文献简介

出版社:Clinic Rev Allerg Immunol

作  者:Ralph M. Trüeb & Maria Fernanda Reis Gavazzoni Dias2

编  号:

关键字:斑秃;发病机制

年  份:2018   点击量:57

文献摘要 全文翻译

Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. A meta-analysis of published trials on treatment of alopecia areata states that only few treatments have been well evaluated in randomized trials. Nevertheless, depending on patient age, affected surface area and disease duration, an empiric treatment algorithm can be designed with corticosteroids and topical immunotherapy remaining the mainstay of therapy. The obviously limited success of evidence-based therapies points to a more important complexity of hair loss. At the same time, the complexity of pathogenesis offers opportunities for the development of novel targeted therapies. New treatment opportunities based on the results of genome-wide association studies that implicate T cell and natural killer cell activation pathways are paving the way to new approaches in future clinical trials. Currently, there are ongoing studies with the CTLA4-Ig fusion protein abatacept, anti-IL15Rβ monoclonal antibodies and the Janus kinase inhibitors tofacitinib, ruxolitinib and baricitinib. Ultimately, the options available for adapting to the disease rather than treating it in an effort to cure may also be taken into consideration in selected cases of long-standing or recurrent small spot disease.

斑秃是一种常见脱发疾病,表现为突发性非瘢痕性脱发,通常为特定区域小斑块到广泛或低频弥漫性受累。目前认为该疾病是一种遗传性毛囊器官特异性自身免疫性疾病。全基因组关联研究证实先天免疫和获得性免疫参与发病机制,而对斑秃小鼠模型发病机制的研究也特别提示干扰素γ驱动的免疫反应,包括干扰素γ,干扰素γ诱导趋化因子和细胞毒性CD8 T细胞是疾病发病的主要驱动因素。一项对已发布的斑秃治疗试验的荟萃分析表明,仅有少数治疗方法在随机试验中得到了很好评估。然而,根据患者年龄、受累面积和疾病持续时间,可采取经验治疗方法,而皮质类固醇和局部免疫疗法仍然是主要治疗方法。基于证据的疗法治疗成功案例有限,表明发病机制的复杂性。同时,发病机制的复杂性为新型靶向治疗的发展提供了机会。基于全基因组关联研究结果的新的治疗机会提示T细胞和自然杀伤细胞激活通路正为未来临床试验的新方法铺平道路。目前,正对CTLA4-Ig融合蛋白阿巴西普,抗IL15Rβ单克隆抗体和Janus激酶抑制剂托法替尼、鲁索替尼和巴瑞克替尼进行研究。最后,在某些长期或反复发生的点状病例中,也可考虑适应该疾病而不是治愈该疾病。