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To optimize the treatment of acne in Germany, the German Society of Dermatology (DDG) and the Association of German Dermatologists (BVDD) initiated a project to develop consensus-based guidelines for the management of acne. The Acne Guidelines focus on induction therapy, maintenance therapy and treatment of post-acne scarring. They include an evaluation of the most commonly used therapeutic options in Germany. In addition, they offer detailed information on how to administer the various treatments and on contraindications, adverse drug reactions, and drug interactions, taking into account gender and special conditions such as pregnancy and lactation. The Acne Guidelines were developed following the recommendations of the Association of Scientific Medical Societies in Germany (AWMF). The treatment recommendations were developed by an expert group and finalized by an interdisciplinary consensus conference. The first choice treatments for acute acne according to acne type are as follows: 1) comedonal acne: topical retinoids; 2) mild papular/pustular acne: fixed or sequential combinations of BPO and topical retinoids or of BPO and topical antibiotics; 3) moderate papular/pustular acne: oral antibiotic plus BPO or plus topical retinoid, or in a fixed combination 4) acne papulo-pustulosa nodosa and acne conglobata: oral antibiotic plus topical retinoid plus BPO or oral isotretinoin. For maintenance treatment: topical retinoid or its combination with BPO. Particular attention should be paid to compliance and quality of life. Additional treatment options are discussed in the main body of the text.

Background: As a modification of patch testing, the strip patch test was established to obtain more sensitive and reliable test results. Comparative data on diagnostic accuracy for both tests are missing., Objectives: To compare the diagnostic accuracy of strip patch tests and patch tests in detecting sensitizations in patients with suspected allergic contact dermatitis by using patient history as the reference standard., Patients/methods: In a multicentre, prospective, investigator-blinded study 790 patients were enrolled. The defined reference standard was established prior to patch testing. Patch tests were performed with nickel sulfate, potassium dichromate, and lanolin alcohol. Duplicate tests were simultaneously performed on both sides of the back, of which one randomly chosen side was tape stripped beforehand, according to a standardized procedure. Primary outcome was the difference in sensitivity between strip patch test and patch test., Results: Seven hundred and eighty-seven patients were included in the analysis. Strip patch tests detected considerably more sensitization to nickel sulfate and potassium dichromate than patch tests: differences of sensitivities were 16.4% (95% CI, 8.7-24.1%) for nickel sulfate and 25.0% (95% CI, 8.9-41.0%) for potassium dichromate, both favouring the strip patch test., Conclusions: The standardized strip patch test proved to be accurate and clinically safe and is promising to improve diagnosis of allergic contact dermatitis beyond the patch test.

Neutralization of the normally acidic stratum corneum (SC) has deleterious consequences for permeability barrier homeostasis and SC integrity/cohesion attributable to serine proteases (SPs) activation leading to deactivation/degradation of lipid-processing enzymes and corneodesmosomes (CD). As an elevated pH compromises SC structure and function, we asked here whether SC hyperacidification would improve the structure and function. We lowered the pH of mouse SC using two polyhydroxyl acids (PHA), lactobionic acid (LBA), or gluconolactone (GL). Applications of the PHA reduced the pH at all levels of SC of hairless mouse, with further selective acidification of SC membrane domains, as shown by fluorescence lifetime imaging. Hyperacidification improved permeability barrier homeostasis, attributable to increased activities of two key membrane-localized, ceramide-generating hydrolytic enzymes (beta-glucocerebrosidase and acidic sphingomyelinase), which correlated with accelerated extracellular maturation of SC lamellar membranes. Hyperacidification generated "supernormal" SC integrity/cohesion, attributable to an SP-dependent decreased degradation of desmoglein-1 (DSG1) and the induction of DSG3 expression in lower SC. As SC hyperacidification improves the structure and function, even of normal epidermis, these studies lay the groundwork for an assessment of the potential utility of SC acidification as a therapeutic strategy for inflammatory dermatoses, characterized by abnormalities in barrier function, cohesion, and surface pH.

