Department of Dermatology, Rambam Healthcare Campus, Haifa, Israel.
Department of Dermatology, University of Illinois at Chicago, Chicago, IL, USA.
J Eur Acad Dermatol Venereol. 2019 Dec;33(12):2239-2252. doi: 10.1111/jdv.15816. Epub 2019 Oct 14.
Autoimmune blistering diseases comprise a group of heterogenous conditions characterized by the loss of tolerance and subsequent development of autoantibodies targeting epidermal and subepidermal adhesion proteins. Blisters and erosions form on the skin and mucous membranes leading to significant morbidity and mortality. Traditional therapies rely on systemic immunosuppression. Advancements in our understanding of the pathophysiology of pemphigus and pemphigoid have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. In this review, we outline the novel therapeutic strategies including B-cell depletion, T-regulatory cell repletion, cell signalling inhibitors and small molecular inhibitors, inhibitory monoclonal antibodies, as well as complement inhibition. We additionally review their current level of clinical evidence. We lastly review therapeutics targets gleaned from the experimental epidermolysis bullosa acquisita mouse model. These emerging treatments offer an exciting progression from basic science discoveries that have the potential to transform the treatment paradigm in autoimmune blistering diseases.
自身免疫性水疱病包括一组异质性疾病,其特征是对表皮和表皮下黏附蛋白的自身抗体的耐受性丧失和随后的发展。水疱和糜烂形成于皮肤和黏膜上,导致发病率和死亡率显著增加。传统的治疗方法依赖于全身免疫抑制。对天疱疮和类天疱疮病理生理学的认识的提高,导致了针对参与诱导和持续疾病的特定途径的分子的发展。在这篇综述中,我们概述了新的治疗策略,包括 B 细胞耗竭、T 调节细胞补充、细胞信号抑制剂和小分子抑制剂、抑制性单克隆抗体以及补体抑制。我们还回顾了它们目前的临床证据水平。我们最后还回顾了从实验性获得性大疱性表皮松解症小鼠模型中获得的治疗靶点。这些新出现的治疗方法是基础科学发现的令人兴奋的进展,有可能改变自身免疫性水疱病的治疗模式。