Variation in barrier impairment and inflammation of human skin as determined by sodium lauryl sulphate penetration rate

BACKGROUND: Skin irritability after a brief exposure to the model skin irritant, sodium lauryl sulphate (SLS), is known to vary considerably between individuals. A difference in the skin barrier to SLS may contribute to this variation. To date, no human in vivo data have been available on SLS penetration into the skin. OBJECTIVES: We studied whether the SLS penetration rate into the stratum corneum (SC) is related to impairment of the water barrier function and inflammation of the skin. METHODS: The penetration of SLS into the SC was assessed using a noninvasive tape-stripping procedure in 20 volunteers after a 4-h exposure to 1% SLS. Additionally, the effect of a 24-h exposure to 1% SLS on the skin water barrier function was assessed by measuring the transepidermal water loss (TEWL). The accompanying inflammation was quantified by measuring erythema. RESULTS: The mean +/- SD diffusivity of SLS (D) and the SLS permeability coefficient (Kp) were 1.4 +/- 0.6 x 10(-8) cm2 h(-1) and 1.5 +/- 0.7 x 10(-3) cm h(-1), respectively. A multiple regression analysis showed that the baseline TEWL, SC thickness and SLS penetration parameters K (SC/water partition coefficient) and D clearly influenced the increase in TEWL after the 24-h irritation test (explained variance: r2 = 0.80). Change in erythema was mainly influenced by SC thickness. CONCLUSIONS: We found that variation in the barrier impairment and inflammation of human skin depends on the SLS penetration rate, which was mainly determined by SC thickness.     

Increased permeability for polyethylene glycols through skin compromised by sodium lauryl sulphate

In this in vivo human study we assessed the influence of skin damage by sodium lauryl sulphate (SLS) on percutaneous penetration of polyethylene glycols (PEGs) of different molecular weights (MW). Percutaneous penetration of PEGs was determined using tape stripping of the stratum corneum (SC). The forearm skin of volunteers was pretreated with 5% w/w SLS for 4 h, and 24 h later patches with PEGs were applied for 6 h. The penetration parameters were deduced by data regression to Fick's law for unsteady-state diffusion. The trans-epidermal water loss (TEWL) increased after SLS treatment from 6.3 +/- 2.1 to 17.9 +/- 8.7 g/m(2)/h. The diffusion coefficient for all PEGs was increased in the SLS-damaged skin. The increase was smaller for higher MW. In addition, the partition coefficient of PEGs between SC and water was larger in the SLS-compromised skin and showed a tendency to increase with MW. The permeability coefficient decreased gradually with increasing MW of PEGs in both control and SLS-compromised skin. SLS caused a threefold increase in the permeability coefficient for all MWs ranging in control skin from 0.34 to 0.70 x 10(-5) cm/h and in the SLS-compromised skin from 1.20 to 2.09 x 10(-5) cm/h for MW of 590-282 Da. The results of this study show the deleterious effect of SLS on the skin barrier for hydrophilic PEGs. A defective skin barrier will facilitate absorption of other chemicals and local skin effects.     

Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients

Involved regions of the skin in atopic dermatitis (AD) patients have an altered barrier function. Whether uninvolved skin also has a diminished barrier is controversial. To assess the barrier function of uninvolved skin in AD patients, the percutaneous penetration of polyethylene glycols (PEGs) of various molecular sizes was determined in vivo in AD patients and control subjects using tape stripping of the stratum corneum (SC). The diffusion and partition coefficients were determined using Fick's second law of diffusion. The SC thickness was similar in both groups; however, the trans-epidermal water loss was higher in atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was twice as high as through normal skin, and decreased with increasing molecular weight (MW) in both groups. The partition coefficient in the skin of AD patients was half of that for normal skin but as for normal skin, there was no MW dependency. Although atopic skin exhibited altered barrier with respect to diffusion and partitioning, the permeability coefficients were nearly the same for atopic and normal skin. The results support the assumption of altered skin barrier of AD patients even in the skin that is visibly unaffected by disease.     

