[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.

Ultraviolet irradiation induces acute changes in melanocytic nevi.

Ultraviolet (UV) light represents one of the factors that might play a role in the initiation and promotion of malignant transformation of human melanocytes. To determine the short-term effects of UV irradiation on melanocytic nevi in vivo, we investigated one half of symmetric melanocytic nevi after a single UV exposure with double the patient's minimal erythema dose. This half was compared with the nonirradiated, shielded half of the same nevus. The different parts were examined histologically for differences and immunohistochemically for the presence of HMB-45 antigen and proliferating cell nuclear antigen. The features were assessed quantitatively by image analysis. One week after the single UV irradiation, we observed a significant increase of suprabasally located melanocytes and a markedly enhanced expression of HMB-45, whereas proliferative activity of the cells was unchanged. In nevi that were excised 2 or 3 weeks after irradiation, no significant differences were observed between the irradiated and the nonirradiated part. The results indicate that a single UV irradiation may induce transient melanocytic activation with morphologic and histologic changes. Although these data do not formally assess resemblance to melanoma, these changes may be similar to those of melanoma in situ.

Surfactant-induced stratum corneum hydration in vivo: prediction of the irritation potential of anionic surfactants.

After repeated contact, many surfactants will cause skin irritation and, especially, dryness and scaliness. Earlier in vitro investigations suggested that the irritation potential of anionic surfactants was related to the induction of hydration of isolated stratum corneum membranes. We have now investigated early surfactant-stratum corneum interaction in vivo. Sodium salts of n-alkyl sulfates with variable carbon chain length (n = 8-14) were tested for the promotion of stratum corneum hydration by measurements of skin surface water loss and electrical capacitance measurements in healthy adult human volunteers. The surfactant-induced increase in water uptake was confirmed in vitro by means of isolated stratum corneum samples and surfactant solutions labeled with tritiated water. In a parallel experiment the irritation potential of these compounds was investigated by 24-h patch testing in human volunteers. The irritant responses were quantified non-invasively by erythema (skin color reflectance measurements) and transepidermal water loss measurements. Hydration of stratum corneum exposed for 5 min to surfactant solutions significantly exceeded that of controls (phosphate-buffered saline). It increased with application time and was concentration dependent, saturable with increasing concentration, and rapidly reversible. Baseline hydration was re-established only 10-15 min after treatment termination. Induction of hydration was closely correlated with the irritation potential of the investigated compounds. It initially increased with increasing carbon chain length. The maximum response was obtained for the C12 analogue (sodium lauryl sulfate). With further increases in molecular size induction of stratum corneum hydration subsequently decreased. We have demonstrated that anionic surfactants increase stratum corneum hydration in vivo. The present results suggest that the mechanisms responsible for the hydration are related to the irritation properties of these compounds.

Altered x-ray diffraction pattern is accompanied by a change in the mode of cross-link formation in lipodermatosclerosis.

We studied the molecular packing of collagen fibrils by x-ray diffraction in skin specimens of patients with lipodermatosclerosis and in controls. A difference in the tilt angles of the collagen molecules relative to the fiber axis is suggested by a D-stagger that is 1 nm larger in sclerotic skin than in normal skin. In parallel, the collagen cross-links in the skin specimens were analyzed, and a marked increase of both hydroxylysylpyridinoline and lysylpyridinoline, the trivalent mature cross-links characteristic of skeletal tissues, was found. The content of hydroxylysylpyridinoline and lysylpyridinoline was higher in the deep layer of the affected dermis than in the superficial dermis. This increase was always accompanied by an increase in the hydroxylysylpyridinoline/lysylpyridinoline ratio, suggesting that hydroxylysylpyridinoline is a sclerosis-associated cross-link. In addition, lysyl hydroxylation was increased in affected skin, and this increase was apparently restricted to the collagen telopeptides, which are crucial anchoring structures for lysyl dependent cross-links.

Investigations on plasma levels of mast cell mediators in acute atopic dermatitis.

Skin mast cells have been proposed to be involved in the pathogenesis of acute and chronic phases of atopic dermatitis (AD). The aim of the present study was to investigate the significance of different mast cell mediators during acute exacerbation of this frequent skin disease. Plasma levels from 19 patients with AD were screened for elevation of the mast cell-specific protease tryptase, the biogene amine histamine, and the arachidonic acid metabolite prostaglandin D2. None of the patients showed elevated plasma levels of these three mediators, whereas the mean serum IgE level was strongly elevated. We conclude that the investigated mediators are either only active on the cutaneous level or that other mediators are responsible for the development of the acute eczematous and pruritic skin reactions. Alternatively, the assays could have been insufficiently sensitive since some studies have demonstrated increased plasma histamine levels, e.g. after food challenge of such patients.

