Percutaneous penetration of sodium lauryl sulphate is increased in uninvolved skin of patients with atopic dermatitis compared with control subjects

BACKGROUND: Involved regions of the skin in patients with atopic dermatitis (AD) have been shown to have higher transepidermal water loss (TEWL), indicating a compromised skin barrier. Whether uninvolved skin also has diminished barrier characteristics is controversial. OBJECTIVES: To study the penetration of sodium lauryl sulphate (SLS) into uninvolved skin of patients with AD compared with the skin of control subjects. METHODS: Percutaneous penetration was assessed using the tape stripping technique on the stratum corneum (SC). Twenty patients with AD and 20 healthy subjects were exposed to 1% SLS for 4 h on the mid-volar forearm. After the end of exposure the SC was removed by adhesive tape. The amount of SLS was determined in each consecutive strip. Fick's second law of diffusion was used to deduce the diffusivity and the partition coefficient of SLS between water and the SC. RESULTS: The SC thickness was similar in both groups; however, the TEWL was higher in patients with AD compared with that of the control group (mean+/-SD 8.4+/-4.3 and 6.3+/-2.0 g m-2 h-1, respectively). There was a correlation between SC thickness and TEWL in control subjects but no correlation was found in patients with AD. The diffusivity of SLS through uninvolved AD skin was higher compared with normal skin (mean+/-SD 12.7+/-5.8x10(-9) and 6.2+/-3.0x10(-9) cm-2 h-1, respectively), while the partition coefficient between SC and water was lower (mean+/-SD 137+/-64 and 196+/-107, respectively). CONCLUSIONS: The results show a different penetration profile of SLS into the SC of patients with AD compared with control subjects. This indicates that even noninvolved skin in patients with AD has altered barrier characteristics, emphasizing the importance of skin protection and prevention of skin contact with chemicals.     

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.     

The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion

Background. Atopic dermatitis (AD) results from an altered skin barrier associated with defects in the lipid composition of the skin. Dogs with AD present similar clinical symptoms to humans, and may be a useful model for investigations into AD. Aim. To analyse the changes occurring in the lipids of the stratum corneum (SC) of dogs with AE after 3 weeks of topical treatment with an emulsion containing ceramides, free fatty acids (FFAs) and cholesterol (skin lipid complex; SLC). Methods. Nonlesional SC was collected by tape stripping from control and treated areas. Free and protein‐bound lipids were purified, and the various classes were isolated by column chromatography, analysed by thin‐layer chromatography and assayed. Results. Ceramides, FFA and cholesterol were all found to be lower in the skin of untreated dogs with AD than in normal dogs, and the topical treatment resulted in significantly increased values for ceramides. Conversely, only trace amounts of glucosylceramides were present in normal SC, but a high concentration (27 μg per mg protein) was detected in canine atopic SC, which disappeared after treatment with SLC. There was a heterogeneous distribution of all of the lipids in the different layers of canine atopic SC, which was more pronounced for protein‐bound than for free lipids. Following topical treatment, the protein‐bound lipid content normalized. Conclusions. Topical treatment with SLC resulted in a significant improvement of the lipid biosynthesis of keratinocytes in atopic dogs, thereby potentially enabling the formation of a tighter epidermal barrier.     

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.     

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.     

Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care products

The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring.     

Macrophage migration inhibitory factor (MIF) in the stratum corneum: a marker of the local severity of atopic dermatitis

Different biomarkers are used to evaluate the severity of atopic dermatitis (AD); however, it remains difficult to determine the severity of localized skin lesions. MIF plays an essential role in the pathophysiology of skin inflammation. To establish whether the MIF level in the stratum corneum (SC) serves as a marker of the severity of AD lesions, we examined the SC MIF (scMIF) levels in AD patients. The SC of the cheek, neck and upper arm skin was collected using tape stripping, and the scMIF levels were measured. Consequently, the scMIF levels were found to be significantly higher in the involved skin lesions than the uninvolved areas within the same patient. Moreover, the scMIF levels were significantly correlated with the severity of local skin lesions. These findings suggest that the scMIF level can be used as an effective marker for evaluating the local severity of AD.     

Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy

The presence of congenitally impaired skin barrier followed by atopic dermatitis (AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum (SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite (HDM) antigen (defined as a novel “atopic march animal model”), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream (pH2.8) or neutral cream (pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD‐like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy.     

Decreased hydration state of the stratum corneum and reduced amino acid content of the skin surface in patients with seasonal allergic rhinitis

Recent studies of the stratum corneum (SC) in patients with atopic dermatitis (AD) have disclosed various functional impairments even in clinically unaffected skin. However, it has not been clear whether the presence of atopic background itself has any influence on the function of the SC. In this study, we conducted functional studies of the SC in the mid-portion of the flexor surface of the forearm of 49 skin lesion-free patients with allergic rhinitis to Japanese cedar pollen (atopic respiratory disease; ARD) in early spring, their disease-active season, by comparing the findings obtained with those in 28 patients with AD and 57 age-matched healthy control subjects. The results showed that the patients with ARD had significantly lower skin surface hydration levels assessed by high-frequency conductometry than those of the healthy control subjects. These levels were, however, not as low as those noted in moderately or severely affected patients with AD. Moreover, by measuring the amounts of water-soluble amino acids contained in the superficial portions of the SC, we found that these are also decreased at a marginal level ( P  = 0.051) in patients with ARD compared with levels in healthy control subjects. In contrast, the water barrier function of the SC evaluated by measurements of transepidermal water loss in patients with ARD was not different from that of the healthy control subjects. These results suggest that, although their skin appears normal clinically, the SC of the patients with ARD has functional deficiency in water-holding capacity.     

Alteration of stratum corneum ceramide profiles in spontaneous canine model of atopic dermatitis

Ceramides (CERs) in the stratum corneum (SC) are thought to play a key role in cutaneous barrier function. It has been reported that human SC contains 11 free CER classes and that their profiles are altered in humans with atopic dermatitis (AD). Although decreased proportions of free CERs or quantities of protein-bound CERs in the SC have been reported in dogs with AD, the overall profile of CERs in the canine SC has not been fully elucidated. The aim of this study was thus to investigate the profile of free CERs in the canine SC and to identify alterations in the CER profiles in dogs with AD. Normal-phase liquid chromatography-electrospray ionization-mass spectrometry indicated 11 clusters of peaks for free CER classes, similar to those recognized in the human SC. The fractions of free SC CER in dogs with AD and in breed- and age-matched healthy dogs were quantitatively compared using high-performance thin-layer chromatography. CER[EOS], CER[EOP] and CER[NP], which are known to be decreased in the skin of humans with AD, were also decreased in the skin of dogs with AD. These findings highlight canine AD as a spontaneous animal model for investigating the disruption of CER-associated cutaneous barrier functions in the corresponding human disease.     

Topical acidic cream prevents the development of atopic dermatitis‐ and asthma‐like lesions in murine model

Long‐standing or repeated skin barrier damage followed by atopic dermatitis (AD) is the initial step of the atopic march that eventually progresses to respiratory allergies. Maintenance of an acidic pH in the stratum corneum (SC) is an important factor for normal skin barrier function. We performed this study to determine whether an oxazolone (Ox)‐induced AD murine model can develop airway inflammation by topical application and nasal inhalation of a house dust mite, Dermatofagoides pteronyssinus (Dp), which is a novel ‘atopic march animal model’, and whether an acidic SC environment, made by repeated application of acidic cream, can interrupt this atopic march. During repeated treatment with Ox and Dp to make an atopic march murine model, acidic cream (pH 2.8) and neutral cream (pH 7.4) adjusted by citric acid and sodium hydroxide mixed with vehicle were applied twice daily. Repeated treatment with Ox and Dp to hairless mice induced AD‐like skin lesions followed by respiratory allergy, defining it as an atopic march model. Acidic cream inhibited the occurrence of respiratory allergic inflammation as well as AD‐like skin lesions. These results indicate that a novel atopic march animal model can be developed by repeated topical and nasal treatments with house dust mite on Ox‐induced AD mice and that the acidification of SC could be a novel intervention method to block the atopic march.     