Objectives: To describe methodological issues and strategies relevant to conducting a community-based longitudinal study., Methods: Study participants (N=1117 youth/parent pairs) residing in neighborhoods that were randomly selected using a multistage sampling procedure and 2000 census data. Data were collected annually using in-home, in-person, computer-assisted interviewing methods. Numerous retention methods were used to track and retain participants., Results: The initial response rate was 61%. The retention rate is 97%, and the valid interview completion rate is 93% after nearly 4 waves of data collection., Conclusions: In order for community-based longitudinal studies to overcome barriers to enrollment and retention, particular attention must be given to appropriate planning and available resources.

Background: Youth participation in sexual risk behaviours continues to be a critically important public health topic. Additionally, as youth are frequently being left alone during the day without adult supervision, there are increased opportunities for sexual risk-taking behaviour. This study examined how the relationships of nine youth assets and sexual activity may vary according to the stratification of youth into two groups: self-care and supervised., Methods: Data were collected through at-home, in-person interviews from a random sample of inner-city youth (mean age = 15.4 years; 51.5% female; 48.8% White; 22.4% Black; 18.5% Hispanic; 10% Native American) and their parents (n = 1079 parent/youth pairs). Nine youth assets were analysed using multiple logistic regression. Examples of assets youth may possess are: positive role models, family communication, school connectedness, constructive use of time and aspirations for the future. The item used to assess sexual intercourse was 'Have you ever had sexual intercourse ("done it", "had sex", "made love", "gone all the way")?'. Asset/risk behaviour associations that were unique to one of the two strata were the focus of the study., Results: Thirty-seven per cent of youth spent two or more hours per day home alone. Youth who were supervised had a greater number of unique significant associations between assets and sexual activity than youth who were in the self-care group., Conclusions: Youth in supervised settings may be less likely to participate in sexual activity because of the presence of assets. Certain assets may also be important in deterring sexual activity for youth who are in self-care.

A modern skin care concept involving physiological lipids should be matched to the state of the skin, the season of the year and the presence of dermatoses. Also desirable would be substances that regulate the moisture status and barrier function of the stratum corneum, e.g. glycerin, in relevant concentrations. Of central importance in diseases associated with destruction of the uppermost layer of the skin, for example, neurodermatitis, is regular skin care with moisturizing products and a lipid composition that is as physiological as possible. In addition, the water and lipoid content of the skin care formulation should be matched to disease stage and the season of the year.

Background: The skin is exposed to numerous environmental assaults that can lead to premature aging. Of these agents, perhaps none is more ubiquitous than the ultraviolet (UV) wavelengths of sunlight. The primary immediate defense against environmental skin damage is the antioxidant capacity of the skin. However, this defense system can be compromised by moderate exposure to UV light. Therefore, bolstering the antioxidant defense system of the skin is a potentially important strategy for reducing environmentally induced skin damage., Aim of the Study: This clinical trial was designed to study the efficacy of lutein and zeaxanthin, two potentially important antioxidants found naturally in the skin, upon five skin physiology parameters (surface lipids, hydration, photoprotective activity, skin elasticity and skin lipid peroxidation - malondialdehyde) of human subjects. These xanthophyllic carotenoids were administered either orally, topically, or in combination (both oral and topical routes)., Results: The results obtained indicate that the combined oral and topical administration of lutein and zeaxanthin provides the highest degree of antioxidant protection. However, oral and topical administration of these antioxidants individually also provides significant activity in the skin. In addition, oral administration of lutein may provide better protection than that afforded by topical application of this antioxidant when measured by changes in lipid peroxidation and photoprotective activity in the skin following UV light irradiation., (Copyright 2007 S. Karger AG, Basel.)

