Thomas Rosenbach

S3 – Guidelines on the treatment of psoriasis vulgaris (English version). Update

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5% to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, surveys have shown that patients still do not received optimal treatments. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologi sche Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence‐based guidelines for the management of psoriasis. They were first published in 2006 and updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate and severe plaque‐type psoriasis in adults including systemic therapy, UV therapy and topical therapies.

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).

German S3-guidelines on the treatment of psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance (Richards et al. in J Am Acad Dermatol 41(4):581–583, 1999). To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis first published in 2006 and now updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. This short version of the guidelines presents the resulting series of therapeutic recommendations, which were based on a systematic literature search and discussed and approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs, as well as detailed information on how best to apply the treatments described (for full version please see Nast et al. in JDDG Suppl 2:S1–S104, 2011 or http://www.psoriasis-leitlinie.de).

Phototherapy of urticaria pigmentosa: clinical response and changes of cutaneous reactivity, histamine and chemotactic leukotrienes.

SummaryTen patients with moderate to very severe urticaria pigmentosa were studied for the therapeutic effect of photochemotherapy (PUVA; six adults) and selective ultraviolet phototherapy (SUP; four adolescents). Despite a high mean PUVA dosage (138.6 ±63.4 J/cm2), only two patients had a very good response, while three had a good response and one had a fair response. On the reduction of the frequency of treatments, the symptoms gradually recurred, and several months after the discontinuation of therapy, the clinical status had reached the level prior to PUVA. The results with SUP were even less encouraging. A number of biophysical and biochemical parameters of the skin were studied in five patients before PUVA treatment, immediately after several months of PUVA treatment and again 5 months after the discontinuation of PUVA treatment. Weal and erythema reactions to intracutaneous skin tests remained unchanged after PUVA, while wealing with topically applied dimethylsulfoxide (DMSO) decreased. Transepidermal water loss was markedly reduced over DMSO weals. Histamine levels, which were elevated in lesional but not in normal skin, dropped with PUVA treatment, but after the discontinuation of treatment, they increased again in the lesions. On reverse-phase high-performance liquid chromatography, two main chemotactic factors, leukotriene B4 and 5-HETE, were identified in lesional skin. Chemotactic activity was elevated in both lesional and uninvolved patient skin, reached normal levels at both sites after PUVA and maintained these low levels for several months after the discontinuation of treatment. Our data suggest that PUVA has reversible anti-inflammatory effects on human skin, because it increases epidermal-barrier function and decreases the synthesis of mediators of inflammation. These observations show the transitory therapeutic benefit of PUVA in patients with urticaria pigmentosa.

Immunoreactive Leukotrienes in Nettle Plants (Urtica urens)

In order to clarify the mechanisms of urtication after contact with stinging plants, nettle (Urtica urens) hair and whole-plant extracts were examined for the presence of leukotriene (LT) B4 and LTC4 by reverse phase high-pressure liquid chromatography (RP-HPLC) and radioimmunoassay (RIA) and for in vitro neutrophil chemotactic activity and histamine contents. Both hair and plant extracts contained high levels of LTB4 and LTC4 by RIA as well as histamine. The presence of LTB4 was supported by RP-HPLC elution profiles and by in vitro chemotaxis. Nettle hairs therefore resemble insect venoms and cutaneous mast cells with regard to their spectrum of mediators.

The bulge is the source of cellular renewal in the sebaceous gland of mouse skin.

