Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. OBJECTIVES: To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. METHODS: Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. RESULTS: Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. CONCLUSIONS: Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.

Occupational skin cancer induced by ultraviolet radiation and its prevention.

Skin cancer is by far the most common kind of cancer diagnosed in many western countries and ultraviolet radiation is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although employees at several workplaces are exposed to increased levels of UV radiation, skin cancer due to long-term intense occupational exposure to UV radiation is often not considered as occupational disease. The actually available evidence in the epidemiological literature clearly indicates that occupational UV radiation exposure is a substantial and robust risk factor for the development of cutaneous SCC and also clearly shows a significant risk for developing BCC. There is enough scientific evidence that outdoor workers have an increased risk of developing work-related occupational skin cancer due to natural UV radiation exposure and adequate prevention strategies must be implemented. The three measures which are successful and of particular importance in the prevention of nonmelanoma skin cancer in outdoor workers are changes in behaviour regarding awareness of health and disease resulting from exposure to natural UV radiation, protection from direct UV radiation by wearing suitable clothing, and regular and correct use of appropriate sunscreens.

[Skin and occupational artificial UV-radiation]. / Haut und berufliche UV-Strahlung künstlicher Quellen.

In various areas of professional activity, exposure of skin to ultraviolet radiation coming from artificial sources may occur. These UV rays differ from the solar UV radiation due to their intensity and spectrum. We review current developments with the introduction of statutory exposure limit values for jobs with UV radiation from artificial sources, a selection of relevant activities with artificial UV exposure and an overview of the occurrence of skin disorders and dermatologically relevant skin diseases caused by these specific occupational exposures. The latter is relevant for medical advice in occupational dermatology and occupational medicine. On the basis of existing studies on welders and studies regarding occupations with "open flames" (using the example of the glassblower) it is evident that so far no reliable data exist regarding the chronic photodamage or the occurrence of UV-typical skin cancers, but instead clear evidence exists regarding the regular occurrence of acute light damage in these occupations.

Classification of skin sensitizing substances: a comparison between approaches used by the DFG-MAK Commission and the European Union legislation.

A systematic classification of substances (or mixtures of substances) with regard to various toxicological endpoints is a prerequisite for the implementation of occupational safety strategies. As its principal task the "Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area" of the "Deutsche Forschungsgemeinschaft" (DFG-MAK Commission) derives and recommends maximum workplace concentrations and biological tolerance values (MAK and BAT values) based exclusively on scientific arguments. Several endpoints are evaluated separately in detail, e.g. carcinogenicity, risks during pregnancy, germ cell mutagenicity or contribution to systemic toxicity after cutaneous absorption. Skin- and airway sensitization is also considered; the present paper focuses on these two endpoints.

[Induction of occupational leucoderma and vitiligo. Can butylated hydroxytoluene induce vitiligo similarly to p-tert-butylphenol?]. / Beruflich bedingte Leukoderme und Vitiligo. Kann Butylhydroxytoluol ähnlich dem p-tert.-Butylphenol eine Vitiligo auslösen?

BACKGROUND: While vitiligo is usually idiopathic, some cases are caused by chemicals. If occupational exposure to p-tert-butylphenol (ptBP) leads to vitiligo, the legal requirements for occupational disease Nr. 1314 can be fulfilled in Germany. Chemicals of similar structure can induce local and more widespread symmetrical depigmentation with genital involvement, making the differential diagnosis more complicated. Occupationally caused depigmentation from other chemicals can also be treated according to § 9 sec. 2 of the occupational disease regulations. MATERIALS AND METHODS: Some substances can cause leukoderma only in animals; others in animals and humans; in some cases systemic vitiligo-like changes develop. The effects on human skin cannot always be predicted from the structural analogies of the involved chemicals. RESULTS: Based on a case of occupational exposure to butyl hydroxytoluene with possible induction of vitiligo, a careful updated literature analysis of substances inducing depigmentation is presented. CONCLUSION: The literature contains discrepancies in the evidence for the ability of some substances-especially BHT-to cause vitiligo. A more exact analysis indicates that BHT does not cause vitiligo or leukoderma.

