上期回顾
每日常规局部使用强效糖皮质激素可清除患者大部分皮损。通常，由于害怕应用糖皮质激素，不坚持使用而使疗效不佳。对于疗效不佳的其他解释为，过敏接触性皮炎自身对糖皮质激素无效，或触发因素继发刺激特应性皮炎。此外，少数患者（少于1%）对糖皮质激素无效。
自2002年以来，外用钙调磷酸酶抑制剂（吡美莫司和他克莫司）已批准用于特应性皮炎的抗炎治疗。即使长期使用，也不会导致皮肤萎缩，也无糖皮质激素常见的副作用（激素诱发性酒渣鼻，口周皮炎）。
在所有研究中，无论成人和儿童，外用钙调磷酸酶抑制剂已被证明明显优于安慰剂(2, 20, e1)。对照试验表明，外用钙调磷酸酶抑制剂与中效糖皮质激素疗效相当(e15–e17)。应用局部钙调磷酸酶抑制剂可减少使用局部糖皮质激素；此外，即使长期使用，其疗效也不会降低。
常见的不良反应是短暂的灼热或烧灼感。局部钙调磷酸酶抑制剂不会增加细菌感染的风险，但病毒感染如单纯疱疹病毒的风险略微升高10-20％。
2006年3月27日欧洲药品管理局（EMEA）的立场文件警告申明，现有数据无法排除使用局部钙调磷酸酶抑制剂后癌症风险增加，并提出当治疗特应性皮炎时，应权衡其风险利弊。在个别病例中，医生曾报道给予局部钙调神经磷酸酶抑制剂他克莫司和吡美莫司治疗期间或治疗后，出现癌症的病例，但这样的报道十分罕见，很可能是两个独立的巧合事件。局部钙调磷酸酶抑制剂批准11年后，仍没有表明应用这些药物与皮肤癌或淋巴瘤(26–28, e19–e21)之间相关联的基于登记报告或纵向的研究。也尚未证明其可引发光毒性或光过敏反应。
特应性皮炎受累皮肤，依据其严重程度，在50~90%的病例中寄生有金黄色葡萄球菌；在正常对照组中，其比率仅有5~10%。轻度至中度的特应性皮炎，对局部糖皮质激素或钙调磷酸酶抑制剂反应良好，通常不需要额外的抗生素治疗，随着细菌数目的减少，皮肤得到改善(e22)。临床上，皮炎斑疹出现感染可采用局部抗菌药物进行治疗。由于会有诱发耐药菌株的风险以及引起过敏性接触皮炎，因此不应使用局部抗生素。
除金黄色葡萄球菌外，通常腐生马拉色菌属可增加另外一种被称为头-颈-肩皮炎的风险。伴有持续性或顽固性疾病的患者可应用系统抗真菌药治疗。同时也可治疗对马拉色菌属敏感的特应性皮炎患者。
通常口服应用H1-抗组胺药治疗特应性皮炎。尚未有对照研究明确证实其疗效。大多数研究显示，抗组胺疗法仅能缓解轻微瘙痒(31, e1)。儿童不推荐使用强烈镇静作用的H1-抗组胺药（多西拉敏、苯海拉明、茶苯海明、异丙嗪）。抗炎疗法是治疗瘙痒最有效的方法。
系统性抗炎疗法适用于严重的特应性皮炎患者；约10％的成人患者在疾病发病过程中接受系统抗炎疗法，而儿童很少应用。
短期口服糖皮质激素（3天~3周）可用于中断严重特应性皮炎患者的急性发作。由于会出现很多长期不良反应，特应性皮炎患者不推荐长期系统应用糖皮质激素。
环孢菌素是唯一批准用于治疗成人特应性皮炎的系统性免疫抑制剂。各种禁忌症，如高血压和肾功能不全限制了其使用。短期数月的低剂量环孢菌素治疗后疾病终止状态优于长期持续疗法。在英美国家，已应用硫唑嘌呤治疗成人特应性皮炎多年;对照研究表明临床评分可改善50%(e23)。此外，甲氨蝶呤和霉酚酸酯可用于治疗对环孢菌素无效或禁忌的成人特应性皮炎患者(e24, e25)。所有这些免疫抑制药物，在仔细考虑其禁忌后，以超药品说明书应用的方式应用于严重的儿童特应性皮炎患者。
临床上，当证实相关IgE-介导的敏感过敏原存在时，可应用特异性免疫疗法治疗呼吸道过敏性疾病（过敏性鼻炎，轻度过敏性哮喘）。对照研究显示，对于伴有特应性皮炎的呼吸道过敏性疾病（过敏性鼻炎，轻度过敏性哮喘）的患者，应使用特异性免疫疗法进行治疗。一项大型多中心研究显示，采用房屋尘螨过敏的特异性免疫疗法治疗严重的成人患者，其皮损得到了中度改善。最近一项荟萃分析表明，特异性免疫疗法治疗特应性皮炎具有显著疗效。
此外，正在临床研究生物制剂（抑制过敏性炎症的抗体，如那些针对IL-4R，IL-13，IL-31或胸腺基质淋巴细胞[TSLP]的抗体）对特应性皮炎的有效性(e24)。但近期内并不会被常规使用。光疗法（UV治疗）——特别是中等剂量的（高达50 J/cm2）的UVB311 nm和UVA1，依据疾病的慢性和严重程度，可联合局部皮质类固醇进行治疗。不推荐光疗法与局部钙调磷酸酶抑制剂或全身免疫抑制剂联合应用。在特殊病例中，对于12岁以下的儿童仅应采用光疗法。
在德国联邦卫生部(BMS; Bundesministerium für Gesundheit)以及国家医疗保险基金协会(GKV-Spitzenverband)的资助下，对动态结构化教育方案进行了测试。在研究显示的可显著改善皮肤状态（甚至在试验1年后）的基础上，自2007年以来，医疗保险基金全国协会推荐了该项培训，并且该项培训是由医疗保险计划扶持。此类项目必须包括医生，心理学家/心理治疗师和营养师。结构化的跨学科项目对于家长和患者都是可用的;其可通过搜索www.neurodermitis schulung.de查询。
个体心理疗法有时也可用于特应性皮炎；通常建议采用行为疗法。心理疗法通常仅推荐给具有明确症状的，如个人相关的触发因素或特应性皮炎引起的心理问题或由患者或家人特应性皮炎继发的心理问题。
特应性皮炎治疗方法有效性的评估见框6；其基于欧洲特应性皮炎指南。
Regular daily treatment with sufficiently potent topical glucocorticosteroids can clear most lesions in most patients. A lack of response is often explained by non-adherence because of fear of glucocorticosteroids. Other explanations for a poor response are an allergic contact dermatitis to the corticosteroid itself, or a continued provocation of the atopic dermatitis by trigger factors. In addition there is a small group (less than 1%) of patients who do not respond sufficiently to glucocorticosteroids (non-responders).
