Skin barrier function in patients with completely healed atopic dermatitis

Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.     

中间丝蛋白与特应性皮炎皮肤屏障功能

特应性皮炎的病因复杂,发病机制尚未明确,可能是遗传、环境、皮肤屏障功能缺陷及免疫相互作用的结果.中间丝蛋白基因是表皮分化复合物基因簇的成员之一,与细胞膜形成及表皮终末分化密切相关.中间丝蛋白基因突变是特应性皮炎发病的重要易患因素之一,中间丝蛋白的减少和缺失,可能是引起特应性皮炎等十燥性皮肤病的主要原因.     

特应性皮炎患者皮肤屏障与水闸蛋白1表达的相关性研究

目的 研究特应性皮炎（AD）患者皮肤屏障功能情况,并分析其与水闸蛋白1（claudin-1）表达的相关性。 方法 纳入AD患者和健康人各11例。应用皮肤经表皮失水率测定仪和皮肤高频超声检测仪测定受试者经表皮失水率、表皮厚度与表皮致密度,并用双抗体夹心ELISA法定量检测血清中脱落claudin-1表达量。应用单因素方差分析和t检验比较不同组别之间相关参数的差异;应用Pearson相关系数分析不同参数之间的相关性。 结果 AD患者皮疹部位经表皮失水率为（36.9 ± 34.2） g·m-2·h-1,非皮疹部位为（9.1 ± 6.0） g·m-2·h-1,均高于健康对照［（4.4 ± 3.1） g·m-2·h-1］;AD患者皮疹部位表皮厚度（0.23 ± 0.04） mm,显著高于非皮疹部位［（0.18 ± 0.03） mm］和健康对照［（0.18 ± 0.02） mm］。AD患者皮疹部位有其特征性表皮下低回声带。AD患者claudin-1表达量为（0.80 ± 0.88） ng/ml,显著低于健康人［（1.73 ± 1.85） ng/ml］;claudin-1与表皮厚度显著负相关（r = -0.61）,与经表皮失水率的倒数显著正相关（r = 0.44）。 结论 AD患者损伤的皮肤屏障功能与claudin-1表达相关,屏障功能状态可用经表皮失水率、经表皮失水率倒数和表皮厚度进行定量表述。     

Correlation of clinical features and skin barrier function in adolescent and adult patients with atopic dermatitis

BACKGROUND: Xerotic changes in atopic skin are considered to be related to a decrease in the water permeability barrier. Whether abnormal skin barrier function is the main cause of atopic dermatitis (AD) or a secondary change of the disease is still controversial. Noninvasive bioengineering methods, including the measurement of the transepidermal water loss (TEWL) and water capacitance, have been commonly used to evaluate skin barrier function. AIM: To evaluate the correlation between the clinical features of each evaluation site (severity of AD) and skin barrier function. METHODS: TEWL, capacitance, and pH were checked on five evaluation sites: postauricle, forearm, abdomen, thigh, and popliteal fossa. The subjects included 25 patients, both adolescents and adults, with AD and 25 age-matched normal controls. The clinical severity, from 0 (no clinical manifestation) to 3 (severe), was also scored for erythema, induration/papulation, lichenification, and xerosis on each evaluation site of the AD patients. RESULTS: Based on the data, we found that the clinical severity score was correlated with TEWL and capacitance in more than one-half of the evaluation sites. Erythema and induration/papulation showed a statistically significant correlation with TEWL in most cases (P < 0.05, four sites). Lichenification and xerosis showed a significant correlation with capacitance in most cases (P < 0.05, four sites). In most cases, severity scoring of the clinical features did not show a significant correlation with skin pH. The patients showed higher TEWL and lower capacitance than normal controls (P < 0.05, all five sites). CONCLUSIONS: The results of our study suggest that skin barrier function, measured by TEWL and capacitance, and clinical severity show a statistically significant correlation in patients with AD.     

