Chapter 057. Photosensitivity and Other Reactions to Light (Part 4)

Immunologic Effects Exposure to solar radiation causes local (inhibition of immune responses to antigens applied at the irradiated site) and systemic (inhibition of immune responses to antigens applied at remote unirradiated sites) immunosuppression. The action spectrum for UV-induced immunosuppression closely mimics the absorption spectrum of DNA. Pyrimidine dimers in LCs may inhibit antigen presentation. The absorption spectrum of epidermal urocanic acid closely mimics the action spectrum for UV-B-induced immunosuppression. Trans-cisisomerization of urocanic acid in the stratum corneum leads to its systemic absorption and consequent immunosuppressive effects. Furthermoreadministration of modest doses of UV-B to human skin reduces the degree ofallergic...
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Chapter 057. Photosensitivity and Other Reactions to Light (Part 4) Chapter 057. Photosensitivity and Other Reactions to Light (Part 4) Immunologic Effects Exposure to solar radiation causes local (inhibition of immune responses toantigens applied at the irradiated site) and systemic (inhibition of immuneresponses to antigens applied at remote unirradiated sites) immunosuppression.The action spectrum for UV-induced immunosuppression closely mimics theabsorption spectrum of DNA. Pyrimidine dimers in LCs may inhibit antigenpresentation. The absorption spectrum of epidermal urocanic acid closely mimicsthe action spectrum for UV-B-induced immunosuppression. Trans-cisisomerization of urocanic acid in the stratum corneum leads to its systemicabsorption and consequent immunosuppressive effects. Furthermoreadministration of modest doses of UV-B to human skin reduces the degree ofallergic sensitization to the potent contact allergen, dinitrochlorobenzene. This isassociated with ROS-induced depletion of epidermal LCs. Higher doses of UV-radiation evoke diminished immunologic responses toantigens introduced either epicutaneously or intracutaneously at sites distant fromthe irradiated site. These suppressed responses are also associated with theinduction of antigen-specific suppressor T lymphocytes and may be mediated byas yet undefined factors that are released from epidermal cells at the irradiated site.One important consequence of chronic sun exposure and the concomitantimmunosuppression is enhanced risk of skin cancer. Perhaps the most graphicdemonstration of the role of immunosuppression in enhancing the risk ofnonmelanoma skin cancer has come from studies of patients receiving organtransplantation who are on chronic immunosuppressive antirejection drugregimens. More than 50% of transplant patients develop BCCs and SCCs, andthese cancers are the most common malignancy arising in immunosuppressedsolid-organ transplant recipients. Human papilloma viruses (HPVs) may also playa role in the increased risk of SCCs in these patients since tumors display an HPVDNA carriage rate of almost 80%. These patients require close periodicmonitoring and rigorous photoprotection using sunscreens, protective clothing,and sun avoidance. Photosensitivity Diseases The diagnosis of photosensitivity requires a careful history to define theduration of the signs and symptoms, the length of time between exposure tosunlight and the development of subjective complaints, and visible changes in theskin. The age of onset can also be a helpful clue; for example, the acutephotosensitivity of erythropoietic protoporphyria almost always begins inchildhood, whereas the chronic photosensitivity of porphyria cutanea tarda (PCT)typically begins in the fourth and fifth decades. A history of exposure to topicaland systemic drugs and chemicals may provide important clues. Many classes ofdrugs can cause photosensitivity on the basis of either phototoxicity orphotoallergy. Fragrances such as musk ambrette that were previously present innumerous cosmetic products are also potent photosensitizers. Examination of the skin may also offer important clues. Anatomic areasthat are naturally protected from direct sunlight such as the hairy scalp, the uppereyelids, the retroauricular areas, and the infranasal and submental regions may bespared, whereas exposed areas show characteristic features of the pathologicprocess. These anatomic localization patterns are often helpful, but not infallible,in making the diagnosis. For example, airborne contact sensitizers that are blownonto the skin may produce dermatitis that can be difficult to distinguish fromphotosensitivity, despite the fact that such material may trigger skin reactivity inareas shielded from direct sunlight. Many dermatologic conditions may be caused or aggravated by sunlight(Table 57-2). The role of light in evoking these responses may be dependent ongenetic abnormalities ranging from well-described defects in DNA repair thatoccur in XP to the inherited abnormalities in heme synthesis that characterize theporphyrias. In certain photosensitivity diseases, the chromophore has beenidentified, whereas in the majority, the energy-absorbing agent is unknown. Table 57-2 Classification of Photosensitivity Diseases Type Disease Genetic Erythropoietic porphyria Erythropoietic protoporphyria Porphyria cutanea tarda—familial Variegate porphyria Hepatoerythropoietic porphyria ...