[Challenges in neonatal dermatology : An introduction]. / Besonderheiten und Herausforderungen der neonatalen Dermatologie : Eine Einführung in die Problematik.

In order to support dermatologists' interest for the fascinating area of neonatal dermatology, we provide (1) an introduction to the specifics of skin barrier in premature and full-term neonates as well as their clinical implications and (2) an example of age-dependent differential diagnoses and approach to a facial vascular stain in a neonate.

Use and Cutaneous Side Effects of Skin Antiseptics in Extremely Low Birth Weight Infants - A Retrospective Survey of the German NICUs.

UNLABELLED: Background Nosocomial infections are a serious problem in the treatment of extremely low birth weight infants (ELBW, <1 000 g). In these patients, effective skin antisepsis is critical to prevent hospital-acquired infections and their sequelae. However, serious side effects of topical antiseptics have been repeatedly reported in extremely preterm infants and no agreement has been reached on the best product in this population. Therefore, we conducted a survey of the German NICUs aiming to investigate current practices and safety of topical antiseptics in ELBW neonates. METHODS: We sent anonymized questionnaires to 166 German NICUs with the highest level of care. RESULTS: Usable questionnaires were returned by 64 NICUs (39%). These NICUs had treated a total of 2130 patients with a birth weight<1 000 g in 2012. Octenidine without phenoxyethanol (OwPh) and Octenisept(®) were the predominantly used skin antiseptics for intensive-care procedures. At least one skin complication was reported by 27% (n=17) of the NICUs. In 9 cases Octenisept(®) was used, and in 6 cases octenidine was used. CONCLUSIONS: According to our knowledge, this is the first study surveying practices and safety of skin antisepsis in ELBWs in the German NICUs. Most German NICUs use octenidine, however, in different preparations. Skin complications including blistering, necrosis and scarring were seen with all octenidine products, a fact which has not been previously reported.

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

[Connective tissue diseases in adolescents]. / Kollagenosen bei Jugendlichen.

In this article we provide a brief review of systemic lupus erythematosus, juvenile dermatomyositis, systemic scleroderma, and mixed connective tissue disease in adolescents. As skin manifestations often belong to the presenting symptoms and may have a significant impact on the quality of life, dermatologists play an important role in the management of patients with connective tissue diseases. Early diagnosis and therapy onset are crucial for the patients' long-term outcome.

[Parallels between wound healing, chronic inflammatory skin diseases and neoplasia: clinical aspects]. / Parallelen zwischen Wundheilung, chronisch entzündlichen Dermatosen und Neoplasien: Wissenswertes für die Praxis.

Chronic wounds, scars, burns and recalcitrant chronic inflammatory skin lesions can give rise to malignancy. These neoplasias are usually squamous cell carcinomas but basal cell carcinomas can also develop. Tumorigenesis is a severe complication of chronic ulcers as well as certain inflammatory skin diseases; early diagnosis is critical for prognosis. This article describes parallels between wound healing, chronic inflammatory skin diseases and carcinogenesis and provides advice on practical aspects of diagnosis and therapy.

Two cases of lupus vulgaris in childhood and review of the clinical challenges.

BACKGROUND: Lupus vulgaris (LV) is the most common form of cutaneous tuberculosis (TB) in Europe, nevertheless the overall incidence is low. It constitutes about 1.5% of all extra-pulmonary cases worldwide. A slight raise in TB incidence rates among children was recently registered in Germany, which can be explained by the increased immigration. PATIENTS AND METHODS: We present 2 cases of immigrated children who were diagnosed with Lupus vulagris, both clinically and histopathologically. Although the symptoms and the duration of the skin lesions were very different, both patients had a non-healing skin ulceration.In our cases cultures of the skin biopsy were positive for Mycobacterium tuberculosis and the lesions showed marked improvement in response to antituberculous treatment. In the first patient, it took 6 years between occurrence of skin lesions and final diagnosis. The second patient had an extracutaneous focus, namely abdominal TB. CONCLUSION: We report our experience and emphasize on recent advances in the diagnosis and treatment of paediatric skin TB.

Dermal absorption of permethrin following topical administration.

OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabies patients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.

Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue.

In recent years, the exposure of human skin to environmental and artificial UV irradiation has increased dramatically. This is due not only to increased solar UV irradiation as a consequence of stratospheric ozone depletion, but also to inappropriate social behaviour with the use of tanning salons still being very popular in the public view. Besides this, leisure activities and a lifestyle that often includes travel to equatorial regions add to the individual annual UV load. In addition to the common long-term detrimental effects such as immunosuppression and skin cancer, the photo-oxidative damage due to energy absorption of UV photons in an oxygenized environment leads to quantitative and qualitative alterations of cells and structural macromolecules of the dermal connective tissue responsible for tensile strength, resilience and stability of the skin. The clinical manifestations of UV/reactive oxygen species (ROS)-induced disturbances result in photoaged skin with wrinkle formation, laxity, leathery appearance as well as fragility, impaired wound healing capacities and higher vulnerability. Strategies to prevent or at least minimize ROS-induced photo-ageing and intrinsic ageing of the skin necessarily include protection against UV irradiation and antioxidant homeostasis.

