2 CONCENTRATIONS OF TOPICAL TRETINOIN (RETINOIC ACID) CAUSE SIMILAR IMPROVEMENT OF PHOTOAGING BUT DIFFERENT DEGREES OF IRRITATION - A DOUBLE-BLIND, VEHICLE-CONTROLLED COMPARISON OF 0.1-PERCENT AND 0.025-PERCENT TRETINOIN CREAMS

Background and Design: The efficacy of topical tretinoin (all-tuans-re tinoic acid) in treating photoaging is well established. Questions tha t remain are (1) whether irritation causes all or part of the improvem ent; (2) the concentration of tretinoin that maximizes clinical respon se with minimal side effects; and (3) the effects of longterm treatmen t on components of the cutaneous immune system. To address these issue s, 99 photoaged patients completed a 48-week study using 0.1% tretinoi n cream (n=32), 0.025% tretinoin (n=35), or vehicle (n=32) once daily in a double-blind manner. Before and after treatment, we assessed hist ologic features, keratinocyte expression of HLA-DR and intercellular a dhesion molecule-1, numbers of epidermal Langerhans' cells and epiderm al and dermal T lymphocytes, and vascularity as measured by dermal end othelial cell area. Results: Both 0.1% and 0.025% tretinoin produced s tatistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically sign ificant differences in efficacy between the two concentrations of tret inoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar stat istically significant epidermal thickening (by 30% and 28%, respective ly) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By v arious analyses, irritant side effects (erythema and scaling) were sta tistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared. Conclusions: Tret inoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence o f irritation with the higher concentration. The separation between cli nical improvement and irritation suggests that mechanisms other than i rritation dominate tretinoininduced repair of photoaging in humans.