慢性自发性荨麻疹中的2型炎症：表现、作用与管理

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中文摘要

慢性自发性荨麻疹（CSU）是一种异质性炎症性皮肤病，以反复发作的风团、血管性水肿和瘙痒为特征，对生活质量有显著影响。尽管肥大细胞活化仍是核心效应事件，但越来越多的证据提示2型炎症通路参与CSU，并表明该病与已确立的2型炎症性疾病（包括特应性皮炎、哮喘、慢性痒疹和慢性鼻窦炎伴鼻息肉）具有共同的生物学特征。本综述探讨2型炎症对CSU的贡献、其与已确立的自身免疫内型的关系、相关生物标志物，以及对当前和新兴治疗的意义。2型细胞因子，包括IL-4、IL-5、IL-13和IL-31，连同上皮警报素和神经免疫通路，与IgE依赖性、自身免疫性及其他机制相互作用，放大肥大细胞活化、炎症和瘙痒。重要的是，2型炎症不应被视为已确立的I型自身变应性/IIb型自身免疫分类的替代，而应视为一个部分重叠且表达程度可变的炎症轴。目前尚无经过验证的生物标志物可定义2型高表达CSU内型或可靠地指导个体化治疗选择；总IgE、嗜酸性粒细胞、嗜碱性粒细胞、自身抗体和功能性嗜碱性粒细胞检测可提供互补的机制或预后信息，但仍不足以用于精准处方。不断扩展的治疗格局反映了这种生物学复杂性。奥马珠单抗靶向IgE依赖性活化，度普利尤单抗直接抑制IL-4/IL-13信号传导，而瑞布替尼等BTK抑制剂则通过多种上游机制干扰细胞内肥大细胞和嗜碱性粒细胞信号传导。新兴的KIT导向疗法通过直接靶向肥大细胞区室扩展了这一策略。然而，异质性的细胞因子特征和多变的治疗反应不支持将CSU定义为统一的2型驱动疾病。未来的进展将需要前瞻性验证的生物标志物特征、按生物标志物分层的试验、新兴疗法的比较研究，以及对无治疗缓解和潜在疾病修饰的长期评估。界定2型炎症在CSU更广泛病理生物学中的贡献和边界，最终可能促进CSU从机制理解向临床可操作的精准医学转变。

英文摘要

Chronic spontaneous urticaria (CSU) is a heterogeneous inflammatory skin disease characterized by recurrent wheals, angioedema, and pruritus, with substantial effects on quality of life. Although mast-cell activation remains the central effector event, increasing evidence implicates type 2 inflammatory pathways in CSU and suggests that the disease shares biological features with established type 2 inflammatory disorders, including atopic dermatitis, asthma, chronic prurigo, and chronic rhinosinusitis with nasal polyps. This review examines the contribution of type 2 inflammation to CSU, its relationship with established autoimmune endotypes, associated biomarkers, and implications for current and emerging therapies. Type 2 cytokines, including IL-4, IL-5, IL-13, and IL-31, together with epithelial alarmins and neuroimmune pathways, interact with IgE-dependent, autoimmune, and other mechanisms to amplify mast-cell activation, inflammation, and pruritus. Importantly, type 2 inflammation should not be regarded as an alternative to the established type I autoallergic/type IIb autoimmune classification, but rather as a partly overlapping and variably expressed inflammatory axis. No validated biomarker currently defines a type 2-high CSU endotype or reliably guides individual treatment selection; total IgE, eosinophils, basophils, autoantibodies, and functional basophil assays provide complementary mechanistic or prognostic information but remain insufficient for precision prescribing. The expanding therapeutic landscape reflects this biological complexity. Omalizumab targets IgE-dependent activation, dupilumab directly inhibits IL-4/IL-13 signaling, whereas BTK inhibitors such as remibrutinib interfere with intracellular mast-cell and basophil signaling across multiple upstream mechanisms. Emerging KIT-directed therapies extend this strategy through direct targeting of the mast-cell compartment. Nevertheless, heterogeneous cytokine signatures and variable therapeutic responses argue against defining CSU as a uniformly type 2-driven disease. Future progress will require prospectively validated biomarker signatures, biomarker-stratified trials, comparative studies of emerging therapies, and long-term evaluation of treatment-free remission and potential disease modification. Defining the contribution and boundaries of type 2 inflammation within the broader pathobiology of CSU may ultimately facilitate the transition from mechanistic understanding to clinically actionable precision medicine in CSU.