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皮科寶典丨特應(yīng)性皮炎的診斷及分級治療(1)

 geminini 2016-06-22


1
摘要



背景:特應(yīng)性皮炎是兒童最常見的皮膚病,發(fā)病率為10%~15%,并且在成人中也普遍存在。初級保健醫(yī)生與??漆t(yī)生之間的密切配合,對于慢性和重癥患者的充分治療是至關(guān)重要的。


研究方法:本文回顧了在Pubmed選擇性檢索的相關(guān)論文,并進(jìn)一步參考了德國醫(yī)學(xué)科學(xué)社團(tuán)協(xié)會(AWMF)和歐洲皮膚病學(xué)論壇的指南。


結(jié)果:觸發(fā)因素如皮膚刺激、過敏原、微生物病原體以及心理因素可以影響不同個體的皮膚狀態(tài),應(yīng)進(jìn)行個性化的評估。為避免特異性和非特異性刺激物,同時應(yīng)用皮膚保濕霜或潤膚劑是非常重要的,因為這些患者的皮膚屏障受到了損害。應(yīng)用糖皮質(zhì)激素或鈣調(diào)磷酸酶抑制劑的局部抗炎療法是治療特應(yīng)性皮炎的核心部分;在一些特殊病例中,嚴(yán)重的患者可應(yīng)用全身抗炎藥治療。多學(xué)科的患者教育已成為管理這種復(fù)雜疾病的有效工具。慢性和重癥患者的診斷和治療存在特殊的挑戰(zhàn)。


結(jié)論:在分子水平基礎(chǔ)上,對皮膚屏障障礙和先天性獲得性免疫紊亂的最新研究,為特應(yīng)性皮炎的治療帶來了新方法。




特應(yīng)性皮炎(特應(yīng)性濕疹)是兒童最常見皮膚病,學(xué)齡前的發(fā)病率為10-15%。大約一半的患者伴有中度至重度特應(yīng)性皮炎。該疾病可在任何時間自發(fā)愈合,但1~2%的成人也可受累。該病具有重大的經(jīng)濟(jì)意義,因為其是一種十分常見的慢性疾病(2, e1)。通常,這種皮炎與其他特應(yīng)性疾病,如食物過敏、哮喘和過敏性鼻炎相關(guān)。食物過敏的患者伴有嚴(yán)重特應(yīng)性皮炎的患病率約為30%左右。



2
學(xué)習(xí)目標(biāo)


讀完本文后,讀者應(yīng)能夠


    確定特應(yīng)性皮炎最重要的誘發(fā)因素,同時做出適當(dāng)?shù)脑\斷以及給出治療方案。

    了解過敏原的作用并且制定分級診斷方法。

    熟悉局部和全身療法的最新建議。


3
特應(yīng)性皮炎臨床特征



特應(yīng)性皮炎的臨床特征取決于疾病發(fā)病階段(急性或慢性)以及患者年齡(表1)。最難忍受的特征通常為慢性或慢性復(fù)發(fā)性瘙癢癥;另一個痛苦原因與社會歧視相關(guān)。該疾病發(fā)病的嚴(yán)重程度及持續(xù)時間有很大不同。即使出現(xiàn)輕度癥狀,也可能極大的干擾患者生活,引起情緒緊張。與健康對照組相比,特應(yīng)性皮炎患者通常更易抑郁或焦慮,其可能由于其痛苦經(jīng)歷導(dǎo)致。感染是特應(yīng)性皮炎常見并發(fā)癥,并且十分嚴(yán)重(圖1和圖2,框1)。


Table 1 Characteristic age-dependent features of atopic dermatitis

表1:特應(yīng)性皮炎年齡相關(guān)特征



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

圖1:特應(yīng)性皮炎的皮膚感染。a)傳染性軟體動物;  b)皰疹性濕疹。



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.

