activates RAR-beta and -gamma in preference to RAR-alpha. The other is that there is already increased formation of retinoic acid in the psoriatic lesion. Answering these questions should result in better use of these drugs in the treatment of psoriasis. Oral administration of acitretin remains one of the first therapeutic choices for severe psoriasis, particularly in association with ultraviolet light therapy, of which it may decrease the carcinogenic risk. Topical tazarotene is suitable for moderate plaque psoriasis. Its efficacy and tolerability can be enhanced by the addition of topical corticosteroids; its irritative potential is counterbalanced by a sustained therapeutic effect after the treatment is stopped.