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[特应性皮炎全身治疗的新进展]

[New aspects in systemic treatment of atopic dermatitis].

作者信息

Werfel T, Wollenberg A, Pumnea T, Heratizadeh A

机构信息

Abteilung für Immundermatologie und experimentelle Allergologie, Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.

Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, München, Deutschland.

出版信息

Hautarzt. 2018 Mar;69(3):217-224. doi: 10.1007/s00105-018-4131-8.

DOI:10.1007/s00105-018-4131-8
PMID:29470609
Abstract

In severe cases of atopic dermatitis (AD) systemic treatment is indicated. So far, cyclosporine and systemic glucocorticosteroids represented the only systemic treatment options approved for the indications of AD in Germany; however, from clinical practice there is increasing evidence for beneficial therapeutic effects in AD by other immunosuppressive or immunomodulatory substances, such as mycophenolate, methotrexate, alitretinoin and ustekinumab. Beyond this, ongoing research activities focus on a better understanding of genetic and immunological aspects of this chronic inflammatory skin disease. Regarding treatment with mycophenolate, genetic polymorphisms in AD patients could be identified that might predict responsiveness to this medication. Moreover, several new substances specifically targeting inflammation in AD are currently being studied and the first promising treatment effects on skin condition and pruritic symptoms of AD could be observed. As an exceptional result of this development in September 2017 in Europe and therefore in Germany the first biologic as first-line treatment was approved for the indication of moderate to severe AD in adults. Dupilumab is a human monoclonal IgG4 antibody that blocks a subunit of the interleukin (IL)-4 and IL-13 receptors, thus inhibiting the proinflammatory effects of these cytokines. Furthermore, the cytokine IL-13 itself, the IL-31 receptor, which is of particular relevance for pruritus in AD, the histamine-4-receptor and Janus kinases represent further promising targets currently being investigated in clinical trials for the treatment of AD.

摘要

在重度特应性皮炎(AD)病例中,需要进行全身治疗。到目前为止,环孢素和全身性糖皮质激素是德国仅有的被批准用于AD适应症的全身治疗选择;然而,从临床实践来看,越来越多的证据表明,其他免疫抑制或免疫调节物质,如霉酚酸酯、甲氨蝶呤、阿利维A酸和乌司奴单抗,对AD具有有益的治疗效果。除此之外,正在进行的研究活动聚焦于更好地理解这种慢性炎症性皮肤病的遗传和免疫学方面。关于霉酚酸酯治疗,已在AD患者中鉴定出可能预测对该药物反应性的基因多态性。此外,目前正在研究几种专门针对AD炎症的新物质,并且可以观察到对AD的皮肤状况和瘙痒症状有初步的良好治疗效果。作为这一进展的一个特殊成果,2017年9月在欧洲以及德国,第一种生物制剂被批准作为成人中重度AD适应症的一线治疗药物。度普利尤单抗是一种人源化单克隆IgG4抗体,可阻断白细胞介素(IL)-4和IL-13受体的一个亚基,从而抑制这些细胞因子的促炎作用。此外,细胞因子IL-13本身、对AD瘙痒特别重要的IL-31受体、组胺-4受体和Janus激酶,是目前在AD治疗临床试验中正在研究的更有前景的靶点。

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本文引用的文献

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Methotrexate and azathioprine for severe atopic dermatitis: a 5-year follow-up study of a randomized controlled trial.甲氨蝶呤和硫唑嘌呤治疗重度特应性皮炎:一项随机对照试验的 5 年随访研究。
Br J Dermatol. 2018 Jun;178(6):1288-1296. doi: 10.1111/bjd.16240. Epub 2018 Apr 10.
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[Atopic eczema in childhood or primary immunodeficiency - what needs to be considered?].[儿童特应性皮炎或原发性免疫缺陷——需要考虑哪些因素?]
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Therapeutic pipeline for atopic dermatitis: End of the drought?
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特应性皮炎的治疗领域:干旱的尽头?
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Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a randomized, placebo-controlled clinical trial.度普利尤单抗治疗可改善中重度特应性皮炎成人患者的生活质量:一项随机、安慰剂对照临床试验的结果。
Br J Dermatol. 2018 Feb;178(2):406-414. doi: 10.1111/bjd.15905. Epub 2018 Jan 11.
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When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.特应性皮炎何时需要全身治疗?国际特应性皮炎理事会专家小组的建议。
J Am Acad Dermatol. 2017 Oct;77(4):623-633. doi: 10.1016/j.jaad.2017.06.042. Epub 2017 Aug 10.
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Two Cases of Successful Treatment of Refractory Chronic Inflammatory Skin Disease, Atopic Dermatitis and Psoriasis with Oral Alitretinoin.口服阿利维A酸成功治疗难治性慢性炎症性皮肤病(特应性皮炎和银屑病)两例
Ann Dermatol. 2017 Aug;29(4):503-506. doi: 10.5021/ad.2017.29.4.503. Epub 2017 Jun 21.
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Methotrexate for Severe Childhood Atopic Dermatitis: Clinical Experience in a Tertiary Center.甲氨蝶呤治疗儿童重度特应性皮炎:三级中心的临床经验
Pediatr Dermatol. 2017 Sep;34(5):528-534. doi: 10.1111/pde.13209. Epub 2017 Jul 21.
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IL-4Rα Inhibitor for Atopic Disease.白介素-4 受体α 抑制剂治疗特应性疾病。
Cell. 2017 Jul 13;170(2):222. doi: 10.1016/j.cell.2017.06.046.
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Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis.白细胞介素-31 和白细胞介素-31 受体在特应性皮炎瘙痒中的新作用。
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