慢性自发性荨麻疹的现状与未来

Q3 Medicine
Susanne Melchers,  Jan P. Nicolay
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引用次数: 0

摘要

慢性自发性荨麻疹(CsU)是一种慢性炎症性皮肤病,其病因尚不完全清楚。在受影响的患者中,它通常与健康相关生活质量的高度限制有关,这需要有效的治疗管理。不同的免疫细胞群,如肥大细胞、嗜酸性粒细胞和嗜碱性粒细胞以及T细胞参与了CsU的发病机制,其中肥大细胞起着关键作用。此外,在一定比例的患者中发现了带有自身IgE抗体的I型自身过敏反应或带有自身IgG抗体的IIb型自身免疫反应。目前的国际指南最初建议使用第二代H1抗组胺药,首先是标准剂量,然后是标签外四倍剂量。随后,应添加抗ige抗体omalizumab。然而,这种治疗算法并不能使所有患者都没有表现。因此,目前正在评估各种靶向治疗在CsU中的疗效,例如标签外使用抗白细胞介素受体α (IL4Rα)抗体dupilumab,抗il - 17a抗体secukinumab,或使用mepolizumab, reslizumab或benralizumab阻断白细胞介素- 5。此外,新的有前景的化合物,如布鲁顿酪氨酸激酶(BTK)抑制剂remibrutinib和fenebrutinib,抗ckit抗体barzolvolimab,抗siglec8抗体lirentelimab,抗tslp抗体tezepelumab,抗c5ar1抗体advoralimab,或Syk激酶抑制剂的局部应用正在测试中,这些化合物是根据对CsU发病机制的新见解而开发的。BTK抑制剂fenebrutinib目前没有进行研究,因为与remibrutinib和抗ige抗体ligelizumab相比,fenebrutinib的副作用更小,而ligelizumab在3期研究中优于omalizumab治疗。总的来说,迫切需要新的治疗策略来更好地治疗CsU的症状和治疗。这需要更全面地了解疾病的发病机制,以便开发新的靶向治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chronic spontaneous urticaria—status quo and future

Chronic spontaneous urticaria (CsU) is a chronic inflammatory dermatosis whose etiology is not yet fully understood. In affected patients, it is often associated with a high limitation of health-related quality of life, which necessitates effective therapeutic management. Different immune cell populations such as mast cells, eosinophilic and basophilic granulocytes, and T cells are involved in the pathogenesis of CsU, whereby mast cells playing a key role. In addition, type I autoallergic reactions with auto IgE antibodies or type IIb autoimmune reactions with auto IgG antibodies have been identified in a proportion of patients. The current international guideline initially recommends the use of second-generation H1 antihistamines, first in standard, then in off-label quadruple dosing. Subsequently, the anti-IgE antibody omalizumab should be added. However, this therapy algorithm does not lead to freedom from manifestations in all patients. Therefore, various targeted therapies are currently being evaluated for their efficacy in CsU, such as off-label use of the anti-interleukin receptor alpha (IL4Rα) antibody dupilumab, the anti-IL-17A antibody secukinumab, or interleukin‑5 blockade using mepolizumab, reslizumab, or benralizumab. In addition, new promising compounds such as the Bruton tyrosine kinase (BTK) inhibitors remibrutinib and fenebrutinib, the anti-cKIT antibody barzolvolimab, the anti-SIGLEC8 antibody lirentelimab, the anti-TSLP antibody tezepelumab, the anti-C5aR1 antibody advoralimab, or the topical application of Syk kinase inhibitors are being tested, which were developed according to new insights into the pathogenesis of CsU. The BTK inhibitor fenebrutinib is currently not being pursued due to a less favorable side effect profile compared to remibrutinib, as well as the anti-IgE antibody ligelizumab, which was inferior to omalizumab therapy in a phase 3 study. Overall, there is a high need for new therapeutic strategies to better treat CsU both symptomatically and curatively. This requires a more comprehensive understanding of pathogenesis of the disease in order to develop new targeted therapies.

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来源期刊
Allergo Journal International
Allergo Journal International Medicine-Immunology and Allergy
CiteScore
4.60
自引率
0.00%
发文量
31
期刊介绍: Allergo Journal International is the official Journal of the German Society for Applied Allergology (AeDA) and the Austrian Society for Allergology and Immunology (ÖGAI). The journal is a forum for the communication and exchange of ideas concerning the various aspects of allergy (including related fields such as clinical immunology and environmental medicine) and promotes German allergy research in an international context. The aim of Allergo Journal International is to provide state of the art information for all medical and scientific disciplines that deal with allergic, immunological and environmental diseases. Allergo Journal International publishes original articles, reviews, short communications, case reports, and letters to the editor. The articles cover topics such as allergic, immunological and environmental diseases, the latest developments in diagnosis and therapy as well as current research work concerning antigens and allergens and aspects related to occupational and environmental medicine. In addition, it publishes clinical guidelines and position papers approved by expert panels of the German, Austrian and Swiss Allergy Societies. All submissions are reviewed in single-blind fashion by at least two reviewers. Originally, the journal started as a German journal called Allergo Journal back in 1992. Throughout the years, English articles amounted to a considerable portion in Allergo Journal. This was one of the reasons to extract the scientific content and publish it in a separate journal. Hence, Allergo Journal International was born and now is the international continuation of the original German journal. Nowadays, all original content is published in Allergo Journal International first. Later, selected manuscripts will be translated and published in German and included in Allergo Journal.
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