FUNCTIONAL ASSESSMENT OF THE STRATUM-CORNEUM UNDER THE INFLUENCE OF ORAL AROMATIC RETINOID (ETRETINATE) IN GUINEA-PIGS AND HUMANS - COMPARISON WITH TOPICAL RETINOIC ACID TREATMENT

Clinically we have noted that the skin of patients treated with long-term oral etretinate becomes uniformly soft and smooth to touch, like facial skin that becomes smoother and less wrinkled following treatment with topical tretinoin. This suggests that retinoids, whether used systemically or topically, alter the physical properties of the skin, particularly of the stratum corneum (SC). To study the influence of retinoids on the SC, we serially assessed the functional properties of the SC non-invasively in retinoid-treated humans and experimental animals. SC hydration and barrier function were assessed by measurement of high-frequency conductance and transepidermal water loss (TEWL), respectively. Daily application of topical retinoic acid creams was found to rapidly induce a time- and dose-dependent, linear increase in SC hydration of the forearm skin of healthy adults over a 2-week period and to compromise its water barrier function in a similar fashion. Systemic administration of high-dosage etretinate, 4 or 8 mg/kg/day, to guinea-pigs also induced dose-dependent increases in both SC hydration and TEWL measured on the plantar skin after 1 month. Moreover, in the animals given etretinate 4 mg/kg/day we confirmed a slight but significant decrease in the number of cell layers of the plantar SC. Likewise, patients with various dermatoses began to show similar functional changes of the SC in the uninvolved skin of the flexor surface of the forearms 3 weeks after the start of oral etretinate treatment, consisting of 50 mg daily for 2 weeks, followed by gradual dose tapering. Thus, it is reasonable to speculate that oral etretinate changes the properties of the SC to produce smoother skin over the whole body surface, probably by increasing amounts of water-binding substances in the SC as well as by exerting a keratolytic effect, in a fashion similar to that induced by topical tretinoin application.