Cutaneous phototoxicity due to psoralens.
Psoralen phototoxicity has several features which distinguish it from other cutaneous responses to UV radiation, with or without an exogenous photosensitizing agent. Erythema resulting from psoralen phototoxicity shows a longer latent period between irradiation and onset, during which no visible cutaneous changes are present. The dose-response curve is steeper, with blistering reactions occurring in some subjects after as little as three to four times the minimum phototoxic dose of UV radiation at 320-400 nm (UVA). The acute phase of psoralen phototoxicity is followed by a more marked increase in epidermal pigmentation than is seen after most other phototoxic reactions or following UV irradiation alone. The pathways leading to the development of cutaneous phototoxicity have not been identified. The importance of the cross-linking of DNA as the initiating event is suggested but not proved by comparative data on different psoralen compounds with different cross-linking abilities and by wavelength-dependent selective photochemistry. The subsequent pathways leading to erythema and the mediators which are liberated have not been identified. In contrast to erythema induced by UVA and UV at 290-320 and at 220-290 nm (UVB and UVC, respectively), no evidence for the involvement of prostaglandins has been demonstrable. Histopathologic studies show changes in the epidermis and dermis, with damage to keratinocytes and an inflammatory infiltrate in the dermis, both of which occur later and are of longer duration than the damage induced by UVA, UVB, or UVC alone. Despite the widespread application of psoralen phototoxicity in humans in the form of PUVA treatment, much work remains to be done before we can elucidate the important mechanisms and pathways leading to the inflammatory and therapeutic responses which are induced in the skin. Improvement of our knowledge in this area is central to the evolution of safer and more effective forms of photochemotherapy.
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004890:Erythema / Q000139:chemically induced; D006801:Humans; D008730:Methoxsalen / Q000633:toxicity; D011701:PUVA Therapy / Q000009:adverse effects*; D010778:Photochemotherapy / Q000009:adverse effects*; D010787:Photosensitivity Disorders / Q000139:chemically induced*; D011453:Prostaglandins / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology
D011453:Prostaglandins; D004247:DNA; D008730:Methoxsalen