Niels Sönnichsen

High-dose UVA1 therapy for atopic dermatitis: Results of a multicenter trial

BACKGROUND The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance.

Products of lipid peroxidation (malonaldehyde, Schiff-bases) were detected in human skin. These products were increased after UV-light exposition, on chronically sun-exposed areas as well as with advancing age. Malonaldehyde cross linked epidermal glucose-6-phosphate-dehydrogenase and diminished their activity.

Comparison of the Effects of Calcipotriol, Prednicarbate and Clobetasol 17-Propionate on Normal Skin Assessed by Ultrasound Measurement of Skin Thickness

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

Studies on the effects of a high dose UVA-1 radiation therapy on surface markers and function of epidermal Langerhans cells

Recently, high-dose UVA-1 therapy (340–400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

Prolongation of skin graft survival in mice by in vitro PUVA treatment and failure of induction of specific immunological memory by PUVA-treated grafts

SummaryTreatment of murine skin grafts in vitro with 8-methoxypsoralen and longwave ultraviolet radiation prolonged their subsequent survival on allogeneic recipients, but not in cases where the recipients had been presensitized by a former skin graft of the same donor strain. In contrast to normal skin, grafts pretreated with 8-methoxypsoralen and longwave ultraviolet radiation were not able to induce an immunological memory as revealed by a second transplantation of normal skin. The results show that primary and secondary skin graft rejections can be affected by the combined action of psoralen and ultraviolet radiation.

Stimulation of the recruitment of epidermal Langerhans cells by splenopentin

SummarySplenopentin (SP-5: Arg-Lys-Glu-Val-Tyr), a pentapeptide corresponding to the residues 32–36 of the splenic hormone splenin, increases dose-dependently the number of bone marrow colonies (M and GM colonies). Therefore, we tested the stimulatory effect of SP-5 on the recruitment of epidermal Langerhans cells in skin deprived of these cells. A high dose of cyclophosphamide or dexamethasone led to a drastic decrease of LC density in murine skin with slow and incomplete restoration. SP-5 accelerated Langerhans cell recruitment and led to pretreatment levels of Langerhans cell density in the skin. These results indicate that SP-5 may possibly be used to treat disorders (e.g., HIV infection) where impaired Langerhans cell density and function can lead to secondary cutaneous infections.

The influence of topical dermatological treatment modalities on epidermal Langerhans cells and contact sensitization in mice

The influence of the widely used topical dermatological treatment modalities anthralin, coal tar and pyrogallol on surface markers of epidermal Langerhans cells and contact sensitization was studied and compared with that of a PUVA treatment. A common effect of all dermatological therapies found was inhibition of Langerhans cell ATPase, whereas an effect on MHC class H antigens was round only after PUVA or tar treatment. The induction of contact hypersensitivity was inhibited only by PUVA, and not by the other treatments. These results show that various forms or topical therapy influence surface markers and immunological function of epidermal Langerhans cells differently.

Untersuchungen zum Wirkungsmechanismus von Dithranol: Erhöhte Lipidperoxydation und Enzymhemmung

The results reported in connection with previously published data suggest the importance of increased lipid peroxidation in the epidermis after Dithranol treatment. Malonaldehyde, one of the main prod

The influence of interferon-gamma, interleukin-2, prostaglandin E2, and cyclosporine on the polyclonal and anti-DNA, antibody secretion in lymphocyte cultures derived from patients with systemic lupus erythematosus

SummaryThe influence of various immunoregulatory substances was studied in lymphocyte cultures derived from patients suffering from systemic lupus erythematosus (SLE) by using the model of spontaneous secretion of polyclonal immunoglobulin G (IgG)/immunoglobulin M (IgM) and anti-DNA autoantibodies. Compared with healthy donors, lymphocytes derived from patients with active SLE disease showed an elevated secretion of total IgG as well as anti-DNA-IgG in vitro, which was associated with an increase in the proportion of activated (HLA-class II +) T cells in their peripheral blood. Recombinant interferon-gamma increases the total IgG/IgM as well as anti-DNA-IgG/IgM secretion, which suggests that it has a possible role in the pathogenesis of SLE disease. Recombinant interleukin-2 and prostaglandin E2 normalize the high, spontaneous total IgG secretion, but elevate anti-DNA-IgG/IgM secretion. These results suggest that autoreactive B-cell clones are regulated differently in SLE patients. Cyclosporine inhibits total IgG/IgM secretion in all patients and anti-DNA-IgG/IgM secretion in six of eight patients. The possible therapeutic use of such immunomodulatory substances in SLE disease is discussed.

Hautsarkoidose (M. Besnier-Boeck-Schaumann)

Die Abhandlung der Sarkoidose (S.) im Rahmen der granulomatosen Erkrankungen an dieser Stelle mus sich schwerpunktmasig auf die Hautbefunde bzw. die speziell den Dermatologen interessierenden Fragen beschranken. Versucht man eine Charakterisierung der Erkrankung, so lassen sich folgende Merkmale herausstellen: Die S. ist eine Systemerkrankung unklarer Atiologie und Pathogenese. Sie ist histologisch durch nichtverkasende Epitheloidzellengranulome ausgezeichnet. Sie hat charakteristische immunologische Veranderungen. Neben obligatem intrathorakalem Befall konnen praktisch alle Organe befallen sein (Tabelle 1).