特应性皮炎瘙痒机制的研究进展

【摘要】 特应性皮炎（AD）瘙痒是一种典型的非组胺相关瘙痒，涉及复杂的神经传导通路。多种细胞因子和神经肽类物质以及皮肤屏障功能障碍、皮肤菌群失调也参与瘙痒信号的产生和传递。本综述聚焦近年AD瘙痒发病机制和治疗的主要研究进展。     

Reactions to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients.

Skin reactions and itch or burning pain sensations following intradermal injection of the neuropeptide substance P and topical application of the substance P releasing agent mustard oil were studied in 20 atopic dermatitis patients and 20 healthy controls. Changes in skin blood flow were measured with a Laser Doppler flowmeter. Areas of wheal and flare reactions were evaluated planimetrically. Simultaneous with Laser Doppler flowmeter measurements, subjective itch and burning pain ratings were verbally reported on a category partitioning scale at 10-second intervals. Substance P evoked dose-dependent wheal, flare, and itch reactions in both patients and controls. However, substance P doses of 10(-9) -10(-11) mol elicited smaller flares in patients than in the controls whereas the wheal sizes were similar in both groups. Substance P-induced itch ratings were lower in patients at a dose of 10(-10) mol, and the onset of itching was delayed at all substance P levels applied. Mustard oil elicited similar neurogenic inflammatory reactions in both groups, although pain sensations were significantly delayed in atopic dermatitis patients at two mustard oil concentrations, which is further indication of a desensitization of afferent nerve endings contributing to the neurogenic inflammatory reactions in the skin of these patients.     

Contact allergy to Dermatophagoides in atopic dermatitis patients and healthy subjects

To compare different house-dust-mite-derived allergenic materials and to correlate the presence of IgE LO Dermatophagoides with patch test results, 313 atopic dermatitis (AD) patients and 100 healthy volunteers (HV) underwent patch tests with: Dermatophagoides Pteronyssimus (DPT) lyophilized purified alpha fraction in buffered saline/glycerol 50% and or in petrolatum (Bayropharm); 540% DPT and 50% Dermatophagoides farinae (DF) whole bodies in petrolatum and petrolatum oil (Allergopharma-Bracco); DPT and DF whole bodies in petrolatum and petrolatum oil (Lofarma). We found 39% positive reactions among AD subjects and 13% in HV The presence of serum-specific IgE did not influence the patch test results. with of AD patch-lest-positive patients and 5 of 13 HV respectively, showed a positive prick less and or RAST lo Dermatophagoides. Similar sensitization rates were observed with the allergenic material from Bayropharm (54% positivities) and Allergopharma-Bracco (51% positivities), whereas the preparations from Lofarma gave a 20% response rate.     

儿童特应性皮炎患者外周血单一核细胞IL-31与疾病严重程度相关性分析

目的 探讨IL-31在儿童特应性皮炎发病机制中的作用以及与特应性皮炎瘙痒的相关性。方法 22例特应性皮炎患儿与22例健康儿童外周血单一核细胞在葡萄球菌肠毒素B（SEB）刺激或非刺激状态下，应用实时PCR方法分析IL-31表达情况；酶联免疫吸附法测定其血清IgE水平；对患儿病情进行病情严重程度评分，分析IL-31 mRNA与IgE水平、疾病严重程度及瘙痒的相关性。结果 特应性皮炎患儿外周血单一核细胞IL-31表达显著增加，是对照组的23.2倍（P < 0.01）。特应性皮炎组和对照组外周血单一核细胞受SEB刺激后IL-31表达均有不同程度升高，以特应性皮炎组IL-31表达增加更显著，是对照组的20.44倍。患儿血清总IgE水平中位数为260.05 IU/mL（范围5.9 ～ 1131.01 IU/mL），对照组为17.7 IU/mL（范围5 ～ 140.7 IU/mL），两组比较，P < 0.01。IL-31与患儿病情严重程度以及血清总IgE水平无显著相关性（r = 0.07，P > 0.05；r = 0.22，P > 0.05）。结论 IL-31可能参与儿童特应性皮炎发病，其作用机制可能不依赖血清IgE；SEB能诱导正常人外周血单一核细胞快速表达IL-31，是IL-31产生的重要调节因素。     