Normal recovery of the stratum corneum barrier function following damage induced by tape stripping in patients with atopic dermatitis

Patients with atopic dermatitis (AD) constantly inflict mechanical damage to their skin by scratching induced by pruritus. On excoriated lesions of the cheek we found exceedingly high levels of transepidermal water loss (TEWL) as compared to those in the normal skin of healthy subjects. However, it is not clear whether the skin of patients with AD also shows an abnormally slow recovery after mechanical damage. We compared the recovery of the barrier function of the stratum corneum (SC). after its complete removal by tape stripping, in patients with AD and age-matched healthy control subjects. On the normal-looking skin of the flexor forearm, we found no difference in the recovery process of the water barrier function of the SC between the two groups. This suggests that ability to reconstruct SC barrier function after mechanical damage is not impaired in AD patients.     

Effect of Aqueous Cream BP on human stratum corneum in vivo

Background Aqueous Cream BP is widely prescribed to patients with eczema to relieve skin dryness. The formulation contains sodium lauryl sulphate (SLS), a chemical that is a known skin irritant and a commonly used excipient in personal care and household products. The chronic effects of Aqueous Cream BP application on skin barrier function have not been determined. Objectives To characterize and assess skin barrier function of healthy skin after application of Aqueous Cream BP and to study the physical effects of the formulation on the stratum corneum (SC). Methods The left and right volar forearms of six human volunteers were each separated into treated and control sides. The treated sides of each forearm were subjected to twice daily applications of Aqueous Cream BP for 4 weeks at the end of which concomitant tape stripping and transepidermal water loss (TEWL) measurements were made. The untreated sides of the forearms were not exposed to any products containing SLS during the study period. Results Changes in SC thickness, baseline TEWL and rate of increase in TEWL during tape stripping were observed in skin treated with Aqueous Cream BP. The mean decrease in SC thickness was 1·1 μm (12%) (P = 0·0015) and the mean increase in baseline TEWL was 2·5 g m^?2 h^?1 (20%) (P < 0·0001). Reduced SC thickness and an increase in baseline TEWL, as well as a faster rate of increase in TEWL during tape stripping, were observed in 16 out of 27 treated skin sites. Conclusions The application of Aqueous Cream BP, containing ～1% SLS, reduced the SC thickness of healthy skin and increased its permeability to water loss. These observations call into question the continued use of this emollient on the already compromised barrier of eczematous skin.     

Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function

We have used microdialysis in the dermis for assessing penetration kinetics of salicylic acid (SA) in healthy volunteers (n = 18), following application on the volar aspect of the left forearm. Penetration was monitored at four locations: in normal (unmodified) skin and in skin with perturbed barrier function from (i) repeated tape stripping (ii) irritant dermatitis from 1 or 2% sodium lauryl sulphate (SLS) for 24 h and (iii) delipidization by acetone. The order of the treatments was randomized according to a latin square design. Epidermal barrier function and skin irritation were assessed in each location using evaporimetry and colorimetry. Transepidermal water loss (TEWL) values confirmed that both mild (acetone), moderate (1% SLS) and severe barrier damage (tape stripping and 2% SLS) had occurred. Microdialysis sampling with two parallel probes in the dermis was performed in each of the four treatment areas for every subject. SA (5% in ethanol) was applied in a chamber glued to the skin overlying the microdialysis probes and sampling was continued for 4 h. SA was detectable in all samples and measurable in all samples from penetration through perturbed skin. Comparing the SA penetration in barrier-perturbed skin with the penetration in unmodified skin in the same subject, the mean SA penetration increase was 2.2-fold in acetone-treated skin (P = 0.012), 46-fold in mild dermatitis and 146- and 157-fold in severe dermatitis and tape stripped skin, respectively (P < 0.001). The penetration of SA significantly correlated with the measurements of barrier perturbation by TEWL (P = 0.01) and erythema (P = 0.02) for each individual. Microdialysis sampling of SA penetration was more sensitive than non-invasive measuring techniques in detecting significant barrier perturbation in acetone-treated skin. A positive dose-response relationship for the percutaneous penetration of SA in response to increasing SLS pretreatment concentrations and thus the degree of irritant dermatitis was found. When analysing data by location on the forearm, a tendency towards an intraregional variation in the reactivity to barrier damage was found, with the most proximal location displaying higher reactivity scores than the most distal location in response to the same barrier perturbation procedures. The penetration of SA was not significantly different between locations. In conclusion, using microdialysis in the dermis to obtain real-time dermal pharmacokinetics in the target organ, this study demonstrates highly increased and differentiated cutaneous penetration of SA in barrier-perturbed skin. The measured drug penetration was demonstrated to correlate with non-invasive quantification of barrier damage.     

