COMPARISON OF CD271 (ADAPALENE) AND ALL-TRANS-RETINOIC ACID IN HUMAN SKIN - DISSOCIATION OF EPIDERMAL EFFECTS AND CRABP-II MESSENGER-RNA EXPRESSION

A new synthetic retinoid analogue, adapalene (6-[3-(1-adamantyl)-4-met hoxyphenyl]-2-naphthoic acid, CD271), which is relatively selective fo r retinoic acid receptor beta, was noted to be an effective comedolyti c 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 actio n after 4 d of occluded topical treatment. The objective of the study was to elucidate further those parameters associated with potential cl inical 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 aci d 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 oth er treatments). By immunohistochemical analysis: all-trans retinoic ac id increased expression of epidermal transglutaminase, involucrin, and calgranulin (p < 0.05 versus all other treatments). In contrast to th ese data, both CD271 and all-trans retinoic acid caused marked and sig nificant (p < 0.05) elevation of cellular retinoic acid-binding protei n-II (CRABP-II) messenger ribonucleic acid steady-state levels as judg ed by quantitative RNA blot analysis. Although CD271 treatment did not lead to erythema or affect epidermal morphology, its ability to induc e a marker of retinoid action (i.e., CRABP-II) was 70% the potency of all-trans retinoic acid. This study suggests that CRABP-II gene expres sion may be a more sensitive indicator of retinoid biologic activity i n skin than are erythema or changes in epidermal morphology and differ entiation.