Non‐invasive assessment of tryptophan fluorescence and confocal microscopy provide information on skin barrier repair dynamics beyond TEWL

The stratum corneum (SC) serves a primary function of skin barrier and understanding the kinetics of SC formation may provide great insight for skin diagnosis and evaluation of therapies. Besides trans‐epidermal water loss (TEWL), few methods have been characterized to assess skin barrier non‐invasively in vivo, particularly for dynamic measurements on the same specimen over time. The objective of this study was to characterize alternative non‐invasive methods to evaluate the dynamic processes involved in the recovery of normal human SC after total removal. TEWL, tryptophan fluorescence and reflectance confocal microscopy (RCM) were used to determine skin barrier function, cell turnover and epidermal morphology over a period of 10 days after total removal of the SC by tape stripping. The results show a biphasic recovery of TEWL over time, which contrasted with a linear increase of 2.3 μm/day in SC thickness. Tryptophan assessment of cell turnover also demonstrated a biphasic pattern attaining a maximum three to four times the levels of the control site 3 days after injury that slowly returned to baseline and displayed great correlation (R² > 0.95) to viable epidermis thickness that also achieved a maximum about 3 days after injury with an approximate increase of 55%. When plotting the change of TEWL versus SC thickness, a single exponential function is observed [Δ‐TEWL = 55 exp (?0.157×)] which contrasts with other proposed models. These methods were able to present rates for SC recovery processes beyond skin barrier (TEWL) that may provide new insights on kinetics of barrier formation for evaluation of skin conditions and treatments.     

Skin barrier response to occlusion of healthy and irritated skin: Differences in trans‐epidermal water loss,erythema and stratum corneum lipids

Background. Occlusion of the skin is a risk factor for development of irritant contact dermatitis. Occlusion may, however, have a positive effect on skin healing. No consensus on the effect of occlusion has been reached. Objectives. To investigate skin barrier response to occlusion on intact and damaged skin. Methods. In study A, the response to occlusion (nitrile glove material) for either 8 hr daily for 7 days or for 72 consecutive hours, respectively, was determined and compared with that of non‐occluded skin. In study B, the response to occlusion of for 72 consecutive hours of skin that had been damaged by either sodium lauryl sulfate (SLS) or tape stripping, respectively, was determined and compared with that of to non‐occluded pre‐damaged skin. Skin barrier function was assessed by measurements of trans‐epidermal water loss (TEWL) and erythema. In study A, stratum corneum lipids were analysed. Results. Occlusion of healthy skin did not significantly influence skin barrier function, ceramide profile or the ceramide/cholesterol ratio. Occlusion of the skin after SLS irritation resulted in higher TEWL than in the control (P = 0.049). Occlusion of the skin after tape stripping resulted in lower TEWL than in control skin (P = 0.007). Conclusions. A week of occlusion did not significantly affect healthy skin, but was found to decrease healing of SLS‐damaged skin, and to improve healing of tape‐stripped skin.     

Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling

Background Filaggrin gene (FLG) loss‐of‐function mutations have been shown to represent the strongest so far known genetic risk factor for atopic dermatitis (AD). Whereas the barrier characteristics in FLG mutation carriers under baseline conditions have been investigated, there are only limited data on the permeability barrier function in filaggrin‐AD under compromised conditions. Aim We investigated: (i) stratum corneum (SC) integrity/cohesion; (ii) barrier recovery after controlled mechanical and irritant‐induced barrier abrogation; and (iii) the lipid composition of the non‐lesional and lesional skin of AD patients harbouring the European R501X, 2282del4, 3702delG, R2447X or S3247X FLG variants. Methods Thirty‐seven AD patients (14 FLG mutation carriers and 23 non‐carriers) and 20 healthy controls participated in the study. Stratum corneum integrity/cohesion was assessed by measurement of transepidermal water loss (TEWL) and amount of removed protein following sequential tape stripping. Barrier recovery was monitored by repeated measurements of TEWL and erythema up to 96 h after barrier abrogation. Samples for lipid analysis were obtained from non‐lesional and lesional skin using the cyanoacrylate method. Results Tape stripping revealed distinct genotype‐related impairment of the SC integrity/cohesion. No differences in the rate of barrier recovery among the groups were found. The SC lipid analysis revealed significant differences regarding the percentage amount of cholesterol, ceramide/cholesterol ratio and triglycerides in the uninvolved skin as well as the amounts of free fatty acids, CER[EOH] and triglycerides in the skin lesions of the AD FLG mutation carriers. Conclusions Our results provide evidence for discernible FLG‐related barrier integrity phenotypes in atopic eczema.     

