Microsoft Word - SPP003BF.rtf

From a clinical point of view, therapy with vitamin A acid originates from the thought that different pharmacokinetics of retinol in systemic or topical treatment would correspondingly entail a different metabolization and development of derivatives of vitamin A acid. Tumor development in the skin of mice caused by benzpyrene as well as therapy of ichthiosiform keratoses indicated that a therapeutic effect can only be achieved with systemic retinol administration. Henceforth, retinol metabolites applied topically resulted only in effects equivalent to those of systemic retinol treatment. Furthermore, clinical administration of tretinoin showed pharmacological characteristics exceeding the effect of retinol. The vitamin A story began in 1958/ 1959 with the discovery of its efficacy in retention hyperkeratoses and in senile (actinic) keratoses [1] and also its influences on normal skin with ‘smoothing’ effects on the skin surface. Topical tretinoin (0.05%) treatment of photoaged skin with atrophy, wrinkles and pigmentation by Kligman et al. [2] and the confirmation and consolidation by Ellis and Voorhees [3] inaugurated a new area in scientific dermatologic cosmetology. The clinical indications for treatment with tretinoin had to be compiled from an increasing number of anecdotic individual cases, in which keratinization processes of malign as well as of benign nature showed therapeutic results. Furthermore, the stimulation of a lymphocytic infiltration of epithelial malignancies was soon related to immunologic parameters [4] (fig. 1-3). In a daily dose of 100 mg orally, tretinoin suggested a therapeutic effect, which was generally more pronounced in retention keratoses. In the field of oncology, cancer en cui-rasse and multiple basaliomas showed a decrease in proliferation kinetics [4-6]. Individual adverse effects as severe edema on the 2nd day of administration (psoriasis) or unconsciousness lasting for 4 days with a completely stable circulatory system and subsequent awakening without complications necessitated careful observation exceeding the already present toxicological data. In retrospect, these side effects can be attributed to the tox-icity of tretinoin, which is higher than that of the synthetic retinoids of today. Local treatment was followed by skin irritations, which have their own problems in dermatologic practice; this situation was basically changed when Kligman et al. [7] introduced the local treatment of acne with isotre-tinoin in 1969. In 1978/1979, Peck et al. [8] initiated the oral treatment of cystic acne. Prof. Dr. med. G. Stüttgen © 1993 Kissinger Strasse 12 S. Karger AG, Basel D-14199 Berlin (FRG) 1011-0283/93/ 0O65-OO03S2.75/O Fig. 1. Tumor induced by benz-pyren. The beginning of vitamin A acid research in Düsseldorf in 1958.