Department of Dermatology, Philipps University, Baldingerstr., Marburg, Germany; Department of Surgical and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy.
Department of Dermatology, Philipps University, Baldingerstr., Marburg, Germany.
Curr Opin Pharmacol. 2019 Jun;46:34-43. doi: 10.1016/j.coph.2018.12.007. Epub 2019 Feb 13.
Pemphigoid is the most common autoimmune blistering disease. IgG and IgE autoantibodies against the hemidesmosomal antigens Bullous Pemphigoid (BP) 180 and BP230 are of pathogenic relevance, since autoantibody-antigen binding results in complement activation, immune cells infiltration, impaired hemidesmosomal function, and loss of dermal-epidermal adhesion. Systemic steroids and immunosuppressants are frontline therapies in pemphigoid, but result in substantial morbidity and increased mortality. A large randomized multicenter study highlighted doxycycline as a feasible alternative to systemic corticosteroids in patients not suitable for long-term steroid use. In recent years, new targeted therapies, including intravenous immunoglobulin (IvIg), rituximab, omalizumab, and immunoadsorption, have proven efficacy in the refractory setting, but, with the exception of IVIG, large randomized trial has not been performed yet. Basic research studies have now shed light on the pathogenic role of eosinophils and autoreactive T-helper 2 cells in pemphigoid, inducing tissue damage and sustaining autoantibody production by autoreactive B-cells, respectively. Indeed, eosinophils and Th2-related cytokines have become attractive therapeutic options. Moreover, Interleukin-17 related inflammatory pathways have been also shown to participate in the blistering process. This review discusses current evidence for the use of targeted therapies in pemphigoid as well as most relevant pharmacologic advances and new drugs currently under clinical investigation.
天疱疮是最常见的自身免疫性水疱病。针对桥粒芯糖蛋白 180（BP180）和桥粒芯糖蛋白 230 这两种半桥粒抗原的 IgG 和 IgE 自身抗体与疾病的发病机制相关，因为自身抗体与抗原结合会导致补体激活、免疫细胞浸润、半桥粒功能受损以及真皮-表皮连接丧失。全身性类固醇和免疫抑制剂是天疱疮的一线治疗方法，但会导致大量发病率和死亡率增加。一项大型随机多中心研究强调，多西环素是不适合长期使用皮质类固醇的患者替代全身皮质类固醇的可行选择。近年来，新的靶向治疗方法，包括静脉注射免疫球蛋白（IVIg）、利妥昔单抗、奥马珠单抗和免疫吸附，已被证明在难治性疾病中有效，但除了 IVIg 外，尚未进行大型随机试验。基础研究现在已经揭示了嗜酸性粒细胞和自身反应性辅助性 T 细胞 2 型（Th2）细胞在天疱疮发病机制中的作用，分别诱导组织损伤和维持自身反应性 B 细胞产生自身抗体。事实上，嗜酸性粒细胞和 Th2 相关细胞因子已成为有吸引力的治疗选择。此外，白细胞介素-17 相关炎症途径也被证明参与了水疱形成过程。本文讨论了目前在天疱疮中使用靶向治疗的证据，以及最相关的药理学进展和目前正在临床研究中的新药。