The sebaceous gland (SG) is implicated in the pathogenesis of several skin disorders including different forms of acne and some skin tumors. Therefore, the question of the origin of the stem cells, which provide a permanent source of sebocytes, is a fundamental issue in dermatology. Since the hair follicle (HF) epithelium and the SG originate from the same epidermal bud during fetal development, it is likely that these structures have the same cellular source for renewal. Currently, the so-called bulge area of the outer root sheath (ORS), located at the level of insertion of the arrector pili muscle, is considered to be a site of pluripotent epithelial stem cells (Cotsarelis et al. 1990), and may also give rise to sebocytes. Although the bulge region and the SG are neighboring structures in normal HF, they are separated from each other by the perifollicular dermis, so that only the cells of the SG duct directly communicate with the ORS of the HF. Therefore, the remote possibility exists for the passage of replenishing proliferative cells in the SG. However, the compelling question does not concern the pathway, but rather the cellular origin of sebocyte precursors. In this study, we explored whether bulge cells are capable of generating sebocytes. In order to better understand how bulge cells and sebocytes might interact, we studied the skin of HRS/J hairless mice to observe and manipulate direct interactions between these two cell populations. HRS/J hairless mice are an inbred strain with a recessive mutation at the hairless (hr) locus, a putative transcription factor with restricted expression in the brain and skin (Cachon-Gonzalez et al. 1994). At birth, hairless mutants develop a normal hair coat. At the initiation of the first catagen, however, their HFs disintegrate, resulting in loss of the ability to retain the hair shafts and subsequent failure to produce new ones. Within 3 weeks of birth, the mutant animals become completely hairless (Panteleyev et al. 1999). Due to hr gene-dependent HF disintegration at an early age, the skin of adolescent hr mice contains only non-cycling remnants of the HF. These remnants include the socalled “utriculi”, which correspond to the infundibular portion of the normal ORS, the dermal cysts, which originate from the proximal lower ORS, and active, well-developed SG connected with the skin surface via the utricular cavity (Panteleyev et al. 1998). Recently, we described a population of relatively undifferentiated epithelial cells in the skin of hairless mice, which are strikingly different from the keratinocytes of the utricular epithelium (Panteleyev et al. 1998a). The location of these compact cell clusters just beneath the SG and their intimate association with the arrector pili muscle (Figs. 1A, and 2B) suggests that they correspond to the bulge cells of the normal HF. This hypothesis was further confirmed by the ability of these cells to undergo spontaneous growth activity, which results in the formation of downward-oriented outgrowths (Panteleyev et al. 1998b). Therefore, hr skin is a unique model for the study of bulge-sebocyte interactions since the HFs in hr skin are morphologically split into separate units and, as a result of ORS disintegration, the bulge cells are physically separated from the rest of the HF epithelium. The utility of hr skin as a model for studies of SG-bulge interactions is underscored by the difference in skin morphology between hairless (hr/hr) mice Andrei A. Panteleyev · Thomas Rosenbach · Ralf Paus · Angela M. Christiano

Cyclosporine therapy in dermatology

JDDG | 5 ̇2009 (Band 7)

S3-Leitlinie zur Therapie der Psoriasis vulgaris Update 2011

Alexander Nast, Wolf-Henning Boehncke, Ulrich Mrowietz, Hans-Michael Ockenfels, Sandra Philipp, Kristian Reich, Thomas Rosenbach, Adel Sammain, Martin Schlaeger, Michael Sebastian, Wolfram Sterry, Volker Streit, Matthias Augustin, Ricardo Erdmann, Joachim Klaus, Joachim Koza, Siegrid Müller, Hans-Dieter Orzechowski, Stefanie Rosumeck, Gerhard Schmid-Ott, Tobias Weberschock, Berthold Rzany (1) Division of Evidence Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin (2) Zentrum der Dermatologie und Venerologie, Klinikum der Johann Wolfgang Goethe Universität, Frankfurt/M. (3) Klinik für Dermatologie, Venerologie, Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel (4) Hautund Allergieklinik, Klinikum Hanau (5) Psoriasisstudienzentrum, Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin (6) Dermatologikum Hamburg (7) Niedergelassener Dermatologe, Osnabrück (8) Niedergelassener Dermatologe, Oldenburg (9) Niedergelassener Dermatologe, Mahlow (10) Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin (11) Niedergelassener Dermatologe, Buchholz (12) Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Dermatologie und Venerologie, Hamburg (13) Deutscher Psoriasis Bund e.V. (14) Pflegevertreterin, Ravenstein (15) Institut für Klinische Pharmakologie und Toxikologie, Charité – Universitätsmedizin Berlin (16) Berolina Klinik, Löhne

Topical long‐term therapy of psoriasis with vitamin D3 analogues, corticosteroids and their two compound formulations: position paper on evidence and use in daily practice

Current data from daily practice show that vitamin D3 analogues, corticosteroids and their fixed combination products are used heterogeneously for topical long‐term treatment of psoriasis.

The promoter of the HaCaT keratinocyte differentiation-related gene keratin 4 contains a functional AP-2 binding site

Abstract The nuclear transcription factor AP-2 appears to be a key regulator mediating programmed gene expression during embryonic morphogenesis and adult cell differentiation. AP-2 has also been considered to be involved in epidermal gene regulation, but its precise role is not yet defined. The level of AP-2 transcripts increases during culturing of HaCaT keratinocytes preceding the expression of the differentiation-related gene keratin 4 (K4). The current study was aimed at investigating whether AP-2 transactivates K4 transcription. We cloned and sequenced the promoter region of K4 and found, in addition to canonical sequences, an AP-2 consensus site in the vicinity of the transcriptional start. In order to provide functional evidence for a regulation of K4 transcription by AP-2, we cloned various parts, which did or did not contain the AP-2 site of the K4 upstream sequence, into Cat reporter plasmids. These constructs were ballistically transfected into differentiating HaCaT keratinocytes. The determination of the resulting Cat activity revealed that the AP-2 site in the vicinity of the transcriptional start was functional for K4 transcription. Thus, the role of AP-2 in the process of keratinocyte differentiation appears to be considerable. In addition, further regulatory elements were found to be necessary for full transcription of K4.