湿疹与特应性皮炎皮损处细菌学研究

目的 探讨湿疹和特应性皮炎(AD)皮损处的细菌学特点及金黄色葡萄球菌(金葡菌)在湿疹及AD发病中的作用。方法 多中心随机双盲对207例湿疹患者和119例AD患者皮损及非皮损处取材做细菌培养,并对所分离到的金葡菌进行常规药敏试验和噬菌体分型。结果 207例湿疹患者皮损处的细菌检出阳性率、金葡菌的比例及定植均明显高于非皮损处,差异有显著性(P<0.01)。119例AD患者皮损处的细菌检出阳性率及金葡菌的定植明显高于非皮损处,差异有显著性。对分离到的141株金葡菌进行噬菌体分型。Ⅰ组占6.3%,Ⅱ组占7.0%,Ⅲ组占3.5%,Ⅴ组占0.7%,杂组占1.4%,不能分型占56%,MRSA分型噬菌体26株混合组占6.3%。药敏试验结果表明在常用的6种外用抗菌药物中莫匹罗星对金葡菌和表皮葡萄球菌的抗菌活性最强,其MIC范围、MIC₉₀和MIC₅₀是6种抗菌药物中最低的。且莫匹罗星对金葡菌及其中的各噬菌体分型和表皮葡萄球菌中的耐甲氧西林和耐甲氧西林凝固酶阴性菌株也有较好的抑菌能力。结论 湿疹和AD的发病与细菌感染密切相关,其中金葡菌是最重要的细菌,对湿疹和AD患者外用药治疗合并使用外用抗菌药物是必要的,根据对金葡菌抗菌活性的测定,莫匹罗星的效果较好。     

特应性皮炎患儿皮损局部金黄色葡萄球菌外毒素检测

目的 了解特应性皮炎(AD)患儿皮损局部金黄色葡萄球菌(金葡菌)的带菌率及其分泌外毒素的情况,探讨金葡菌及其分泌的外毒素在AD发病中的作用.方法 AD皮损局部分离金葡菌,反向被动乳胶试验方法检测其外毒素表达,并与对照组进行统计学比较.结果 与对照组相比,AD患儿无论是皮损局部还是非皮损区金葡菌带菌率明显升高(P值均<0.01),且与疾病严重性呈正相关性(P<0.01).但AD皮损局部的金葡菌与对照组金葡菌相比,两者分泌外毒素的情况差异无显著性(P>0.05),并且皮损局部的金葡菌是否分泌外毒素与疾病严重性无直接相关性(P>0.05),但伴有血清总IgE水平升高的AD患儿,疾病相对较重(P<0.01).结论 AD患儿皮损区金葡菌带菌率为43.24%,其中47.46%分泌外毒素,以金葡菌肠毒素B(SEB)最常见.     

特应性皮炎和湿疹皮肤金黄色葡萄球菌肠毒素及中毒休克综合征毒素-1的检测

目的 探讨皮肤金黄色葡萄球菌(金葡菌)肠毒素及中毒休克综合征毒素-1(TSST-1)在特应性皮炎及湿疹中的致病作用。方法 反向被动乳胶凝集法测定来自117例特应性皮炎和199例湿疹患者皮肤共140株金葡菌的肠毒素/TSST-1。结果 140株金葡菌中60株产生超抗原,阳性率为42.9%,其中43株只产生一种超抗原,17株产生至少两种超抗原。特应性皮炎组超抗原总阳性率为51.5%,皮损与非皮损处无差别。湿疹组超抗原总阳性率为34.7%,阳性株均为皮损处菌。特应性皮炎组超抗原总阳性率、皮损处超抗原总阳性率及中毒休克综合征毒素-1阳性率均高于湿疹组。结论 与湿疹相比,特应性皮炎与金葡菌超抗原的关系较为密切。     