[Cutaneous malignancies in occupationally-induced scars]. / Maligne Hauttumoren in beruflich verursachten Narben.

BACKGROUND: The occurrence of neoplasms in injury scars--as consequence of occupational accidents--may lead to compensation according to the statutory accident insurance regulations. According to newer regulatory attempts in occupational dermatology, certain criteria have to be met before the diagnosis of a neoplasm induced by a scar is accepted and compensation is due. MATERIAL AND METHODS: Based on a retrospective analysis of 217 dermatological claim files between 2007 and 2009 of the IPA (including 22 follow-ups), medical opinions on neoplasms developing in possible occupational scars were re-evaluated using criteria of the German social accident insurance and the Bamberg medical bulletin, part II (Bamberger Merkblatt, BM II) to see how well they qualified for recognition as an occupational or accident-related disorder. RESULTS: Three cases were identified where a neoplasm was suspected of having developed in an occupationally-related scar. One of the insured events entitled for compensation. Following the guidelines of the BM II, this case was approved as an occupational disease secondary to injuries with resultant reduction in earning capacity, whereas the others did not meet the requirements. CONCLUSIONS: Two problems in evaluating malignant tumors in occupational scars are the long latency period and the documentation of a scar. The tumor excision specimen should be histologically re-examined to document the presence of an associated scar.

Basal cell carcinoma risk and solar UV exposure in occupationally relevant anatomic sites: do histological subtype, tumor localization and Fitzpatrick phototype play a role? A population-based case-control study.

BACKGROUND: A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates. OBJECTIVES: To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure. METHODS: Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated. RESULTS: Participants with high versus no (OR 2.08; 95% CI 1.24-3.50; p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15-3.65; p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses. CONCLUSION: The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.

[Skin protection. From TRGS 401 to guidelines on "occupational skin protection products"]. / Hautschutz. Von der TRGS 401 bis zur Leitlinie "Berufliche Hautmittel".

The technical standards for hazardous substances (TRGS) reflect the currently achievable technical safety, occupational-medical, hygienic and scientific standards for production, distribution and handling of hazardous substances. The TRGS 401 "Risks resulting from skin contact--determination, evaluation, measures" gives important information regarding occupational hazardous exposure of the skin and the measures for prevention. A definition for wet work is given under which occlusion by moisture impermeable protective gloves and contacts to wet environments are included. Both the TRGS 401 and the AWMF S1 guidelines on "Occupational protection products" place emphasis on the fact that the protective effectiveness of topical skin products for protection, care and cleansing should be proven by in vivo methods.

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 Gaucher's 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.

Improved barrier structure formation in air-exposed human keratinocyte culture systems.

The epidermis (including stratum corneum) of human keratinocytes cultured at the air-liquid interface attached to an appropriate substrate shows a morphology closely mimicking that of its in vivo counterpart. In spite of the histologic similarities, the barrier function seems to be impaired. The aim of the present study was to characterize development and structure of the epidermal permeability barrier in two human skin recombinants using electron microscopy (including ruthenium tetroxide-post fixation technique) and analysis of lipid composition. The epidermis was reconstructed by growing human keratinocytes either on de-epidermized dermis or on a bovine collagen-containing matrix with active fibroblasts (Living Skin Equivalent). Ultrastructurally both culture systems showed a) an abnormal lamellar body delivery system, b) disturbance of transformation into lamellar lipid bilayers, c) an impaired structural organization and distribution of the epidermal lipids in the intercellular spaces. In either of the systems used, prolongation of the culture period did not induce any significant improvement in the stratum corneum lipid organization. Whereas the Living Skin Equivalent showed only sparse lamellar bodies, the number of lamellar bodies in the human keratinocyte culture on de-epidermized dermis grown in regular medium seemed to be comparable to native skin. Contrary to the Living Skin Equivalent, the keratinocyte culture on de-epidermized dermis contained a higher number of intracorneocytic lipid droplets correlating with a higher triglyceride content in the lipid analyses. By reconstructing the keratinocyte culture on de-epidermized dermis with the same medium as used for the Living Skin Equivalent, both lipid composition (lower triglyceride, higher ceramide contents) and structural organization were improved, and regular lamellar lipid bilayers comparable to those of native skin appeared.

