[History of the textbook]. / Geschichte des Lehrbuches.

The textbook "Dermatologie und Venerologie" originated with the 1st (1961) and 2nd (1969) German editions by Keining and Braun-Falco from the Departments of Dermatology at the Universities of Mainz and Marburg. The 3rd German edition was written by Braun-Falco, Plewig and Wolff (1984). The three authors became editors with the 4th German edition. Until now three English and several other foreign editions appeared. New editors are now Plewig, Burgdorf, Landthaler, Ruzicka and Hertl. Not only in German speaking countries but also in many other parts of the world the textbook is frequently used by students, residents, and dermatologists. With this retrospective view, the story of the revised editions of the book and its distribution is told.

Reactive angioendotheliomatosis: is it 'intravascular histiocytosis'?

We report the case of a 68-year-old female with reactive angioendotheliomatosis (RAE). This case highlights the benign course of this condition and suggests that this entity might be an intravascular histiocytosis.

Changes in function and morphology of normal human skin: evaluation using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive morphological method for investigating human skin. It allows high-resolution in vivo imaging of inflammatory skin diseases and tumours. Because it is a newly developed method, systematic studies on standardization and on evaluation of factors influencing the representation of the skin have not yet been performed. OBJECTIVES: In this study, normal human skin was treated with various external stimuli which induce changes of function and morphology. Changes in stratum corneum thickness as well as changes induced by pigmentation, oedema and erythema were investigated using OCT. METHODS: Healthy skin of human volunteers was treated with tape stripping, ultraviolet A irradiation, water, histamine, nicotinic acid and various ointments. RESULTS: In the tape stripping experiment, the thickness of the horny layer was quantified and monitored. Pigmentation increased the light attenuation of the tissue, whereas hydration and erythema led to a slight decrease of scattering. Topical treatment of the skin gave a nonspecific increase of penetration depth of the light due to the lower reflectivity of the surface. CONCLUSIONS: There are various physiological conditions which influence optical properties of the skin. These parameters should be considered when performing standardized OCT studies.

Human skin mast cells rapidly release preformed and newly generated TNF-alpha and IL-8 following stimulation with anti-IgE and other secretagogues.

Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF-alpha and IL-8 as well as the pro-allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE-dependent or IgE-independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF-alpha and IL-8 following activation with either anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and time-dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytokines. In accordance with this, using lysates of highly purified (>90%) skin mast cells, we could demonstrate that both TNF-alpha and IL-8 mRNA and protein were present in both unstimulated as well as stimulated mast cells. In stark contrast to these results, no significant levels of either IL-4, IL-5 or IL-13 were detected, regardless of the secretagogue used or the period of stimulation. These results show that human skin mast cells are capable of rapidly secreting pro-inflammatory cytokines like TNF-alpha and IL-8 following IgE-dependent activation and stimulation by the neuropeptide substance P, SCF and the basic polypeptide analogue compound 48/80. In contrast to other types of human mast cells however, human skin mast cells were incapable of secreting IL-4, IL-5 or IL-13 in these settings.

Mercuric chloride enhances immunoglobulin E-dependent mediator release from human basophils.

Mercuric chloride (HgCl2) is an industrial agent known to cause autoimmune disorders and induce IgE synthesis, which plays a crucial role in the manifestation of allergic diseases. In rodents, the immunomodulatory effects of HgCl2 have been shown to involve the enhancement of mast cell-derived IL-4 secretion, which facilitates both Th2-lymphocyte development and IgE production. In humans, rapid allergen-dependent release of IL-4 and the related cytokine IL-13 from histamine-containing cells occurs primarily in basophils, along with other proinflammatory mediators such as histamine and LTC4. In this study, we therefore investigated the effects of HgCl2 on the release of the above basophil mediators, either due to the compound alone or in conjunction with IgE-dependent stimulation. HgCl2 (10(-9) to 10(-6) M) did not induce mediator secretion alone but significantly enhanced the release of histamine, LTC4, IL-4, and IL-13 caused by anti-IgE. Higher concentrations of HgCl2 (10(-5) to 10(-3) M) strikingly reduced cell viability; however, toxicity varied depending on cell density and incubation time. Removal of HgCl2 following a short incubation with basophils did not reverse the potentiating effects on basophil mediator secretion to anti-IgE and the concentration of free mercury in the supernatants significantly diminished by up to 20% after incubation with the cells, indicating irreversible Hg binding to cells. By upregulating IgE-dependent human basophil mediator release, our results clearly indicate that HgCl2 potentially exacerbates allergic disorders and promotes a Th2-cytokine profile.

Calcitriol 3 microg g-1 ointment in combination with ultraviolet B phototherapy for the treatment of plaque psoriasis: results of a comparative study.