搔抓诱发或加重特应性皮炎的机制

特应性皮炎是一种慢性、复发性、炎症性皮肤病,临床表现为剧烈瘙痒,严重影响患者心身健康.近年来特应性皮炎发病率增加,然而其病因和发病机制尚未完全阐明,且无有效的控制方法.搔抓可能是重要的诱发和加重因素,可刺激角质形成细胞释放趋化因子及促炎症细胞因子而诱发瘙痒-搔抓循环,破坏皮肤屏障而易于发生微生物感染,导致自身抗原的释放.瘙痒-搔抓循环、微生物感染及自身抗原均在特应性皮炎的发病中起重要作用.通过外用保湿剂、戴棉手套、湿包疗法、心理干预及剪短指甲等方法可避免搔抓.     

特应性皮炎患者血清CXC、CC及C亚家族趋化因子的检测

目的 了解部分CXC、CC及C亚家族趋化因子在特应性皮炎患者血清中的水平和相互关系,及与Th1及Th2相关的细胞因子的关联。方法 用双抗体夹心ELISA方法检测51例特应性皮炎患者血清γ-干扰素诱导的单核因子（Mig）、胸腺和活化调控的趋化因子（TARC）、皮肤T细胞趋化因子（CTACK）及淋巴细胞趋化因子（Ltn）等水平。以SCORAD对特应性皮炎患者进行评分。结果 特应性皮炎患者血清Mig、TARC、CTACK及Ltn水平均显著高于正常人对照组（P < 0.05或 < 0.01）。患者血清CTACK水平与SCORAD呈显著正相关;血清Mig、TARC、CTACK及Ltn水平均与皮损体表面积百分比（BSA%）呈正相关;患者血清Ltn与TARC和CTACK显著相关。结论 CXC、CC及C亚家族的趋化因子在特应性皮炎的发病中可能起作用。血清CTACK水平可能是评估特应性皮炎严重度的一个较好的指标。     

Comparative study of staphylococci from the skin of atopic dermatitis patients and from healthy subjects

BACKGROUND: Bacterial infections occur frequently on the skin of atopic dermatitis (AD) patients. The objectives of this study were to evaluate the microbiology of the skin of AD patients for staphylococci, the frequency and density of each species, and their susceptibility to antimicrobial drugs. METHODS: To study the staphylococci present on the skin of 21 AD outpatients and of 12 healthy subjects (HS), cutaneous organisms were obtained using the contact-plate method. RESULTS: Staphylococcus aureus was isolated in 85.7% of AD patients (mild type, 77.8%; moderate type, 87.8%; and severe type, 100%) and in 25% of HS, while Staphylococcus epidermidis was isolated in 83.3% of HS and in 38.1% of AD patients. Among the coagulase-negative staphylococci (CNS) identified, S. epidermidis was the common type and several other CNS were detected in both AD patients and HS. As the eruption grade of dermatitic skin became more severe, the average density of S. aureus increased (severe, 2.68 +/- 0.86; moderate, 2.49 +/- 0.48; mild, 2.28 +/- 0.44). A reversed tendency was seen in S. epidermidis (severe, 1.80; moderate, 1.90; mild, 2.10). Among nine antimicrobial drugs tested against S. aureus, S. epidermidis, and some other types of CNS isolates, vancomycin (VCM) and minocycline (MINO) were the most active, gentamycin (GM) was the less active, and ampicillin (ABPC) was the least active. CONCLUSIONS: The skin of AD patients was more frequently colonized with S. aureus than that of normal controls. As the severity of the AD lesions increased, the numbers of S. aureus isolated increased. The skin of HS was more colonized with S. epidermidis. Other species of CNS were isolated from several cases of AD patients and HS. In addition, S. aureus, S. epidermidis, and the other CNS showed poor susceptibility to some of the tested antimicrobial drugs.     