Topical calcineurin inhibitors (pimecrolimus and tacrolimus) have been approved since 2002 for anti-inflammatory therapy in atopic dermatitis. Even with prolonged use, they do not lead to skin atrophy and do not cause the facial side effects so common with glucocorticosteroids (steroid-induced rosacea, perioral dermatitis).
In all studies, topical calcineurin inhibitors have proven clearly better than placebo both for adults and children (2, 20, e1). Comparative trials indicate that topical calcineurin inhibitors are as effective as moderately effective glucocorticosteroids (e15–e17). Therapy with topical calcineurin inhibitors makes it possible to reduce the use of topical glucocorticosteroids; in addition, they do not lose effectiveness even when employed over a long period of time.
The most common side effect is a transient feeling of warmth or burning. Topical calcineurin inhibitors do not increase the risk of bacterial infections but the risk of viral infections such as herpes simplex virus is slightly elevated at 10–20%.
The European Medicines Agency (EMEA) in a position paper on 27 March 2006 warned that the available data did not allow them to exclude an increased risk of cancer following use of topical calcineurin inhibitors and concluded that this risk should be weighed against the benefits when treating atopic dermatitis. In individual cases, physicians have reported an association of cancers during or following therapy with the topical calcineurin inhibitors tacrolimus and pimecrolimus, but such reports are so uncommon that they probably reflect two independent coincidental events. Eleven years after the approval of topical calcineurin inhibitors, there still are no registry-based reports or longitudinal studies showing an association between the use of these agents and skin cancer or lymphoma (26–28, e19–e21). There is also no evidence that they cause phototoxic or photoallergic reactions in humans.
The affected skin in atopic dermatitis is, depending on severity, colonized in 50–90% of cases with Staphylococcus aureus; in normal controls, the rate is only 5–10%. Mild to moderate atopic dermatitis that responds well to topical glucocorticosteroids or calcineurin inhibitors generally does not require additional antibiotic therapy, as the number of bacteria decreases as the skin findings improve (e22). Patches of dermatitis which appear to be clinically superinfected can be treated with topical antiseptic drugs. Topical antibiotics should not be employed because of the risks of in ducing resistant bacterial strains and causing allergic contact dermatitis.
