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.     

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.     

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。     

Sensitization to cockroach allergens evaluated by skin tests in children with atopic dermatitis

INTRODUCTION: Cockroach and house dust mites (Dermatophagoides pteronyssinus, Dp and farinae, Df) are the most often implicated aeroallergens in severe asthma, hay fever and conjunctivitis. Cockroach allergy is still unknown in atopic dermatitis.PATIENTS AND METHOD: 146 children with atopic dermatitis-aged 6 months to 15 years- have been patch tested with the European standard series and some aeroallergens. We have studied the sensitisation to cockroach allergens and compared to Dp and Df.RESULTS: 113 children reacted positively at least to one of the 3 aeroallergens (77 p. 100), 61 children had a positive reaction to cockroach (42 p. 100) and 29 simultaneously to the 3 allergens.DISCUSSION: Delayed hypersensitivity to house dust mites in young children with atopic dermatitis suggests early epicutaneous sensitization due to an altered epidermal barrier. For us, cockroach could also be implicated in some flare-ups of atopic dermatitis. Eviction of cockroach and house dust mite should be proposed for children with a positive patch test to cockroach.     

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。     

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.     

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.     

The epidermal barrier in atopic dermatitis

Epidermal barrier function is abnormal in individuals with atopic dermatitis (AD). It is controversial whether primary epidermal barrier abnormalities alone account for the physiological and clinical abnormalities found in those persons with AD or whether the observed barrier dysfunction is a consequence of primary immunologic abnormalities. Recent evidence is strengthening the argument for the former hypothesis. Attention to epidermal barrier care (ie, gentle skin care) has long been an important part of the therapy of AD. Advances in our understanding of the biology of the epidermal barrier and how this relates to the clinical manifestations of this disease has important consequences for new therapeutic approaches in the management of AD.     

皮肤屏障功能与特应性皮炎

目前认为特应性皮炎发病机制不清,可能具有遗传缺陷的个体,在环境等因素的作用下皮肤的蛋白、脂质等的代谢出现异常,进而出现皮肤屏障结构的异常,导致天然保湿因子、抗菌肽减少、经皮失水率增加和pH值的升高等病理生理改变。本文将对皮肤屏障结构异常与特应性皮炎的关系进行综述。     

'Dry' skin in atopic dermatitis. I. A clinical study

A common finding in patients with atopic dermatitis is the occurrence of 'dry' skin on non-eczematous regions. 'Dry' skin is here defined as a clinical condition meaning a rough, finely scaling non-inflamed skin surface. The frequency and extension of 'dry' skin were examined in 50 patients with atopic dermatitis and were compared with those in 50 non-atopics. A discrepancy was found in both groups between the subjective opinion of the presence of 'dry' skin and the objectively noted 'dry' skin. Among the atopics, 48% were found to have 'dry' skin compared with 14% among the controls (p less than 0.01). The most frequent location of 'dry' skin in both groups was the back. Intolerance to wool was found to be significantly high (p less than 0.01) in the atopic group, although it was also quite common in non-atopics. In order to correlate the clinical observation to skin morphology, a replica-technique was used to visualize the surface of 'dry' skin in the scanning electron microscope.     

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.     

Multihormonal response to dexamethasone. A study in atopic dermatitis and normal controls.

Although minor disturbances of the circadian serum cortisol rhythm and diminished excretion of steroid metabolites have been reported in patients with atopic dermatitis, test assays regarding subtle neuroendocrine alterations have not been employed so far. We therefore studied the serum concentrations of cortisol, prolactin and adrenocorticotropin under baseline conditions, after 1 mg dexamethasone and after a defined methylprednisolone treatment in 15 patients with atopic dermatitis, in comparison with 10 healthy controls. The assessment of the hormones revealed no remarkable differences between either group at any of the blood sampling time points. However, in 3 patients and 2 control subjects, though exhibiting no concomitant disease, we could find no suppression of endogenous cortisol to below 5 micrograms/dl after oral intake of 1 mg dexamethasone. These cortisol non-suppressors showed lower dexamethasone serum concentrations in the morning after its administration, as compared with the suppressors. Acute (1 mg dexamethasone) or prolonged (40 mg methylprednisolone over 6 days) intake of glucocorticoids suppressed prolactin levels in both groups, demonstrating that the effect of glucocorticoids on the hormone system is not restricted to the hypothalamic-pituitary-adrenal axis. Our results indicate an intact feedback response of this hormonal axis to 1 mg dexamethasone and the ability of long-term as well as acute glucocorticoid administration to influence the prolactin secretion in patients with atopic dermatitis.