特应性皮炎患者皮损和非皮损处细菌定植分析

采集127例特应性皮炎(AD)患者皮损与非皮损处和健康人正常皮肤处的标本进行细菌培养,观察病原菌分布以及金黄色葡萄球菌(以下简称金葡菌)的检出率,采用湿疹面积与严重度指数(EASI)评价病情严重程度.AD皮损处、非皮损处和健康人对照组细菌阳性率分别为77.2％、20.5％和3.4％,差异具有统计学意义(P ＜0.05);AD皮损处和非皮损处金葡菌构成比分别为61.4％和11.0％,差异有统计学意义(P＜0.05),健康人对照组只分离到1株金葡菌.EASI评分和菌落密度在红斑、渗出、糜烂、皲裂和水肿等部位比较差异具有统计学意义(P＜0.05),经Spearman相关分析显示EASI评分和菌落密度呈正相关(r=0.529,P＜0.05).细菌定植尤其是金葡菌定植与AD的发生发展密切相关,菌落密度与AD的病情进展具有显著相关性.     

寻常型银屑病患者血管内皮生长因子及单核细胞趋化因子-1表达的研究

目的 探讨血管内皮生长因子(VEGF)、单核细胞趋化因子-1(MCP-1)在银屑病患者皮肤中的表达及其意义。方法 用免疫组化法检测银屑病患者皮损、非皮损及正常人皮肤中VEGF、MCP-1的表达与分布。用双抗体夹心酶联免疫吸附法检测患者血清中VEGF、MCP-1水平。结果 ①银屑病患者皮损及非皮损中VEGF表达较正常人皮肤明显增强(P<0.05).皮损中MCP-1表达较非皮损及正常人皮肤明显增强(P<0.05).②患者血清中VEGF水平明显高于正常人(P<0.05),MCP-1水平与正常人比较差异无显着性(P>0.05).③皮损角质形成细胞中VEGF、MCP-1的表达与PASI评分无显着相关性(P>0.05)。结论 VEGF、MCP-1的表达增强在银屑病的发病机制中可能起重要作用。     

干细胞因子及其受体在寻常型白癜风表皮中的表达

目的 探讨SCF/c-kit信号通路在白癜风发病中的作用。方法 采用免疫组化和RT-PCR法检测17例寻常型稳定期白癜风患者和10例正常对照标本中表皮角质形成细胞的干细胞因子表达及基底层黑素细胞c-kit的表达情况。结果 白癜风非皮损区干细胞因子、c-kit蛋白表达与正常对照无明显差异(P>0.05),皮损区干细胞因子表达显著高于正常对照皮肤(P<0.05),而c-kit表达显著低于正常对照皮肤(P<0.05)。白癜风非皮损区表皮干细胞因子、c-kit mRNA表达平均水平与正常对照近似(P>0.05);皮损区干细胞因子mRNA表达水平高于非皮损区及正常对照组差异有统计学意义(P<0.05);皮损区c-kit mRNA表达水平显著低于非皮损区及正常对照组(P<0.05)。结论 SCF/c-kit的异常表达可能与白癜风的发病有关。     

银屑病患者皮损中转化生长因子-β1及受体基因表达的研究

目的 研究银屑病患者皮损及非皮损处转化生长因子-β1(TGF-β1)、转化生长因子β受体(TGF-βRⅡ)及CD105的基因(mRNA)表达,并初步探讨其临床意义。方法 采用异硫氰酸胍法抽提皮肤组织中的RNA;采用逆转录聚合酶链反应(RT-PCR)检测皮肤组织中mRNA的表达。结果 银屑病患者皮损组织TGF-β1及TGF-βRⅡmRNA的表达均低于非皮损组织及正常人(P<0.05);非皮损组织及正常人皮肤组织中mRNA的表达量差异无显著性(P>0.05)。而银屑病皮损组织CD105的mRNA表达量高于非皮损组及正常人(P<0.05);非皮损组织和正常人皮肤组织比较P>0.05。结论 银屑病皮损中TGF-β1及TGF-βRⅡ表达降低和CD105的表达上调可能与银屑病的表皮过度增殖及真皮炎症细胞浸润有关。     

