皮肤屏障与特应性皮炎

皮肤屏障结构与功能异常是特应性皮炎的主要病理生理改变,而皮肤屏障的修复已成为特应性皮炎的基础治疗。该文就皮肤屏障主要结构及与特应性皮炎发病的关系以及皮肤屏障修复在特应性皮炎治疗中的作用作一简要阐述。     

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。     

特应性皮炎与皮肤屏障相关性研究进展

特应性皮炎（Atopic dermatitis,简称AD）是一种慢性、复发性疾病,以皮肤瘙痒、干燥和炎症为特点,影响着全世界20％～30％的儿童,其中90％于5岁以内发病。其发病机制尚不清楚,可能与遗传、神经免疫失调、皮肤屏障功能异常及环境因素密切相关,目前认为遗传性或获得性皮肤屏障功能障碍在AD的发病中起着重要作用。     

玉泽皮肤屏障修护剂对儿童特应性皮炎的干预治疗

目的 观察玉泽皮肤屏障修护剂在儿童特应性皮炎治疗中作用.方法 将67例特应性皮炎患者随机分为治疗组和对照组.对照组34例,外涂糠酸莫米松乳膏1次/d,2周后隔日1次,治疗4周,观察8周;治疗组33例,同时将玉泽皮肤屏障修护剂涂于患处及皮肤特别干燥部位2次/d,连用8周.分别于治疗后第1、2、4和8周对患儿进行随访.结果 第1周2组比较差异无统计学意义（P＞0.05）,第2、4周,治疗组较对照组疗效显著,2组比较差异均有统计学意义（P＜0.05）.治疗组患儿皮肤干燥程度均较治疗前明显好转,与对照组各时间段之间比较差异均有统计学意义（P＜0.05）.第8周复诊时,2组临床治愈患者治疗组7例复发,对照组10例复发,2组比较差异有统计学意义（P＜0.01）.结论 玉泽皮肤屏障修护剂在儿童特应性皮炎治疗中明显改善皮肤屏障功能,提高疗效,降低复发率。     

IL-33和IL1RL1基因单核苷酸多态性与特应性皮炎相关性研究

目的：分析IL-33和IL1RL1基因单核苷酸多态性(SNPs)与特应性皮炎（AD）的相关性。方法：PCR-SSP方法检测89例AD患者和138名正常对照组受试者IL-33和IL1RL1编码基因的等位基因和基因型频率。结果：AD患者的IL-33 rs1800925 C等位基因的频率高于对照组，而T等位基因和rs764706552等位基因G低于对照组（均P＜0.001）。IL-33 rs1800925基因型CC和rs764706552基因型CG与AD显著正相关（均P＜0.001）。两组患者的IL1RL1基因的等位基因和基因型频率无明显差异（均P＞0.05）。结论：IL-33基因可能与AD的发病相关。     

特应性皮炎相关细胞因子对皮肤屏障的影响

【摘要】 皮肤是人体最大的器官,是一个重要的屏障。特应性皮炎患者存在皮肤屏障功能异常,同时其细胞因子的组成与健康人不同。在特应性皮炎患者皮肤中发现的许多细胞因子能够影响角质形成细胞的分化和角化过程。本文综述了特应性皮炎相关细胞因子的最新进展及其对皮肤屏障功能的影响,这些结果有利于了解特应性皮炎的发病机制,并可能为特应性皮炎的治疗提供新的方向。     

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。     

表皮角质层屏障功能与特应性皮炎相关研究进展

 皮肤持续暴露于外界病原体,其屏障功能对皮肤的稳态至关重要。既往研究表明,屏障功能的紊乱和缺陷是特应性皮炎重要的发病机制之一。本文从角质层屏障以下几个方面进行概述：①丝聚蛋白减少;②脂质改变;③角质化包膜形成异常;④角质细胞的脱落失衡;⑤皮肤微生物区的变化,总结了表皮角质层是如何形成的,并回顾了它与特应性皮炎病理机制的联系。     

