Summary:Long-wavelength ultraviolet A (340-400 nm UVA1) phototherapy has been reported to be effective in atopic dermatitis, localized scleroderma and other T-cell-derived skin diseases. UVA1 as an adjunct to systemic immunosuppressive treatment was found to be safe, and effective in 10 patients with chronic cutaneous (seven lichenoid and three sclerodermoid) graft-versus-host disease (GVHD) after stem cell transplantation. Complete and partial responses were achieved in six (60%), and in three (30%) patients, respectively. One patient had improvement of sclerotic skin lesions. At a median follow-up of 14 months, two patients with lichenoid lesions relapsed. Both responded to another treatment cycle. Furthermore, we treated seven patients with UVA1 as primary therapy for acute cutaneous GVHD grades II and III in a pilot experience. Five patients had a complete response with no relapse at a median follow-up of 9 months after UVA1. Two patients showed no response and systemic steroids had to be started. UVA1 therapy is feasible, well tolerated and can be effective in treating chronic as well as acute GVHD confined to the skin thereby avoiding systemic steroids. Our results should be confirmed in larger studies and the effectiveness of UVA1 compared to other established treatment modalities. Bone Marrow Transplantation (2005) 35, 515-519.
Exposure to UVB results in the isomerization of trans-urocanic acid (UCA), localized in the stratum corneum, to cis-UCA. Cis-UCA can mediate at least some of the immunosuppressive effects of UVB, though the mechanism of cis-UCA action remains incompletely defined. Alterations in Langerhans cells, and other dendritic antigen presenting cell populations in the skin, may contribute to the loss of skin immune function following UVB exposure. Hence, this study was designed to investigate whether cis-UCA directly can induce changes in the immunostimulatory capacity of dendritic cells (DC) and the development of DC from precursor cells. Murine DC were generated from C57BL/6 bone marrow (BM) using granulocyte-macrophage colony-stimulating factor (GM-CSF), and were used as stimulator cells in mixed lymphocyte reactions (MLR) using BALB/c lymph node cells (LNC) as responders. The addition of cis- and trans-UCA at concentrations ranging from 0.1-500 micrograms/ml to the MLR did not affect proliferative responses. Cis- or trans-UCA (100 micrograms/ml) was added to GM-CSF stimulated mouse BM cells on day 0, day 3 or day 5 of culture, and the phenotype and allo-stimulatory function of the DC were analysed on day 7. Treatment with cis- or trans-UCA did not affect the numbers or the viability of cells in the BM cultures. In addition, the expression on DC of Iab, CD11c or the costimulatory molecules ICAM-1, B7-1, B7-2 and CD40 was not altered by the addition of cis-UCA to BM cultures. The inability of cis-UCA to alter the development of DC in vitro was confirmed by analysing the functional capacity of DC in MLR. DC generated in the presence of cis-UCA were equally efficient in the induction of allo-stimulation, when compared with control DC. These results suggest that cis-UCA does not exert its immunosuppressive activity through direct effects on DC. Such activity may be independent of DC, or alternatively, cis-UCA may influence DC function indirectly, through the induction of secondary mediators.
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The availability of biologics for the therapy of psoriasis has radically changed the options for systemic therapy of this disease. Their use is often coupled with a variety of restrictions--as a rule they are to be used as a 'last-line' therapy. The status of previous systemic therapy as a basic requirement for the use of biologics is analyzed and simultaneously, the possibilities of the physician to use the indication spectrum of biologics for the benefit of the patient are demonstrated by case reports.
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