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates

Background Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Methods Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0·25%]. Results Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0·0001 for both groups). The skin barrier of normal‐looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0·002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0·02). Conclusion Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.     

Dirt‐binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three‐step programme of occupational skin protection

Background In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt‐binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. Objectives Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. Methods Three cleansing preparations – (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder – were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. Results After a 3‐week treatment, a significant global treatment effect (P < 0·0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone. Conclusions Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three‐step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.     

Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

Plant‐derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA‐d₃₄). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA‐d₃₄ and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose‐dependent manner, with the highest increase from treatment with pure OA. OA‐d₃₄ penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA‐d₃₄ permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions.     

International guidelines for the in vivo assessment of skin properties in non‐clinical settings: Part 2. transepidermal water loss and skin hydration

Background

There is an emerging perspective that it is not sufficient to just assess skin exposure to physical and chemical stressors in workplaces, but that it is also important to assess the condition, i.e. skin barrier function of the exposed skin at the time of exposure. The workplace environment, representing a non‐clinical environment, can be highly variable and difficult to control, thereby presenting unique measurement challenges not typically encountered in clinical settings.

Methods

An expert working group convened a workshop as part of the 5th International Conference on Occupational and Environmental Exposure of Skin to Chemicals (OEESC) to develop basic guidelines and best practices (based on existing clinical guidelines, published data, and own experiences) for the in vivo measurement of transepidermal water loss (TEWL) and skin hydration in non‐clinical settings with specific reference to the workplace as a worst‐case scenario.

Results

Key elements of these guidelines are: (i) to minimize or recognize, to the extent feasible, the influences of relevant endogenous‐, exogenous‐, environmental‐ and measurement/instrumentation‐related factors; (ii) to measure TEWL with a closed‐chamber type instrument; (iii) report results as a difference or percent change (rather than absolute values); and (iv) accurately report any notable deviations from this guidelines.

Conclusion

It is anticipated that these guidelines will promote consistent data reporting, which will facilitate inter‐comparison of study results.     

Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity

Background Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous‐type lesions with xerosis as the prominent clinical sign. Objectives To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langeland’s criteria. Methods Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. Results A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). Conclusion Biophysical measurements of skin barrier in non‐lesional skin of AD may work as an evaluation factor for AD severity.     

Specific barrier response profiles after experimentally induced skin irritation in vivo

Background

Recently, natural moisturizing factors (NMFs) and corneocyte surface topography were suggested as biomarkers for irritant dermatitis.

Objectives

To investigate how exposure to different irritants influences corneocyte surface topography, NMF levels and the barrier function of human skin in vivo.

Methods

Eight healthy adult volunteers were exposed to aqueous solutions of 60% n‐propanol, 0.5% sodium lauryl sulfate (SLS), 0.15% sodium hydroxide, and 2.0% acetic acid, and distilled water, in a repeated irritation test over a period of 96 hours. Erythema, transepidermal water loss (TEWL), skin hydration, the dermal texture index (DTI) and NMF levels were measured at baseline, and after 24 and 96 hours.

Results

SLS and sodium hydroxide had the most pronounced effects on erythema and TEWL. Although n‐propanol caused only slight changes in TEWL and erythema, it showed pronounced effects on skin hydration, NMF levels, and the DTI. NMF was the only parameter that was significantly altered by all investigated irritants. The changes in the DTI were inversely associated with NMF levels and skin hydration.

Conclusion

Skin barrier impairment and the inflammatory response are irritant‐specific, emphasizing the need for a multiparametric approach to the study of skin irritation. NMF levels seem to be the most sensitive parameter in detecting irritant‐induced skin barrier alterations.     

The self-recovery of facial skin barrier and erythema after nanochip treatment

Objective: To determine the degree of acute skin damage and the time required for the recovery of facial skin barrier function after the skin was treated with micro-needles and nanochips of various tip lengths. Methods: For this split face comparative study, a total of 16 subjects were enrolled and randomly divided into 2 groups. In the first group, one of the facial side of each subject was treated with 0.25-mm long nanotips for a total of 6 times while the other facial side was treated with 0.25-mm traditional micro-needles with a straight blade for a total of 6 times. In the second group, one of the facial side was treated with 0.5-mm nanotips for a total of 6 times while the other facial side was treated with 0.5-mm traditional micro-needles with a straight blade for a total of 6 times. Evaluations for trans-epidermal water loss (TEWL), skin hydration and erythema were carried out at baseline, 0, 4, 8, 24, 48 and 72 hours after the treatment. Results: There was no significant difference in TEWL, skin hydration and erythema between the two facial sides of the subjects in the Group one who were treated with 0.25 mm nanochips and traditional micro-needles. However, in the subjects of the Group two, the mean TEWL of the facial side treated with 0.5 mm nanochips was relatively lower than that of the 0.5 mm traditional micro-needles treated facial side at 0, 4, 8 and 24 hours after the treatment. Mean erythema of the facial side treated with 0.5-mm nanochips micro-needles was also relatively lower than that of the 0.5-mm traditional micro-needles treated facial side at 8 hours after the treatment. Rapid recovery of skin barrier function was observed within 4–8 hours after treatment with various lengths of nanochips while it took at least 48–72 hours for recovery of skin barrier function after treatment with various lengths of traditional micro-needles as measured by TEWL. Conclusion: The skin disruption caused by nanotips treatment recovers quicker than the traditional microneedle treatment at equal lengths.     

