Immunomolecular mechanism of drug photosensitivity and screening for photoallergenicity of drugs

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Photocontact dermatitis is one of the major occupational skin diseases and an undesirable adverse effect produced by chemicals and drugs in our environment. This dermatitis is caused by skin application of photosensitive agents plus ultraviolet light irradiation. There exist both primary irritant and allergic mechanisms in this dermatosis. While the former is induced by the phototoxic reactions, the latter allergic type is mediated by Langerhans cells, T lymphocytes, and various cytokines and chemokines, and thus occurs via a well-orchestrated and well-elucidated immunological mechanism. The photoallergic type has a higher incidence and more severe skin eruptions than the primary irritation. Photoconjugation of epidermal cells with a photohaptenic halogenated chemical is the initial step, and Langerhans cells serve as antigen-presenting cells. Causative photohaptens are bound to MHC class II molecules/self peptide on Langerhans cells upon exposure to UVA. The photomodified Langerhans cells sensitize and elicit antigen-specific T cells that mediate photoallergy. Thus, this photoallergy is induced by well-orchestrated photochemical and immunological mechanisms.