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Occupational exposure of hairdressers to hair dyes has been associated with the development of allergic contact dermatitis (ACD) involving the hands. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) have been implicated as important occupational contact allergens. To conduct a quantitative risk assessment for the induction of contact sensitization to hair dyes in hairdressers, available data from hand rinsing studies following typical occupational exposure conditions to PPD, PTD and resorcinol were assessed. By accounting for wet work, uneven exposure and inter-individual variability for professionals, daily hand exposure concentrations were derived. Secondly, daily hand exposure was compared with the sensitization induction potency of the individual hair dye defined as the No Expected Sensitization Induction Levels (NESIL). For PPD and PTD hairdresser hand exposure levels were 2.7 and 5.9 fold below the individual NESIL. In contrast, hand exposure to resorcinol was 50 fold below the NESIL. Correspondingly, the risk assessment for PPD and PTD indicates that contact sensitization may occur, when skin protection and skin care are not rigorously applied. We conclude that awareness of health risks associated with occupational exposure to hair dyes, and of the importance of adequate protective measures, should be emphasized more fully during hairdresser education and training.

Objective The objective of this study was to prove training-specific effects in children with atopic dermatitis (AD) and their parents concerning coping with the disease after their participation in a training program. In the 1-year follow-up, the changes in the training group were compared to the changes in a waiting control group while controlling the effects of the changes in severity scores. Methods One hundred eighty-five children aged 8–12 years and their parents participated in the study. Complete data sets at the 1-year follow-up were available for 185 parent-child pairs (102 training group; 83 waiting control group). In addition to the severity of the AD [measured with the Scoring Atopic Dermatitis (SCORAD)], data on children's itching-scratching cognitions and coping behavior and on parents handling their affected children were used in the analysis. To study whether the intervention group experienced an additional psychological benefit, which is not due to the SCORAD values, analyses of covariance with repeated measures with standardized residual change scores of the SCORAD as covariate were calculated. Results The intervention group showed greater improvement in children's coping behavior and in parents' handling their affected children. Additional effects of the training program not due to somatic improvement could be seen in the scales of itching-scratching cognitions and in three of four scales on parents dealing with their affected children. Conclusion The training program, which was tested in the German Atopic Dermatitis Intervention Study, had effects on almost all explored psychological variables. Therefore, additional psychological benefit in the training group does not only depend on the greater improvement of SCORAD values in this group.

Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products.

The so-called "forest kindergartens" have been increasingly popular in Germany since the beginning of the 1990s. These are nurseries located in forested areas where children spend all-season full-time outdoors. Fifty-three kindergartens in the state of Baden-Wurttemberg, Germany participated in this study. In a prospective clinical cohort study, the child's personal data, history, protective parental habits concerning tick bites, number of tick bites, and cases of borreliosis were recorded monthly (March-October 2004) using a questionnaire. Altogether, 1,707 children of 25 "forest kindergartens" (506 children) and 28 conventional kindergartens (1,201 children) were included. The response rate was 75% in "forest kindergartens" and 65% in conventional kindergartens. In the "forest kindergartens", 1,503 tick bites especially on the trunk and on the head were found, whereas 502 tick bites were registered in conventional kindergartens. Sixteen cases of borreliosis were diagnosed (10 in "forest kindergartens", six in conventional kindergarten), most frequently manifesting as erythema migrans. Children attending a "forest kindergarten" have a 2.8 times increased risk of experiencing tick bites and a 4.6 times increased risk of suffering from borreliosis compared to conventional kindergarten in Germany, although protective parental behavior in "forest kindergarten" children was significantly better than that in conventional kindergarten.

This study aims to describe the range of treatment comparisons, study designs and quality of reporting of randomized clinical trials (RCTs) in psoriasis published in a variety of medical and dermatological journals, and to analyze time trends with quality items. Hand-searching of clinical trials of psoriasis published from 1977 to 2000 in 13 medical or dermatological journals, selected as relevant to a European readership, was performed. A total of 249 trials published in 226 papers were classified as RCTs. Of these, 139 (55.8%) employed a parallel control group design, 107 (43.0%) studies adopted a self-control design and 3 (1.2%) a cross-over design. The median number of patients recruited per study was 40 (range 6-699). Overall, 55 different treatment modalities, including topical, ultraviolet-based, systemic, and other miscellaneous therapies were assessed. Only 31 (12.5%) RCTs were comparative studies of treatment modalities in different therapeutic classes. Most of the studies were short-term with a median study duration of 7 weeks (range 1-104), with only 18 studies (7.2%) lasting for more than four months. A variety of outcome measures including 44 different score systems were employed. According to the conclusions of the authors, 196 (78.7%) studies were judged to provide striking or definite observations in favor of one of the treatments examined. No important variations over time were documented for quality items. Based on our survey we have identified an enormous range of treatments that have been evaluated for psoriasis over the examined period. Most studies were short-term, and only a handful compared treatment options in different therapeutic classes. Since we did not examine all the relevant journals, the number of treatment options may be even greater than we have documented. There is an urgent need to reset the research agenda focusing on long-term comparative RCTs. Editors of major medical and dermatological journals are urged to take a role in improving the quality of RCT reporting.

