Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California San Diego.
Research Service, San Diego Veterans Affairs Healthcare, San Diego, California, USA.
Curr Opin Allergy Clin Immunol. 2020 Jun;20(3):253-260. doi: 10.1097/ACI.0000000000000633.
Angioedema without urticaria is composed of an increasing subtype's variety and presents a challenging diagnosis. This review summarizes the subtypes recently described and subsequent new findings helpful within their classification.
New methods to measure cleaved high molecular weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Three new subtypes of hereditary angioedema (HAE) with normal C1 inhibitor were described in the past two years: HAE due to mutation in plasminogen gene, in kininogen gene, and in angiopoietin-1 gene; implicating the fibrinolytic and contact systems, and the regulation of vasculature, respectively. The understanding of some mechanisms in angioedema has been improved, compatible to the dominant-negative for some C1 inhibitor variants; furthermore, the increased activation of truncated F12 mutants by plasma kallikrein; and the diminished binding of angiopoietin-1 to its receptor.
The validation of biomarkers for the contact system activation could be beneficial in differentiating bradykinin - from histaminergic-mediated angioedema. Currently, the available laboratorial tests are still somewhat restricted to the evaluation of the complement activation and the mediators of nonhistaminergic and nonbradykinin-mediated angioedema remain to be identified.
无荨麻疹的血管性水肿由越来越多的亚类组成，其诊断具有挑战性。本篇综述总结了最近描述的亚类，以及随后对其分类有帮助的新发现。
新的方法来测量已被切割的高分子量激肽原和激活的血浆激肽释放酶，作为识别缓激肽介导的血管性水肿的潜在生化检测手段已经出现。在过去两年中，描述了三种新的遗传性血管性水肿（HAE）亚类，其 C1 抑制剂正常：由于纤溶酶原基因、激肽原基因和血管生成素-1 基因突变引起的 HAE；分别涉及纤溶和接触系统，以及血管的调节。对血管性水肿某些机制的理解有所提高，与某些 C1 抑制剂变异体的显性负作用一致；此外，血浆激肽释放酶对截断 F12 突变体的激活增加；以及血管生成素-1 与其受体的结合减少。
接触系统激活的生物标志物的验证可能有助于区分缓激肽介导的血管性水肿与组胺能介导的血管性水肿。目前，可用的实验室检测仍然在一定程度上局限于补体激活的评估，非组胺能和非缓激肽介导的血管性水肿的介质仍有待确定。