Increased stratum corneum serine protease activity in acute eczematous atopic skin

Background Atopic dermatitis (AD) is a chronic inflammatory disease associated with changes in stratum corneum (SC) structure and function. The breakdown of epidermal barrier function in AD is associated with changes in corneocyte size and maturation, desquamation, lipid profiles, and some protease activities. Objectives The purpose of this study was: (i) to examine physiological changes in lesional (L) skin of acute eczematous AD, compared with nonlesional (NL) AD skin and healthy (H) skin, using sequential tewametry and SC protein analysis to estimate SC thickness; and (ii) to assess which serine proteases might be involved in pathogenesis. Methods Six subjects with H skin, six AD patients with NL skin and six AD patients with mild to moderate eczema (L skin) were enrolled. Skin was assessed using several noninvasive techniques but SC thickness was estimated using tewametry and SC protein content of D‐Squame strippings. SC integrity was determined by sequential tape stripping (D‐Squame) and infrared densitometry. Kallikreins, plasmin, urokinase and leucocyte elastase protease activities together with a novel SC tryptase‐like enzyme activity were quantified. Results Transepidermal water loss (TEWL) levels after D‐Squame stripping were elevated in L compared with NL and H skin at all sampling points (P < 0·05). Conversely, the amount of SC removed by sequential tape stripping was decreased in L skin, indicating increased intracorneocyte cohesion (P < 0·05). By correlating 1/TEWL values and SC removed as an estimate of SC thickness, a significantly thinner SC was observed in L compared with NL and H skin (P < 0·05). Elevated extractable serine protease activity was measured in AD skin in the order: SC tryptase‐like enzyme (45×), plasmin (30×), urokinase (7·1×), trypsin‐like kallikreins (5·8×) and chymotrypsin‐like kallikreins (3·9×). Leucocyte elastase activity was not detected in H and NL skin but was observed in AD SC samples (L skin). All enzymes were elevated in the deeper layers of L SC compared with NL and H SC samples. All consistently elevated SC protease activities were significantly correlated with the bioinstrumental data. Conclusions We report increased serine protease activities in acute eczematous AD, especially in deeper layers of the SC, including SC tryptase‐like enzyme, plasmin, urokinase and leucocyte elastase activities. These elevations in protease activities were associated with impaired barrier function, irritation, and reduced skin capacitance. Increased SC cohesion was apparent despite elevated TEWL during tape stripping, which would indicate reduced SC thickness in acute eczematous lesions of AD. Indeed, this was observed using an estimate of SC thickness.     

Ceramide analogue 14S24 selectively recovers perturbed human skin barrier

BACKGROUND: Topical ceramide application is an effective therapeutic approach in skin disorders with disturbed barrier function, including atopic dermatitis and psoriasis. OBJECTIVES: To evaluate ceramide analogue N-tetracosanoyl-(l)-serine tetradecyl ester (14S24) using a novel ex vivo model. METHODS: Freshly excised human skin was disrupted by lipid extraction, tape stripping and sodium lauryl sulphate (SLS) treatment. Barrier perturbation was evaluated by the measurement of transepidermal water loss (TEWL), skin hydration and the penetration of model compound, theophylline (TH), assessed by microdialysis. The effect of topical 5% 14S24 was compared with a commercial formulation containing a skin lipid mixture (LR) and control formulation with no skin lipids (L). RESULTS: Both LR and 14S24 produced significant recovery of TEWL and TH penetration in extracted and tape-stripped skin with 14S24 being significantly more effective. In SLS-treated skin, 14S24 decreased TEWL but not TH penetration; LR was inactive. L improved skin hydration but not barrier characteristics. Weak correlation between TEWL and TH penetration was observed in extracted and tape-stripped skin but not in SLS-treated skin. CONCLUSIONS: Cutaneous microdialysis can serve as a useful tool for the evaluation of skin barrier recovery by topical formulations ex vivo whereas TEWL may not be an appropriate measure of skin barrier function in such studies. The excellent barrier repair activity of 14S24 could be beneficial in skin disorders with ceramide deficiency.     

