Psoralen UV-A Therapy Research Articles

Psoralen UVA therapy for linear and generalized morphea

APL is characterized histologically by delicate, thin-walled, vascular spaces lined by endothelium in the papillary dermis. The vascular spaces form channels that run horizontally and have a dissection of appearance. There is no cellular atypia. In some cases the lesion extends to the mid and reticular dermis and even to the subcutis, and the vascular spaces in the deep tissue are smaller and have irregular appearance. 5 Immunohistochemical studies have given inconsistent results. Wilson Jones et al. 5 found that the lesional endothelial cells were UEA-1 positive and factor VIII-related antigen negative. Rosso, Gianelli, and Carnevali 9 found that factor VIII-related antigen was positive, whereas UEA1 was inconsistently reactive in the endothelial cells. Tadaki et al. 4 reported that in their case endothelial cells did not stain with either factor VIII-related antigen or UEA-1. Zhu et al. 6 found type IV collagen and desmin surrounding the vascular channels, suggesting that APL is a hamartoma that contains blood and lymphatic vessels as well as smooth muscle.

P53 Mutation in Squamous Cell Carcinomas from Psoriasis Patients Treated with Psoralen + UVA (PUVA)

Individuals suffering from psoriasis are treated with a combination of psoralen and UVA radiation, commonly referred to as "PUVA" therapy. Epidemiologic studies have shown that PUVA therapy is a risk factor for skin cancer in psoriasis patients. Although PUVA treatment induces skin cancer in laboratory animals, it is unknown whether the increased incidence of skin cancer reported in PUVA-treated psoriasis patients is due to the carcinogenic effects of PUVA or due to other factors such as UVB. Because UV and PUVA induce different types of DNA damage resulting in unique types of p53 mutation, we investigated whether skin cancers from PUVA-treated psoriasis patients have PUVA-type or UV-type p53 mutations. Analysis of 17 squamous cell carcinomas (SCCs) from Austrian PUVA-treated patients revealed a total of 25 p53 mutations in 11 SCCs. A majority of p53 mutations occurred at 5'TpG sites. Although previous studies have shown that 5'TpA sites are the primary targets for PUVA mutagenesis, substitutions at 5'TpG sites are also quite common. Interestingly, a sizable portion of p53 mutations detected were C-->T or CC-->TT transitions, characteristic of UV-induced mutations. Because some psoriasis patients had substantial exposure to UVB before PUVA therapy and because the light sources used in PUVA therapy contained small but significant wavelengths in the UVB region, it is possible that the C-->T and CC-->TT transitions detected in SCCs from PUVA-treated patients were induced by UVB. Nonetheless, our results indicate that both PUVA and UVB may play a role in the development of skin cancer in Austrian psoriasis patients who undergo PUVA therapy.

Cyclosporin A Suppresses ICAM-1 Expression by Papillary Endothelium in Healing Psoriatic Plaques

To analyze the mode of action of Cyclosporin A (CsA) in psoriasis, we examined the phenotypic profile of resident and passenger skin cells in seven psoriatic patients before and after 2 weeks of CsA treatment using a large panel of monoclonal antibodies in a three-step immunoperoxidase technique. For comparison, skin biopsies from psoriatic patients receiving psoralen + UVA (PUVA) therapy were examined. Although both treatment protocols were equally effective in inducing resolution of psoriatic lesions, the phenotypic changes induced by CsA differed greatly from those seen after PUVA. In CsA-treated patients there was a dramatic reduction in the ICAM-1 expression by papillary endothelial cells, but density, pattern, and phenotype of infiltrating inflammatory cells remained essentially unchanged. In contrast, PUVA therapy had no visible effect on ICAM-1 expression by papillary endothelial cells, but resulted in a significant reduction of the hemopoietic resident and infiltrating mononuclear cells within the epidermis. These results favor, but do not prove, the assumption that the CsA regimen chosen in this study exerts its anti-psoriatic effect primarily at the level of the keratinocyte, i.e., by inhibiting events leading to keratinocyte proliferation as well as by interfering with the secretion of mediators responsible for ICAM-1 expression by papillary endothelial cells.

Photoprotection by psoralen-UVA therapy

Photoprotection by psoralen-UVA therapy