Improved barrier function observed in cultured skin substitutes developed under anchored conditions

Background/purpose: The current method of producing cultured skin substitutes (CSS) is focused on providing treatments for severe skin wounds/burns. We have developed a modified growth method to make them more suitable for in vitro product‐testing/toxicity‐testing purposes. Method: CSS grown in Petri dishes were either transferred to Franz diffusion cells on day 5 (modified method) or left in the Petri dish (standard method) and maintained in these environments for the remainder of the growth phase. Mitochondrial metabolism (MTT assay) was measured on days 5, 10 and 14 and histology was studied on days 5, 10 and 14. Barrier function for all tissues was evaluated by transferring them to Franz cells (standard method) and measuring transepidermal water loss (TEWL), ³H₂O penetration and ¹⁴C‐niacinamide permeability on days 7, 14 and 21. Results: CSS grown by the standard and modified methods showed comparable cell viability and tissue morphology. Barrier function, however, was markedly improved in CSS grown by the modified method. The average improvement at days 7 and 14 was 1.3‐fold for TEWL, 2.1‐fold for ³H₂O penetration and 6.4‐fold for ¹⁴C‐niacinamide permeability. The barrier function of CSS grown by the modified method was still significantly lower than that of human cadaver skin tested by the same methods. Conclusions: CSS developed using the anchored multi‐cell system showed similar cell viability and morphology and improved barrier function compared with CSS produced by the standard Petri dish method, thereby improving its potential as an in vitro skin permeability and toxicity model.     

Improvement of skin barrier function during treatment of atopic dermatitis

Background: Active dermatitis causes a disturbance in skin barrier function. This can be evaluated by the measurement of transepidermal water loss (TEWL) and percutaneous absorption of hydrocortisone.Objective: The study objective was to evaluate changes in skin barrier function during treatment of atopic dermatitis.Methods: Nine patients with widespread atopic dermatitis were studied longitudinally by measuring the severity of the dermatitis and TEWL at intervals of 1 to 3 days. Percutaneous absorption of hydrocortisone was measured at entry and during treatment.Results: At entry, both TEWL and percutaneous absorption of hydrocortisone were elevated. Four to six days later, a significant decline was observed in both variables, indicating rapid improvement in skin barrier function. Individual changes in TEWL correlated with the changes in the systemic absorption of hydrocortisone.Conclusion: TEWL reflects changes in the systemic absorption of topical hydrocortisone during treatment of atopic dermatitis.     

Ability to estimate relative percutaneous penetration via a surrogate maker – trans epidermal water loss?

Aims: This study measures the dynamic change of the trans‐epidermal water loss (TEWL) rate and in vitro skin permeation data of tritiated water and [¹⁴C]‐clonidine HCl in order to refine our knowledge in the relationship between percutaneous penetration and TEWL. Measures: TEWL values were measured before and during the experimental period. Single application of tritiated water and [¹⁴C]‐clonidine HCl were dosed at the same time on dermatomed human skin samples collected from 12 donors in a flow through diffusion cell system. Radioactivity of absorbed dose: stratum corneum, epidermis, dermis, receptor fluid collected every 4 hours, as well as removable dose residue was counted to determine accountability, percent dose, μg equivalent, and flux rate. These data were further combined with TEWL values to analyze their possible relationship. Results: Results showed that baseline TEWL values correlated with the thickness of dermatomed skin (r=?0.44, P=0.007), and with tritiated water fluxes (r=0.34, P=0.04) and [¹⁴C]‐clonidine HCl (r=0.36; P=0.03). The fluxes of tritiated water and [¹⁴C]‐clonidine HCl were correlated (r=0.67, P<0.001). When TEWL and permeation data were compared, the pattern of tritiated water expressed as a percent dose permeated in receptor fluid resembled the TEWL pattern. Conclusion: The methodology described provides evidences of the correlation of TEWL and skin integrity and skin permeation and further demonstrates to be a rapid alternative to tritiated water permeation for measuring skin barrier functions in vitro. To develop TEWL measurement as a possible predictive model to assess in vitro percutaneous absorption, however more chemicals with various physical‐chemical properties need to be examined, and the relationships to TEWL and tritiated water flux better defined.     

