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【综述】特应性皮炎的诊断及分级治疗(1)

皮肤科周讯2021-11-02 08:29:26

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1
摘要



背景:特应性皮炎是儿童最常见的皮肤病,发病率为10%~15%,并且在成人中也普遍存在。初级保健医生与专科医生之间的密切配合,对于慢性和重症患者的充分治疗是至关重要的。


研究方法:本文回顾了在Pubmed选择性检索的相关论文,并进一步参考了德国医学科学社团协会(AWMF)和欧洲皮肤病学论坛的指南。


结果:触发因素如皮肤刺激、过敏原、微生物病原体以及心理因素可以影响不同个体的皮肤状态,应进行个性化的评估。为避免特异性和非特异性刺激物,同时应用皮肤保湿霜或润肤剂是非常重要的,因为这些患者的皮肤屏障受到了损害。应用糖皮质激素或钙调磷酸酶抑制剂的局部抗炎疗法是治疗特应性皮炎的核心部分;在一些特殊病例中,严重的患者可应用全身抗炎药治疗。多学科的患者教育已成为管理这种复杂疾病的有效工具。慢性和重症患者的诊断和治疗存在特殊的挑战。


结论:在分子水平基础上,对皮肤屏障障碍和先天性获得性免疫紊乱的最新研究,为特应性皮炎的治疗带来了新方法。




特应性皮炎(特应性湿疹)是儿童最常见皮肤病,学龄前的发病率为10-15%。大约一半的患者伴有中度至重度特应性皮炎。该疾病可在任何时间自发愈合,但1~2%的成人也可受累。该病具有重大的经济意义,因为其是一种十分常见的慢性疾病(2, e1)。通常,这种皮炎与其他特应性疾病,如食物过敏、哮喘和过敏性鼻炎相关。食物过敏的患者伴有严重特应性皮炎的患病率约为30%左右。



2
学习目标


读完本文后,读者应能够


    确定特应性皮炎最重要的诱发因素,同时做出适当的诊断以及给出治疗方案。

    了解过敏原的作用并且制定分级诊断方法。

    熟悉局部和全身疗法的最新建议。


3
特应性皮炎临床特征



特应性皮炎的临床特征取决于疾病发病阶段(急性或慢性)以及患者年龄(表1)。最难忍受的特征通常为慢性或慢性复发性瘙痒症;另一个痛苦原因与社会歧视相关。该疾病发病的严重程度及持续时间有很大不同。即使出现轻度症状,也可能极大的干扰患者生活,引起情绪紧张。与健康对照组相比,特应性皮炎患者通常更易抑郁或焦虑,其可能由于其痛苦经历导致。感染是特应性皮炎常见并发症,并且十分严重(图1和图2,框1)。


Table 1 Characteristic age-dependent features of atopic dermatitis

表1:特应性皮炎年龄相关特征



Figure 1: Skin infections in atopic dermatitis. a) Molluscacon tagiosa; b) Eczema herpeticum.

图1:特应性皮炎的皮肤感染。a)传染性软体动物;  b)疱疹性湿疹。



Figure 2: Clinical features. a) Lichenified flexural dermatitis; left antecubital fossa is excoriated; right is moist and weeping; b) Dermatitis of nape in adult; c) Chronic eyelid dermatitis.

图2:临床特征。a)褶皱处苔癣样皮炎;左肘窝表皮剥脱;右肘窝潮湿并有脓液渗出;b)成人颈背皮炎;c)慢性眼睑皮炎






4
病因,病理生理以及预防



遗传易感性(皮肤屏障缺陷以及先天和获得性免疫受损)和触发因素是诱发、加重特应性皮炎的重要因素。近年来,丝聚合蛋白功能缺失突变受到了特别关注。丝聚合蛋白是分化角质形成细胞中的一种结构蛋白质。丝聚合蛋白的功能性缺失突变导致皮肤屏障缺陷,细菌防御降低,并增加皮肤的pH值。丝聚蛋白突变与特应性皮炎风险增加相关(OR 3.1-4.8)。约25%的特应性皮炎患者伴有这种突变。此外,这些患者发展成过敏、哮喘以及疱疹性湿疹(众所周知,其为特应性皮炎的一种严重并发症)的风险增加。


儿童早期感染的发病率下降,引出David Strachan所谓的“卫生假说”, 其已涉及近几十年来特应性皮炎的发病率增加(根据研究,增长4-8倍);同样的趋势已见于其他特应性疾病。