Background: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment for patients with atopic dermatitis. Objective: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 0.1% hydrocortisone-17-butyrate ointment, a midpotent to potent topical corticosteroid, in the treatment of adult patients with moderate-to-severe atopic dermatitis. Methods: Patients applied ointment twice daily to all affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve as a percentage of baseline. Results: Five hundred seventy patients were randomized and received treatment. Discontinuations included 22 of 193 patients from the 0.03% tacrolimus group, 22 of 191 patients from the 0.1% tacrolimus group, and 17 of 186 patients from the hydrocortisone butyrate group. The median mEASI mean area under the curve as a percentage of baseline was 47.0%, 36.5%, and 36.1% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 0.1% hydrocortisone butyrate, respectively. There was no statistically significant difference between 0.1% tacrolimus and 0.1% hydrocortisone butyrate; however, the lower improvement in mEASI for 0.03% tacrolimus was statistically significant when compared with 0.1% tacrolimus ( P P = .002). Skin burning and pruritus at the application site showed a higher incidence in the tacrolimus treatment groups than in the hydrocortisone butyrate group ( P Conclusions: The efficacy of 0.1% tacrolimus ointment was similar to that of 0.1% hydrocortisone butyrate ointment and was lower for 0.03% tacrolimus ointment. No serious safety concerns were identified. (J Allergy Clin Immunol 2002;109:547-55.)

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Dendritic cells (DC) are increasingly used as a vaccine. Unfortunately, a satisfactory cryopreservation of DC in the absence of FCS is not yet available, so that laborious repeated generation of DC from fresh blood or frozen peripheral blood mononuclear cells for each vaccination has been required to date. We now aimed at developing an effective cryopreservation method, and by testing several variables found that it was crucial to combine the most advantageous maturation stimulus with an improved freezing procedure. We generated monocyte-derived DC from leukapheresis products by using GM-CSF and IL-4 and showed that amongst several known maturation stimuli the cocktail consisting of TNF-alpha+IL-1 beta+IL-6+PGE(2) achieved the highest survival of mature DC. We then systematically explored cryopreservation conditions, and found that freezing matured DC at 1 degrees C/min in pure autologous serum+10% DMSO+5% glucose at a cell density of 10x10(6) DC/ml gave the best results. Using this approach 85-100% of the frozen DC could be recovered in a viable state after thawing (Table 1). The morphology, phenotype, survival as well as functional properties (allogeneic mixed leukocyte reaction, induction of influenza matrix or melan A peptide-specific cytotoxic T cells) of these thawed DC were equivalent to freshly prepared ones. The addition of CD40L or TRANCE/RANKL further improved DC survival. Importantly, we demonstrate that DC can effectively be loaded with antigens (such as Tetanus Toxoid, influenza matrix and melan A peptides) before cryopreservation so that it is now possible to generate antigen-preloaded, frozen DC aliquots that after thawing can be used right away. This is an important advance as both the generation of a standardized DC vaccine under GMP conditions and the carrying out of clinical trials are greatly facilitated.