Compared with youth of other races/ethnicities, Native American youth (ages 15-19 years) are more likely to have participated in sexual intercourse, thus placing them at greater risk for sexually transmitted diseases (STDs) and unintended pregnancies. This study's purpose was to investigate relationships among protective factors (assets) and sexual intercourse in a Native American youth population. Data were collected from Native American youth and their parents (N=126 youth/parent pairs) living in randomly-selected households using in-person, in-home interview methods. Nine youth assets were the independent variables and never had sexual intercourse was the dependent variable. Data were analyzed using logistic regression. One significant (p<.05) asset main effect and one asset by youth age interaction were found. Youth with the Non-Parental Adult Role Models asset were 3.8 times more likely to have never had sex compared with youth without the asset. Further study of the influence of protective factors among Native American youth is warranted.

Background and Objectives: This study explores youth and parent agreement about conversations on specific topics related to sexual risk behavior and youth-parent relationship. The study's objective was to determine if the amount of agreement was associated with youth sexual behavior., Methods: Data were collected using a computer-assisted data entry system from one parent and one youth in 1,350 randomly selected households in inner-city areas of two Midwestern cities., Results: Youth-parent positive agreement scores about these conversations were significant after controlling for youth age, race, gender, family structure, and parental income and education. Scores were associated with youth abstinence and with the use of contraception if the youth had become sexually active., Conclusions: In this study, youth-parent agreement regarding their communication was associated with positive youth behaviors, including abstinence and the use of contraception if sexually active.

Objective: To investigate the prevalence of human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpesvirus) infection in patients with lymphoproliferative skin diseases such as large-plaque parapsoriasis (LPP) and mycosis fungoides compared with inflammatory cutaneous conditions or healthy control subjects., Design: A survey study was undertaken in 123 subjects with various clinical conditions., Setting: All patients had been seen in the Dermatology Department of the San Gallicano Dermatology Institute, Rome, Italy, in the last 2 years., Patients: Forty-five patients with inflammatory or autoimmune cutaneous diseases, 50 healthy control subjects, 10 patients with LPP, 12 patients with mycosis fungoides, and 6 patients with classic Kaposi sarcoma were included in the study., Main Outcome Measures: The prevalence of HHV-8 infection was investigated with serologic studies using the gold standard assay based on body cavity-based B-cell lymphoma-1 cells latently infected with HHV-8. The presence of HHV-8 conserved sequence, corresponding to open reading frame 26, was also assessed in the peripheral blood and lesion tissue samples from patients with lymphoproliferative cutaneous diseases with nested polymerase chain reaction. The presence and distribution of cell types infected with HHV-8 in the lesion tissues was determined with immunohistochemical staining with the monoclonal antibody directed against the latent nuclear antigen-1 of HHV-8 encoded by open reading frame 73., Results: In healthy control subjects and patients with inflammatory skin diseases, 13.9% were found to have antibody against HHV-8, consistent with the seroprevalence population in Italy. A highly significant association of HHV-8 infection and LPP was found (100%) compared with mycosis fungoides (25%). The peripheral blood mononuclear cells in 8 of 10 patients with LPP were found to harbor viral sequences at nested polymerase chain reaction, whereas none of them had a detectable serum viral load. All LPP lesion tissue samples were positive for HHV-8-encoded open reading frame 26, and the presence of HHV-8-infected cells was confirmed by immunohistochemistry profiles performed on paraffin-embedded tissues from 4 of 10 patients. The positive cell types included endothelial cells and the infiltrating dermal lymphocytes, characteristic hallmarks of LPP. Analysis of T-cell receptor gamma chain rearrangements in lesion tissue from our patients confirmed the lack of a significant association between T-cell clonality and LPP., Conclusion: These data suggest that HHV-8 may play a role in the onset of LPP, a disease whose cause and evolution are still undefined and which has often been considered the early stage of mycosis fungoides.

