Department of Clinical Medicine and Nephrology, University Hospital of Parma, Parma, Italy.
Curr Opin Rheumatol. 2012 Jan;24(1):24-30. doi: 10.1097/BOR.0b013e32834d85ce.
Churg-Strauss syndrome (CSS) has a clear clinical phenotype but its pathogenesis is not fully elucidated. Recent studies have focused on its immunogenetic aspects and cytokine and chemokine-mediated pathogenetic mechanisms, providing the rationale for the use of newer targeted therapies. This study will review recent findings on the pathogenesis of CSS and its therapeutic approaches.
CSS is usually considered a Th2-mediated disease, but Th1 and Th17 responses might also play a role; the reported association between CSS and HLA-DRB4 further underlines the pathogenetic relevance of CD4 T cells which, thanks to their ability to secrete cytokines such as IL4, IL5, and IL13, promote allergic and eosinophilic reactions. Resident cells such as endothelial and epithelial cells might also amplify the immune response by producing eosinophil-attracting chemokines such as eotaxin-3 and CCL17. Conventional immunosuppressive therapies offer high chances of achieving sustained remission, but steroid exposure remains high. Targeting IL5 with mepolizumab seems promising in sparing steroids, but relapses often follow its withdrawal. B-cell depletion using rituximab has proved effective in refractory CSS cases.
Current knowledge on CSS pathogenesis is evolving; the identification of key molecular mechanisms will pave the way for newer, more specific treatments.
变应性肉芽肿性血管炎（CSS）具有明确的临床表型，但发病机制尚未完全阐明。最近的研究集中在其免疫遗传方面以及细胞因子和趋化因子介导的发病机制，为新型靶向治疗提供了依据。本研究将综述 CSS 的发病机制及其治疗方法的最新发现。
CSS 通常被认为是一种 Th2 介导的疾病，但 Th1 和 Th17 反应也可能起作用；CSS 与 HLA-DRB4 之间的报道相关性进一步强调了 CD4 T 细胞的发病相关性，CD4 T 细胞通过分泌白细胞介素 4（IL4）、白细胞介素 5（IL5）和白细胞介素 13（IL13）等细胞因子，促进过敏和嗜酸性粒细胞反应。内皮细胞和上皮细胞等固有细胞也可以通过产生嗜酸性粒细胞趋化因子，如 eotaxin-3 和 CCL17，来放大免疫反应。传统的免疫抑制疗法有很高的机会实现持续缓解，但皮质类固醇的暴露仍然很高。使用美泊利珠单抗靶向 IL5 似乎有望避免使用皮质类固醇，但停药后常复发。利妥昔单抗对难治性 CSS 病例的 B 细胞耗竭已被证明有效。
CSS 发病机制的现有知识正在不断发展；确定关键分子机制将为更新、更特异的治疗方法铺平道路。
