Manigé Fartasch

Age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial

Abstract Objective To determine the effects of age related, structured educational programmes on the management of moderate to severe atopic dermatitis in childhood and adolescence. Design Multicentre, randomised controlled trial. Setting Seven hospitals in Germany. Participants Parents of children with atopic dermatitis aged 3 months to 7 years (n = 274) and 8-12 years (n = 102), adolescents with atopic dermatitis aged 13-18 years (n = 70), and controls (n = 244, n = 83, and n = 50, respectively). Interventions Group sessions of standardised intervention programmes for atopic dermatitis once weekly for six weeks or no education (control group). Main outcome measures Severity of eczema (scoring of atopic dermatitis scale), subjective severity (standardised questionnaires), and quality of life for parents of affected children aged less than 13 years, over 12 months. Results Significant improvements in severity of eczema and subjective severity were seen in all intervention groups compared with control groups (total score for severity: age 3 months to 7 years - 17.5, 95% confidence intervals - 19.6 to - 15.3 v - 12.2, - 14.3 to - 10.1; age 8-12 years - 16.0, - 20.0 to - 12.0 v - 7.8, - 11.4; - 4.3; and age 13-18 years - 19.7, - 23.7 to - 15.7 v - 5.2, - 10.5 to 0.1). Parents of affected children aged less than 7 years experienced significantly better improvement in all five quality of life subscales, whereas parents of affected children aged 8-12 years experienced significantly better improvement in three of five quality of life subscales. Conclusion Age related educational programmes for the control of atopic dermatitis in children and adolescents are effective in the long term management of the disease.

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gauchers disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.

Painful stimuli evoke itch in patients with chronic pruritus Central sensitization for itch

Background: Central sensitization for pain is important for patients with chronic pain. The authors investigated a possible role of central sensitization for itch in patients with chronic pruritus. Methods: Noxious stimuli were applied in lesional and visually nonlesional skin areas of 25 patients with atopic dermatitis, in lesional skin areas of 9 patients with psoriasis vulgaris, and in 20 healthy subjects. The stimuli included mechanical pinpricks, electrical stimuli, contact heat, and injection of low-pH solution. Intensities of itch and pain were assessed separately on a numeric rating scale. Results: All the noxious stimuli primarily evoked pain in control subjects and patients with psoriasis vulgaris. In patients with atopic dermatitis, however, itch was evoked instead of burning pain. In their lesional skin, itch was the predominant sensation. Chemical stimuli evoked intense itch in lesional and visually healthy skin areas (the area under the curve of itch rating compared with the control, mean ± SEM, 668 ± 166 and 625 ± 192 vs 38 ± 23; p < 0.001; p < 0.01). Chemically induced itch also was observed in healthy subjects after a conditioning histamine stimulus of 15 minutes, but not after a conditioning histamine stimulus of 2 minutes. Conclusion: The chronic barrage of pruriceptive input may elicit central sensitization for itch so that nociceptive input no longer inhibits itch but on the contrary is perceived as itch. In contrast to the well-known A-fiber-mediated alloknesis and hyperknesis, this type of central sensitization appears to be elicited by C-nociceptors.

The European baseline series in 10 European Countries, 2005/2006 : results of the European Surveillance System on Contact Allergies (ESSCA)

Background: Continual surveillance based on patch test results has proved useful for the identification of contact allergy.

Epidermal barrier in disorders of the skin.

The water permeability barrier of the stratum corneum (SC) seems primarily to be regulated by the lamellarly arranged lipid bilayers between the corneocytes, which originate largely from polar lipid precursors provided by the cells of stratum granulosum via exocytosis of the lamellar body (LB) content. In particular, the structural organization of these intercellular lipid lamellae seems to be responsible for the very low water permeability of the intact skin, and these lipid‐rich structures might also influence the desquamation process in the SC. The aim of this study was to obtain further insight into the distribution and organization of the epidermal lipids (EL) and the mechanism involved in desquamation and barrier function in normal human skin and scaling skin disorders. Biopsies of healthy human skin (n = 12), of inflammatory skin diseases (atopic dry skin (n = 9), psoriatic skin lesions [n = 2]), and of hereditary keratinization disorders (autosomal recessive ichthyoses congenita (n = 3), X‐chromosomal ichthyosis (XCI) [n = 3]) were analyzed utilizing a special fixation protocol with ruthenium tetroxide (RuO4) postfixation. While the atopic dry skin revealed normal barrier structures, the psoriasis lesions were characterized by severe alteration of the lipid structures leading to an abnormal interaction with the desmosomal unit. While the intercellular domains in some of the studied keratinization disorders showed an impaired distribution of the EL (autosomal recessive ichthyoses), X‐chromosomal ichthyosis showed normal lipid architecture. Dry and scaly skin disorders are therefore not always accompanied by an impairment of the water permeability barrier. Microsc. Res. Tech. 38:361–372, 1997.

