ABSTRACT
The observation in the 1920s that vitamin A deficiency may induce follicular hyperkeratosis of the skin (so called phrynoderma) was the rationale for later testing high-dose vitamin A therapy in various hyperkeratotic skin disorders, also in the absence of laboratory or ocular signs of vitamin A deficiency. This “antikeratinizing” effect of natural vitamin A was, however, soon recognized to be associated with a significant risk of developing hypervitaminosis A, that is, headache due to increased intracranial pressure, alopecia, hepatotoxicity, bone pains, etc. These problematic side-effects and the discovery in the 1960s of retinoic acid (RA) as a vitamin A metabolite, initiated a search for more effective, synthetic retinoids with a better therapeutic ratio (effect/side-effect) than vitamin A.