Solar UV irradiation and dermal photoaging.

The skin is increasingly exposed to ambient UV-irradiation thus increasing risks for photooxidative damage with long-term detrimental effects like photoaging, characterized by wrinkles, loss of skin tone and resilience. Photoaged skin displays alterations in the cellular component and extracellular matrix with accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) which deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in clinical and biochemical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be briefly discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS-induced photoaging.

Liver cytochrome P450 CYP1A2 is markedly inhibited by systemic but not by bath PUVA in dermatological patients.

BACKGROUND: Methoxsalen (8-MOP) may cause important pharmacokinetic drug interactions as it has been shown to inhibit and/or induce several drug-metabolizing enzymes in vitro, in animal models and in humans. OBJECTIVES: In order to assess the clinical importance of acute and chronic 8-MOP effects on the liver cytochrome P-450 enzyme CYP1A2 in vivo, we measured caffeine clearance in dermatological patients before the onset of systemic or bath psoralen + ultraviolet A radiation (PUVA) (8-MOP + UVA) therapy, on the first day and after 1 week of treatment. METHODS: Data from four patients with systemic PUVA and seven patients with bath PUVA were available (age range 23-71 years, five women and six men). RESULTS: For all of the patients, individual pre-PUVA caffeine clearance values were above the lower limit of previously assessed reference ranges. Systemic PUVA markedly decreased caffeine clearance by factors of 0.17 [90% confidence interval (CI) 0.07-0.42] on the first day and 0.14 (90% CI 0.05-0.36) after 1 week of treatment, respectively, and values thus dropped below the reference ranges. In contrast, bath PUVA had no obvious effect on pre-PUVA clearance values as the latter changed by factors of 1.00 (90% CI 0.81-1.23) and 1.05 (90% CI 0.75-1.49) on the first day and after 1 week of treatment, respectively. CONCLUSIONS: Systemic PUVA causes pronounced inhibition of liver CYP1A2, while bath PUVA has no such effect. The extent of interaction makes a dose adjustment for most CYP1A2 substrates such as theophylline mandatory in patients undergoing systemic PUVA.

Problems and perspectives of phenotyping for drug-metabolizing enzymes in man.

Pronounced interindividual differences in drug disposition are mainly caused by differences in the activity of liver drug-metabolizing enzymes. These depend on known and unknown covariates, including genetic as well as environmental factors. Phenotyping, i.e. assessment of enzyme activities in vivo after administration of a test dose, seems to be a promising tool for determining actual metabolic capacities. Although it is a well-established experimental approach, phenotyping has not yet found its way into clinical practice. Main reasons for this are lack of validation for many probes and assays used, complicated procedures, invasiveness, semi-quantitative test results, non-compliance on behalf of the subjects tested, high costs, and lack of prospective clinical studies to assess the benefit of phenotyping for patients. Problems and perspectives of phenotyping are exemplified for the cytochrome P-450 enzymes CYP1A2 and CYP3A4, two major human drug-metabolizing enzymes.

Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test.

A pronounced variability limits the usefulness of CYP1A2 phenotyping for drug therapy, for evaluating liver function, and for assessing the role of this enzyme in carcinogenesis. To identify and quantify sources of this variation, we estimated CYP1A2 activity in 863 healthy Caucasians using caffeine clearance derived from saliva concentrations before and 5-7 h after a caffeine test dose. Data from 786 individuals were eligible for evaluation (mean age 39 years, 415 women including 94 taking oral contraceptives, 401 non-smokers). Overall geometric mean (geometric SD) caffeine clearance was 1.34 ml min(-1) kg b.w.(-1) (1.65). The effect of the following covariates was evaluated by analysis of covariance: age, sex, oral contraceptives, body height, body weight, body mass index, number of cigarettes smoked, tar exposure from smoking, several indices of dietary caffeine consumption, intake of sauerkraut, and country of residence (Germany, Bulgaria or Slovakia). Estimated changes relative to arbitrarily defined basal caffeine clearance (male, non-smoking, German resident) exerted by significant (P < 0.05) covariates were: coffee, 1.45-fold per litre of coffee drunk daily; body mass index, 0.99-fold per kg m(-2); smoking, 1.22-fold, 1.47-fold, 1.66-fold, and 1.72-fold for 1-5, 6-10, 11-20, and > 20 cigarettes smoked per day, respectively; oral contraceptives, 0.72-fold; country of residence, 0.81-fold and 0.74-fold for Bulgaria and Slovakia, respectively; female, 0.90-fold. These covariates explained 37% of overall variation. The 95% confidence interval of individual clearance was 0.46-2.20 times the predicted value. No relevant polymorphism was found for CYP1A2 activity when adjusted for covariate effects.