Visual and cutaneous toxicity which occurs during N-(4-hydroxyphenyl) retinamide therapy for psoriasis

Abstract

Vitamin A (retinol) has been used both topically and systemically in the treatment of skin disease for approximately 40 years (Berson, 1983). Retinol taken in high doses over a period of time can cause fatigue, headaches, cheilitis, anorexia, peeling of the skin and can cause papillary oedema and hepatotoxicity (Dahl et al., 1977). These symptoms form the hypervitaminosis A syndrome and can be caused by acute or chronic intoxication with vitamin A or vitamin A analogues (retinoids). Because of this toxicity and the only marginal therapeutic benefit, the use of systemic vitamin A declined. Since 1977 two synthetic retinoids, isotretinoin (13‐cis‐retinoic acid) (Korner & Vollum, 1975) and etretinate (Meyskens et al., 1983) have been found to be of clinical use in the treatment of acne, psoriasis and the disorders of keratinization. These drugs have been found to be of such therapeutic benefit to patients that some of their side‐effects (Moon et al., 1979) have become acceptable. The realization of the therapeutic potential of retinoids for skin disease has led to an expansion in retinoid pharmacology research. As a consequence new retinoids are reaching the stage of clinical testing in patients. We report our experience of unusual side‐effects which occur during a phase II clinical trial of (N‐[4‐Hydroxyphenyl] retinamide)(4HPR) in the treatment of severe chronic plaque psoriasis.