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.     

Stratum corneum hydration and skin surface pH in patients with atopic dermatitis

Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.     

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.     

Molecular weight dependence of polyethylene glycol penetration across acetone-disrupted permeability barrier

Abstract Previous studies have demonstrated that permeability barrier disruption by acetone treatment significantly enhances skin permeability to both hydrophilic and amphipathic compounds, but not to highly lipophilic compounds. The purpose of the present study was to investigate the dependence of permeability on molecular weight (MW) in acetone-disrupted hairless mouse skin in contrast to normal skin. Penetration of polyethylene glycol (PEG) 300, 600, and 1000 over 12 h was measured using diffusion cells. High-performance liquid chromatographic methods with refractive index detection were used to separate and quantitate the individual oligomeric species in the PEG samples. Percutaneous penetration of PEGs exhibited slightly steeper MW dependency at a transepidermal water loss (TEWL) of 30–41 g/m² per h in comparison with TEWLs of 0–10 (control skin), 10–20, and 20–30 g/m² per h, with a higher percentage of smaller oligomer PEGs penetrating than larger ones. Increasing the TEWL of the skin increased the penetration of all the PEG oligomers, and the degree of the enhancement relative to penetration through control skin increased with MW and was maximal for oligomers with a MW ranging from 326 to 414 Da. Within the limit of quantitation of the assay, the MW cut-off for PEG penetration across mouse skin with TEWLs of 0–10, 10–20, and 20–30 g/m² per h was 414, 590, and 942 Da, respectively, while all the measurable oligomers up to MW 1074 Da were able to penetrate skin with TEWLs in the range 30–41 g/m² per h. The results suggest that not only higher amounts but also more varieties of chemicals may penetrate skin with a compromised barrier than normal skin, implying a higher risk of intoxication and hypersensitization by environmental agents through diseased skin with impaired barrier function. Received: 24 October 2000 / Revised: 20 January 2001 / Accepted: 3 March 2001     

Biophysical assessment of atopic dermatitis skin and effects of a moisturizer

BACKGROUND: The mechanisms of the skin barrier impairment in patients with atopic dermatitis (AD) are still unknown and need further studying. OBJECTIVE: We evaluated the skin of healthy subjects and of patients having atopic dermatitis with an instrument measuring electrical impedance and other noninvasive methods (transepidermal water loss, capacitance) and studied the effects of a new emollient [Proderm (Pro-Q in the USA)]. METHODS: After a 2-week washout period, we treated clinically noneczematous skin on the forearm of 24 patients with AD and assessed the effects with the noninvasive methods. 22 healthy subjects were used as controls. RESULTS: The findings indicate that barrier function and hydration, and certain patterns of electrical impedance of AD skin are abnormal compared with normal skin. Moreover, there was an increase in hydration in patients' skin after treatment and a reversal of certain impedance indices towards normal. CONCLUSIONS: Our findings demonstrate that the moisturizer we used changes some biophysical parameters when applied to atopic skin. In addition, a technique based on electrical impedance seems to give valuable information in atopic skin studies, especially the effects of moisturizers.     

