Two 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% and 0.025% tretinoin creams
C. E. Griffiths, S. Kang, C. N. Ellis, K. J. Kim, L. J. Finkel, L. C. Ortiz-Ferrer, G. M. White, T. A. Hamilton and J. J. Voorhees
Department of Dermatology, University of Michigan Medical Center, Ann Arbor, USA.
BACKGROUND AND DESIGN: The efficacy of topical tretinoin
(all-trans-retinoic acid) in treating photoaging is well established.
Questions that remain are (1) whether irritation causes all or part of the
improvement; (2) the concentration of tretinoin that maximizes clinical
response with minimal side effects; and (3) the effects of long-term
treatment on components of the cutaneous immune system. To address these
issues, 99 photoaged patients completed a 48-week study using 0.1%
tretinoin 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 histologic features, keratinocyte expression of HLA-DR and
intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells
and epidermal and dermal T lymphocytes, and vascularity as measured by
dermal endothelial cell area. RESULTS: Both 0.1% and 0.025% tretinoin
produced statistically significant overall improvement in photoaging of the
face compared with vehicle; there were no clinically or statistically
significant differences in efficacy between the two concentrations of
tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar
statistically significant epidermal thickening (by 30% and 28%,
respectively) compared with vehicle (11% decrease) and increased
vascularity (by 100% and 89%, respectively) compared with vehicle (9%
decrease). By various analyses, irritant side effects (erythema and
scaling) were statistically 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:
Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes
in patients with photoaging, despite significantly greater incidence of
irritation with the higher concentration. The separation between clinical
improvement and irritation suggests that mechanisms other than irritation
dominate tretinoin-induced repair of photoaging in humans.