Angiolymphoid hyperplasia with follicular mucinosis.

Follicular mucinosis is described to our knowledge for the first time in angiolymphoid hyperplasia. In general, follicular mucinosis may be regarded as a peculiar, nonspecific histological reaction pattern in follicular epithelium that may occur on its own or in association with other pathological processes, particularly lymphomas. The unusual and characteristic features of angiolymphoid hyperplasia revealed by electron microscopy are irregular vessels lined by atypical endothelial cells with convoluted nuclei and large cytoplasmic vacuoles.

Monocytic leukemia. Clinically appearing as 'malignant reticulosis of the skin'.

Enzyme cytochemical (hydrolytic enzymes for cell differentiation), immunocytologic (B and T lymphocyte differentiation), and electron microscopic studies of skin infiltrates facilitate the proper diagnosis of myelomonocytic and lymphoreticular proliferations. With use of these methods, the original clinical diagnosis of malignant reticulosis of the skin was corrected to monocytic leukemia in a 65-year-old woman. Because primary involvement of the skin preceded monocytosis of the blood, it was concluded that the cutaneous infiltrates in our patient resulted from proliferation of tumor cells in the skin rather than from homing of the cells to, or settling of the cells in, the skin.

Localized and disseminated pagetoid reticulosis. Diagnostic immunophenotypical findings.

Pagetoid reticulosis (PaRet) is a rare skin disease with an intraepidermal infiltrate of atypical lymphocytes. We performed phenotypic studies on two patients with classic localized PaRet (Woringer-Kolopp disease) and one patient with the disseminated type (Ketron-Goodman disease) and compared these with all published reports of cases; both variants show intraepidermal, highly activated, proliferating T cells with variable loss of pan-T-cell antigens, contrasting with nonactivated dermal reactive T cells. This pattern is unique among cutaneous lymphomas and can be used for diagnosis. Despite the fact that localized PaRet does not show a malignant course, recent genotypic analysis of one patient showed monoclonality. Comparable constellations are found in other diseases like lymphomatoid papulosis, which also represent monoclonal disorders of activated T cells with a benign course. To unify these seeming discrepancies, we introduce the concept of "benign cutaneous lymphomas."

Congenital multiple plaquelike glomus tumors.

We encountered two patients with congenital multiple plaquelike glomus tumors. These lesions were present at birth and enlarged with body growth, attaining a diameter of up to 13 cm. The diagnosis was confirmed by histologic and electron-microscopic examination, which revealed the typical changes of glomus tumors. Immunocytochemistry findings demonstrated the tumor cells to be vimentin- and alpha-smooth muscle-actin-positive and desmin-negative. On ultrastructural examination, typical dense bodies and attachment plaques were easily found within the tumor cells. Glomus cells were coated by a thick basal lamina.

Inhibition of interleukin-4 and interleukin-13 release from immunologically activated human basophils due to the actions of anti-allergic drugs.

Human basophils have recently been shown to rapidly produce and release interleukin (IL-)4 and IL-13 as well as histamine and eicosanoids. Since both IL-4 and IL-13 can initiate and maintain late phase allergic reactions we addressed whether some widely used anti-allergic drugs can inhibit the anti-IgE induced release of these cytokines from enriched human basophils. Basophils were enriched (47-92% purity) by Ficoll density centrifugation followed by elutriation and negative selection of contaminating cells using immunomagnetic beads. Basophils were stimulated with sub-optimal dilutions of anti-IgE in the presence or absence of various drugs and the release of histamine and cytokines were measured after 30 min and 4 h, respectively. The beta-2 agonist salmeterol, the H1-receptor antagonist terfenadine and the phosphodiesterase inhibitor theophylline inhibited the release of IL-4 and IL-13 by more than 50% following 4 h of basophil stimulation with anti-IgE. These drugs also inhibited the release of histamine following 30 min stimulation, although with less efficacy than for IL-4 and IL-13. Short preincubation of basophils with salmeterol or terfenadine before stimulation gave rise to significantly greater inhibition of histamine release but had less effect on the inhibition of cytokine release. The effects of theophylline, however, were not significantly affected by preincubation of the cells with the drug. In contrast to the aforementioned drugs, salbutamol and cetirizine were ineffective at inhibiting both histamine and cytokine release from basophils. These results suggest that a number of anti-allergic drugs may mediate their effects, in part, in reducing late phase allergic responses due to their actions on IL-4 and IL-13 secretion from basophils.

Cutaneous pseudolymphoma at the site of prior herpes zoster eruption.