特应性皮炎皮损金黄色葡萄球菌检出情况的研究

目的 :　探讨特应性皮炎 (AD)皮损微生物定植情况 ,为临床合理选用抗菌药物有效控制该病提供依据。方法 :　无菌生理盐水浸湿的棉拭子于 4 3例AD患者皮损处取标本 ,同时对 39例患者非皮损处及 10例健康人取标本作对照 ,进行细菌培养及菌落计数 ,金葡菌予常规药敏试验。结果 :　AD患者皮损细菌阳性率为 74 .4 2 % ,金葡菌为主要的致病菌 ,占 6 5 .6 3% ;非皮损处也可分离出细菌 ,但金葡菌阳性率及密度均明显低于皮损处 (P <0 .0 0 1)。结论 :　微生物感染因素 ,尤其金葡菌感染或定植 ,在AD的发病中起着重要的作用     

大疱性类天疱疮患者黏膜受累与糖皮质激素控制量的相关性

目的 探讨大疱性类天疱疮(bullous pemphigoid,BP)患者黏膜受累与糖皮质激素控制量的相关性。方法 对1988-2002年103例BP住院患者平均糖皮质激素起始控制量、皮损全部消退时间和糖皮质激素开始减量时间进行回顾性研究,按照患者入院时皮损累及部位分为黏膜受累组和无黏膜受累组。结果 103例患者,黏膜受累组37例占35.9%,无黏膜受累组66例占64.1%,黏膜受累组控制病情所需的糖皮质激素量高于无黏膜受累组(t=3.49,P<0.001),两组患者皮损全部消退时间和糖皮质激素首次减量时间差异无显著性(t=0.82和t=0.41,P>0.05)。结论 BP黏膜损害与糖皮质激素控制量相关。     

特应性皮炎和湿疹患者血清白介素4和干扰素γ水平的检测

目的 探讨血清白介素4(IL-4)和干扰素γ(IFN-γ)水平变化在特应性皮炎、湿疹发病机制中的作用,以及糖皮质激素联合抗生素(治疗组)和单独糖皮质激素(对照组)外用治疗前后两种细胞因子的变化。方法 采用双抗体夹心ELISA法检测治疗前后患者血清IL-4和IFN-γ水平 结果 特应性皮炎、湿疹患者IL-4、IFN-γ水平明显高于正常人对照(P<0.05)。治疗28d后,治疗组IL-4水平明显下降(P<0.05),而IFN-γ无明显变化;对照组两种细胞因子水平变化无统计学意义(P>0.05)。结论 特应性皮炎、湿疹患者存在循环IL-4和IFN-γ水平明显异常。糖皮质激素联合抗生素外用治疗特应性皮炎、湿疹可干扰IL-4水平取得较好疗效,较单独外用糖皮质激素疗效显著。     

Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial

BACKGROUND: Staphylococcus aureus has a peculiar ability to colonize the skin of patients with eczema and atopic dermatitis (AD), and is consistently found in eczematous skin lesions in these patients. A correlation between the severity of the eczema and colonization with S. aureus has been demonstrated, and it has been determined that bacterial colonization is an important factor aggravating skin lesions. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. OBJECTIVES: To investigate the colonizing features of S. aureus in the lesional and nonlesional skin of patients with eczema and AD in China and to compare the therapeutic effect of mupirocin plus hydrocortisone butyrate with vehicle ointment plus hydrocortisone butyrate. METHODS: A multicentre, double-blind randomized trial was conducted. Eczema Area and Severity Index (EASI) scores were evaluated before the start of the trial and on the 7th, 14th and 28th day of treatment. Swabs for bacterial isolation were taken from lesional skin before the start of the trial and on the 7th, 14th and 28th day of treatment, and from nonlesional skin only before the start of the trial. A combination topical therapy with mupirocin plus hydrocortisone butyrate ointment was used in the experimental group, with vehicle ointment plus hydrocortisone butyrate ointment as a control. RESULTS: Of 327 patients enrolled in the study, 208 had eczema and 119 had AD. Bacteria were isolated from 70.2% of lesional and 32.7% of nonlesional skin samples from patients with eczema, of which S. aureus accounted for 47.3% and 27.9%, respectively. Bacteria were isolated from 74.8% of lesional and 34.5% of nonlesional skin samples from patients with AD, of which S. aureus accounted for 79.8% and 80.5%, respectively. The colonization density of S. aureus was markedly higher in lesional than in nonlesional skin, both in patients with eczema and with AD (P < 0.01, P < 0.05), and was positively correlated with lesion severity. Considering the EASI scores before and after treatment and the final effective rate, good therapeutic effects were obtained in both the combination experimental groups and the control groups (P < 0.01), and there were no differences in the global therapeutic effect between the two groups in patients with eczema and with AD (P > 0.05). However, in patients with eczema with a clinical score of > 8 or in patients with AD with a clinical score of > 7, the therapeutic effect in the experimental groups was superior to that in the control groups (P < 0.05) on the 7th day of treatment. There were no differences between the two groups on the 14th and 28th days of treatment (P > 0.05). Following the improvement of symptoms and signs of eczema and AD, the positive rates of bacteria and S. aureus were reduced on the 7th day of treatment. CONCLUSIONS: This study confirmed that lesional skin of patients with eczema and AD was more frequently colonized with S. aureus than was nonlesional skin. The more severe the eczema, the higher the colonization rate of S. aureus, and S. aureus was also more often present in lesional and nonlesional skin in patients with AD than in those with eczema. Staphylococcus aureus infection is related to the pathogenesis of eczema and AD. An antibiotic-corticosteroid combination and corticosteroid alone both gave good therapeutic effect in eczema and in AD, and both reduced colonization by S. aureus. Early combined topical therapy is beneficial to patients with moderate to severe eczema and AD, and it is unnecessary to use antibiotics at later stages of disease or in mild eczema or AD.     

Effects of tacrolimus ointment on Toll-like receptors in atopic dermatitis

Background. Alterations of Toll‐like receptors (TLRs) seem to play a role in susceptibility to atopic dermatitis (AD). Aim. To investigate the expression of TLRs in moderate to severe chronic AD in adults before and after a 3‐week treatment with 0.1% tacrolimus ointment, compared with 0.1% topical hydrocortisone‐17‐butyrate. Methods. In total, 21 adult patients with AD were enrolled: 11 were given tacrolimus ointment and 10 were given hydrocortisone butyrate; a further 6 healthy adults formed the control group. The clinical efficacy of the treatment was assessed using the SCORing Atopic Dermatis (SCORAD) index. Biopsies were taken from lesional skin before and after treatment, which were stained immunohistochemically with monoclonal antibodies to TLR‐1, ‐2, ‐4 and ‐9. Results. Both 3‐week topical treatments improved signs and symptoms in all 21 patients considered, with no significant difference between the two groups. In the skin of patients with AD, TLR‐1 was overexpressed and TLR‐2 underexpressed compared with healthy controls, whereas no differences were found for TLR‐4 and TLR‐9. Staining for TLR‐1 was decreased in both groups after treatment. AD specimens had higher levels of TLR‐2 expression after either treatment compared with baseline, and levels were higher after tacrolimus treatment than after hydrocortisone butyrate. Neither tacrolimus nor hydrocortisone butyrate affected expression of TLR‐4 or TLR‐9. Conclusion. Short‐term therapy with tacrolimus ointment reduced expression of TLR‐1, which may inhibit the antimicrobial potential of TLR‐2, and also reversed the impairment of TLR‐2 in AD lesions. Expression of TLR‐4 and TLR‐9 was not affected by tacrolimus.     