Increased stratum corneum turnover induced by subclinical irritant dermatitis

The chronic effects of the irritant sodium lauryl sulphate (SLS) on stratum corneum (SC) barrier function, determined by transepidermal water loss (TEWL) measurements and on epidermal cell kinetics, estimated by stratum corneum turnover time (SCTT) determination (dansyl chloride staining method), were investigated in 18 healthy female volunteers. SLS (7.5%) was applied without occlusion for 20 min once daily, over a period of 3 weeks (5 days a week) on dansyl chloride-stained skin and on untreated skin. SCTT of untreated skin (19.3 +/- 0.8 days; mean +/- SEM) was not changed by daily treatment with water (control) (19.3 +/- 2.0) but was significantly reduced by SLS (10.9 +/- 0.6; P less than or equal to 0.0001; compared to controls). However, TEWL was increased in SLS-treated sites 1.5-fold after 4 days of treatment (5.3 +/- 0.6 vs. 3.5 +/- 0.3; P less than 0.001). At the end of the second week, TEWL was increased 2.6-fold and after 3 weeks TEWL was 3.3 times higher than in controls 13.0 +/- 1.6 vs. 3.9, P less than or equal to 0.0001). The intensity of SLS-induced irritation as measured by TEWL was significantly correlated with baseline TEWL (r = 0.50; P less than or equal to 0.02) and significantly negatively correlated with SCTT of SLS treated sites (r = -50; P less than or equal to 0.02) but not with SCTT of untreated skin (r = 0.19).     

The effect of aqueous cream BP on the skin barrier in volunteers with a previous history of atopic dermatitis

Background The emollient aqueous cream BP is frequently used for the treatment of atopic dermatitis (AD), yet it is associated with a high rate of adverse cutaneous reactions. It contains the harsh anionic surfactant sodium lauryl sulphate, a known negative environmental factor associated with the exacerbation of AD. Objectives To investigate the effect of aqueous cream BP on stratum corneum (SC) integrity and skin barrier function in volunteers with a predisposition to a defective skin barrier. Methods Thirteen volunteers with a previous history of AD (no symptoms for 6 months) applied aqueous cream BP twice daily to the volar side of one forearm for 4 weeks. The other forearm was left untreated as a control. Permeability barrier function and SC integrity were determined before and after treatment by measuring transepidermal water loss (TEWL) in conjunction with tape‐stripping. For comparison, 13 volunteers with current AD were recruited for assessment, without treatment, of SC integrity and skin barrier function at unaffected sites. Results Topical application of aqueous cream BP resulted in significant elevation of baseline TEWL and a concomitant decrease in SC integrity. Measurements made after no treatment in volunteers with current AD, at unaffected sites, suggest that application of aqueous cream BP negatively affects the skin barrier towards the damaged state associated with onset of flares of the disease. Conclusions Aqueous cream BP used as a leave‐on emollient caused severe damage to the skin barrier in volunteers with a previous history of AD. Aqueous cream BP should not be used as a leave‐on emollient in patients with AD.     

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.     

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.     

Skin barrier function and dermal inflammation. An experimental study of transepidermal water loss after dermal tuberculin injection compared with SLS patch testing

The reaction of the skin water barrier to dermal inflammation was studied in 15 healthy volunteers. Dermal inflammation was induced either by injection of tuberculin (Mantoux test) or by a 24-h sodium lauryl sulphate (SLS) patch test on the volar forearm. Measurement of transepidermal water loss (TEWL) was used for evaluation of the skin barrier function. Inflammation was quantified by assessment of blood flow by laser-Doppler flowmetry. Measurement from uninvolved skin in the test region > 7 cm distant from the test sites served as control. Measurements were performed twice, separated by an interval of 6 days. Throughout the study. TEWL values were higher in the SLS test sites than in the Mantoux reactions, although the blood flow was significantly increased in Mantoux reactions compared with SLS test sites. This indicates that the impaired skin barrier function caused by SLS is due to a direct cytotoxic effect, and TEWL were significantly higher on the arm with the Mantoux test than the arm with SLS patch test. The significant inflammation caused by the Mantoux reaction may cause functional alterations in the clinically normal skin > 7 cm distant from the test area.     