Long-Term Efficacy and Safety of Pimecrolimus Cream 1% in Adults with Moderate Atopic Dermatitis

Background: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). Objective: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. Methods: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. Results: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. Conclusion: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients’ quality of life.

Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier

Alpha-hydroxy acids (AHA) such as glycolic acid have recently been used extensively in cosmetic and dermatological formulas. In low concentration (2– 5%) glycolic acid is believed to facilitate progressive weakening of cohesion of the intercellular material of the stratum corneum (SC), resulting in uniform exfoliation of its outermost layers (the stratum disjunctum). Since thinning of the SC as well as changes of intercellular lipids could theoretically compromise the barrier functions of the skin, we investigated the mode of AHA action on the SC to determine whether enhanced desquamation compromises the barrier structures of the SC and changes transepidermal water loss (TEWL) values. Electron microscopy of the epidermis biopsied from the volar forearm of human volunteers after 3 weeks of treatment with a 4% glycolic acid formulation twice daily was employed to evaluate 1) epidermal morphology and thickness of the SC, (2) the lamellar body and SC lipid bilayer organization, and (3) desquamative events based on degradation of desmosomes. TEWL values and SC hydration were recorded prior to and at the end of the study. Electron microscopy revealed no ultrastructural changes in the nucleated layers of the epidermis. The lamellar body (LB) secretory system in the stratum granulosum (SG), and intercellular lipid lamellae in the SC in both vehicle- and glycolic acid-treated samples were comparable to normal human SC. Within the SC, enhanced desmosomal breakdown, promoting loss of cohesion and desquamation, was restricted to the stratum disjunctum while desmosomes of the stratum compactum were unaffected. Treated areas displayed histologically, a more compact appearing SC. TEWL values remained unchanged in glycolic acid- and vehicle-treated skin. Our findings indicate that the barrier structures of the SC are not disrupted by glycolic acid formulations at the concentration used. One of the mechanism of action of AHA on the SC seemed to be a „targeted“ desmosomal (corneosomal) action without compromising the barrier structures of the skin.

Ultrastructure of the epidermal barrier after irritation

The stratum corneum (SC) controls the diffusion and penetration of chemical substances and drugs into and through the skin. Surprisingly, knowledge of the SC structure and reaction to the various irritants is still poorly understood. Routine transmission electron microscopy has not been effective in demonstrating the epidermal lipids (EL) of SC which are believed to morphologically represent the water permeability barrier. To gain a better understanding of the interaction of chemically different irritants with the SC, we investigated the ultrastructural changes of epidermal lipids resulting from the topical application of sodium dodecyl sulfate (SDS 0.5% and 1% w/v) and absolute acetone. The disturbance of barrier function by these irritants was determined by the increase of transepidermal water loss (TEWL). Punch biopsies from the treated sites showed a maximum increase of TEWL. To visualize the EL which derive from lamellar body (LB) lipids (sheets), we used a special fixation method utilizing 0.5% ruthenium tetroxide/0.25% KFe(CN)6 as the postfixative. The 0.5% SDS caused cell damage to the nucleated cells of the epidermis with disturbance of LB lipid extrusion and the transformation into the lipid bilayers. However, the upper portions of SC displayed intact intercellular lipid layers. With the acetone treatment, the EL lamellae showed disruption and loss of cohesion between the lamellae at all levels of the SC. The more polar LB lipids appeared more resistant to acetone. The results of this study suggest that different irritants induce distinct and characteristic alterations to reflect the specific interaction with the epidermal permeability barrier. Microsc. Res. Tech., 37:193–199, 1997.

Resolution requirements for digital images in dermatology

BACKGROUND The digital image has become an important tool in dermatology because of the rapid development of computer hardware, networks, and the World Wide Web. OBJECTIVE Our purpose was to examine the resolution requirements for digital images. METHODS Slides 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. RESULTS Images 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. CONCLUSION For digital images in dermatology a resolution of 768 x 512 x 24 is suitable to recognize the relevant details of the source image.

High molecular compounds (polysaccharides and proanthocyanidins) from Hamamelis virginiana bark: influence on human skin keratinocyte proliferation and differentiation and influence on irritated skin.

Although extracts from Hamamelis bark have long been used in therapy of skin diseases and in cosmetic formulas there are only few pharmacological investigations verifying the activity of distinct Hamamelis bark constituents. Therefore two major classes of constituents, namely polymeric proanthocyanidins and polysaccharides were isolated from Hamamelis bark and tested concerning their influence on proliferation and differentiation of cultured human keratinocytes. While the polysaccharide fraction, consisting mainly of arabans and arabinogalactans, did not effect human keratinozytes, the proanthocyanidins strongly increased the proliferation of the cells, while the differentiation was not influenced significantly. Within a preliminary cumulative in vivo study on SLS-irritated skin, proanthocyanidins (ProcyanoPlus) were proven to reduce transepidermal water loss and erythema formation. Furthermore, a clinical scoring indicated that procyanidins can influence irritative processes significantly.