Oral synthetic retinoids have been established as effective systemic therap
y for psoriasis since their introduction for clinical use in the 1970s; a c
ompound for topical use, tazarotene has been recently marketed. Despite the
demonstrated clinical success of retinoid therapy in psoriasis, its mechan
ism of action has not been fully elucidated, and investigators are confront
ed with two paradoxes. One is that the binding of retinoids to nuclear reti
noic acid receptors (RARs) does not match their therapeutic efficacy: acitr
etin activates the three receptor subtypes, RAR-alpha, -beta and -gamma, wi
thout 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 psoria
tic 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 choic
es for severe psoriasis, particularly in association with ultraviolet light
therapy, of which it may decrease the carcinogenic risk. Topical tazaroten
e 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 tr
eatment is stopped.