Adaptation of the skin to repeated influence of exogenous irritants is called the hardening phenomenon. We investigated the stratum corneum lipid composition before and after induction of a hardening phenomenon. Irritant contact dermatitis was induced in 23 non-atopic volunteers by repeated occlusive application of 0.5% sodium lauryl sulfate (SLS) over 3 weeks. At 3, 6 and 9 weeks after irritation, the SLS responses of pre-irritated skin and normal skin were compared. The horny layer lipid composition (ceramides 1-7, cholesterol and free fatty acids) was assessed before irritation and 3, 6 and 9 weeks after irritation. During the first 2 weeks of irritation the transepidermal water loss increased continuously and seemed to decrease during the third week (effect of adaptation). The barrier function of pre-irritated sites was more stable to SLS challenge. Three weeks after irritation, there was a significant increase of ceramide 1 (p<0.001). The only volunteer without hardening phenomenon showed no increase of ceramide 1. Ceramide 1 seems to play a key role as a protection mechanism against repeated irritation.

Background: Keratinocytes participate in initiation and amplification of T-cell-mediated skin diseases. During these disorders, histamine can be released from both residents skin cells and immigrating leukocytes, and can affect the functions of dendritic cells, monocytes, and lymphocytes. Little information is available on the effects of histamine on keratinocytes., Objective: To examine the presence of functional H1 receptors on human keratinocytes and the capacity of histamine to modulate the expression of inflammatory molecules in these cells., Methods: Primary cultures of resting and cytokine-activated keratinocytes from healthy subjects were analyzed for histamine H1 receptor expression and the production of inflammatory mediators after exposure to histamine receptor agonists and antagonists., Results: Cultured keratinocytes constitutively expressed the H1 receptor mRNA and protein, which was not influenced by IFN-gamma, TNF-alpha, or IL-4. H1 but not H2 agonists induced calcium fluxes in keratinocytes. Treatment of keratinocytes with histamine (10 -7 to 10 -4 mol/L) or beta-histine increased the IFN-gamma-induced expression of membrane intercellular adhesion molecule 1 and MHC class I but not MHC class II molecules. Moreover, H1 stimulation promoted basal CC chemokine ligand (CCL)-5/RANTES and GM-CSF secretion and augmented IFN-gamma-induced release of the chemokines CCL2/monocyte chemoattractant protein 1, CCL5/RANTES, CCL20/macrophage inflammatory protein 3alpha, and CXC chemokine ligand 10/IFN-induced protein of 10 kd, as well as GM-CSF. Administration of the H1 antihistamine levocetirizine, but not of the H2 antihistamine cimetidine, abolished histamine-dependent expression of all of the investigated proinflammatory molecules in a dose-dependent manner (0.01-10 mumol/L). Levocetirizine at higher doses also reduced intercellular adhesion molecule 1, CCL5/RANTES, and GM-CSF release induced solely by IFN-gamma., Conclusion: Histamine exerts proinflammatory effects on keratinocytes via the H1 receptor, and these effects are efficiently inhibited by levocetirizine.

Both exposure of stratum corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and stratum corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of stratum corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and stratum corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and stratum corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized stratum corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that stratum corneum neutralization alone provokes stratum corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased stratum corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.

Hermansky-Pudlak syndrome is an autosomal recessive disease characterized by pigment dilution and prolonged bleeding time. At least 15 mutant mouse strains have been classified as models of Hermansky-Pudlak syndrome. Some of the genes are implicated in intracellular vesicle trafficking: budding, targeting, and secretion. Many of the Hermansky-Pudlak syndrome genes remain uncharacterized and their functions are unknown. Clues to the functions of these genes can be found by analyzing the physiologic and cellular phenotypes. Here we have examined the morphology of the melanosomes in the skin of 10 of the mutant mouse Hermansky-Pudlak syndrome strains by transmission electron microscopy. We demonstrate that the morphologies reflect inhibition of organelle maturation or transfer. The Hermansky-Pudlak syndrome strains are classified into morphologic groups characterized by the step at which melanosome biogenesis or transfer to keratinocytes is inhibited, with the cappuccino strain observed to be blocked at the earliest step and gunmetal blocked at the latest step. We show that all Hermansky-Pudlak syndrome mutant strains except gunmetal have an increase in unpigmented or hypopigmented immature melanosomal forms, leading to the hypopigmented coat colors seen in these strains. In contrast, the hypopigmentation seen in the gunmetal strain is due to the retention of melanosomes in melanocytes, and inefficient transfer into keratinocytes.

