Comparison of CD271 (Adapalene) and All-Trans Retinoic Acid in Human Skin: Dissociation of Epidermal Effects and CRABP-II mRNA Expression

A new synthetic retinoid analogue, adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, CD271), which is relatively selective for retinoic acid receptor β, was noted to bean effective comedolytic agent in the rhino mouse model and to have clinical efficacy against acne. In pursuit of this observation, we studied the effects of CD271 on the development of erythema, spongiosis, and epidermal hyperplasia as well as other well-characterized markers of in vivo retinoid action after 4 d of occluded topical treatment. The objective of the study was to elucidate further those parameters associated with potential clinical efficacy. Twenty-five subjects were treated with 0.1% all-trans retinoic acid cream, all-trans retinoic acid vehicle, 0.1% CD271 gel, or CD271 vehicle under occlusion for 4 d.Only all-trans retinoic acid induced erythema (p <0.01 versus all other treatments). Similarly, histologic analysis revealed that epidermal hyperplasia and spongiosis were induced only by all-trans retinoic acid (p <0.01 versus all other treatments). By immunohistochemical analysis: all-trans retinoic acid increased expression of epidermal transglutaminase, involucrin, and calgranulin (p < 0.05 versus all other treatments). In contrast to these data, both CD271 and all- trans retinoic acid caused marked and significant (p