N-acetyltransferase 2 acetylation polymorphism: prevalence of slow acetylators does not differ between atopic dermatitis patients and healthy subjects

The genetic polymorphism of human N-acetyltransferase 2 (NAT2) divides the human population into groups with rapid, intermediate and slow acetylator status. Slow acetylator status has been considered a predisposing factor for allergic diseases, lupus erythematosus, toxic epidermal necrolysis or Stevens-Johnson syndrome. The aim of this study was to investigate whether Caucasian patients suffering from atopic dermatitis differed from healthy individuals with regard to the genotype and phenotype of NAT2. Twenty unrelated healthy Caucasian volunteers (9 females and 11 males, aged from 22 to 59 years) and twenty unrelated Caucasian patients suffering from atopic dermatitis (9 females and 11 males, aged between 20 and 54 years) participated in this study. For each one, the NAT2 genotype was determined by polymerase chain reaction with DNA extracted from peripheral blood, using specific primers for the wild-type allele (wt) and the 3 most frequent mutated alleles of NAT2 (C481-->T, G590-->A and G857-->A). The NAT2 phenotype was evaluated with dapsone as a test substrate using high-pressure liquid chromatography. Statistical analysis was performed using the chi(2) test. Phenotype and genotype were distributed as follows: (1) of the healthy subjects, 60% were rapid acetylators (RA) and 40% were slow acetylators (SA); 10% of the RA and 15% of the SA were homozygous, 50% of the RA and 25% of the SA were heterozygous; (2) of the patients, 55% were RA, 40% were SA and 5% were intermediate acetylators (IA); 10% of the RA and 10% of the SA were homozygous, 45% of the RA and 35% of the SA were heterozygous. No significant statistical difference was found between the two groups for genotypes (p = 0.75) or phenotypes (p = 0.60). The phenotyping and genotyping results of healthy subjects were comparable to those found in previous studies. The absence of a significant statistical difference between healthy subjects and atopic dermatitis patients is in contrast to the results of previous studies. Some authors considered that allergic patients are mostly SAs. This could be explained by the fact that we only considered patients suffering from atopic dermatitis whereas, in other studies, patients suffered from different (one or several associated) allergic diseases. NAT2 polymorphism does not differ between patients suffering from atopic dermatitis and healthy subjects. The importance attributed to the SA status, which was previously considered a predisposing factor for allergic diseases such as atopic dermatitis, should be reviewed.     

A double blind trial of H1 and H2 receptor antagonists in the treatment of atopic dermatitis

Summary Eighteen patients with atopic dermatitis were randomly chosen for a clinical trial to compare the action of the H₂ receptor antagonist cimetidine in combination with the H₁ receptor antagonist chorpheniramine against chlorpheniramine alone and against placebo. Each treatment period lasted for 4 weeks. Intensity of puritus was recorded daily by the patient on an analogue scale. Global clinical assessment was graded on a 5-point scale every 2 weeks by the investigators and weekly by the patient himself. Further study parameters were: quantity of the corticosteroid ointment used for emergencies, immunoglobulin E level, and eosinophil count. The data of 16 patients was evaluated. These was no significant difference in any of the study parameters during the three treatment periods. On the basis of this study, the combined administration of H₁ and H₂ receptor antagonists is of no benefit in the treatment of atopic dermatitis.     

Cutaneous reactions and sensations after intracutaneous injection of vasoactive intestinal polypeptide and acetylcholine in atopic eczema patients and healthy controls

Received: 24 July 1997     

Production of interleukin-2 by mononuclear cells in vitro in patients with atopic dermatitis and psoriasis. Comparison with serum interleukin-2 receptor levels.

