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Introduction: Atopic dermatitis (AD) is a complex disease with a variety of possible treatment regimens. The study objective was to demonstrate that methoxsalen used in conjunction with the Uvar XTS photopheresis system (Therakos, Exton, Pa., USA) is safe and can have a clinical effect on the skin manifestations and the quality of life in patients with severe, refractory AD. Methods: Single-arm, open-label treatment using the Uvar XTS photopheresis system. Seven patients (4 male and 3 female, median age: 47 years) with severe (SCORAD >45) AD of at least 12 months duration who in the preceding 12 months had been refractory to all 3 of the first-line therapies for AD, i.e. topical steroids, topical calcineurin inhibitors and one form of phototherapy (UVA, UVB or PUVA), or to one of the second-line therapies like systemic steroids or cyclosporine were included in the study. Treatment consisted of two extracorporeal photopheresis treatments (ExP) on successive days every 2 weeks for a minimum of 12 weeks to a maximum of 20 weeks. Quality of life assessment was performed with the SF-36 Health Survey and the Functional Assessment of Chronic Illness Therapy FACT-G Survey. Clinical improvement was documented with SCORAD assessment. Results: ExP led to a significant decrease in the SCORAD score from 77.7 after 10 cycles to 55.6. Patients reported that they had begun to notice improvement of their skin conditions after 5 cycles of photopheresis. The FACT-G score showed significant improvement from 64.8 to 72.9 (p < 0.05) and the SF-36 Health Survey showed significant improvement in the emotional well-being subscores (p < 0.05). Conclusions: ExP can have a significant therapeutic effect on the skin and quality of life improvement in a selected group of patients with severe AD who are refractory to conventional forms of therapy. However, larger studies are needed to further evaluate its therapeutic potential.

Our findings demonstrate that UVA1 irradiation may effect structural and functional modifications leading to immediate initiation of apoptosis followed by early membrane rupture, whereas UVB irradiation leads to DNA damage followed by delayed apoptosis, obviously without initial membrane alteration.

Pilot studies have shown an improvement of atopic dermatitis in approximately 65% of patients during extracorporeal photopheresis (ExP) therapy. The purpose of the present clinical trial was to investigate the response to ExP by controlling clinical and laboratory parameters during short term ExP therapy in patients with severe generalised atopic dermatitis. Thirty-five patients with severe, therapy-resistant atopic dermatitis were treated with ExP in an open clinical trial at two week intervals over a period of 6 to 10 cycles. Disease activity was measured before each cycle by SCORAD index together with a standardized protocol for blood samples. ExP led to a significant decrease (p < 0.05) in SCORAD from 74.4 +/- 15.5 before to 36.8 +/- 16.8 after ExP therapy (mean 10 cycles). Approximately 70% (24/33 patients = responder) of patients had a favourable response to ExP requiring at least 6 cycles. The decrease in SCORAD was accompanied by a significant decrease of eosinophil cationic protein (27%), sE-selectin (37%) and sIL-2R (53%) levels in serum (p < 0.05). No significant correlation between a decrease in these levels and values of blood eosinophils or lymphocytes was found (p > 0.05). In comparison to responders, most non-responders were characterised by very high levels of total IgE before and during therapy (p < 0.05). The present clinical trial confirms that short term ExP is an effective treatment for certain patients with severe atopic dermatitis based on anti-inflammatory mechanisms. Total IgE could be a predictor of outcome in ExP treatment.

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BackgroundIt would be a benefit if time-saving, non-invasive methods could give hints for diagnosing systemic sclerosis. To investigate the skin of patients with systemic sclerosis using confocal laser scanning microscopy in vivo and to develop histometric parameters to describe characteristic cutaneous changes of systemic sclerosis observed by this new technique, we conducted an exploratory study.Materials and MethodsFifteen patients with systemic sclerosis treated with extracorporal photopheresis were compared with 15 healthy volunteers and 10 patients with other disorders also treated with extracorporal photopheresis. All subjects were investigated using confocal laser scanning microscopy in vivo.ResultsMicromorphologic characteristics of skin of patients with systemic sclerosis and measuring parameters for melanisation, epidermal hypotrophy, and fibrosis for dislocation of capillaries by collagen deposits in the papillary dermis were evaluated. An interesting finding was an increased thickness of the tissue in the dermal papillae superior to the first dermal papilla vessel. It was also possible to reproduce characteristic histologic features by confocal laser scanning microscopy in vivo. Histometric parameters for fibrosis and vascular features developed in this study showed significant differences in patients with systemic sclerosis compared to controls.ConclusionsAlthough the predominant histopathological features in systemic sclerosis are findings of the reticular dermis and the subcutis, and in histopathological investigation the epidermis seems to remain unaffected by the disease, we have demonstrate some characteristic differences in the epidermis and papillary dermis by confocal laser scanning microscopy in vivo. Some of them have not been described so far. However, to use this technique as a tool for diagnosis and/or staging of systemic sclerosis, further studies are needed investigating the sensitivity and specificity of the histometric parameters developed in this study.

Background: The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL). Objective: Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL. Methods: c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR. Results: Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 ± 0.5) versus MF (1.2 ± 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 ± 31,960.32 AU in SS vs. 1,226.35 ± 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 × 10^–2 ± 2.27 × 10^–2 in SS vs. 0.91 × 10^–2 ± 1.18 × 10^–2 in MF vs. 0.24 × 10^–2 ± 0.11 × 10^–2 in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 × 10^–2 and 10.78 × 10^–2 ± 7.24 × 10^–2). Conclusion: Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.

During the past few years, bath PUVA has become established as an effective treatment for various dermatoses and especially for psoriasis. Using 3,4,5 trimethylpsoralen (TMP) in combination with subsequent UVA irradiation, a shower PUVA has been developed as an alternative in local PUVA therapy. This involves moistening the patient's skin - with the exception of the head and neck area - in a shower using water containing psoralen (TMP concentration 0,27 mg/l). The advantages of shower PUVA method are that time, space and cost savings are possible and that only a slight amount of physical exertion is required by the patient standing in the shower compared to immersing the whole body during bath PUVA therapy. The efficacy and practicability of shower PUVA were evaluated using the minimal phototoxic dose (MPD) for healthy volunteers assessing water temperature (33-38 degrees C), shower time (5-10 min), and UVA dose (0,06-1,0 J/cm(2)). Additionally, the time course of TMP-induced photosensitivity was observed over a period of 4 hours after the shower. Using a TMP concentration of 0,27 mg/l, the MPD for skin type I-II lay between 0,125-0,375 J/cm(2) and for skin type III-IV between 0,375-1,0 J/cm(2). Photosensitivity was induced by shower PUVA within 5-10 minutes shower time and at 33-38 degrees C water temperature. MPD exhibited an inverse correlation to temperature but no differences were apparent for shower times between 5 and 10 minutes. Photosensitivity completely disappeared within 2 hours. Minimal phototoxic doses using TMP in shower PUVA are comparable with classical bath PUVA when taking skin type into account. These results support the therapeutic use of shower PUVA using TMP.