A 55-year old woman with a history of herpes zoster in the dermatome supplied by the mandibular branch of the trigeminal nerve developed cutaneous red papules and umbilicated nodules within the same segment. The clinical and histological diagnosis was pseudolymphoma. The lesions showed a polymorphous infiltrate without germinal center formation. Immunologic phenotyping with monoclonal antibodies revealed the predominance of helper T cells and distinct compartmentalization of B and T cells. The lesions healed up within 7 weeks. The development of pseudolymphomas at the site of previous herpes zoster eruptions seems to be extremely rare.

Steatocystoma multiplex: anatomic reevaluation, electron microscopy, and autoradiography.

Histologic and electron-microscopic features of steatocystoma multiplex were investigated. Specimens from 25 patients (8 females, 17 males) were serially cut and three-dimensional drawings constructed. Steatocystoma multiplex is a nevoid sebaceous duct and sebaceous gland tumor, originating from sebaceous follicles, but is not a dermoid tumor. One pilary unit continuously produces vellus hairs, which are trapped in the cystic cavity or in the pilary canal (trichostasis). Steatocystoma multiplex is connected to the epidermis by a straight or meandering epithelial cord, the remnant of the follicular infundibulum. This infundibulum is a more or less solid strand, often containing sebocytes or sebaceous lobulelike structures. A lumen, partly present in a few areas of the cord, is filled with cellular debris of keratinocytes, corneocytes, sebocytes, or trapped hairs. Steatocystoma multiplex has electron-microscopical features similar to the sebaceous duct and sebaceous glands of sebaceous follicles. The 3H-thymidine labeling index of the cyst wall with or without sebaceous acini is lower than in sebaceous follicles. Steatocystoma multiplex suppurativum, characterized by spontaneous rupture of the cyst, inflammation and scarring, mimics acne conglobata with hidradenitis-suppurativa-like lesions as seen in the acne triade or tetrade.

[Erythema elevatum diutinum. I. Electron microscopy of a case with extracellular cholesterosis (author's transl)]. / Erythema elevatum diutinum. I. Elektronenmikroskopie eines Falles mit extracellulärer Cholesterinose.

1. A typical case of Erythema elevatum diutinum (E.e.d.) with extracellular cholesterosis is described clinically and histologically in a 48-year-old woman. The disease had a course of 15 years. 2. Electron microscopy confirmed the histological and immunfluorescent findings of leucocytoclastic vasculitis. In older lesions, histiocytes/macrophages predominate. Intra- and extracellular lipid depositions showed a variety of ultrastructural characteristics which differed from electron microscopical findings described in other disorders associated with lipid deposition. 3. The findings are in accordance with the hypothesis that the primary event in E.e.d. is a special type of chronic leukocytoclastic vasculitis. Subsequently, the damage of the vessel walls and focal necrosis may lead to secondary lipid deposition.

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.

[Erythema elevatum diutinum. II. Immunoelectronmicroscopical study of leukocytoclastic vasculitis within the intracutaneous test reaction induced by streptococcal antigen (author's transl)]. / Erythema elevatum diutinum. II. Immunelektronenmikroskopische Untersuchung der leukocytoklastischen Vaskulitis in einer Intrakutanreaktion mit Streptokokkenantigen.

A leukocytoclastic vasculitis was induced by intracutaneous injection of streptococcal antigen in a patient with erythema elevatum diutinum (E.e.d.). The immunoelectronmicroscopical demonstration of C3 was performed by use of the peroxidase-antiperoxidase multistep technique 24 h after the injection of the antigen. Deposits of C3 were found between endothelial cells, on the outer surface of endothelial cells, pericytes, and smooth muscle cells, as well as within the multilayered basal lamina of small vessels. Intact and disintegrating neutrophils accumulate within the vessel walls and in their surroundings. Necrosis and fibrin deposition are present in advanced stages. The findings demonstrate the sequence of events in leukocytoclastic vasculitis at the ultrastructural level. They also support the hypothesis that in E.e.d. an Arthus type reaction induced by bacterial antigens may be of pathogenetic significance.

Analysis of the age-related composition of human skin collagen and collagens synthesized by fibroblast culture.

Age-related differences in the composition and the post-translational modifications of human skin collagens were examined in the present study. The data were compared with results of collagen synthesis from in vivo-aged fibroblasts in culture. Skin extracts and newly synthesized collagen from fibroblast cultures derived from both old and young donor groups showed the same ratio of collagen III to collagen I. Furthermore, no difference was noted in the degree of prolyl and lysyl hydroxylation of collagen I and collagen III Young and old fibroblasts synthesized a similar quantity of collagen in vitro. The data suggest that fibroblasts maintain a uniform level of collagen production, composition and modification independent of the age of the donor.