A strikingly constant ratio exists between Langerhans cells and other epidermal cells in human skin. A stereologic study using the optical disector method and the confocal laser scanning microscope.

Langerhans cells play an important part in the immune surveillance of the human epidermis. Therefore, a certain distribution and numerical relationship to other epidermal cells can be expected. To quantify epidermal Langerhans cells population extensive studies have been performed using two-dimensional quantification methods on vertical sections or epidermal sheet preparations. Whereas methods using vertical sections were complicated considerably by the sampling procedure, the dendritic shape, and the suprabasal, nonrandom distribution of Langerhans cells, epidermal sheet preparations have their limitations regarding the numerical relationship of Langerhans cells to total epidermal cells and the epidermal morphology as such. In order to improve the validity of data the three-dimensional dissector method combined with confocal laser scanning microscopy has been applied to quantify the number of Langerhans cells and other epidermal cell nuclei per volume unit in cryosections of 24 punch biopsies of normal breast skin of eight women. Furthermore, the ratio of Langerhans cells to other epidermal cells, their number per biopsy, and per skin surface area were calculated. To minimize the bias by shrinkage the reference volume was estimated using Cavalieri's principle. A constant ratio of one Langerhans cells to 53 other epidermal cells was identified in breast skin (interindividual correlation coefficient: 0.952, p < 0.0001). Thus, Langerhans cells represent 1.86% of all epidermal cells; however, a wide interindividual range was found for the number of Langerhans cells per mm2 (912-1806; mean +/- SD 1394 +/- 321) and other epidermal cells per mm2 (47,315-104,588; mean +/- SD 73,952 +/- 19,426). This explains the conflicting results achieved by conventional morphometric assessments relating cell numbers to skin surface area, ignoring the varying thickness of the epidermis. The surprisingly constant relationship of Langerhans cells to other epidermal cells stresses the hypothesis of an epidermal Langerhans cells unit where one Langerhans cells seems to be responsible for the immune surveillance of 53 epidermal cells.

Apolipoprotein E deficiency leads to cutaneous foam cell formation in mice.

Apolipoprotein E deficiency leads to familial dysbetalipoproteinemia characterized by increases in serum lipid levels, atherosclerosis, and cutaneous xanthoma. Apolipoprotein E is synthesized in many tissues in the body, including the epidermis. In the present study, we determined whether transgenic mice deficient in apolipoprotein E develop cutaneous xanthoma and the effect of dietary fat intake on these lesions. We also determined whether apolipoprotein E-deficient mice have abnormalities in cutaneous barrier function or stratum corneum structure. Homozygous apolipoprotein E-deficient mice (-/-) fed a high-fat diet displayed a diffuse inflammatory infiltrate in the dermis surrounding fat droplets in macrophages. In homozygous mice (-/-) fed a low-fat diet, similar lesions were seen but they tended to be focal and less prominent. In heterozygous mice (+/-) fed the high-fat diet, a few inflammatory cells were present in the dermis but foam cells were not seen. Control mice (+/+) fed a high-fat diet displayed scattered inflammatory cells in the dermis. Heterozygous mice (+/-) fed a low-fat diet were similar to control mice (+/+) fed a low-fat diet. The extent of foam cell formation correlated directly with the degree of atherosclerosis. There were no abnormalities in permeability-barrier function or stratum corneum structure in apolipoprotein E-deficient mice. Thus, the lack of apolipoprotein E production in the epidermis does not appear to lead to any detectable abnormality in structure or function of the stratum corneum. However, lack of apolipoprotein E leads to cutaneous foam cell formation, presumably secondary to disturbances in lipoprotein metabolism.

Normal ultrastructure, but altered stratum corneum lipid and protein composition in a mouse model for epidermolytic hyperkeratosis.

