C. Pieck

Medium-dose UVA1 cold-light phototherapy in the treatment of severe atopic dermatitis

BACKGROUND Recently, conventional high-dose UVA1 phototherapy (340-400 nm) has been shown to be more effective than combined UVA-UVB therapy in the treatment of severe atopic dermatitis (AD). However, there are limitations of this treatment, such as intense sweating caused by the immense heat load during therapy and the high cumulative UVA1 doses that are required. For this reason, lavish UVA1 equipment was developed containing an advanced filtering and cooling system resulting in almost complete absence of heat load and sweating during therapy. OBJECTIVE In this study we compared the monotherapeutic efficacy of conventional medium-dose UVA1, medium-dose UVA1 cold-light, and combined UVA-UVB phototherapy in the treatment of severe AD. METHOD The study involved 120 patients with severe AD. Fifty patients each received conventional UVA1 or UVA1 cold-light phototherapy (15 days, 50 J/cm(2)/day), and 20 patients were treated with combined UVA-UVB (15 days, minimal erythema dose dependent). Severity of AD was scored by means of the SCORAD score, and clinical improvement was additionally monitored by serologic cytokine markers. RESULTS Six (12%) of 50 patients treated with UVA1, 2 (4%) of 50 patients treated with UVA1 cold-light therapy, and 4 (20%) of 20 patients treated with combined UVA-UVB therapy discontinued treatment prematurely because of an unsatisfactory clinical outcome or adverse reactions. Skin status improved or even cleared completely in 77.3% of the patients treated for 3 weeks with conventional UVA1 therapy and in 85.4% of the patients treated for 3 weeks with UVA1 cold-light therapy, resulting in a significant decrease in the SCORAD score in both UVA1 groups (P <.05 each). In the group treated with combined UVA-UVB, the SCORAD score also decreased but significantly less than in both groups treated with UVA1 photo-therapy (P <.05 each). At follow-up after 4 weeks, the patients treated with UVA1 displayed a more prolonged therapeutic benefit than the patients treated with UVA-UVB therapy. Plasma levels of soluble interleukin 2 receptors and soluble interleukin 4 receptors significantly decreased under both UVA1 and UVA1 cold-light phototherapy but not under combined UVA-UVB phototherapy. CONCLUSION Our study demonstrates that medium-dose UVA1 cold-light phototherapy displays advantages compared with conventional UVA1 phototherapy caused by the almost complete absence of heat load and intense sweating and is more effective than UVA-UVB phototherapy in the treatment of severe AD.

Topical vitamin B12: a new therapeutic approach in atopic dermatitis: evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial

Background  Vitamin B12 is an effective scavenger of nitric oxide (NO). As the experimental application of a NO synthase inhibitor, Nω‐nitro‐l‐arginine, led to a clear decrease in pruritus and erythema in atopic dermatitis, it would be reasonable to assume a comparable effect of vitamin B12.

Mechanisms of apoptosis: UVA1‐induced immediate and UVB‐induced delayed apoptosis in human T cells in vitro†

Objective The decreased number of lymphocytes combined with the induction of apoptosis and necrosis seems to be the key mechanism of many phototherapeutic agents. The purpose of our study was to determine the regulating pathway, time course and dose dependence of UVA1‐ vs. UVB‐induced cell death in human T lymphocytes.

Opposing effects of UVA1 phototherapy on the expression of bcl-2 and p53 in atopic dermatitis

Abstract Recently, medium-dose UVA1 phototherapy (50 J/cm 2 ) has been introduced as an effective treatment for severe atopic dermatitis (AD). In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement in skin status in patients with AD, biopsy specimens from ten patients before and after treatment were analysed immunohistochemically for features of apoptosis. We sought to determine the extent to which UVA1 irradiation was able to modulate the balance between p53 and bcl-2 expression in vivo using monoclonal antibodies labelling these proteins. As compared with lesional skin of patients with AD before UVA1 irradiation, the number of dermal cells, apparently lymphocytes, that were positive for p53 had significantly increased after treatment and, in addition, some basal keratinocytes showed slight positive staining for p53. An increased expression of the bcl-2 gene before treatment in predominately dermal lymphocytes was significantly downregulated by UVA1 therapy. The increase in p53 + cells and the decrease in bcl-2 + cells were closely linked to a significant reduction in dermal T cells (CD3 + ) and a substantial clinical improvement in skin condition. In summary, medium-dose UVA1 irradiation led to a marked modulation of the expression of p53 and bcl-2, and this plays a key role in regulating UVA1-induced apoptosis.

UVA1 irradiation induces deoxyribonuclease dependent apoptosis in cutaneousT-cell lymphoma in vivo

Cutaneous T‐cell lymphoma (CTCL) is a malignancy of mature T‐cells, predominantly of the helper phenotype, that primarily invade the skin. Different photo‐ and chemotherapeutic treatments are known to be beneficial in early‐stage CTCL. This observation has initiated prospective investigations into the efficacy of phototherapeutic regimens. The purpose of our study was to investigate the ability of medium‐dose UVA1 phototherapy (60 J/cm2) to induce apoptosis (programmed cell death) in skin infiltrating T‐cells of CTCL in vivo. We describe the results of three different staining methods for formalin‐fixed, paraffin‐embedded tissue sections. The in situ end‐labeling (ISEL) procedure, nuclear staining using the DNA‐binding fluorochrome Hoechst 33342, and immunohistochemistry using polyclonal antibodies against recombinant mouse deoxyribonuclease I (DNase I) demonstrated that UVA1 irradiation was able to induce marked apoptosis in CTCL. Thereby, ISEL and Hoechst staining clearly revealed DNA‐condensation and nuclear fragmentation, accompanied by the formation of typical “apoptotic bodies”. The accumulation of DNase I immunoreactivity in the cytoplasm of lymphocytes in UVA1 irradiated skin indicated that DNase I or DNase I‐related endonucleases may have acted as apoptotic endonuclease(s) which were synthesized after UVA1 irradiation prior to their apoptotic elimination.