To gain a better understanding of the interaction of the model detergent sodium lauryl sulfate (SLS) with the stratum corneum, we investigated systematically the ultrastructural changes of the epidermal barrier and the nucleated parts of the epidermis after the occluded application of different concentrations of SLS in human. Different application models were investigated. Two of the three irritation procedures (long duration exposure and the repetitive exposure for 3 d) provoked damage of the nucleated parts of the epidermis and alterations of the lower parts of the stratum corneum. Here, the extrusion and transformation of lamellar body derived lipids into lamellar lipid bilayers were disturbed; however, the upper portions of stratum corneum displayed intact intercellular lipid layers that contradict the long-standing belief that surfactants damage the skin by delipidization. Furthermore, we investigated ultrastructurally and by measurement of transepidermal water loss the influence and protective capacity of a lipophilic barrier cream on acute irritant contact dermatitis. The irritant contact dermatitis was induced by the standardized cumulative short application model with two SLS concentrations (0.5% and 0.75%). The cumulative type of exposure simulates daily living more realistically. Because most of the previous tests have been performed on the human forearm or back, we analyzed whether the pattern of response was similar on both sites. The back showed a higher level of irritant reaction, but the pattern of irritant response proved to be similar to the forearm. Application of the barrier cream before and during irritation showed a decrease of transepidermal water loss enhancement with 0.5% SLS by 58% (back) and 49% (arm) and after irritation with 0.75% SLS by 56% (back) and 43% (arm). Because the experimental result correlated with the clinical experience, the development of the cumulative short exposure model might help to predict and to discriminate the efficacy of barrier creams. Journal of Investigative Dermatology Symposium Proceedings 3:121–127, 1998

The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD).The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy.Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16).With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy.This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Background: Atopic dermatitis is a common multifactorial disease that seems to be increasing in frequency. Objective: Our purpose was to determine the increased prevalence of atopic dermatitis in North Europe. Methods: Approximately 3000 7-year-old school children in Denmark, Germany, and Sweden were enrolled in a cross-sectional questionnaire study that was conducted in the autumn of 1992 with common protocols and standardized procedures. Results: The response rate was 90%. The frequency of atopic dermatitis was calculated to be 15.6% (95% confidence interval 14.2% to 17%) with some regional differences. Girls more often had flexural eczema and outnumbered boys in a ratio of 1.3:1.0. Boys more often had a personal history of asthma, whereas girls more often had a family history of asthma. Conclusion: The increasing prevalence of atopic dermatitis has been confirmed. This simple questionnaire model works well, is cost effective, and is sufficiently sensitive and specific to conduct large-scale epidemiologic investigations in school children.

In order to determine the relative importance of genetics and the environment on the occurrence of atopic diseases, we investigated the familial aggregation of atopic eczema, allergic rhinitis, and allergic asthma in the relatives of 426 patients with atopic eczema and 628 subjects with no history of eczema (5,136 family members in total). Analyses were performed by regression models for odds ratios (OR) allowing us to estimate OR for the familial aggregation and simultaneously to adjust for other covariates. Three models were analyzed assuming that the OR i) is the same among any two members of a family, ii) depends on different familial constellations, i.e., whether the pairs are siblings, parents, or parent/sibling pairs, and iii) is not the same between the father and the children and between the mother and the children. The OR of familial aggregation for atopic eczema was 2.16 (95% confidence interval (95%-Cl) 1.58–2.96) if no distinction was made between the degree of relationship. Further analyses within the members of the family showed a high OR among siblings (OR=3.86; 95%-Cl 2.10–7.09), while the OR between parents and siblings was only 1.90 (95%-Cl 1.3 1–2.97). Only for atopic eczema was the familial aggregation between mothers and siblings stronger than the aggregation between fathers and siblings (ms: OR=2.66; fs: OR=1.29). This can be explained by stronger maternal heritability, shared physical environment of mother and child, or environmental events that affect the fetus in utero . Since for all atopic diseases a stronger correlation was found between siblings than between siblings and parents, our study indicates that environmental factors, especially during childhood, seem to explain the recently observed increased frequencies of atopic diseases.

The diagnostic reliability of ultrastructural and immunohistochemical examinations on routinely processed biopsy specimens of cutaneous histiocytic proliferations (histiocytosis X, n = 7; juvenile xanthogranuloma, n = 4; necrobiotic xanthogranuloma, n = 2; traumatic granuloma of the tongue, n = 1) was evaluated. S-100 protein, peanut agglutinin, and the antibody Mac-387 were used as markers for histiocytes. The frequency of Birbeck granule-containing cells in seven histiocytosis X lesions did not correspond with the number of S-100+ or peanut agglutinin+ cells. All neoplastic histiocytosis X cells were positive for S-100 protein and peanut agglutinin but were negative for Mac-387. Histiocytes of juvenile xanthogranuloma, necrobiotic xanthogranuloma, and traumatic granuloma were strongly positive for Mac-387 but were negative for S-100 protein and peanut agglutinin, except for the peanut agglutinin-reactive Touton giant cells. Mac-387 reliably differentiates histiocytic proliferations of the monocyte/macrophage system from those of the dendritic cell system. For the diagnosis of histiocytosis X, both S-100 protein and peanut agglutinin positivity in histiocytes is as reliable as ultrastructural demonstration of Birbeck granules.