Influence of phospholipid liposomes (PLL) on UVB-induced erythema formation.

Application of liposomal phospholipids (Natipide II) caused a significant decrease in erythema induced by UVB (280-312 mm) in patients with skin types II and III (n = 31). In accordance with findings in other organs, e.g. liver, the present findings suggest that phospholipids are capable of reducing H2O2 formation and/or increasing glutathione synthesis in human skin, thus reducing erythema formation by preventing oxidative stress.

Effects of basophil-priming and stimulating cytokines on histamine release from isolated human skin mast cells.

Cell priming and stimulation of different cytokines (which include chemokines and growth factors) are typical features of human basophils. Recently, it has been shown that the macrophage chemotactic protein-1 (MCP-1), RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are potent direct secretagogues for human basophils and that interleukin-3 (IL-3), IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are priming factors for subsequent potentiation of mediator release from basophils induced by different stimuli. This observation may be clinically important for the activation and recruitment of inflammatory cells in different immune responses of the skin (e.g. late-phase reactions). The aim of the present study was to investigate whether cytokines and chemokines are also capable of priming or stimulating isolated human skin mast cells (SMC). SMC were either stimulated directly with the cytokines alone or preincubated with these factors for 10 min before being activated with suboptimal concentrations of anti-IgE, A23187 or substance P. IL-3, IL-5, GM-CSF, platelet factor-4 (PF-4), IL-8, MCP-1 and MIP-1 alpha (each at concentrations of 1 ng/ml to 1 microgram/ml, log steps) did not significantly modulate histamine release from SMC induced by the three different secretagogues. RANTES exhibited a weak but significant potentiating effect on IgE-mediated activation. Stem cell factor (SCF) as a positive control was able to prime mast cell histamine release strongly. In addition, PF-4, MCP-1, RANTES and MIP-1 alpha were incapable of inducing direct histamine release from SMC. In experiments with isolated human peripheral basophils, however, we observed potent Fc epsilon RI-mediated priming effects evoked through IL-3, IL-5 and GM-CSF. We conclude that SMC derived from healthy donors are not targets of (immuno)modulatory factors that prime or stimulate basophils.

Autoantibodies to cartilage collagens in relapsing polychondritis.

Relapsing polychondritis is a systemic disease associated with a destruction of cartilage in various parts of the body. Sera from six patients with relapsing polychondritis and one patient with microscopic polyarteritis nodosa as well as from six controls were analyzed by immunoblotting and ELISA. All patients had autoantibodies against native collagens II and IX. The serum from one patient showed a strong reaction with all three collagen chains of the high molecular weight fraction of collagen IX after denaturation; sera from four patients showed autoantibodies against alpha 2 (XI) and sera from three patients showed autoantibodies against the covalently cross-linked gamma component of collagen XI. The presence of autoantibodies against collagens II, IX, and XI, which form the major fibrillar scaffold in cartilage and mediate the interaction of collagen fibrils and proteoglycan, suggests that autoantibodies against cartilaginous collagen may play a crucial role in the pathogenesis of relapsing polychondritis and microscopic polyarteritis nodosa.

Collagen synthesis in (sun-) aged human skin and in fibroblasts derived from sun-exposed and sun-protected body sites.

Endogenous and sun-induced aging of the skin cause distinct morphological alterations. In this study, we have analysed the ratio of collagen III to collagen III plus I in extracts of sun-exposed (face) and sun-protected (abdomen) aged skin, as well as in collagens synthesized by fibroblasts during in vitro culture derived from actinically damaged and sun-protected skin of other subjects (face, medial aspect of the upper arm vs. abdomen, lateral aspect of the forearm). Furthermore, the amount and extent of post-translational modifications of newly synthesized collagens were determined. Chronic sun exposure of the skin does not have an impact on the quantity of collagenous proteins newly synthesized in cell culture. The proportion of collagen III in pepsin extracts of sun-damaged skin is increased relative to sun-protected skin. However, fibroblasts derived from sun-exposed skin synthesize a lower proportion of collagen III than cells from sun-protected skin. The hydroxylation of lysyl residues in newly synthesized alpha 2(I) and alpha 1(III) collagen chains is reduced by UV irradiation, whereas hydroxylation of lysyl residues in alpha 1(I) chains and of prolyl residues in alpha 1(I), alpha 2(I) and alpha 1(III) chains is unaffected by UV irradiation. These data provide circumstantial evidence to indicate that collagen synthesis is influenced independently by endogenous and sun-induced aging.