PATHOGENESIS AND TREATMENT OF HIV-ASSOCIATED PSORIASIS

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Psoriasis and pruritic papular eruptions, including eosinophilic folliculitis, may be among the first manifestations of human immunodeficiency virus (HIV) infection, and in this setting may be severe and difficult to treat. In both diseases, HIV transcripts have been found in skin cells by in situ hybridization or polymerase chain reaction (PCR), suggesting that HIV could cause these diseases by directly influencing epidermal gene expression or indirectly through cytokine modulation in infected or uninfected cells. Although HIV associated psoriasis may respond temporarily to zidovudine administration, many patients with both conditions often require ultraviolet light therapy for control. However, recent data involving transfections of HIV in vitro and mice transgenic for HIV genes suggest that the HIV virus is activated by ultraviolet light (UVL), so the safety of giving light to patients is questionable. On the other hand psoralen plus UVA may inactivate HIV in vitro, and could hypothetically be beneficial . This proposal will address the hypothesis that HIV virus may trigger psoriasis through gene regulation or through the production of cytokines which induce epidermal proliferation. Biopsies from patients and controls will be studied for HIV RNA transcripts of env/pol/gag, tat, or nef by quantitative in situ hybridization (ISH), and interpreted using the laser scanning confocal microscope. PCR-DNA will be used to quantitate HIV in skin lesions, and to sequence tissue specific HIV strains. Cytokine expression by HIV+ and HIV- monocytes will be assessed using monoclonal antibodies and ISH. In part 2 of the study we will test the hypothesis that UVL administration activates the expression of HIV in skin or systemically. Skin biopsies before and after light will be compared, as above. HIV in subsets of peripheral blood cells will be quantitated with flow cytometry using fluorescent in situ hybridization (FISH) and antibody staining. Blood cell populations, p24 antigen, and cutaneous immune system will be measured over time with UVL administration. The effect of UVL on HIV in skin in vivo is of utmost importance for the safety of HIV+ patients with skin disease who receive UVL, as well as for the general health of all HIV infected individuals.