Thomas L. Diepgen

The occurrence of atopic dermatitis in North Europe: An international questionnaire study

BACKGROUNDnAtopic dermatitis is a common multifactorial disease that seems to be increasing in frequency.nnnOBJECTIVEnOur purpose was to determine the increased prevalence of atopic dermatitis in North Europe.nnnMETHODSnApproximately 3000 7-year-old 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.nnnRESULTSnThe 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.nnnCONCLUSIONnThe 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.

High-dose UVA1 radiation therapy for localized scleroderma

BACKGROUNDnFibrotic skin lesions in patients with localized scleroderma can cause muscle atrophy, disfigurement, and flexion contractures. There is no effective therapy for this disease. Skin fibrosis is thought to be caused by decreased collagenase activity. Collagenase activity can be induced in dermal fibroblasts by UVA1 irradiation.nnnOBJECTIVEnOur purpose was to assess whether UVA1 radiation therapy is effective for patients with localized scleroderma.nnnMETHODSnPatients with localized scleroderma (n = 17) were exposed 30 times to 130 J/cm2 UVA1 (high-dose UVA1 therapy; n = 10) or 20 J/cm2 UVA1 (low-dose UVA1 therapy; n = 7). Therapeutic effectiveness was assessed by evaluation of (1) clinical features, (2) thickness of sclerotic plaques, and (3) cutaneous elastometry. Sequential biopsy specimens from treated lesions were analyzed for collagenase I messenger RNA (mRNA) expression by semiquantitative reverse transcriptase-polymerase chain reaction.nnnRESULTSnIn all patients, high-dose UVA1 therapy softened sclerotic plaques, and complete clearance was observed in four of 10 patients. High-dose UVA1 therapy significantly reduced thickness and increased elasticity of plaques. These changes could not be detected in unirradiated control plaques and were still present in 9 of 10 patients 3 months after cessation of therapy. For all factors assessed, high-dose UVA1 was superior to low-dose UVA1 therapy (p = 0.001). High-dose UVA1 therapy increased collagenase I mRNA expression about 20-fold in treated plaques.nnnCONCLUSIONnHigh-dose UVA1 therapy is effective in the treatment of localized scleroderma. Effectiveness is UVA1 dose dependent and is associated with induction of collagenase I expression.

Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics.

Summary A characteristic feature of non‐eczematous atopic dry skin (DS) appears to be an impaired water permeability barrier (WPB) function. The WPB is constituted by intercellular lipid lamellae, located between the horny cells of the stratum corneum (SC), which are provided by exocytosis of lamellar bodies (LB). The aim of this study was to elucidate whether alterations in the dynamics of LB‐extrusion could be responsible for this WPB disturbance. In an ultrastructural morphometric comparison the relative volume of LB in the two uppermost subcorneal layers in DS of atopics (n=9) and healthy skin of controls (n=7) was determined. The LBs were differentiated into extracytoplasmic LB. i.e. with the cell membrane already fused, and intracytoplasmic LB. i.e. entirely located within the cell. The total volume in the two cell layers of the stratum granulosum did not differ between atopics and controls. However, separate evaluation of the two LB‐compartments revealed statistically significant differences between atopics and healthy controls. In the second uppermost cell layer of the stratum granulosum only 13% of the total LB volume of this layer had already fused with the cell membrane in the atopics as opposed to 42% in the controls. On the other hand more LB remained undelivered within the cells of the uppermost SG cell layer of the atopics (26% in atopics versus 8% in controls, P<0.01). These findings suggest that a pathological extruding mechanism of LB in DS may be at least partly responsible for the recently detected biochemical alterations of epidermal lipids, and for the deficient WPB.

The human serum paraoxonase—Polymorphism and specificity

Human serum contains EDTA‐sensitive (Ca++‐dependent) and EDTA‐stable (albumin) paraoxonases which hydrolyse paraoxon, 0,0‐diethyl,0–4‐nitrophenyl phosphate. In Caucasians the EDTA‐sensitive enzyme shows a genetically determined polymorphism which is governed by two alleles. In typical Mongoloid or Negro populations this polymorphism is expressed to a lesser degree, and in a few samples (e.g. Aborigines) it cannot be observed at all. The distribution of the activity of the EDTA‐stable (albumin) paraoxonase is unimodal. Many authors supposed that paraoxonase is an arylesterase (EC 3.1.1.2) which means that it is also able to hydrolyse phenylacetate or β‐naphthylacetate. New investigations have shown that the human serum fractions splitting paraoxon can be separated from those hydrolysing phenylacetate and related substrates. The polymorphism of the EDTA‐sensitive human serum paraoxonase can be applied to investigations concerning specificity. From this it becomes evident that this enzyme is rather specific....

