[Epidermal barrier disorders in dermatoses]. / Epidermale Barrierestörung bei Dermatosen.

The permeability barrier plays an important role in numerous skin diseases. Particularly well known is the importance of this barrier in eczema. In irritative-toxic contact dermatitis, the first step in the pathogenesis is the disturbance of the permeability barrier by irritative-toxic noxious substances. Only after damage to the barrier is achieved can irritants and allergens penetrate into the living epidermis. In atopic eczema due to an impaired barrier, allergens penetrate from the environment into the skin and cause or worsen the eczema. In psoriasis-the other common chronic inflammatory dermatosis-the role of the permeability barrier is only partly understood. In exanthema, infectious agents or drugs cause systemic inflammation, whereby the inflammation of the skin is followed by a barrier disorder. In principle, disturbed permeability of the skin barrier is present in all inflammatory diseases.

[Aged skin and skin care]. / Altershaut und Hautpflege.

BACKGROUND: Aged skin is the sum of chronological und UV-induced aging. Light-exposed skin is unattractive, with irregular pigmentation, roughness und scaliness. The skin is often dry and itches. METHODS: The present paper provides an overview of diseases of aging skin and describes how to prevent or reduce disease by prophylactic and therapeutic skin care. RESULTS: Aged skin can develop into several skin diseases, e.g., different types of eczema and skin cancer. In the body folds we often find an irritant contact eczema caused by friction from skin to skin, sweating, and urinary and fecal incontinence. In the bedridden, bed sores can also develop. Furthermore, there is a delay in wound healing owing to old age. Use of adequate creams and ointments is very helpful in preventing and improving most skin diseases of mature skin. However, the knowledge of aged people and healthcare professionals about the importance of skin care is low. Older people are often unable to care for their skin because they are lacking the physical and mental ability. CONCLUSION: Healthcare professionals are not sufficiently trained about the value of proper skin care. Adequate studies on the role of skin care and selection of the correct preparation in various aged-related diseases are lacking.

Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis.

Dietary consumption of food supplements has been found to modulate skin functions and can therefore be useful in the treatment of skin aging. However, there is only a limited number of clinical studies supporting these claims. In this double-blind, placebo-controlled study, the effectiveness of the specific bioactive collagen peptide (BCP) VERISOL® on eye wrinkle formation and stimulation of procollagen I, elastin and fibrillin biosynthesis in the skin was assessed. A hundred and fourteen women aged 45-65 years were randomized to receive 2.5 g of BCP or placebo, once daily for 8 weeks, with 57 subjects being allocated to each treatment group. Skin wrinkles were objectively measured in all subjects, before starting the treatment, after 4 and 8 weeks as well as 4 weeks after the last intake (4-week regression phase). A subgroup was established for suction blister biopsies analyzing procollagen I, elastin and fibrillin at the beginning of the treatment and after 8 weeks of intake. The ingestion of the specific BCP used in this study promoted a statistically significant reduction of eye wrinkle volume (p < 0.05) in comparison to the placebo group after 4 and 8 weeks (20%) of intake. Moreover a positive long-lasting effect was observed 4 weeks after the last BCP administration (p < 0.05). Additionally, after 8 weeks of intake a statistically significantly higher content of procollagen type I (65%) and elastin (18%) in the BCP-treated volunteers compared to the placebo-treated patients was detected. For fibrillin, a 6% increase could be determined after BCP treatment compared to the placebo, but this effect failed to reach the level of statistical significance. In conclusion, our findings demonstrate that the oral intake of specific bioactive collagen peptides (Verisol®) reduced skin wrinkles and had positive effects on dermal matrix synthesis.

[Aged-related principles of topical therapy]. / Altersspezifische Prinzipien der topischen Therapie.

Topical therapy should always be adapted to patients' age due to changes in skin physiology. This is particularly applicable when choosing a cream or ointment and the active substances. The expectations for therapy also change with age. The motivation to perform therapy as well as the physical ability to do so also changes with age. Children and elderly patients often need help in applying topical agents. In addition, range and cause of diseases varies considerably within age groups. Finally, the penetration of the active substance from creams and ointments may also change with age.

Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study.

Various dietary supplements are claimed to have cutaneous anti-aging properties; however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of collagen hydrolysate (CH) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind, placebo-controlled trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH or placebo once daily for 8 weeks, with 23 subjects being allocated to each treatment group. Skin elasticity, skin moisture, transepidermal water loss and skin roughness were objectively measured before the first oral product application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo. After 4 weeks of follow-up treatment, a statistically significantly higher skin elasticity level was determined in elderly women. With regard to skin moisture and skin evaporation, a positive influence of CH treatment could be observed in a subgroup analysis, but data failed to reach a level of statistical significance. No side effects were noted throughout the study.

Expression of antimicrobial peptides and toll-like receptors is increased in tinea and pityriasis versicolor.

In superficial tinea and pityriasis versicolor, the causative fungi are for the most part confined to the stratum corneum which is barely reached by leukocytes. Therefore, a role of non-cellular components in the epidermal antifungal defence was suggested. To investigate the presence of such factors in these infections, the expression of human beta defensins 2 and 3 (hBD-2, hBD-3), RNase 7, psoriasin, toll-like receptors 2, 4 and 9 (TLR2, TLR4 and TLR9) and dectin 2 was analysed by use of immunostainings in skin biopsies. We found that hBD2, hBD3, psoriasin, RNase7, TLR2 and TLR4 were significantly more often expressed in distinct layers of lesional epidermis as compared with uninfected epidermis. In both infections but not in normal skin, hBD2 and hBD3 were commonly expressed within the stratum corneum and in the stratum granulosum. Similarly, psoriasin was seen more often in the upper skin layers of both infections as compared with normal skin. No significant differences between normal and infected skin were found for the expression of TLR9 and dectin 2. Our findings clearly show the expression of specific antimicrobial proteins and defence-related ligands in superficial tinea as well as in pityriasis versicolor, suggesting that these factors contribute to fungal containment.

Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.

BACKGROUND: Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD. OBJECTIVE: This study elucidates the mode of action of topical BM and pimecrolimus cream in AD. METHODS: Lesional AD skin samples after topical treatment with either BM or pimecrolimus were subjected to gene expression profile analysis. RESULTS: Betamethasone valerate resulted in a significant reduction in mRNA levels of genes encoding markers of immune cells and inflammation, dendritic cells, T cells, cytokines, chemokines, and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. CONCLUSION: The gene expression profiles are consistent with our previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Corticosteroids are still the main treatment for severe and acutely exacerbated AD; pimecrolimus may be preferable for long-term treatment and stabilization.

[New insights into the pathogenesis of sensitive skin]. / Neue Erkenntnisse zur Pathogenese der empfindlichen Haut.

Many persons in the developed countries report sensitive skin. Persons with sensitive skin have a predisposition to several skin diseases, most importantly dry skin, but also atopy, seborrheic dermatitis, acne vulgaris, rosacea, and perioral dermatitis. Their complaints may be triggered by environmental factors such as low temperature, wind, high temperature, sun exposure and stress. Various skin care products and cosmetics are not tolerated. A disturbed skin barrier function and reduced stratum corneum water content are most important in the pathophysiology of sensitive skin. Environmental factors and cosmetics may induce irritation of the skin because of the disturbed skin barrier. Of further importance for the pathogenesis are neurogenic factors including stress and hyper-excitability. Mechanisms in signal transduction involve cytokines and neurotransmitters, but the exact pathways are unknown.

[Diaper dermatitis]. / Windeldermatitis.

Diaper dermatitis is one of the most common skin diseases during infancy and childhood. It is a type of irritant contact eczema resulting from a complex interaction between urine and feces under occlusive conditions in combination with the hyperhydration of the stratum corneum, pressure and friction under the diaper. These conditions pave the way for Candida albicans infection, which is often associated with diaper dermatitis. The anogenital region can be involved by a variety of dermatoses, so a precise skin examination, detailed history and sometimes histologic examination are needed for a precise diagnosis. Therapeutically, frequent diaper changes and adequate skin care are most important.