BACKGROUND: Combinations of topical treatments and ultraviolet (UV) B phototherapy for plaque psoriasis may be more beneficial than either type of treatment used alone. OBJECTIVES: To determine the efficacy of calcitriol 3 microg g-1 ointment in combination with UVB phototherapy in treating plaque psoriasis. METHODS: Calcitriol ointment with UVB was compared with vehicle plus UVB in a randomized, double-blind study in 104 patients. RESULTS: Mean global improvement scores for both groups increased over the 8-week study period; there was a statistically significant difference (P < 0.05) in favour of the calcitriol/UVB combination from week 1. At end-point, 45% of the calcitriol/UVB group showed considerable improvement or clearing of psoriasis, compared with 21% of the control group. The superiority of calcitriol plus UVB was also reflected in the global severity and Psoriasis Area and Severity Index (PASI) scores; at end-point the mean percentage decrease in PASI score was 65% for the calcitriol/UVB group and 43% for vehicle/UVB (P = 0.0014). The incidence of skin-related adverse events was low (< 12%) and similar in the two treatment groups. No clinically significant changes in blood chemistry, in particular calcium levels, occurred. The greater efficacy of combined calcitriol and phototherapy allowed a 34% decrease in total UVB exposure. CONCLUSIONS: Calcitriol 3 microg g-1 ointment and UVB phototherapy in combination provides a promising therapy for managing chronic plaque psoriasis.

[Morphological changes in melanocytic nevi induced by exogenous factors]. / Morphologische Veränderungen in melanozytären Nävi durch exogene Faktoren.

Malignant melanoma is the most important differential diagnosis in both clinical and histologic examination of melanocytic nevi. UV exposure with an erythemogenic dose and mechanical irritation of melanocytic nevi are able to induce reversible morphologic changes which simulate malignant melanoma. These changes are associated with an increased expression of HMB-45 antigen. In addition, an increased proliferation and repair activity is observed after UV exposure. The increased number of melanocytes located in suprabasal layers of the epidermis is accompanied by a change in keratinocyte adhesion molecule expression. The UV light is also able to influence the adhesive properties of melanocytes in vitro. Therefore, both keratinocyte-derived factors and direct influence of UV on the melanocyte system are probably responsible for the morphologic changes. While these exogenously evoked changes are reversible, the potential biologic relevance--especially a possible role in the initiation of the carcinogenesis cascade--requires clarification.

Feature selection for optimized skin tumor recognition using genetic algorithms.

In this paper, a new approach to computer supported diagnosis of skin tumors in dermatology is presented. High resolution skin surface profiles are analyzed to recognize malignant melanomas and nevocytic nevi (moles), automatically. In the first step, several types of features are extracted by 2D image analysis methods characterizing the structure of skin surface profiles: texture features based on cooccurrence matrices, Fourier features and fractal features. Then, feature selection algorithms are applied to determine suitable feature subsets for the recognition process. Feature selection is described as an optimization problem and several approaches including heuristic strategies, greedy and genetic algorithms are compared. As quality measure for feature subsets, the classification rate of the nearest neighbor classifier computed with the leaving-one-out method is used. Genetic algorithms show the best results. Finally, neural networks with error back-propagation as learning paradigm are trained using the selected feature sets. Different network topologies, learning parameters and pruning algorithms are investigated to optimize the classification performance of the neural classifiers. With the optimized recognition system a classification performance of 97.7% is achieved.

[Calciphylaxis of the skin as a sequela of terminal kidney failure. Report and discussion of 3 cases]. / Calciphylaxis der Haut in Folge einer terminalen Niereninsuffizienz. Bericht und Diskussion von 3 Fällen.

Calciphylaxis is a rare syndrome mostly affecting patients with secondary hyperparathyroidism and in some cases with functional protein C or protein S deficiency. Skin lesions begin as superficial painful patches that progress to deep necrotic lesions. The findings are often misdiagnosed as livedo vasculitis and the prognosis is poor. Histopathologically, calcification in the media of small arteries and arterioles with intimal hyperplasia is seen. It is unclear if this morphologic hallmark is pathogenetic. Therapeutically, the calcium-phosphate product should be lowered pharmacologically by an intensified and modified dialysis treatment and parathyroidectomy.

[Ehlers-Danlos syndrome]. / Ehlers-Danlos-Syndrom.

