Historical aspects of the oral use of retinoids in acne

A number of investigations of the effects of vitamin A deficiency in animals and man and its treatment with natural products containing vitamin A were carried out in the twenties and thirties. In 1942, a clinical study in patients with acne treated with vitamin A yielded encouraging results. Further trials in the forties and fifties, trying to confirm the beneficial effect of oral vitamin A in acne, met with equivocal success. In the sixties, all-trans retinoic acid (tretinoin) became clinically available, and its topical efficacy in acne could be demonstrated. In 1971, oral tretinoin also was shown to be active in patients with acne. Coincidentally, the efficacy of oral 13-cis retinoic acid (isotretinoin) became evident in a series of unpublished studies in Europe. Then, in 1978, a trial carried out at the NIH, Bethesda, Maryland, yielded convincing evidence that isotretinoin is a potent new drug for the treatment of severe cystic acne. In 1982, isotretinoin was registered in the United States and one year later in Europe for the treatment of severe, recalcitrant, cystic acne. Since then, many thousands of patients suffering psychologically and physically from the severity of their disease have been treated successfully with this drug. However, the main concern of physicians prescribing isotretinoin has to focus on its potentially severe side effects, particularly its teratogenicity.