Occurrence of patchy parakeratosis in normal-appearing skin in patients with active atopic dermatitis and in patients with healed atopic dermatitis: a cause of impaired barrier function of the atopic skin

It remains unclear whether an impaired barrier function often seen in areas of normal-appearing skin in patients with active atopic dermatitis (AD) is primary event in nature or secondary to subclinical eczematous change. We then attempted to evaluate the barrier function of normal-appearing skin in both active and healed AD patients, and as well as see whether a subclinical eczematous change exists or not in the normal-appearing skin using a non-invasive method. Transepidermal water loss (TEWL) measurement and exfoliative cytology method for corneal layer were applied in 153 AD patients who have active skin lesions and 29 individuals with completely healed AD for at least 5 years and 40 normal individuals. The TEWL of normal-appearing skin in severe, moderate and mild AD cases was 10.5+/-2.9, 8.3+/-2.4 and 7.3+/-2.1 g/m2 per h, respectively. The TEWL values in severe and moderate cases were significantly higher than the normal controls (6.2+/-1.6 g/m2 per h). However, the TEWL was not deranged in patients with completely healed AD. An exfoliative cytology examination of corneal layer disclosed that patchy parakeratosis appeared in normal-appearing skin in severe, moderate and mild AD cases at a rate of 42, 29 and 19%, respectively. However, no patchy parakeratosis was recognized in patients with completely healed AD. The occurrence of patchy parakeratosis in normal-appearing skin in patients with active AD suggests that an impaired barrier function often seen in normal-appearing skin in AD patients is secondary to subclinical eczematous change in the area.     

Measurement of electrical current perception threshold of sensory nerves for pruritus in atopic dermatitis patients and normal individuals with various degrees of mild damage to the stratum corneum

BACKGROUND: Patients with atopic dermatitis (AD) are well known to be sensitive to irritation from the environment due to the impaired function of the stratum corneum (SC). Electrical current perception threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of the sensory nerves. OBJECTIVE: To study the CPT in a noninvasive fashion using Neurometer CPT/C, together with measurements of various functions of the SC. METHODS: We measured the CPT on the flexor forearm and cheek of AD patients and normal individuals. Subsequently, we evaluated the CPT and skin sensitivity to a 30% aqueous solution of lactic acid after the infliction of various mildly disruptive measures on the SC on the flexor forearm of healthy individuals by the following three methods: (1) removal of the superficial sebum with acetone/ether, (2) scarification with a needle and (3) tape stripping of the SC. Finally, we examined the effect of topical applications of emollients such as petrolatum or a moisturizing cream to the scratched skin. RESULTS: AD patients showed a lower barrier function and lower CPT than normal individuals. In subsequent studies conducted in normal individuals, the CPT was found to be inversely correlated with transepidermal water loss (TEWL) levels after tape stripping. However, most of all, the partial superficial scarification with a needle decreased the CPT and increased the lactic acid stinging response. Prolonged removal of lipids from the SC with acetone/ether for 30 min that increased the TEWL levels for only 1 day decreased the high-frequency conductance value for 2 days and the CPT only on the 2nd day after treatment. Topical applications of emollients were effective to prevent the increased sensitivity caused by scratching. CONCLUSIONS: AD patients showed functional abnormalities of the SC and tended to have more sensitive skin on the cheek and flexor forearm than healthy controls. Even focal SC damage caused by superficial cracking may lead to further disruption of the already damaged SC in AD patients, by eliciting scratching and facilitating the permeation of various environmental allergens and also the induction of hypersensitive skin.     

Functional analyses of the skin surface of the areola mammae: comparison between healthy adult male and female subjects and between healthy individuals and patients with atopic dermatitis

Background Although the nipple and areola of the breast constitute a unique and prominent area on the chest, so far no study has been done on the functional properties of their skin surfaces. Objective To study the stratum corneum (SC) covering the areola using noninvasive methods. Methods Eighteen adult healthy subjects comprising nine men and nine women and 18 age‐ and sex‐matched patients with atopic dermatitis (AD), none of whom had visible skin lesions, participated in the study. Transepidermal water loss (TEWL), skin surface hydration and skin surface lipid levels were measured on the areola and adjacent breast skin. The size of the skin surface corneocytes of these skin regions was assessed. Results All the healthy subjects showed significantly higher TEWL accompanied by smaller sized corneocytes on the areola than on the adjacent breast skin. Only female subjects revealed a significantly higher skin surface hydration state together with significantly increased skin surface lipid levels on the areola than on the adjacent breast skin. These sex differences were observed even in patients with AD. Comparison between healthy individuals and the patients with AD demonstrated higher TEWL, decreased skin surface hydration state and lower skin surface lipid levels associated with smaller sized corneocytes in the areola in the patients with AD, especially in male patients. Conclusions In adults, the SC barrier function and SC water‐binding capacity of the areola were functionally poorer than in the adjacent skin, being covered by smaller sized corneocytes and lower amounts of skin surface lipids, especially in men and in patients with AD.     