Cera-Glow,ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, improves skin barrier function in clinical study

Background

Ceramides are essential lipids in stratum corneum for skin permeability barrier function in that they retain the skin moisture and protect from the invasion of foreign pathogens. Previously, we demonstrated that ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201 enhanced ceramide production in human epidermal keratinocytes. Furthermore, for comprehensive knowledge of this effect, in vitro experiments and multi-omics analysis were conducted to explore the underlying mechanisms.

Aims

This study was designed to identify whether a cosmetic sample (i.e., Cera-Glow) containing the lysates improves the skin barrier function in clinical trials.

Patients/Methods

Twenty-four female participants (45.46 ± 9.78 years) had been enrolled in the transepidermal water loss (TEWL) measurement for 5 days and 21 female participants (50.33 ± 5.74 years) had undergone a skin hydration evaluation for 4 weeks. TEWL and skin hydration were evaluated using a Tewameter and the Epsilon Permittivity Imaging System, respectively. After applying the Cera-Glow sample, all participants recorded a satisfaction survey questionnaire (e.g., satisfaction, efficacy, and adverse reactions).

Results

Application of Cera-Glow significantly improved transepidermal water loss induced by 1% (w/v) sodium lauryl sulfate (p < 0.05–0.01) and increased skin hydration (p < 0.01). Metabolic analysis suggested that Cera-Glow should contain beneficial gradients for skin barrier function. According to the questionnaire, most of participants were satisfied with the skin hydration improvement and efficacy of Cera-Glow.

Conclusions

Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, can significantly improve skin barrier function.     

Patterns of aluminum hydroxychloride deposition onto the skin

Background: Aluminum hydroxychloride (AlCl₃) is an antiperspirant. Aim: To revisit the AlCl₃ deposition in vivo and in vitro on glass slides and stratum corneum (SC) harvested by cyanoacrylate skin surface strippings (CSSS). Methods: Transepidermal water loss (TEWL) was assessed following application of 5% AlCl₃ on the forearms. The AlCl₃‐coated skin, glass slides and CSSS were observed using two ultraviolet light‐emitting CCD cameras in order to record changes in specular reflectance related to AlCl₃ deposition. In addition, the corneoxenometry bioassay was performed in order to predict AlCl₃ irritation. Results: AlCl₃ deposited on glass slides looked as linear threads and rings of similar sizes. AlCl₃ deposits on skin were almost restricted inside the microrelief lines and as annular deposits at their crossings where acrosyringia are opening. After daily AlCl₃ applications, deposits extended on the CSSS plateaus. At rest in absence of sweating, TEWL was decreased following AlCl₃ applications. During physical exercise, the TEWL increase was limited on the AlCl₃ areas. CSSS appeared unreactive to AlCl₃ at the corneoxenometry bioassay. Conclusion: The similar aspect of AlCl₃ deposits on human SC and on glass slides suggested a physical property of AlCl₃. Repetitive applications of AlCl₃ increased both the deposit area and the barrier function.     

Topical application of a linoleic acid‐ceramide containing moisturizer exhibit therapeutic and preventive benefits for psoriasis vulgaris: a randomized controlled trial

Psoriasis is a chronic skin inflammatory disorder with frequent relapse. Ceramides and their key enzymes are deficient in the lesions, resulting in impaired epidermal permeability barrier, which correlates with disease severity. We evaluated the efficacy of linoleic acid‐ceramide moisturizer (LA‐Cer) as an adjunctive and preventive therapy for psoriasis vulgaris. 106 patients were randomized into two groups. The control group (C₁) received Mometasone Furoate 0.1% Cream (MF) while the treatment group (T₁) was given 0.1% MF in combination with LA‐Cer moisturizer. Psoriasis Area and Severity Index (PASI), pruritus, capacitance (CAP), and transepidermal water loss (TEWL) of normal skin and lesion were evaluated at Week 0, 2, 4, 8. Subsequently, T₁ patients were randomized for another 1 year. LA‐Cer‐group (T₂) maintained the use of moisturizer while control group (C₂) discontinued. CAPs, TEWLs, PASI were assessed after 1 year. Primary endpoints (PASI‐50 at Week 8) revealed superiority of LA‐Cer‐MF versus MF, less relapse, and rebound in LA‐Cer‐group than control (C₂) at Year 1. There were time‐by‐therapy interaction effect on CAPs, lesional TEWL, and PASI. LA‐Cer‐MF induced higher CAP, an earlier reduction of lesional TEWL and PASI than control (C₁). CAPs, lesional TEWL, and PASI remained stable in LA‐Cer‐group. CAPs, lesional TEWL, and PASI were comparable to the baseline levels in control group (C₂). Topical LA‐Cer moisturizer can alleviate psoriasis, and could be a valuable approach for the treatment and prevention of psoriasis.     