皮炎的临床表现(皮肤炎症并伴有表皮受累)是由T细胞、IgE结合抗原呈递树突状细胞以及嗜酸性粒细胞引起的。


在急性和亚急性阶段,许多介质,尤其是TH2细胞因子如白介素4(IL-4)和白介素13(IL-13),引起暂时性屏障蛋白下调。


预防过敏的德国AWMF S3指南第61-13号(Allergieprävention)对高风险家庭的饮食以及预防措施提出了建议。其建议包括母乳喂养4个月(或使用水解蛋白配方的奶粉),并在孩子早期饮食中加入鱼肉。根据2009年版的德国指南,应在第一年给予适龄的固体食物,即使是高危的过敏儿童。



5
诊断和触发因素



一般通过临床诊断。特别要注意详细询问个人史和特应性疾病家族史以及进行全面身体检查。


如果具有典型的病史和临床症状,通常不需要进行皮肤活检,但活检有助于鉴别诊断。最常见的鉴别诊断疾病包括其他类型的皮炎,如过敏或刺激性接触性皮炎、钱币状皮炎,但是成人皮肤T细胞淋巴瘤的早期阶段通常不能通过镜下病理排除。手部皮炎通常表现出特应性、刺激性和变态反应性接触皮炎混合特征;通常依据病因很难将其准确分类。当特应性皮炎累及四肢,可以排除掌跖银屑病和皮肤真菌感染。少见的类似于特应性皮炎样改变的综合征或免疫缺陷见框2。其他一些炎症性(以及感染性)皮肤病,如儿童疥疮,偶尔会与特应性皮炎相混淆。



当疑似特应性性皮炎时,有必要了解其可能的心理社会因素,以及饮食或环境触发因素。触发因素的重要性个体差异很大,但对其认识以及避免或减少是个性化治疗的关键部分。同时,由于屏障功能受损,应意识到未知的皮肤刺激的敏感性阈值降低。


感染和免疫接种均可引起特应性皮炎病情加重。尽管如此,根据疫苗接种的建议常务委员会(STIKO),儿童及成人特应性皮炎患者应进行免疫接种。对于急性加重的患者,应避免接种直到皮肤稳定(德国AWMF S2特应性皮炎[神经性皮炎]指南013–027)。



下附英文原文---


Summary


Background: Atopic dermatitis is the most common skin disease in children, with a prevalence of 10% to 15%, and is common in adults as well. Close coordination between primary care physicians and specialists is essential for the adequate treatment of chronically and severely affected patients.


Methods: This article is a review of pertinent publications that were retrieved by a selective search in Pubmed, with additional consideration of the guidelines of the Association of Medical Scientific Societies in Germany (AWMF) and the European Dermatology Forum.


Results: Trigger factors such as skin irritants, allergens, microbial pathogens, and psychological factors can affect the condition of the skin differently in individual patients and should be individually assessed. The use of skin moisturising creams or emollients along with avoidance of specific and unspecific irritants is of great importancel, as these patients have an impaired cutaneous barrier. Topical anti-inflammatory treatment with glucocorticoids or calcineurin inhibitors is a central part of the management of atopic dermatitis; in exceptional cases, severely affected patients are treated with systemic anti-inflammatory drugs. Interdisciplinary patient education has been found to be an effective tool in the complex management of this disease. Chronically and severely affected patients present special challenges for diagnosis and treatment.


Conclusion: Recent advances in the understanding of the molecular basis of cutaneous barrier disorders and of congenital and acquired immune disorders have led to new approaches to the treatment of atopic dermatitis.


Atopic dermatitis (atopic eczema) is the most common skin disease in children with a prevalence of 10–15% before school age. About half of the patients suffer from moderate to severe atopic dermatitis. Spontaneous healing can occur at any time but 1–2% of adults are also affected. The disease is of great economic importance because it is so common and generally chronic (2, e1). Frequently, the dermatitis is associated with other atopic diseases such as food allergies, asthma, and allergic rhinitis. The prevalence of food allergies in patients with severe atopic dermatitis is believed to be around 30%.


Learning Objectives


After reading this article, the reader should be able to


    identify the most important trigger factors for atopic dermatitis, along with the appropriate diagnostic and therapeutic measures to address them.

    understand the role of allergens and the need for a stepwise diagnostic approach, and

    be familiar with the latest recommendations for topical and systemic therapy.