Malignant melanoma and Wiedemann-Beckwith syndrome in childhood.

Patients with Wiedemann-Beckwith syndrome (WBS, MIM 130650), a congenital overgrowth syndrome, have a known increased tumor risk especially for embryonic tumors. WBS belongs to the "imprinting" syndromes caused by overexpression of IGF2 and/or loss of CDKN1C on chromosome 11p15.5. A 13-year-old boy with WBS developed a spitzoid malignant melanoma (Clark level V, Breslow index 4.8 mm) on the right cheek. Genetic analyses of the patient's blood showed hypermethylation at the H19 locus on chromosome 11p. The (epi)genetic changes of the WBS locus might have played a role in the pathogenesis of melanoma development.

The skin's barrier.

The skin provides an effective barrier between the organism and the environment, preventing the invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes. In this review we provide an overview of several components of the physical barrier, as well as how barrier function is regulated and altered in association with dermatoses. The physical barrier localized primarily in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains. The nucleated epidermis, with its tight, gap and adherens junctions, additional desmosomes and cytoskeletal elements, also contributes to the barrier. Lipids are synthesized in the keratinocytes during epidermal differentiation and are then extruded into the extracellular domains, where they form lipid-enriched extracellular layers. The cornified cell envelope, a robust protein/lipid polymer structure, is located below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides A and B, forming the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC, are covalently bound to cornified envelope proteins. Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils. Cytokines, cAMP and calcium influence the formation and maintenance of barrier function. Changes in lipid composition and epidermal differentiation lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis. A disturbed skin barrier is an important component in the pathogenesis of contact dermatitis, ichthyosis, psoriasis, and atopic dermatitis.

Presumptive frequency of, and review of reports on, allergies to household gloves.

BACKGROUND: Allergies to latex or 'rubber chemicals' in medical or other occupationally used gloves are not uncommon. In contrast, very few articles have reported on latex allergy (type I) or allergic contact sensitization to additives (type IV) associated with household gloves, in spite of some 44 million pairs sold in Germany in, e.g., 2006. OBJECTIVE: We seek to determine the frequency of allergies to household gloves by providing own data and we reviewed the literature. METHODS: The study was based on 105083 consultations of patients with suspected contact allergy (Type IV) in the Information Network of Departments of Dermatology (IVDK) in Germany in the years 1995 to 2006 and on the PubMed databases (last access 7/2008). RESULTS: 1221 patients were identified in whom protective gloves were considered as a possible cause of contact dermatitis and who did not work in occupations associated with above average risk of contact allergy to rubber chemicals. In 178 cases positive reactions to rubber components were reported, while 13 additional cases reacted only to a previously used rubber glove brand, but not to commercial allergens. In the literature only two publications on type I and two on type IV reactions were found in which allergies to rubber household gloves were explicitly reported. CONCLUSIONS: Allergies to rubber household gloves seem to be rare. Factors presumably counteracting contact sensitization by household gloves, compared to occupational use, comprise short intermediate use, loose fitting and the incorporation of e.g. an inner cotton surface reducing skin contact with rubber chemicals.

Protection against dryness of facial skin: a rational approach.

Facial skin is unique in that it gets far more exposure to the external environment than skin on other areas of the body and paradoxically, because it contains the thinnest epidermis and stratum corneum, especially on the eye lid. Environmental attacks contribute to drying of facial skin and damage to the stratum corneum. In recent years, there has been an explosion of new products that contain ingredients that claim to benefit facial skin and protect against environmental damage. This review critically examines the scientific basis, rationale and evidence for inclusion of these ingredients in products for protection of facial skin.

The role of emollients in the management of diseases with chronic dry skin.

