Assessment of the Phototoxicity Risk of New Drugs

Abstract

Photosensitization is the general term to define abnormal reactions of the skin, due to the exposure to UV or visible radiation and an exogenous chemical (Spikes, 1989; Harber and Bickers, 1988; Johnson and Ferguson, 1990). Phototoxicity and photoallergy are the two major types of skin photo sensitization (Beijergsbergen van Henegouwen, 1981; Epstein, 1983; Epstein and Wintroub, 1985; Miranda, 1992; Spikes, 1989). The former appears more frequently and does not involve an immunological mechanism. It should occur in all individuals provided that their skin contains the photosensitizer at the appropriate concentration and is exposed to high enough light doses. Usually, the clinical picture associated with phototoxicity includes burning, itching, erythema, oedema, hyperpigmentation and desquamation. These reactions are confined to the exposed areas of the skin and appear immediately after the first exposure. Photoallergy to chemicals is much less common, although it is still important in interest and severity. It depends on the individual immunological status and is developed in some patients as a modified ability of the skin to react to the combined effect of sunlight plus a photosensitizer. It is associated with a cell-mediated immunity response (Johnson and Ferguson, 1990). Some clinical manifestations are erythema, eczema and/or vesiculobullous eruption. These cutaneous responses are usually restricted to the exposed parts of the skin, but can be extended to the unexposed areas, including previously sensitized distant sites. They do not occur after the first treatment with chemical and light; rather, there is an induction period of one or two weeks before skin reactivity can be demonstrated (Epstein, 1983; Epstein and Wintroub, 1985).