How do the psoralens work?

Psoralen compounds by themselves do not affect the skin in the absence of UVA, but in the presence of UVA (320 to 400 nm), they are potent photosensitizers. Ninety minutes after oral ingestion, absorption of UVA photons photochemically links the DNA by forming cycloadditive products between the intercalated psoralen and the pyrimidine bases of cellular DNA. These psoralen-DNA cross-links cause a decrease in the rate of epidermal DNA synthesis, which some authorities believe to be the primary mechanism of action of these agents. Irradiation of psoralens also induces the formation of reactive oxygen species that can damage both cell membranes and organelles, as well as activate arachidonic acid metabolism. There is considerable evidence that PUVA therapy has a direct effect on the cutaneous immune system, and some authorities feel that this may be more important in terms of the therapeutic effect. The induction of T-cell apoptosis, decreased function of antigen-presenting cells, and altered cytokine profile is likely the most important component of PUVA therapy in most modern views.