圖2:臨床特征。a)褶皺處苔癬樣皮炎;左肘窩表皮剝脫;右肘窩潮濕并有膿液滲出;b)成人頸背皮炎;c)慢性眼瞼皮炎






4
病因,病理生理以及預(yù)防



遺傳易感性(皮膚屏障缺陷以及先天和獲得性免疫受損)和觸發(fā)因素是誘發(fā)、加重特應(yīng)性皮炎的重要因素。近年來,絲聚合蛋白功能缺失突變受到了特別關(guān)注。絲聚合蛋白是分化角質(zhì)形成細(xì)胞中的一種結(jié)構(gòu)蛋白質(zhì)。絲聚合蛋白的功能性缺失突變導(dǎo)致皮膚屏障缺陷,細(xì)菌防御降低,并增加皮膚的pH值。絲聚蛋白突變與特應(yīng)性皮炎風(fēng)險增加相關(guān)(OR 3.1-4.8)。約25%的特應(yīng)性皮炎患者伴有這種突變。此外,這些患者發(fā)展成過敏、哮喘以及皰疹性濕疹(眾所周知,其為特應(yīng)性皮炎的一種嚴(yán)重并發(fā)癥)的風(fēng)險增加。


兒童早期感染的發(fā)病率下降,引出David Strachan所謂的“衛(wèi)生假說”, 其已涉及近幾十年來特應(yīng)性皮炎的發(fā)病率增加(根據(jù)研究,增長4-8倍);同樣的趨勢已見于其他特應(yīng)性疾病。


皮炎的臨床表現(xiàn)(皮膚炎癥并伴有表皮受累)是由T細(xì)胞、IgE結(jié)合抗原呈遞樹突狀細(xì)胞以及嗜酸性粒細(xì)胞引起的。


在急性和亞急性階段,許多介質(zhì),尤其是TH2細(xì)胞因子如白介素4(IL-4)和白介素13(IL-13),引起暫時性屏障蛋白下調(diào)。


預(yù)防過敏的德國AWMF S3指南第61-13號(Allergiepr?vention)對高風(fēng)險家庭的飲食以及預(yù)防措施提出了建議。其建議包括母乳喂養(yǎng)4個月(或使用水解蛋白配方的奶粉),并在孩子早期飲食中加入魚肉。根據(jù)2009年版的德國指南,應(yīng)在第一年給予適齡的固體食物,即使是高危的過敏兒童。



5
診斷和觸發(fā)因素



一般通過臨床診斷。特別要注意詳細(xì)詢問個人史和特應(yīng)性疾病家族史以及進(jìn)行全面身體檢查。


如果具有典型的病史和臨床癥狀,通常不需要進(jìn)行皮膚活檢,但活檢有助于鑒別診斷。最常見的鑒別診斷疾病包括其他類型的皮炎,如過敏或刺激性接觸性皮炎、錢幣狀皮炎,但是成人皮膚T細(xì)胞淋巴瘤的早期階段通常不能通過鏡下病理排除。手部皮炎通常表現(xiàn)出特應(yīng)性、刺激性和變態(tài)反應(yīng)性接觸皮炎混合特征;通常依據(jù)病因很難將其準(zhǔn)確分類。當(dāng)特應(yīng)性皮炎累及四肢,可以排除掌跖銀屑病和皮膚真菌感染。少見的類似于特應(yīng)性皮炎樣改變的綜合征或免疫缺陷見框2。其他一些炎癥性(以及感染性)皮膚病,如兒童疥瘡,偶爾會與特應(yīng)性皮炎相混淆。



當(dāng)疑似特應(yīng)性性皮炎時,有必要了解其可能的心理社會因素,以及飲食或環(huán)境觸發(fā)因素。觸發(fā)因素的重要性個體差異很大,但對其認(rèn)識以及避免或減少是個性化治療的關(guān)鍵部分。同時,由于屏障功能受損,應(yīng)意識到未知的皮膚刺激的敏感性閾值降低。


感染和免疫接種均可引起特應(yīng)性皮炎病情加重。盡管如此,根據(jù)疫苗接種的建議常務(wù)委員會(STIKO),兒童及成人特應(yīng)性皮炎患者應(yīng)進(jìn)行免疫接種。對于急性加重的患者,應(yīng)避免接種直到皮膚穩(wěn)定(德國AWMF S2特應(yīng)性皮炎[神經(jīng)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 (Allergiepr?vention) 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醫(yī)庫軟件馮飛飛 編譯,上海市皮膚病醫(yī)院陳裕充博士審核

原文來自:Dtsch Arztebl Int 2014; 111: 509?20

文章來源:皮膚科周訊

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