The Ehlers-Danlos syndrome (EDS) comprises a heterogenous group of nine hereditary connective tissue disorders, characterized by hyperelasticity of skin and hypermobility of joints to differing extents. The skin is easily injured and wound healing is delayed. The majority of EDS patients belong to EDS-types I-III. The pathogenesis in these cases is not known, although recent data suggest a role for collagen V. In contrast, the etiology of EDS-types IV, VI and VII has been found. While EDS IV is caused by a mutation in the collagen III gene, in EDS VI a mutation in the lysyl hydroxylase gene is present. In EDS VII, the underlying defect is a mutation in the collagen I gene. The EDS-types V, VII and X are very rare; their symptoms resemble those of EDS-type II.

Computer-supported diagnosis of melanoma in profilometry.

Laser profilometry offers new possibilities to improve non-invasive tumor diagnostics in dermatology. In this paper, a new approach to computer-supported analysis and interpretation of high-resolution skin-surface profiles of melanomas and nevocellular nevi is presented. Image analysis methods are used to describe the profile's structures by texture parameters based on co-occurrence matrices, features extracted from the Fourier power spectrum, and fractal features. Different feature selection strategies, including genetic algorithms, are applied to determine the best possible subsets of features for the classification task. Several architectures of multilayer perceptrons with error back-propagation as learning paradigm are trained for the automatic recognition of melanomas and nevi. Furthermore, network-pruning algorithms are applied to optimize the network topology. In the study, the best neural classifier showed an error rate of 4.5% and was obtained after network pruning. The smallest error rate in all, of 2.3%, was achieved with nearest neighbor classification.

Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells.

OBJECTIVES AND DESIGN: The effects of the mucolytic agents ambroxol and N-acetylcystein (NAC) were studied on the release of histamine, leukotrienes, cytokines and superoxide anions from a variety of cells involved in the pathogenesis of allergic inflammation. SUBJECTS: Mast cells were isolated from human adenoids and skin (n = 5-6). Basophils, monocytes and granulocytes were obtained from Buffy-coat blood obtained from healthy blood donors (n = 4-7) and enriched by density centrifugation. TREATMENT AND METHODS: Ambroxol or NAC were added to the cells for different periods before stimulation with various immunological and non-immunological secretagogues. Histamine release from mast cells, basophils and monocytes was assayed either by radioimmunoassay or spectrofluorometrically. LTC4 (basophils), LTB4 (neutrophil/eosinophil granulocytes or monocytes), IL-4 and IL-13 (basophils) were measured by ELISA. RESULTS: Ambroxol inhibited histamine release by more than 50% from human adenoidal mast cells (1000 microM ambroxol) and skin mast cells (100 microM ambroxol) stimulated by Con A and compound 48/80, respectively. Ambroxol (100 microM) strikingly inhibited anti-IgE induced release of both histamine, LTC4, IL-4 and IL-13 from basophils and reduced both histamine and LTB4 release induced by C5a or Zymosan in monocytes. The drug also reduced LTB4 and superoxide anion production in granulocytes stimulated by zymosan or fMLP. In all cell types studied, ambroxol was more efficacious following a short preincubation (5-15 min) of the drug with the cells before stimulation. In contrast, NAC produced no clear effects on any of the different cell types studied, regardless of the preincubation period, the concentration or the stimulus employed. CONCLUSIONS: Unlike NAC, ambroxol is able to not only inhibit acute mediator release from mast cells and leukocytes but also reduce immunomodulatory cytokine generation from basophils and may have beneficial effects in the treatment of allergic respiratory diseases.

SLS-irritated human skin shows no correlation between degree of proliferation and TEWL increase.

It is well known that cutaneous irritants influence epidermal proliferation but the pathogenesis is poorly understood. Recent investigations have shown that the skin barrier integrity influences the proliferation of the basal keratinocytes. Our question was whether the proliferating activity of keratinocytes is indeed regulated by the degree of skin barrier damage or by a direct toxic action of the irritant on the keratinocytes. Therefore various degrees of skin irritation were induced by the application of 0.1%, 0.5% and 2% sodium lauryl sulphate (SLS) solution to the forearm skin of six healthy volunteers. This experiment was performed to evaluate the relationship between SLS concentration and epidermal proliferation. In a second experiment another 14 volunteers were treated with a single SLS concentration (0.5%) to look for interindividual differences in the patterns of skin reaction and susceptibility to the irritant. Skin barrier function was evaluated by measurements of transepidermal water loss (TEWL) before and after irritation. Punch biopsies were taken after 96 h from exposed areas and from unexposed normal skin. Dividing keratinocytes were identified immunocytochemically using three different monoclonal antibodies: PCNA, MIB 1 and KiS1. Exposure to SLS resulted in concentration-dependent increases in both TEWL and epidermal proliferation. However, no significant correlation could be found between the degree of hyperproliferation and the TEWL changes. The results suggest that epidermal proliferation is modulated by a direct interaction of the surfactant with the keratinocytes and/or by release of mediators rather than the consequence of a barrier disturbance.