Noninvasive biophysical assessments of the efficacy of a moisturizing cosmetic cream base for patients with atopic dermatitis during different seasons

BACKGROUND: The use of emollients is recommended for patients with atopic dermatitis (AD) to maintain improved condition. OBJECTIVES: To ascertain objectively the effectiveness of a moisturizing cream for patients with AD during different seasons. METHODS: We conducted clinical evaluations, noninvasive biophysical measurements and biochemical analyses of the stratum corneum (SC) components of the volar forearm skin of 23 patients with AD after a moisturizer was applied twice daily for 4 weeks. The moisturizer was formulated according to the consensus of cosmetic scientists belonging to major Japanese cosmetic companies. The nontreated forearm served as a control. RESULTS: After using the moisturizer treatment, the hydration of the SC significantly increased together with a decrease in the desquamation measurements and an improvement in the regularity of skin surface corneocytes. An improvement was observed in the SC barrier function in winter, but was achieved only after 4 weeks in late spring during which time there even occurred exacerbation of skin conditions in three patients. With use of the moisturizer treatment, we found no change in the SC content of free amino acids or ceramides, the ratio of interleukin (IL)-1 receptor antagonist to IL-1alpha, the ratio of immature to mature cornified envelopes, the size of the corneocytes or the emergence of parakeratotic cells in the skin surface corneocytes. CONCLUSION: Treatment with an adequate moisturizer is beneficial for the dry skin of patients with AD during the dry, cold season but it does not influence the impaired SC barrier function as effectively in the less arid season.     

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。     

Sweat mechanisms and dysfunctions in atopic dermatitis

Skin barrier dysfunction is inherent to atopic dermatitis (AD), causing dryness, irritation, and increased permeability to irritants, allergens and pathogens. Eccrine sweat functions as part of the skin’s protective barrier. Variations in sweat responses have been observed in patients with AD, and altered sweat composition and dynamics are under-recognized as important factors in the disease cycle. This review discusses the role that sweat plays in the pathogenesis of AD, examines evidence on abnormal sweat composition, secretion, and neuro-immune responses to sweat in atopic skin, and highlights the value of sweat management.     

Ratio of immature cornified envelopes does not correlate with parakeratosis in inflammatory skin disorders

We have previously established a non-invasive method to evaluate the maturity of cornified envelopes (CEs), and have reported the appearance of immature CEs in the stratum corneum (SC) with poor barrier function, such as the SC of the face. The purpose of the present study was to evaluate CEs in inflammatory skin disorders, and to clarify the relationship between the appearance of the immature CEs and parakeratosis, which is often used as a marker for defective keratinization in inflammatory skin disorders. Cornified envelopes in the outermost SC of involved areas of psoriasis vulgaris (PV) and atopic dermatitis (AD) were strikingly heterogeneous, and consisted of immature CEs stained with anti-involucrin and mature CEs stained with Nile red, whereas CEs of the uninvolved areas were relatively homogeneous, exhibiting mature phenotype. The ratio of immature CEs was significantly higher in the involved areas of PV and AD than that in the corresponding uninvolved areas, suggesting that defective CE maturation may, at least in part, account for the inflammatory disorders. Simultaneous evaluation of CE maturity and parakeratosis was carried out by a combination of involucrin immunostaining and nuclear staining of detergent-dissociated corneocytes. In the involved area of PV, four types of corneocytes in regard to the combination of involucrin staining and nuclear remnant were observed, while both immature CEs and parakeratosis were more often detected in the involved areas of PV than in the uninvolved areas or the upper arm of healthy subjects as a normal control. Thus, corneocytes with involucrin-positive immature CEs were not always associated with parakeratosis at the cellular level. In the involved areas of PV, the ratio of immature CEs and that of parakeratosis were heterogeneous, depending on the cases, and no correlation between the ratios was observed. Inter-individual and intraindividual variations in CE maturity were also suggested by the heterogeneous localization of involucrin in the psoriatic epidermis as examined by immunohistochemistry. In addition, in the face of healthy subjects, four types of corneocytes were similarly detected, and the ratio of immature CEs was significantly higher than that of parakeratosis. These results obviously suggest that the maturation of CEs and disappearance of nuclei are differentially regulated in the epidermis.