Asero Riccardo, Calzari Paolo, Vaienti Silvia, Cugno Massimo
Clinica San Carlo, Ambulatorio di Allergologia, 20037 Paderno Dugnano, Italy.
Department of Pathophysiology and Transplantation, Scuola di Specializzazione, Allergologia e Immunologia Clinica, Università degli Studi di Milano, 20122 Milan, Italy.
Pharmaceuticals (Basel). 2024 Nov 7;17(11):1499. doi: 10.3390/ph17111499.
Chronic spontaneous urticaria (CSU) is a complex dermatological condition characterized by recurrent wheals and/or angioedema lasting for more than six weeks, significantly impairing patients' quality of life. According to European guidelines, the first step in treatment involves second-generation H1-antihistamines (sgAHs), which block peripheral H1 receptors to alleviate symptoms. In cases with inadequate responses, the dose of antihistamines can be increased by up to fourfold. If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine. To address these unmet needs, several new therapeutic targets are being explored. Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies. These emerging treatments offer new options for patients with difficult-to-treat CSU and have the potential to modify the natural course of the disease by targeting key immune pathways, helping to achieve longer-term remission. Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition. Altogether, the future of CSU treatments that target pathogenetic mechanisms seems promising.
慢性自发性荨麻疹（CSU）是一种复杂的皮肤病，其特征为反复出现风团和/或血管性水肿，持续时间超过六周，严重影响患者的生活质量。根据欧洲指南，治疗的第一步是使用第二代H1抗组胺药（sgAHs），这类药物通过阻断外周H1受体来缓解症状。对于反应不充分的病例，抗组胺药的剂量可增加至四倍。如果尽管进行了这种调整症状仍持续存在，下一步则使用奥马珠单抗，一种单克隆抗IgE抗体，它在大多数病例中已显示出疗效。然而，有一部分患者仍然难治，需要使用环孢素或硫唑嘌呤等免疫抑制剂等替代疗法。为满足这些未得到满足的需求，正在探索几个新的治疗靶点。其中，阻断布鲁顿酪氨酸激酶（BTK）的药物受到了极大关注，例如瑞帕布昔替尼，它可减少肥大细胞活化。靶向白细胞介素-4（IL-4）和IL-13通路的疗法，如度普利尤单抗，也在研究中。此外，靶向Mas相关G蛋白偶联受体X2（MRGPRX2）的分子以及抑制酪氨酸激酶受体Kit的分子，如巴佐伏单抗，在临床研究中显示出前景。这些新兴疗法为难治性CSU患者提供了新的选择，并且有可能通过靶向关键免疫通路改变疾病的自然病程，有助于实现长期缓解。进一步的研究对于更好地阐明CSU的病理生理学以及优化治疗方案以在管理这种疾病中实现长期益处至关重要。总体而言，针对发病机制的CSU治疗的未来似乎很有前景。