Atopic dermatitis is associated with profound immunological alterations, in particular decreased lymphoproliferative responses upon stimulation with T-cell mitogens. T-cell blastogenesis involves the production of the soluble cytokine interleukin-2 (IL-2), which in turn upregulates the expression of its own receptor. To investigate the potential role of this cytokine for the pathomechanisms present in atopic dermatitis, 24-h supernatants of PHA-stimulated peripheral blood mononuclear cells from patients with atopic dermatitis (n = 30) of a moderate to severe disease activity were tested for IL-2 activity. In addition, serum concentrations of soluble interleukin-2 receptor (IL-2R) were measured. Non-atopic healthy controls (n = 19) and patients with psoriasis (n = 20), an inflammatory skin disorder with distinct pathogenesis, served as controls. In comparison with psoriasis patients and normal controls, PHA-stimulated mononuclear cells of atopic dermatitis patients released significantly less IL-2 into supernatants. Moreover, there was an inverse correlation between IL-2 concentrations and body surface involvement or serum IgE levels. In contrast, serum IL-2R levels were significantly elevated in both atopic dermatitis and psoriasis, as compared with healthy controls. Furthermore, IL-2R levels in atopic dermatitis patients showed a significant correlation with IgE levels and body surface involvement. The data indicate that T cell activation may occur in both skin diseases. Atopic dermatitis, however, is further characterized by the decreased capacity of mononuclear cells to release IL-2 upon stimulation in vitro.     

特应性皮炎患者外周血表达不同细胞因子T细胞亚群的检测

目的 探讨特应性皮炎患者外周血表达不同细胞因子T细胞群的频数及其与疾病严重程度的相关性。方法 采用流式细胞仪，检测外周血表达不同胞质内细胞因子（包括IL-4、IL-5、IFN-γ、TNF-α）的CD4+ T、CD8+ T、CLA+ T细胞亚群的频数。利用特应性皮炎皮损面积严重度指数积分法方法，获取特应性皮炎患者病情严重程度积分，分析其与表达不同细胞因子的T细胞频数的相关性。结果 特应性皮炎患者外周血中，胞质内表达IL-4和IL-5的CD4+ T、CD8+ T、CLA+ T细胞频数均高于对照组，胞质内表达IFN-γ的CD4+ T、CLA+ T细胞频数低于对照组；差异均有统计学意义。患者组与正常人对照组中，TNF-α在不同T细胞亚群中表达差异无统计学意义。疾病严重程度与IL-4+CD4+ T细胞和IL-5+CLA+ T细胞群的表达频数相关。结论 患者外周血T细胞存在免疫偏移，表达某些细胞因子的T细胞亚群水平可能作为检测疾病严重程度的指标。     

Infrared-spectroscopic determination of the water content of the horny layer in healthy subjects and in patients suffering from atopic dermatitis

Summary Infrared spectroscopic measurements of hydration of the stratum corneum before and after stripping the skin five and ten times with scotch tape are reported. Investigations on 64 healthy persons show that for individuals over 45 and under 15 years of age the range of the measurement values is strikingly larger than for persons in the age group 15–45 years of age. A small, but not significant reduction in the measurement values is found in females as compared to males. A comparison of the clinically unaffected skin of atopic dermatitis patients with the skin of normal persons points to an increase in the hydration of the stratum corneum of atopic dermatitis patients, which is especially evident in patients who show clinical evidence of dry and rough skin.Supported by the Deutsche Forschungsgemeinschaft (grant Gl 91/4)     

The prevalence of Malassezia yeasts in patients with atopic dermatitis, seborrhoeic dermatitis and healthy controls

Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p<0.01). In the patients with atopic dermatitis, fewer positive cultures were found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive cultures were found in 75% of both lesional and non-lesional skin of patients with seborrhoeic dermatitis (not significant). M. sympodialis dominated in patients with atopic dermatitis (46%) and in healthy controls (69%). In patients with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in 43%. A Malassezia species extract mixture would increase the possibility of detecting IgE sensitization to Malassezia in patients with atopic dermatitis.     

IL-31及其受体在特应性皮炎发病中的作用

特应性皮炎是一种慢性复发性、瘙痒性、炎症性皮肤病,该病发病机制不清,涉及遗传、免疫、感染等多种因素.近年来发现浸润到皮损局部的T细胞,其产生的细胞因子在该病的发生发展过程中起着重要作用,尤其是新发现有四个螺旋结构的细胞因子白介素-31.它主要由Th2细胞产生,与特应性皮炎瘙痒的发生有密切联系.