Testing for irritation with a multifactorial approach: comparison of eight non-invasive measuring techniques on five different irritation types

Backgroundu2003Non‐invasive bioengineering methods are widely used in the assessment of irritant skin reactions.

Resolution requirements for digital images in dermatology

BACKGROUNDnThe digital image has become an important tool in dermatology because of the rapid development of computer hardware, networks, and the World Wide Web.nnnOBJECTIVEnOur purpose was to examine the resolution requirements for digital images.nnnMETHODSnSlides of eight selected images showing characteristic lesions were produced in five different resolutions each, ranging from 192 x 128 x 24 (192 pixels x, 128 pixels y, and 24-bit color depth) up to 3072 x 2048 x 24. They were compared side by side by a group of six experienced dermatologists using a standardized questionnaire.nnnRESULTSnImages at the resolution of 768 x 512 x 24 were perceived as equivalent to higher resolutions, whereas a clear difference was visible between 768 x 512 x 24 and 384 x 256 x 24. The slide projector had a significant influence on the rating of the images.nnnCONCLUSIONnFor digital images in dermatology a resolution of 768 x 512 x 24 is suitable to recognize the relevant details of the source image.

Occupational contact dermatitis in bakers, confectioners and cooks : a population-based study

A population‐based study was performed to investigate incidence rates of occupational skin disease (OSD) in bakers, confectioners and cooks, as well as the rôle of endogenous and exogenous risk factors. In North Bavaria, all closed cases of OSD were recorded systematically in a 3‐year period and the total number of employees in the food industry was known over the same period of time, Incidence rates of OSD and relative risks of atopic skin diathesis (AD) and respiratory atopy (RA) were calculated. The overall incidence rate (I) of OSD (in 3 years per 10,000 employees) was 67 (95% CI 58:76) in these occupations. Bakers had a higher risk of OSD, with an incidence of 191 (95% CI 156:226) compared to confectioners with I=84 (95% CI 55;113) and cooks I=34 (95% CI 28;40). Incidence rates were sex‐and age‐related. Females developed OSD with an incidence rate of 74 (95% CI 64:84) compared to males with I= 58 (95% CI 48:70). OSD occurred mostly between the ages of 15 and 24 years. Irritant contact dermatitis (ICD) was the main type of OSD. 36% of the bakers had an occupationally relevant Type I allergy, while Type I allergies were less frequent in confectioners (16%) and cooks (9%). Assuming a prevalence of 10% of AD in the general population the relative risk (RR) of developing OSD in bakers, confectioners and cooks with AD was 9.7. 10.5 and 5.2, respectively. There were only small differences in calculating sex‐related RR of AD. The etiologic fraction of AD was nearly 50% in bakers and confectioners, whereas cooks had a smaller proportion of AD (30%). Respiratory atopy proved to be relevant in bakers (RR‐4.0). Preexistence of RA is important in bakers, since Type I reactions seem to be triggered. This is the first population‐based study which demonstrates clear differences between OSD in 3 occupations in the food industry, using incidence rate as a parameter. Females have a considerably higher risk of developing OSD. Since AD or RA do not explain sex differences in OSD, different skin sensitivity or different exposure between males and females may be important factors in the development of OSD. ICD is more important than allergic contact dermatitis (ACD). The role of AD and of RA is different in the 3 occupations.

Multicentre study for the development of an in vivo model to evaluate the influence of topical formulations on irritation

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short‐time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2× a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5‐day protocol. Furthermore, in spite of the expected inter‐centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter‐instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres.

Clinical relevance of sonometry-derived tumour thickness in malignant melanoma : a statistical analysis

High‐frequency sonography has been shown to be a useful tool in planning operative strategy in the surgery of malignant melanoma (MM). The purpose of the present study was to compare sonometric and histometric data of tumour thickness in primary cutaneous MM, applying statistical methods in order to evaluate the pre‐operative relevance of sonometry. The thickness of 259 melanomas was measured preoperatively by a 20‐MHz B scan, and postoperatively by histometry. Statistical analysis was performed using Pearsons correlation coefficient and absolute and relative differences. Although the correlation between sonometry and histometry was good (r=0·88), there was a mean difference of 0·39 mm (relative difference 28%). Overall, sonometry was in agreement with the corresponding histological classes in 75% of cases. However, tumours assessed by ultrasound as between 0·55 and 0·95 mm thick were incorrectly classified according to histology in 34%, and those between 1·30 and 1·70 mm were incorrectly classified in 50% of cases.

Immunohistochemical and ultrastructural study of histiocytosis X and non-X histiocytoses

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.