度普利尤单抗在罕见单基因遗传性皮肤病中的应用进展  

Advances of Dupilumab in Treating Rare Monogenic Inherited Skin Diseases

作　　者：张钰乔 曾跃平 ZHANG Yuqiao;ZENG Yueping(Department of Dermatology,State Key Laboratory of Complex Severe and Rare Diseases,National Clinical Research Center for Dermatologic and Immunologic Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Eight-year Degree in Clinical Medicine,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院皮肤科、疑难重症及罕见病国家重点实验室、国家皮肤与免疫疾病临床医学研究中心,北京100730 [2]中国医学科学院北京协和医学院,北京100730

出　　处：《罕见病研究》2023年第2期294-302,共9页Journal of Rare Diseases

基　　金：中央高水平医院临床科研业务费(2022-PUMCH-B-092)。

摘　　要：单基因遗传性皮肤病是一组临床罕见的疾病,包括近1000种表型不同的疾病。通过全球皮肤学科及相关学科研究者的共同努力,这些疾病的病因及发病机制研究在近30年中取得很多重大进展。但需要指出的是,绝大多数单基因遗传性皮肤病的治疗一直是临床医生面对的难题。度普利尤单抗是一种全人源单克隆IgG4抗体,可以特异性结合IL-4受体的α亚基,从而抑制IL-4与IL-13的信号传导通路。该药最早获批用于治疗中重度特应性皮炎,并已在全球范围内广泛使用。近年来,该药开始成功用于治疗具有特应性皮炎临床表现的单基因遗传性皮肤病,如高IgE综合征、Netherton综合征等,并获得疗效。该药后来又被尝试用于治疗其他单基因遗传性皮肤病,如Hailey-Hailey综合征、痒疹型大疱性表皮松解症等疾病,也获得较好疗效。本文对近年来度普利尤单抗治疗单基因遗传性皮肤病相关的文献报道进行回顾性分析,重点探讨其有效性、安全性及可能的治疗机制,为将来该药在罕见单基因遗传性皮肤病领域的应用提供可能的科学依据。Monogenic inherited skin diseases are a group of clinically rare diseases that include nearly 1000 phenotypically distinct disorders.Through the concerted efforts of researchers in dermatological sciences and related disciplines worldwide,many advances have been made in the etiology and pathogenesis of these diseases in the last 30 years.However,it is important to note that the treatment of the majority of monogenic inherited skin diseases remains a challenge for clinicians.Dupilumab is a fully human monoclonal IgG4 antibody that specifically binds to theαsubunit of the IL⁃4 receptor,thereby inhibiting the IL⁃4 and IL⁃13 signaling pathway.It was first approved for the treatment of moderate⁃to⁃severe atopic dermatitis(AD)and has been used worldwide.In recent years,the drug has been successfully used to treat some monogenic inherited skin diseases with AD⁃like clinical manifestations,such as hyper⁃IgE syndrome and Netherton syndrome,with good efficacy.The drug was later tried for the treatment of other monogenic inherited skin diseases,such as Hailey⁃Hailey syn⁃drome and epidermolysis bullosa pruriginosa,where it was also proven to be effective.In this paper,we review literature reports related to dupilumab for the treatment of monogenic inherited skin diseases in recent years,fo⁃cusing on its efficacy,safety and possible therapeutic mechanisms.We aim to provide a possible scientific basis for the future application of this drug in the field of rare monogenic inherited skin diseases.

关 键 词：度普利尤单抗 单基因遗传性皮肤病 Netherton综合征 高IGE综合征 

分 类 号：R75[医药卫生—皮肤病学与性病学]