Twenty subjects with healthy skin were treated with the following formulations for two weeks: drug-free W/O vehicle, 5% ammonium lactate (CAS 52003-58-4) in W/O vehicle, 5% urea (CAS 57-13-6) in W/O vehicle, 3% ammonium lactate + 3% urea in W/O vehicle, 5% ammonium lactate + 5% urea in W/O vehicle. These formulations were applied in randomized order to 6 test areas on the forearms; one area was left untreated. Repetitive washings were additionally performed in the second treatment week. TEWL, stratum corneum water content (corneometry-determined electrical capacitance), and cutaneous blood flow (laser Doppler) were measured at baseline, day 7, and day 14. 5% urea and both ammonium lactate/urea combinations produced significant stratum corneum hydration and improved stratum corneum barrier function; there were no significant differences between these three treatments., (Copyright 2002 S. Karger AG, Basel)

Objective: To determine whether salicylic acid and high dose urea in five different NRF (New German Formulary) formulations have an effect on stratum corneum., Methods: 20 healthy volunteers had their stratum corneum blacked with silver nitrate and a photographic developer, and a chromameter (a*-value) was used to determine the amount of discoloration produced by the study products and the drug free vehicles after 24 hours semiocclusive application and 24 hours later. The change in fingerpad ridge width produced by the study formulations and drugfree vehicles was determined at the same time, using the Hikoscope Dermatoscope after 30 and 35 minutes' use under an occlusive dressing. The results obtained with the two methods were correlated., Results: All study formulations were effective. There were differences in the time course of the effects on the stratum corneum. The fingerpad ridge width method is not a measure of keratolytic activity because there were no significant correlations between the results obtained with the two methods. Also, 40% urea was keratolytic in the silver nitrate test, but had no effect of fingerpad ridge width., Conclusions: All NRF study formulations were effective in the stratum corneum. The fingerpad ridge width method is not a measure of keratolytic activity but rather of an other unknown effect of salicylic acid.

Background: Propionibacterium acnes is the target of antimicrobial treatments for acne vulgaris. Acquired resistance to erythromycin, clindamycin and tetracyclines has been reported in strains from diverse geographical loci, but the molecular basis of resistance, via mutations in genes encoding 23S and 16S rRNA, respectively, has so far only been elucidated for isolates from the U.K., Objectives: To determine whether similar or different resistance mechanisms occur in resistant P. acnes isolates from outside the U.K., Methods: The phenotypes and genotypes of 73 antibiotic-resistant strains of P. acnes obtained from the skin of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were compared. Antibiotic susceptibilities were determined by minimum inhibitory concentration (MIC) measurements, and polymerase chain reaction and DNA sequencing were used to identify mutations in genes encoding rRNA., Results: Most erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross-resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(-1)). As in the U.K., resistance to erythromycin was associated with point mutations in 23S rRNA in 49 of 58 strains. An A-->G transition at Escherichia coli equivalent base 2058 was present in 24 strains. This gave a unique cross-resistance phenotype against a panel of macrolide, lincosamide and type B streptogramin antibiotics. Two further point mutations (at E. coli equivalent bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and these were also associated with specific cross-resistance patterns originally identified in isolates from the U.K. However, nine of 10 erythromycin resistant-strains from Germany did not exhibit any of the three base mutations identified and, in six cases, cross-resistance patterns were atypical. Consistent with previous U.K. data, 34 of 38 tetracycline-resistant strains carried a base mutation at E. coli 16S rRNA equivalent base 1058. Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline, but isolates from the U.S.A. had higher MICs for minocycline (4--16 microg mL(-1)) than isolates from other countries and, in particular, Australia. All the P. acnes isolates resistant to one or more of the commonly used antiacne antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the fluoroquinolone, nadifloxacin. All but one isolate (from the U.K.) were sensitive to trimethoprim., Conclusions: This study shows that 23S and 16S mutations identified in the U.K. conferring antibiotic resistance in P. acnes are distributed widely. However, resistant strains were isolated in which mutations could not be identified, suggesting that as yet uncharacterized resistance mechanisms have evolved. This is the first report of high-level resistance to minocycline and is of concern as these strains are predicted to be clinically resistant and are unlikely to remain confined to the U.S.A. Epidemiological studies are urgently required to monitor how resistant strains are selected, how they spread and to ascertain whether the prevalence of resistance correlates with antibiotic usage patterns in the different countries.