In addition to S. aureus, normally saprophytic Malassezia species may be increased in the variant of atopic dermatitis known as head-neck-shoulder dermatitis. Such patients with persistent or resistant disease may benefit from systemic antimycotic therapy. This is also helpful in patients with atopic dermatitis who are clearly sensitized against Malassezia species.
Oral H1-antihistamines are frequently used in atopic dermatitis. There are no controlled studies that clearly confirm their effectiveness in this setting. Most studies show only limited decrease in pruritus with antihistamine therapy (31, e1).The use of strongly sedating H1-antihistamines (doxylamine, diphenhydramine, dimenhydrinate, promethazine) is not recommended in children. The best treatment for pruritus is effective anti-inflammatory therapy.
Systemic anti-inflammatory therapy is appropriate for severely affected atopic dermatitis patients; about 10% of adult patients receive systemic anti-inflammatory therapy at some point during the course of their disease, while in children it is rarely employed.
Short courses of oral glucocorticosteroids (three days to three weeks) can be used to interrupt acute flares in patients with severe atopic dermatitis. Because of the many long-term side effects, longer courses of systemic glucoglucocorticosteroids are not recommended for atopic dermatitis.
Cyclosporine is the only systemic immunosuppressive agent approved for the treatment of atopic dermatitis in adults. A variety on contraindications such as hypertension and renal insufficiency restrict its use. Courses of several months of low-dose cyclosporine followed by treatment pauses disease status are preferable to long-term continuous therapy. Azathioprine has also been used in Anglo-American countries for adults with atopic dermatitis for many years; controlled studies show a 50% improvement in clinical scores (e23). In addition, methotrexate and mycophenolate mofetil can be used in adults with atopic dermatitis in whom cyclosporine is ineffective or contra indicated (e24, e25). All of these immunosuppressive agents can also be used in children with very severe atopic dermatitis in off-label fashion after a careful consideration of individual contrain dications .
Specific immunotherapy is well established for treating respiratory allergic diseases (allergic rhinitis, mild allergic asthma) when a clinically relevant IgE- mediated sensitization to an allergen has been proven. Controlled studies show that there is no reason not to administer specific immunotherapy for respiratory allergic diseases (allergic rhinitis, mild allergic asthma) in patients who also have atopic dermatitis. A large multi-center study showed a modest improvement in skin disease in severely affected adults treated with specific immunotherapy for house dust mite allergy (35). A recent meta-analysis indicates a highly variable response of atopic dermatitis to specific immuno therapy.
In addition, biologicals (antibodies that down-regulate atopic inflammation such as those directed against IL-4R, IL-13, IL-31 or thymic stromal lymphopoietin [TSLP]) are being tested for efficacy in atopic dermatitis (e24). They will not be available for routine use in the near future. Phototherapy (UV therapy)—especially UVB 311 nm and UVA1 in medium doses (up to 50 J/cm2)—can be combined with topical corticosteroid therapy, depending on the chronicity and severity of the disease. The combination of phototherapy with topical calcineurin inhibitors or with systemic immunosuppressive agents is not recommended. Children under 12 years of age should only be treated with phototherapy in exceptional cases.
Ambulatory structured educational programs have been tested in Germany under the sponsorship of the Federal Ministry of Health (BMS; Bundesministerium für Gesundheit) and the National Association of Health Insurance Funds (GKV-Spitzenverband). On the basis of the positive results of the study showing improved skin status—even one year after participation—the National Association of Health Insurance Funds has recommended since 2007 that such training is to be paid for by health insurance plans. Such programs must include physicians, psychologists/psychotherapists and dieticians. Structured interdisciplinary programs are available both for parents and patients; they can be found under www.neurodermitis schulung.de.
Individual psychotherapy is also sometimes indicated for atopic dermatitis; usually behavioral therapy is recommended. The use of psychotherapy is generally only recommended when there are clear indications such as psychological issues as individually relevant trigger factors or atopic dermatitis or secondary psychosocial issues for the patient or family are attributable to atopic dermatitis.
An evaluation of the efficacy of management approaches to atopic dermatitis is shown in Box 6; it is based on the European guidelines for atopic dermatitis.
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
文章来源：皮肤科周讯
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