Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis.

BACKGROUND: Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. OBJECTIVE: We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. METHODS: Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. RESULTS: UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. CONCLUSION: Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Apoptosis of human dermal endothelial cells as a potential side effect following therapeutic administration of UVA1 irradiation: preliminary results.

Apoptosis is a highly selective form of cell suicide with characteristic morphological and biochemical features. UVA1 phototherapy has been introduced into the treatment of many T cell-derived skin diseases. The aim of our pilot study was to assess apoptosis of endothelial cells in relation to time after irradiation with medium-dose UVA1 using four different staining techniques. With in situ nick end labelling (ISEL) and Hoechst 33342 staining we investigated DNA degradation during apoptosis and used M30 CytoDEATH to selectively stain the cytoplasm of apoptotic cells. Additionally, the expression of the tumour suppressor gene p53 was determined. ISEL and Hoechst 33342 revealed only a few positive endothelial cells 3 h after UVA1 irradiation. After 6 h almost all vessels were positively stained. By 12 h after irradiation this peak concentration had lowered again. The first p53-positive endothelial cells were seen 6 h after UVA1 irradiation and reached a maximum at 12 h after irradiation. Fibroblasts of the lower dermis were positively stained after 6 and 12 h. M30-positive endothelial cells were found from 3 to 12 hours after irradiation. ISEL and Hoechst 33342 staining clearly revealed UVA1-induced apoptotic cell elimination predominantly restricted to endothelial cells as a possible side effect of UVA1 irradiation. The induction of apoptosis was specifically verified by M30 immunostaining of early caspase cleavage. Whereas the p53-positive endothelial cells underwent programmed cell death as demonstrated by M30, ISEL and Hoechst 33342, some fibroblasts seemed to accumulate the p53 antibody, but this did not induce apoptotic cascades.

Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy.

BACKGROUND: During the last decade, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great value within the treatment of severe atopic dermatitis (AD). The purpose of our study was to investigate to what extent UVA1 irradiation is able to modulate the status of protease activity by the use of a monoclonal antibody labeling cathepsin G. METHODS: In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement of skin status in patients with AD, biopsy specimens from 15 patients before and after treatment were analyzed immunohistochemically for proteolytic activation. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the number of cells positive for cathepsin G within the dermal infiltrate decreased significantly after treatment. The decrease of cathepsin G+ cells was closely linked to a substantial clinical improvement in skin condition. CONCLUSIONS: In summary, our findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of the expression of cathepsin G in the dermal inflammatory infiltrate in patients with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and insoluble fibronectin, to provoke proinflammatory events, to degrade the basement membrane, to destroy the tissue inhibitor of metalloproteinases and to increase the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy may induce the reduction of skin inflammation as well as improvement of the skin condition.

Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease in which numerous therapies have been used, with only limited success. Because low-dose UVA1 phototherapy has been shown to be an effective treatment option for localized scleroderma, which shares several similar clinical and histologic features with LS, we initiated a clinical trial with this phototherapeutic modality in patients with LS. METHODS: Ten patients suffering from extragenital LS were treated with low-dose UVA1 phototherapy 4 times weekly with single UVA1 doses of 20 J/cm(2). Forty treatment sessions were performed within 10 weeks, resulting in a cumulative UVA1 dose of 800 J/cm(2). RESULTS: Low-dose UVA1 phototherapy resulted in a marked reduction of the clinical score and a significant (P <.05) decrease of ultrasonographically measured skin thickness as well as a highly significant (P <.001) increase of dermal density. The patients reported a remarkable softening and repigmentation of the affected skin. CONCLUSION: Analogous to the treatment results in localized scleroderma, low-dose UVA1 phototherapy seems to be an effective and well-tolerated treatment option for extragenital LS.