Clinical features of atopic dermatitis


The clinical features of atopic dermatitis vary depending on the stage (acute or chronic) of the disease and the age of the patients (Table 1). The most disabling feature is generally the chronic or chronic-recurrent pruritus; another significant cause of suffering is the associated social stigmatization. The course of the disease is highly variable with flares of varying severity and duration. Even what appears to be mild manifestations can greatly disturb the patient and cause emotional stress. Patients with atopic dermatitis are significantly more often depressed or anxious than healthy control groups, which may be a result of their suffering. Infections are a common complication of atopic dermatitis and can be quite severe (Figures 1 and 2, Box 1).


Etiology, pathophysiology and prevention


Both genetic predisposition (skin barrier defects as well as impaired innate and acquired immunity) and trigger factors play important roles in both the onset of atopic dermatitis and the exacerbations. Filaggrin loss-of-function mutations have received special attention in recent years. Filaggrin is a structural protein in differentiated keratinocytes. Loss-of-function mutations in filaggrin lead to skin barrier defects, reduced bacterial defenses, and an increased skin pH value. Filaggrin mutations are associated with an increased risk to develop atopic dermatitis (Odds Ratio 3.1–4.8). About 25% of patients with atopic dermatitis have such mutations. Moreover, these patients are at increased risk of developing allergies and asthma, as well as eczema herpeticum, which is known to be a severe complication of atopic dermatitis.


The decreased incidence of infections in early childhood led to the so-called ‘hygiene hypothesis' by David Strachan, which has been implicated in recent decades with the increased prevalence of atopic dermatitis (4–8-fold increase, depending on study); the same trend has been seen in other atopic disorders.


The clinical picture of dermatitis (cutaneous inflammation with epidermal involvement) results from the presence of T cells, IgE-binding antigen-presenting dendritic cells and eosinophils.


In the acute and subacute stages, a variety of mediators, especially the TH2 cytokines such as interleukin 4 (IL-4) and interleukin 13 (IL-13), are responsible for the transient down-regulation of barrier proteins.


The German AWMF S3 guidelines No. 61–13 on allergy prevention (Allergieprävention) give the current recommendations for dietary and preventive measures for high-risk families. The recommendations include 4 months of breast feeding (or the use of extensive protein hydrolysate formulas) and the early introduction of fish in the child’s diet. According to the 2009 version of the same German guidelines, age-appropriate solid foods should be started during the first year even in children at high risk for allergies.


Diagnosis and trigger factors


The diagnosis is usually made clinically. Both a detailed history with special attention paid to personal and family history of atopic disorders and a complete physical exam are required.


A skin biopsy is generally not needed if the history and clinical features are typical, but may be useful for differential diagnostic purposes on occasion. The most common differential diagnostic considerations, including other forms of dermatitis such as allergic or irritant contact dermatitis, nummular dermatitis, and in adults an early stage of cutaneous T-cell lymphoma usually cannot be excluded microscopically. Hand dermatitis may often reflect a mixed picture of atopic, irritant and allergic contact dermatitis; it is generally difficult to classify precisely on the basis of etiology. When atopic dermatitis affects the hands and feet, both palmoplantar psoriasis and dermatophyte infections must be excluded. Less commonly one may encounter syndromes or immunodeficiencies which can resemble atopic-dermatitis-like changes (Box 2). Several other inflammatory (also infectious) diseases of the skin, such as scabies in childhood, can occasionally be confused with atopic dermatitis.


When atopic dermatitis is suspected, it is necessary to be aware of possible psychosomatic factors, as well as dietary or environmental trigger factors. The importance of trigger factors varies greatly among individuals, but their identification and then avoidance or reduction are a key part of an individualized treatment approach. One must also be aware of the decreased sensitivity treshold for unspecific skin irritation due to the impaired barrier function.


Both infections and immunizations can cause exacerbations of atopic dermatitis. Nonetheless, according to the Standing Committee on Vaccination Recommendations (STIKO), both children and adults with atopic dermatitis should be immunized. In case of acute exacerbations, vaccinations should be avoided until the skin stabilizes (German AWMF S2 guideline 013–027 on atopic dermatitis [Neurodermitis]).


由MediCool医库软件冯飞飞 编译,上海市皮肤病医院陈裕充博士审核

原文来自:Dtsch Arztebl Int 2014; 111: 509−20