Bifidobacterium longum lysate,a new ingredient for reactive skin

Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2010; 19 : e1–e8. Abstract: Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier’s ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down‐regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non‐replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF‐alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3–1%), the probiotic lysate significantly inhibited capsaicin‐induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double‐blind, placebo‐controlled trial. Sixty‐six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans‐epidermal water loss following barrier disruption induced by repeated tape‐stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self‐assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin.     

Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial

BACKGROUND: Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. OBJECTIVES: To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. METHODS: Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. RESULTS: Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. CONCLUSIONS: Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.     

Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice

BACKGROUND: The skin barrier function in patients with atopic dermatitis is disrupted and prolonged topical steroid therapy produces epidermal barrier disturbance. Olopatadine hydrochloride (olopatadine; Allelock; Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan) is an antiallergic drug with histamine H(1) receptor antagonistic action. This drug alleviates skin inflammation and decreases the number of scratching episodes in a murine model of chronic contact dermatitis. OBJECTIVES: To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice. METHODS: The skin barrier of the ears of mice was disrupted by tape stripping. The recovery of skin barrier function was monitored by measurement of transepidermal water loss (TEWL) after barrier disruption. Epidermal hyperplasia was induced by repeated tape stripping for 7 days. Olopatadine was administered orally once daily from 3 days before the first barrier disruption. Betamethasone 17-valerate (betamethasone) was applied topically once daily from 3 days before barrier disruption. RESULTS: Tape stripping led to a significant increase in TEWL. TEWL decreased with time after tape stripping and the skin barrier function recovered by over 60% within 9 h after tape stripping. The recovery of skin barrier in olopatadine-treated mice was significantly accelerated, compared with that in vehicle-treated mice. In contrast, the skin barrier recovery in mice treated with topical betamethasone was significantly delayed, compared with that in vehicle-treated mice. Combined treatment with olopatadine and betamethasone ameliorated the delay in barrier recovery induced by topical treatment with betamethasone. In addition, olopatadine significantly prevented the increase in epidermal thickness induced by prolonged barrier disruption. CONCLUSIONS: These results suggest that systemic administration of olopatadine accelerates the recovery of skin barrier function and ameliorates the adverse effects of topical steroids on skin barrier recovery.     

Measuring transepidermal water loss: a comparative in vivo study of condenser-chamber, unventilated-chamber and open-chamber systems

Background/aims: Two main systems have been utilized for measuring transepidermal water loss (TEWL): open chamber and closed chamber. Yet, further validation and standardization studies may be necessary to reveal the sensitivity, precision, and robustness of these instruments. Methods: Three instruments are compared for their applicability to assess TEWL: unventilated chamber, open chamber and condenser chamber. The comparative study was performed on human forearm skin (n=6), in the normal condition (baseline), and after (1) 10 tape strippings on both arms, (2) moisturizer cream (Eucerin^®) and petrolatum application for 1 h, and (3) 1% sodium lauryl sulfate (SLS) aqueous solution and distilled water (as control) application for 20 min. Results: The condenser‐chamber system, was the only device among these three that could show the effect of tape stripping on TEWL values as compared with baseline (P<0.001). The effect of moisturization, in terms of % change of TEWL values after application of cream and petrolatum, did not show significant difference between devices (P>0.05). However, only the values obtained from condenser‐chamber device revealed a highly significant change as compared with baseline (P<0.001). Condenser‐chamber system could also discriminate between the effect of moisturizer and petrolatum on TEWL values (P<0.05). The change of TEWL values after SLS application was shown to be significant by unventilated and condenser‐chamber systems (P<0.05). However, none of the devices differentiated between the effect of water and 1% SLS solution applied for 20 min. The values obtained from all three instruments correlate well with each other (P<0.001). Conclusion: Our results highlight the differences between two closed‐chamber TEWL measurement instruments, which are designed based on different measurement principles. This may provide insights to find the best practice to improve the quality, precision and sensitivity of the measurements.