Fagni Filippo, Bello Federica, Emmi Giacomo
Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
Front Med (Lausanne). 2021 Feb 24;8:627776. doi: 10.3389/fmed.2021.627776. eCollection 2021.
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystemic disease classified both amongst hypereosinophilic disorders and ANCA-associated vasculitis. Vessel inflammation and eosinophilic proliferation are the hallmarks of the disease and main effectors of organ damage. Two distinct disease phenotypes have classically been described according to ANCA-status: the ANCA-negative subset with eosinophil-driven manifestation and the ANCA-positive one with vasculitic manifestations. An analogous dichotomization has also been backed by histological findings and a distinct genetic background. EGPA is typically consider a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis. Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils. Thus, the pathogenesis of EGPA seems to be mediated by two coexisting mechanisms. However, the verbatim application of this strict dualism cannot always be translated into routine clinical practice. In the present review we describe the current knowledge on the eosinophilic and ANCA-mediated aspects of EGPA pathogenesis. Finally, we review the rationale of the currently proposed EGPA dichotomy and future research perspectives.
嗜酸性肉芽肿性多血管炎（EGPA）是一种罕见的多系统疾病，既归类于嗜酸性粒细胞增多症，也归类于抗中性粒细胞胞浆抗体（ANCA）相关血管炎。血管炎症和嗜酸性粒细胞增殖是该疾病的标志，也是器官损伤的主要效应因素。根据ANCA状态，经典地描述了两种不同的疾病表型：嗜酸性粒细胞驱动表现的ANCA阴性亚组和血管炎表现的ANCA阳性亚组。组织学发现和独特的遗传背景也支持类似的二分法。EGPA通常被认为是一种Th2介导的疾病，血液和组织嗜酸性粒细胞增多是诊断的基石。此外，已知ANCA通过激活循环中的中性粒细胞诱导内皮损伤和血管炎症。因此，EGPA的发病机制似乎由两种共存机制介导。然而，这种严格二元论的逐字应用并不总能转化为常规临床实践。在本综述中，我们描述了关于EGPA发病机制中嗜酸性粒细胞和ANCA介导方面的当前知识。最后，我们回顾了当前提出的EGPA二分法的基本原理和未来研究前景。