特应性皮炎患儿与健康儿童皮肤屏障功能的对比

目的探讨特应性皮炎(AD)患儿与健康儿童皮肤屏障功能的差异。方法 0～7岁的AD患儿和健康儿童各60名,根据不同年龄段分成2组,0～2岁组和2～7岁组各30例。依次进行角质层含水量、pH值、经表皮水分丢失量(TEWL)的测量,使用SPSS13.0统计软件分析。结果 0～2岁、2～7岁AD患儿与健康儿童比较,角质层含水量除前臂无差异外,前额和颊前均明显低于健康对照组;皮肤表面pH值均明显高于健康对照组;0～2岁的AD患儿TEWL值除前臂无差异外,前额和颊前均明显高于健康对照组,而2～7岁AD患儿TEWL值均明显高于健康对照组。结论 AD患儿与健康儿童比较,皮肤屏障功能存在障碍。表现为角质层含水量、皮肤表面pH值、TEWL值有不同程度的差异。     

Epidermal calcium release (ECR) in vivo sampled with a simple washout chamber technique

Background/aims: Epidermis forms the protective barrier of the skin by its outermost layer, stratum corneum. The purpose of this study was to investigate the epidermal barrier in view of epidermal calcium release (ECR), phosphate release, transepidermal water loss (TEWL) and skin surface pH. Calcium is mainly an intracellular ion. Calcium was sampled introducing a new and simple washout chamber technique for the study of epidermal release in vivo. Methods: Test sites on forearms of 13 healthy subjects were pre-treated with 24 h water occlusion, 24 h 2% sodium lauryl sulphate (SLS) or tape stripped. Both untreated and pre-treated test sites were exposed to a water washout chamber with 200µ deionized water as a solvent. Water washout chambers were removed after two hours and calcium and phosphate in the water was analyzed. Transepidermal water loss and pH were measured before and after the trial. Results: pH increased after tape stripping and after exposure to SLS. Transepidermal water loss increased significantly at all test sites. Calcium was significantly released from SLS-treated sites but not from tape stripped sites. There was generally a correlation between ECR, phosphate release, TEWL and pH. In this study ECR is showed to be a barrier marker of high reproducibility. Conclusions: Epidermal calcium release or ECR is found useful as an indicator of skin barrier function. Calcium release and increase of pH appear mainly to illustrate direct and corrosive damage to epidermal cells and functions contrasting TEWL, in this experiment probably reflecting intercellular damage of fracturing as exemplified by mechanical damage resulting from surface stripping. This new distinction of skin barrier damage into cellular damage resulting from a corrosive chemical trauma and intercellular damage and fracturing resulting from a mechanical trauma is exemplified in SLS provocative testing and tape stripping, the former characterized by increased ECR. The washout chamber technique was deemed technically reliable and reproducible, and has a major potential in experimental dermatology and skin pharmacology for the study of in vivo epidermal release of a range of endogenous and exogenous substances.     

Clinical severity correlates with impaired barrier in filaggrin-related eczema

Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin barrier function, have been shown to be a major predisposing factor for atopic dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin-related AD, we investigated stratum corneum (SC) hydration and transepidermal water loss (TEWL) as parameters of barrier function in AD patients harboring FLG mutations compared to AD patients without any FLG mutation. In filaggrin-related AD, SC hydration was both significantly reduced (P<0.01-0.05) and thicker (P<0.01-0.05) than that in healthy controls. TEWL was demonstrably increased in non-filaggrin AD compared to healthy controls (P<0.01-0.05). The objective score of atopic dermatitis (OSCORAD), a disease clinical severity index, significantly correlated with TEWL (r=0.81, P<0.005), SC hydration (r=-0.65, P<0.05), and SC thickness (r=0.59, P<0.05) in filaggrin-related AD. On the contrary, there was no correlation between these parameters and the OSCORAD in non-filaggrin AD. Furthermore, a significant correlation was obtained between the OSCORAD and specific IgE for house dust (r=0.66, P<0.05), mite allergen (r=0.53, P<0.05), and cat dander (r=0.64, P<0.05) in filaggrin-related AD, but not in non-filaggrin AD. All these data suggest that experimentally demonstrable skin barrier defects due to FLG mutations may play a crucial role in the pathogenesis of AD.     

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.