特应性皮炎患者血清白细胞介素-33水平及其临床意义

<正>特应性皮炎(AD)是一种以皮肤干燥、湿疹样皮损和明显瘙痒为主要临床特征的慢性过敏性皮肤病^[1]。近年来,AD的发病率逐步上升,影响着全球约20%儿童及3%成人^[2-3]。有研究表明免疫失调是AD发病的关键环节,其中辅助性T细胞(Th)1/Th2分化失衡引起细胞因子分泌异常在AD发生和发展中起着重要作用^[4]。     

角质形成细胞与特应性皮炎相关研究进展

角质形成细胞（keratinocytes,KCs）的异常导致角蛋白的表达出现异常,从而导致表皮屏障功能失调。在特应性皮炎(Atopic Dermatitis,AD)皮损中,KC大量表达胸腺淋巴基质生成素、肿瘤坏死因子α以及一些白细胞介素如IL-1α、IL-1β和IL-18等介导皮肤的炎症反应。在AD中KC还可表达模式识别受体,通过先天免疫系统,产生和维持炎症反应。另外,AD皮损中KC损伤导致抗菌肽的表达缺乏可能有助于增加AD患者皮肤对感染病毒、细菌和真菌的易感性。本文对角质形成细胞与特应性皮炎相关研究进展进行综述。     

Role of the epidermal barrier in atopic dermatitis

The skin's permeability barrier protects against extensive water loss and prevents the entry into the skin of harmful substances like irritants, allergens and microorganisms. The permeability barrier is mainly located in the stratum corneum and consists of corneocytes and a lipid‐enriched intercellular domain. The barrier is formed during epidermal differentiation. In atopic dermatitis the skin barrier is disturbed already in non‐lesional skin. The disturbed skin barrier allows the entry of environmental allergens from house dust mites, animal dander and grass pollen into the skin. In predisposed individuals these allergens may trigger via immunologic pathways the inflammation of atopy. The causes for the disturbed epidermal skin barrier are changes in skin lipids and in epidermal differentiation, in particular filaggrin mutations. Filaggrin mutations lead to a disturbed skin barrier and dry skin which are hallmarks in atopic dermatitis. Therapeutic agents influence the skin barrier differently; topical therapy with potent corticosteroids does not lead to the repair of the barrier in atopic dermatitis, whereas therapy with the calcineurin inhibitors and lipid‐containing emulsions support barrier repair.     

The effect of wet-wrap dressing on epidermal barrier in patients with atopic dermatitis

BACKGROUND: Wet-wrap dressing has been shown to be effective for atopic dermatitis; however, the therapeutic mechanism of wet-wrap dressing is only the hypothesis based on the recovery of decreased epidermal barrier function. OBJECTIVES: To examine the therapeutic efficacy as well as the mechanism of wet-wrap dressing in atopic dermatitis patients. METHODS: To examine the difference of non-lesional and lesional atopic skin and to evaluate the change between epidermal barrier function before and after the treatment, SCORAD, epidermal water content, transepidermal water loss, the lipid amount of skin surface, immunohistochemical staining of filaggrin and loricrin, transmission electron microscopic examination, and calcium ion capture cytochemistry method were done in 10 severe form atopic dermatitis patients. RESULTS: In atopic dermatitis patients, SCORAD was clearly decreased, epidermal water content was increased, and transepidermal water loss was decreased after wet-wrap dressing. After wet-wrap dressing, increased release of lamellar body and the recovery of the damaged lamellar structure of intercellular lipid were observed; nevertheless, neither the change in keratinocyte differentiation nor the change of calcium ion gradient was detected. A week after the termination of wet-wrap dressing, increased water content and decreased transepidermal water loss were still maintained. CONCLUSION: We confirmed the abnormality of the epidermal barrier in atopic dermatitis, and the effects of wet-wrap were associated with the recovery of epidermal barrier. In atopic lesions, wet-wrap dressing induced clinical improvement by the release of lamellar body and the restoration of intercellular lipid lamellar structure.     