Characteristics of skin surface morphology and transepidermal water loss in clinically normal-appearing skin of patients with atopic dermatitis: a video-microscopy study

In patients with atopic dermatitis (AD), it is debatable whether clinically normal-appearing skin is equal to non-atopic normal skin. The aim of this study was to quantitatively evaluate the characteristics of normal-appearing skin of AD. We examined the value of skin surface morphological changes using a new, simple, computer-assisted method with a video microscope. We also investigated the physiological function as represented by transepidermal water loss (TEWL) levels in 44 patients with AD and 15 normal controls. The morphological changes were represented by a variation coefficient score that reflected the irregularity of skin ridges, named the surface irregularity index (SII). There were significant differences between the normal-appearing skin of AD and non-atopic normal skin in both SII (P<0.001) and in TEWL (P<0.01). Especially for the SII, there were significant differences between AD subgroups subdivided by peripheral blood eosinophil count (Eo), serum lactate dehydrogenase level, and clinical score. TEWL values were significantly higher in the high-Eo AD group (n=15) than in the low-Eo AD group (n=29) (P<0.05). These findings indicate that clinically normal-appearing skin of AD patients with high disease activity differs from non-atopic normal skin in both surface morphology and physiology and that these changes reflect the current disease activity.     

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.     

Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm)

Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.     

Impairment of skin barrier function is not inherent in atopic dermatitis patients: a prospective study conducted in newborns

We conducted a cohort study to determine whether the barrier dysfunction of the stratum corneum that facilitates the penetration of various exacerbating agents from the environment is inherent in atopic dermatitis patients as suggested by some dermatologists. Clinical observation and biophysical measurements of the skin were performed on the cheek and on the flexor forearm of 24 newborn infants once between 2 and 14 days postnatally and 1, 3, and 6 months later. Nineteen had atopic family histories. Most of the infants had physiologic neonatal xerosis that was observed as a reduced high-frequency conductance without any impairment in the stratum corneum barrier function assessed by transepidermal water loss. Four of the 24 neonates developed atopic dermatitis around 2 to 3 months after birth. In all of them, barrier impairment noted as increased transepidermal water loss was observed only after the development of skin lesions. During their neonatal period, their transepidermal water loss and skin surface hydration state were indistinguishable from those of the neonates whose skin remained lesion-free during the observation period. Therefore, we concluded that the barrier impairment found in atopic dermatitis is not inherent but represents a phenomenon secondary to dermatitic skin changes.     

上海两社区特应性皮炎患儿的皮肤屏障功能研究

【摘要】 目的 探讨上海两个社区特应性皮炎（AD）患儿及健康对照儿童皮肤屏障功能及AD皮损严重程度与皮肤屏障功能的相关性。方法 3 ~ 12岁AD患儿169例和健康对照儿童142例来自上海长宁新泾社区和嘉定菊园社区,检测前臂伸侧、屈侧及脸颊、胫前4个部位非皮损区的角质层含水量和经皮失水量（TEWL）。并用欧洲AD评分标准（SCORAD）对AD患儿临床严重程度进行评分。结果 AD患儿前臂伸侧、屈侧及脸颊、胫前四个部位的TEWL值均高于健康对照儿童（P ＜ 0.05）,角质层含水量在前臂伸侧和胫前均显著低于健康对照儿童（P ＜ 0.05）。AD患儿SCORAD与TEWL均值呈正相关,与角质层含水量均值呈负相关。结论 皮肤屏障功能可以作为评价AD临床严重程度的指标之一。     

Impaired skin barrier and atopic diathesis in perioral dermatitis

Background: Perioral dermatitis (PD) is a common dermatological disease whose aetiology and pathogenesis remain speculative. We investigated skin barrier function and various markers of the atopic diathesis to elucidate their impact on the development of perioral dermatitis. Patients and methods: Forty patients (24 to 69 years of age) with PD were evaluated. Transepidermal water loss was measured in three regions of the face (lateral chin, perinasal cheek and side of the nose) and the patients were assessed for clinical criteria for atopy. Prick tests were performed, and specific IgE against a mixture of aeroallergens (CAP SX1) was measured. The control group consisted of 62 individuals (20 to 68 years of age) without a history of PD or active disease. Results: Transepidermal water loss was significantly increased (P < 0.001) on all regions of the face in the patient over the control group. Significantly (P < 0.001) higher values were also found for the patient group regarding history (52.5 % vs. 17.7 %) and clinical signs of atopic diathesis (≥ 4 features: 72.5 % vs. 0 %), prick test reactivity (≥ 2 reactive prick tests: 60 % vs. 12.9 %), and specific IgE against aeroallergens (CAP SX1 classes ≥ 2: 60.0 % vs. 17.7 %). Conclusions: Our findings emphasize the relevance of impaired skin barrier function as a pathogenic factor in the causation of perioral dermatitis. The susceptibility of atopic skin to irritants increases as soon as the skin becomes eczematous. Therefore, we propose that atopic diathesis serves as an intensifier, supporting development and continued presence of perioral dermatitis after nonspecific irritant mechanisms have induced impaired skin barrier function.     