Recently, we established keratin 10-deficient mice, serving as a model for the hyperkeratotic skin disorder epidermolytic hyperkeratosis. The considerable ichthyosis in these mice suggested alterations in terminal differentiation and in the formation of a functional epidermal barrier. Here, we report on the ultrastructural organization and composition of the stratum corneum lipids and on the expression of two major cornified envelope proteins. Electron microscopy of ruthenium tetroxide postfixed skin samples demonstrated a normal extrusion and morphology of lamellar bodies as well as the formation of bona fide lamellar layers in neonatal keratin 10-deficient mice. When we studied the composition of the major stratum corneum lipids, however, we found significant changes. Most importantly, the analysis of ceramide subpopulations revealed that the total amount of ceramide 2 was elevated in keratin 10-deficient mice, whereas ceramides 1, 3, 4, and 5 were decreased among total stratum corneum lipids. The amount of the ceramide precursors sphingomyelin and glucosylceramide was reduced in the stratum corneum without accompanying changes in the mRNA coding for acid sphingomyelinase. Notably, we found an increased mRNA and protein content for involucrin in neonatal keratin 10-deficient mice, whereas the expression of loricrin was not changed. Our data demonstrate that, although the formation of lipid layers in the stratum corneum appeared to be normal, its lipid composition is significantly altered in keratin 10-deficient mice.

Development and validation of diagnostic scores for atopic dermatitis incorporating criteria of data quality and practical usefulness.

No objective classification criteria for atopic dermatitis (AD) exist. Therefore the diagnosis is usually based on many variables including anamnestic, clinical, and laboratory findings. The aim of this study was to develop and validate a diagnostic score to standardize the diagnosis of atopic skin diathesis for clinical and epidemiological studies. In two separate studies, each consisting of cases and controls, 19 atopic binary features were examined by two independent experienced physicians and these features were classified as "objective," respectively, "subjective." On the basis of these criteria and two additional laboratory measures, we developed a score with high discriminative ability, using the logistic regression model and backward elimination. Ignoring "subjective" variables and the two laboratory measures, two additional models were built that had a worse fit in the original data, but still yielded high estimates of sensitivity (approximately 90%) and specificity (approximately 96%). Using the same data as for the model building, it is well known that these estimates are too optimistic. The validation study allows us to obtain unbiased estimates of sensitivity and specificity for the different scores and to investigate the influence of data quality-here given by the assessment of the reproducibility of the features (objective and subjective)-on the usefulness of diagnostic scores. The results of the validation study show that we developed simple and easy-to-use scores offering a base for a broad practical use in epidemiological and clinical research. In addition, we demonstrate that the criteria classified as "subjective" have no influence on the case-control status in the validation study.

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.

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.

Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications.

BACKGROUND: The infant with Netherton syndrome (NS) typically displays a generalized erythroderma covered by fine, translucent scales, which can be difficult to distinguish clinically from erythrodermic psoriasis, nonbullous congenital ichthyosiform erythroderma, or other infantile erythrodermas. Some infants with NS develop progressive hypernatremic dehydration, failure to thrive, and enteropathy. Such complications can be fatal. Diagnosis is typically delayed until the appearance of a pathognomonic hair shaft anomaly, trichorrhexis invaginata (bamboo hair). To facilitate the early diagnosis of NS, we obtained biopsy specimens from 7 patients with erythrodermic NS and compared their morphologic findings to those of 3 patients with erythrodermic psoriasis and 2 with congenital ichthyosiform erythroderma. Biopsy specimens were processed for light and electron microscopy using postfixation with osmium tetroxide and ruthenium tetroxide. OBSERVATION: In NS, and often in congenital ichthyosiform erythroderma and erythrodermic psoriasis, the stratum corneum layer was largely replaced by parakeratotic cells. A distinctive feature--premature secretion of lamellar body contents--occurred only in NS. Furthermore, lamellar body-derived extracellular lamellae and stratum corneum lipid membranes were separated extensively by foci of electron-dense material. Finally, transformation of lamellar body-derived lamellae into mature lamellar membrane structures was disturbed in NS. CONCLUSIONS: Premature lamellar body secretion and foci of electron-dense material in the intercellular spaces of stratum corneum, features not observed in other erythrodermic disorders, appear to be frequent and relatively specific markers for NS. These ultrastructural features could permit the early diagnosis of NS before the appearance of the hair shaft abnormality. These abnormalities could explain the impaired permeability barrier in NS, and account for hypernatremia and dehydration in infants with NS.

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.

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.