We carried out three studies to evaluate the effects of white zinc shake lotion (Zinkschüttelmixtur DAC), zinc oil ( Zinköl NRF 11.20), Lotio Cordes, PEG ointment (Polyethylenglykolsalbe DAB) and PEG paste on nonmoisturized and moisturized skin. The aim of the study was a clear indication for these vehicles in the clinical practice. Studies 1 and 2 were performed on 20 healthy volunteers. Study 1 was carried out on nonmoisturized skin, while test areas in study 2 were treated with the study products after 1-hour moisturization with hydrophilic aqueous ointment (hydrophile wasserhaltige Salbe DAB), covered with a semiocclusive film dressing. Study 3, carried out on 10 subjects, differed from study 2 by a longer follow-up period. The water content of the horny layer before and after application of the different vehicles was estimated by the capacitance measurement (Corneometer CM 820) and the conductance measurement (Skikon). The glycerol-containing zinc shake lotion and both PEG gels (with or without zinc oxide) produced hydration under the conditions of study 1 and 2. Zinc oil and moisturizer-free Lotio Cordes had little impact on stratum corneum hydration under the conditions of studies 1-3. Therefore, zinc shake lotion and the two PEG ointments can be used in the treatment of dry atopic skin, but not in overhydrated skin, e.g. in intertriginous regions. Zinc oil and Lotio Cordes can be used in overhydrated skin but not in dry skin, for the missing water-binding capacity in the horny layer. On the other hand an effective dehydrating effect cannot be expected.

The influence of vitamin E (tocopherol, CAS 10191-41-0) on stratum corneum hydration was tested in O/W and W/O emulsions. Additionally, the O/W emulsion was used in an in vivo/in vitro method to gravimetrically obtain evidence concerning the water-binding capacity of the stratum corneum. In the W/O emulsion, 2.5%, 5%, and 7.5% vitamin E were compared. With both types of emulsions, vitamin E increased the stratum corneum hydration statistically significantly (p = 0.0002). In addition, we could provide evidence of an enhanced water-binding capacity after treatment with vitamin E (p = 0.05). For the hydrating effect of vitamin E. its concentration is of importance. The optimum concentration turned out to be 5%.

Background: It is known that glycerol in an oil-in-water emulsion has a protective effect against irritating substances., Objective: To answer the question: is the protection effect of glycerol based on a regenerative process?, Methods: Upon irritation by either tape stripping or acetone treatment, we applied glycerol to the skin surface under an occlusive dressing to create transepidermal water movement. As a control we used water under the occlusive dressing on the contralateral forearm. After 5 h we compared the barrier function using biological tests., Results: A significant improvement of the protective barrier function was observed in the glycerol-treated areas, as shown by the alkali resistance and by the irritant effect of dimethyl sulfoxide (DMSO) as well as sodium lauryl sulfate. Surprisingly, at the same time penetration of hexyl nicotinate improved on the glycerol-treated areas. A direct physicochemical protection effect on the surface of the skin was ruled out in additional studies using NaOH and DMSO., Conclusions: Under the given conditions glycerol leads to a more rapid reconstitution of the protective skin barrier and initiates a regenerative skin protection. In contrast to that, it is acting as a penetration enhancer.