Expression of adhesion molecules in atopic dermatitis is reduced by tacrolimus, but not by hydrocortisone butyrate: a randomized immunohistochemical study

Topical tacrolimus represents an effective and well-tolerated treatment for atopic dermatitis (AD). Its known effects include reduced production of proinflammatory cytokines and reduced chemokine gradient. We performed lesional skin biopsies on adult patients affected by moderate-to-severe AD. Then, patients were randomized to receive local treatment with tacrolimus ointment 0.1% and hydrocortisone butyrate ointment 1%. On the 21st day of treatment, another skin specimen was taken. Nine patients treated with tacrolimus and seven treated with hydrocortisone successfully concluded the trial. By immunohistochemistry (alkaline phosphatase/antialkaline phosphatase method), we demonstrated that endothelial leucocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 showed different intensities and patterns of expression in untreated AD lesions. Tacrolimus-treated specimens featured a significant reduction of the expression of ELAM-1, VCAM-1 and ICAM-1, while hydrocortisone-treated lesions did not. Inhibition of adhesion molecule expression may represent another selective mechanism of action of topical tacrolimus in AD.     

特应性皮炎皮损微生物与外用药对比治疗研究

目的 研究特应性皮炎(AD)皮损微生物感染、金黄色葡萄球菌(金葡菌)耐药与外用药的疗效.方法 2001年11月至2002年3月在北京中日友好医院及北京市儿童医院皮肤科门诊,按照Hanifin-Rajka诊断标准,共诊断AD患者71例.治疗前后于皮损处取材进行真菌直接镜检、真菌培养、细菌培养及药敏试验,以SCORAD方法计分,将其中66例患者随机分成两组,分别采用1%硝酸益康唑+0.1%曲安奈德霜与0.1%丁酸氢化可的松软膏外用对比治疗AD患者.结果 AD患者以婴幼儿、儿童为主(≤12岁者占73.24%);皮损细菌培养阳性率为53.51%(金葡菌阳性率为35.21%),真菌阳性率为1.41%;药敏结果显示金葡菌对利福平、万古霉素、丁胺卡那霉素、环丙沙星、头孢唑啉、头孢呋辛等敏感性好;1%硝酸益康唑+0.1%曲安奈德霜与0.1%丁酸氢化可的松软膏外用治疗AD4周时,前者疗效优于后者(P<0.05),细菌阴转率前者高于后者(P<0.01).两组外用药治疗的患者均未见不良反应.结论 具有抗感染与抗炎双重作用的1%硝酸益康唑+0.1%曲安奈德霜治疗AD的疗效优于0.1%丁酸氢化可的松软膏.     

丁酸氢化可的松软膏治疗儿童异位性皮炎临床疗效观察

目的:评价丁酸氢化可的松软膏治疗儿童异位性皮炎的临床疗效。方法:采用自身对照,治疗侧用丁酸氢化可的松软膏;对照侧用0.1％糠酸莫米松霜。结果:共观察了46例异位性皮炎患儿,丁酸氢化可的松软膏的有效率为84.78%,0.1％糠酸莫米松霜的有效率为91.30％,二者差异无显著性(x2=0.93,P>0.05)。二组均未观察到明显的不良反应。结论:丁酸氢化可的松软膏是一种高效、安全的外用皮质类固醇激素制剂,可以应用于治疗儿童异位性皮炎。     

The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study

BACKGROUND: While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. OBJECTIVES: To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. METHODS: Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. RESULTS: CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. CONCLUSIONS: Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.     

早婴儿特应性皮炎发病因素探讨

目的观察纯母乳喂养特应性皮炎(atop ic derm atitis,AD)患儿皮损金黄色葡萄球菌(金葡菌)带菌率,与黄疸的相关性及乳母饮食对AD的影响,探讨以上因素在AD发病中的作用。方法AD皮损局部、非皮损局部分离金葡菌、经皮测定黄疸指数、乳母饮食随机分组,并与对照组进行统计学比较。结果与对照组相比,AD患儿皮损局部金葡菌与对照组金葡菌相比明显升高,黄疸与AD的发病无统计学意义,乳母饮食与AD有关。结论AD患儿皮损区带菌率45.00%,黄疸与AD的发病无相关性,乳母饮食情况参与AD发病。