Historical perspectives of tretinoin.

The vitamin A acid story began when topical application of vitamin A (retinol) produced no therapeutic results in dyskeratotic conditions. It was logical to try metabolites of retinol topically. I published results of studies in 1962 that showed that topical tretinoin was beneficial in ichthyosis, actinic keratoses, and other hyperkeratotic conditions. It was reported in 1969 that topical tretinoin was effective in acne vulgaris, principally by preventing and dislodging comedones. It was subsequently demonstrated that tretinoin produced a distinctive kind of hyperplasia of human epidermis that was associated with early shedding of horny cells. Knowledge that the keratinization process was being profoundly altered stimulated interest in synthesizing retinol derivatives (retinoids) that could be administered orally. The development of 13-cis-retinoic acid was an outcome of this interest, a compound that astonished dermatologists by often producing permanent clearing of acne conglobata. The antitumor effects of tretinoin were already demonstrated by 1974, when it was shown to cause regression in many basal cell cancers. Today the cancer chemopreventive capability of retinoids is being intensively investigated in various organs. An international symposium held in Flims, Switzerland in 1975 demonstrated keen awareness of the therapeutic potential of tretinoin and the rapid growth of basic knowledge of the pharmacology of retinoids. From extensive clinical experience new applications for topical tretinoin came to light, ranging from the treatment of flat warts, lichen planus, and Darier's disease, and most recently in retarding photoaging. Perhaps for the first time in history, dermatologists can take credit for pioneering a drug development program that has had a profound influence on medical practice.