白癜风患者血清白细胞介素33及其可溶性受体ST2水平检测及意义

 目的:探讨白癜风患者血清白细胞介素33（IL-33）及其可溶性受体ST2（sST2）表达水平的变化及其临床意义。方法：采用酶联免疫吸附试验对62例白癜风患者和30例健康对照组血清IL-33和sST2表达水平进行检测,并分析IL-33和sST2在白癜风患者不同分期、面积、病程等分组中的表达差异。结果：白癜风患者外周血中IL-33和sST2水平在进展期及稳定期均明显高于正常对照组（IL-33：t值分别为4.67、2.34,P值分别为0.004、0.031;sST2：t值分别为3.59、2.09,P值分别为0.027、0.045）。白癜风患者自身抗体异常组sST2水平明显高于无自身抗体异常组,差异有统计学意义（t=2.46,P=0.015）;不同分期、性别、白斑面积、家族史、精神应激、微量元素临床亚组间IL-33和 sST2水平差异均无统计学意义（P值均>0.05）。外周血IL-33和 sST2水平与年龄及病程均无明显相关性（P值均>0.05）。结论：IL-33及sST2可能与白癜风的发病密切相关。IL-33水平升高可能主要发生在白癜风起始阶段,与疾病活动度及严重程度无明显相关。sST2水平的升高可能是IL-33介导的炎症反应和免疫应答的负反馈调节机制。     

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.     

IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors

In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.     

The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions

Abstract: The mechanism of action of pimecrolimus (PIM) on atopic lesions is still under consideration. Thus far, we have evidence of its anti‐inflammatory and immunomodulatory activity, and recent papers focus on its effect on epidermal barrier function. This study analysed changes in the expression of genes associated with skin barrier dysfunction in atopic dermatitis (AD) skin lesions after 2 weeks of exposure to PIM 1% cream. A real‐time quantitative PCR analysis of selected epidermal differentiation complex genes and three alternative pathway keratins was performed in skin biopsies from 11 individuals with AD before and after PIM exposure. The real‐time quantitative PCR analysis was compared to non‐lesional skin in the same patients. Involucrin, a small proline‐rich region (SPRR) 2C gene, and alternative pathway keratin 16 showed significant over‐expression in lesional skin followed by significant decrease after PIM therapy. The SPRR1A gene, S100A9, and keratin 6A were also increased; however, the decrease after PIM treatment was not significant. The changes in S100 A2, A7 and A8 followed a similar course with borderline significance. SPRR4 had a significant decrease in expression in lesional versus non‐lesional skin, which persisted after PIM treatment. No significant changes were detected in mRNA expression levels of filaggrin and loricrin. Our results suggest that PIM can be effective in restoring the epidermal barrier in patients with AD at least in part by its impact on expression of genes, which are important for the normal barrier function of skin.     

早期梅毒患者血清IL-27、IL-33水平检测

目的:研究早期梅毒患者血清IL-27、IL-33水平。方法:以我院2014年1月至2015年1月期间接诊的80例早期梅毒患者作为研究对象,根据其治疗效果将其分为梅毒血清转阴组和梅毒治疗无效组两组,每组各40人,然后再选择40例正常人群作为对照组。在治疗前,对三组患者的血清RPR滴度进行检测;在治疗前后,分别对三组患者的血清IL-27和血清IL-33水平进行检测,比较其在治疗前后的不同以及各组患者之间的差异,并对其结果进行分析。结果:治疗前,梅毒血清转阴组以及梅毒治疗无效组的血清RPR滴度均没有明显的差异(P0.05),具有可比性。治疗前,三组患者的血清IL-27水平具有明显的差异(P0.05);治疗后,梅毒血清转阴组患者以及正常对照组患者的血清IL-27水平与治疗前比较,没有明显的变化(P0.05),而梅毒治疗无效组患者的IL-27水平变化明显(P0.05);治疗前,梅毒血清转阴组和梅毒治疗无效组两组患者的血清IL-33水平没有明显的差异(P0.05),而两组患者的血清IL-33水平均明显高于正常对照组(P0.05);治疗后,梅毒治疗无效组患者以及正常对照组患者的血清IL-33水平与治疗前比较,没有明显的变化,差异无统计学意义(P0.05),而梅毒血清转阴组患者的IL-33水平变化明显。结论:在患者的血清中,IL-27及IL-33均参与患者机体对梅毒螺旋体的免疫应答,其中IL-27水平对于机体清除梅毒螺旋体具有更加重要的意义,对于早期的梅毒患者,在患者体内有较高水平的IL-27,则其血清RPR转阴可能性更大,具有临床应用价值,值得推广。