Neuropeptides in the skin of patients with atopic dermatitis

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuro-peptides were examined in lesional and non-lesional skin of AD patients (n= 5) and in normal controls (n= 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9·5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0·05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients hut no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetyleholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD.     

Susceptibility to irritants: role of barrier function, skin dryness and history of atopic dermatitis

The susceptibility of the skin to various irritants was investigated with the aim of determining the role of the barrier function of the stratum corneum, skin dryness and whether a history of atopic dermatitis (AD) was a factor. The transepidermal water loss (TEWL) was measured using an evaporimeter and skin hydration using a Corneometer and by visual scoring. The group with a history of AD (n = 20) had a lower pre-exposure barrier function and a higher TEWL value following irritant exposure than the group with a history of allergic contact dermatitis (n = 18) and a control group (n = 18). Clinically dry skin was more susceptible than normal skin, though no difference was noted in the pre-exposure barrier function. The increased susceptibility to irritants in those with a past history of AD was probably due to impaired barrier function and/or the presence of a dry skin.     

Acute irritant threshold correlates with barrier function,skin hydration and contact hypersensitivity in atopic dermatitis and rosacea

The aim of the study was to disclose interactions between epidermal barrier, skin irritation and sensitization in healthy and diseased skin. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients with atopic dermatitis (AD), rosacea and healthy controls. A 4‐h patch test with seven concentrations of sodium lauryl sulphate was performed to determine the irritant threshold (IT). Contact sensitization pattern was revealed by patch testing with European baseline series. Subjects with a lower IT had higher TEWL values and lower SCH. Subjects with positive allergic reactions had significantly lower IT. In AD, epidermal barrier deterioration was detected on both volar forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters were observed on the facial skin only, suggesting that barrier impediment is restricted to the face in rosacea, in contrast with AD where the abnormal skin physiology is generalized.     

Impairment of skin barrier function in NC/Nga Tnd mice as a possible model for atopic dermatitis

BACKGROUND: The pathogenesis and aetiology of atopic dermatitis (AD) remain unclear. Establishment of suitable animal models should aid elucidation of the pathogenesis and development of therapy. OBJECTIVES: We focused on biophysical and biochemical parameters in the skin of NC/Nga Tnd mice to evaluate similarities to and differences from AD. METHODS: Biophysical (transepidermal water loss and skin surface conductance) and biochemical parameters (ceramide contents and activity of ceramide-metabolizing enzymes) were measured in NC/Nga Tnd mice in which spontaneous dermatitis appeared under ambient laboratory conditions (ALC). RESULTS: Biophysical parameters suggested impairment of water retention properties and barrier function. The amount of ceramide in NC/Nga Tnd mice under ALC decreased significantly. These dermatological features resembled those of AD, as did the clinical signs and histological changes. CONCLUSIONS: The results described here and previous immunological studies on AD suggest that the NC/Nga Tnd mouse may be a suitable model for certain aspects of AD.     

Complement and immunoglobulin deposits in the skin of patients with atopic dermatitis

The immunofluorescent patterns of uninvolved and involved skin biopsies from eight patients with atopic dermatitis were studied, using direct immunofluorescence techniques to identify deposits of the immunoglobulins G, A and M as well as the complement factors C1q, C3, C4, C5, factor B and properdin. Immunoglobulin deposits (mainly IgG) were found in five patients, complement deposits in three patients in the basement membrane zone. In three patients the immunofluorescence was positive for C3, in two patients for C1q, C4 and C5. Regarding the factors of the alternative pathway of the complement system, two patients showed deposits of properdin, one of factor B. The changes were not confined to the eczematous lesions, but were found in uninvolved skin too. The most prominent changes were observed in patients with severe disease.