Dry skin is a common skin condition as well as a key aspect of a number of diseases such as atopic dermatitis and psoriasis but also of other diseases and systemic conditions. Dry skin has an impact on the patient in terms of discomfort, pruritus and impaired quality of life. Within the overall treatment regimen for these diseases, the use of emollients to manage dry skin plays a considerable role in managing skin conditions. In atopic dermatitis and psoriasis, emollients help to improve skin condition and to reduce pruritus alongside more potent pharmacological agents. It is important to choose an emollient that not only soothes and rehydrates the skin but also offers numerous other dermatological supporting roles, especially induction of proper epidermal differentiation. This review will explain the role of emollients within the management of diseases with dry skin as a major symptom and the components of an ideal emollient.

[Rational treatment of first-degree burns]. / Rationale Behandlung von Patienten mit Verbrennungen 1. Grades.

First-degree burns are the most common type of burn, but are often inadequately treated. The methods of treatment and the course of healing are poorly documented owing to the fact that first-degree burns are generally not considered to be a serious injury. First-degree burns can be caused by thermal injury or UV irradiation (sunburn). The pathophysiology and the therapeutic approach are similar, although the damage follows a different time course for each injury--immediate damage after contact with hot objects, liquids or fire, delayed damage after sun exposure. After initial cooling with water, aqueous emulsions with small amounts of well-tolerated lipids (O/W emulsions) are best suited for treating first-degree burns or sunburn. Water evaporates producing cooling and reducing inflammation; the lipids accelerate the repair of the damaged skin barrier and reduce drying. Foam sprays and lotions are ideal because they are easy and painless to apply. The use of topical corticosteroids is not recommended, as superiority to the vehicle has not been shown.

[Therapy of atopic dermatitis]. / Therapie des atopischen Ekzems.

Atopic eczema is one of the most common diseases in dermatology. Patients suffer from both the chronic relapsing skin disease and the associated emotional stress. Itching and visible lesions on the face and hands are the most unpleasant features for many often young patients, seriously reducing their quality of life. New therapeutic approaches have changed the management of atopic eczema in recent years. Relatively potent new drugs with fewer side effects than corticosteroids help to control the disease. This review focuses on the basic principles of modern atopic eczema treatment, emphasizing basic emollient therapy and topical therapy with calcineurin inhibitors.

Intraoral lesions associated with sebaceous nevus syndrome.

The sebaceous nevus syndrome describes the rare association of a sebaceous nevus with systemic features such as mental retardation, seizures and colobomas (among others). It is thought to be a cutaneous mosaic inherited as a paradominant trait. Three cases are provided illustrating the intraoral manifestations of the syndrome. The first histological comparison of contiguous mucosal and cutaneous lesions is provided. We also describe the possible association of SFM syndrome with a benign fibrous histiocytic lesion of the mandible. This and other mandibular tumors associated with the sebaceous nevus syndrome may have significant implications for patients. Awareness of the potential presence or development of significant intraoral lesions in association with the sebaceous nevus syndrome is important for those involved in the care of patients with this syndrome.

Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration.

In this study we analyzed the proteolytic activity of MMP-19 and its impact on keratinocyte migration. In the HaCaT keratinocyte cell line overexpressing wild-type MMP-19 (HaCaT-WT), transmigration through fibrin and type IV collagen matrices was significantly increased compared to cells harboring a catalytically inactive mutant (HaCaT-EA). Studying the expression of MMP-19 in early stages of squamous cell cancer (SCC), we found co-localization of MMP-19 and laminin 5 at the invading tumor front but not in suprabasal epidermis of the tumor. Examination of laminin 5 processing revealed increased processing of the gamma2 chain in the medium and matrix of HaCaT-WT cells and degradation by recombinant human MMP-19 to 105-kDa and 80-kDa fragments. Parental HaCaT grown on the matrix of HaCaT-WT and HaCaT-EA cells displayed differential tyrosine phosphorylation. Using integrin blocking and stimulating antibodies we could attribute these differences to a shift from beta4-integrin-dependent signaling on the HaCaT-EA matrix toward alpha3-integrin-dependent signaling on the HaCaT-WT matrix. As a consequence, parental HaCaT showed increased migration on the matrix of HaCaT-WT cells. These data suggest that the MMP-19-dependent processing of the gamma2 chains leads to the integrin switch favoring epithelial migration and that MMP-19 actively participates in the early stages of SCC invasion.