Hereditary Angioedema.
Hereditary Angioedema.
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DOI：
10.12688/f1000research.channels.70
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Paula J Busse;Sandra C Christiansen
中科院分区：
文献类型：
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作者：
Paula J Busse;Sandra C Christiansen
版权所有 © 2020 马萨诸塞州医学会。遗传性血管性水肿是一种罕见的、可能危及生命的疾病，其特征是皮肤和粘膜下肿胀。 Quincke 首先描述了其临床表现，而 Osler 于 1888 年认识到了常染色体显性遗传模式。1 这种疾病的最初名称是“遗传性血管神经性水肿”，传达了一种偏见，认为它是从神经症发展而来的。在过去的 40 年里，科学研究已确定遗传性血管水肿的根本缺陷是功能性 C1 抑制剂蛋白（丝氨酸蛋白酶抑制剂超家族中的一种蛋白酶抑制剂）的缺乏，2,3 并确定缓激肽是肿胀的生物介质。4,5 2000 年，描述了具有正常 C1 抑制剂水平的遗传性血管水肿，其分子机制正在出现。6,7 尽管在阐明 C1 抑制剂的病理生理学方面取得了进展。遗传性血管性水肿、正确诊断的延迟以及缺乏有效的治疗方法一直阻碍着该疾病的有效治疗，直到最近。然而，2008 年设想的进步8 现在已经实现，基础研究的见解转化为新的疗法。本文回顾了过去十年在阐明遗传性血管性水肿的病理生理机制以及随后针对该疾病的靶向治疗的开发方面取得的进展，预计发病率和死亡率会降低，生活质量也会提高。下面的临床小插图说明了这些治疗的深远影响。
Copyright © 2020 Massachusetts Medical Society. Hereditary angioedema is a rare, potentially life-threatening disorder characterized by attacks of cutaneous and submucosal swelling. Quincke first described its clinical presentation, and Osler’s recognition of the autosomal dominant inheritance pattern followed in 1888.1 The initial name of the disorder, “hereditary angioneurotic edema,” conveyed the bias that it devolved from neurosis. Over the past 40 years, scientific investigations have identified the fundamental defect of hereditary angioedema as a deficiency of functional C1 inhibitor protein, a protease inhibitor in the serpin superfamily,2,3 and have established that bradykinin is the biologic mediator of swelling.4,5 In 2000, hereditary angioedema with normal C1 inhibitor levels was described, for which molecular mechanisms are emerging.6,7 Despite progress in unraveling the pathophysiology of hereditary angioedema, a delay in proper diagnosis and a paucity of effective therapeutic approaches have hampered effective management of the disease until recently. Advances envisioned in 2008,8 however, have now been realized, with insights from basic research translated into novel therapies. This article reviews the progress made during the past decade in elucidating the pathophysiological mechanisms of hereditary angioedema and the subsequent development of targeted treatments for the disorder, with anticipated reductions in morbidity and mortality and an improved quality of life. The clinical vignette below illustrates the profound effect of these treatments.