Department of Immunology, Allergology and Rheumatology, University Hospital Antwerp, Antwerp University, Universiteitsplein 1, Antwerp, Belgium.
Paediatr Drugs. 2010 Aug 1;12(4):257-68. doi: 10.2165/11532590-000000000-00000.
Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, non-pitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 48-72 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. There are no particular laboratory findings in type III HAE. Prophylactic administration of either 17alpha-alkylated androgens or synthetic antifibrinolytic agents has proven useful in reducing the frequency or severity of attacks. Plasma-derived C1-inhibitor concentrate, recombinant C1-inhibitor, ecallantide (DX88; a plasma kallikrein inhibitor) and icatibant (a bradykinin B(2) receptor antagonist) have demonstrated significant efficacy in the treatment of acute attacks, whereas the C1-inhibitor concentrate has also provided a significant benefit as long-term prophylaxis. However, these drugs are not licensed in all countries and are not always readily available.
遗传性血管性水肿（HAE）是一种遗传性疾病，其特征为反复发作、界限清楚、非凹陷性、非瘙痒性、且相当疼痛的皮下肿胀，突然发作，在 48-72 小时内消退，但可持续长达 1 周。病变可为单发或多发，主要累及四肢、喉部、面部、食管和肠壁。HAE 患者发生血管性水肿是由于血浆激肽形成级联反应的控制缺陷所致，该级联反应通过与带负电荷的内皮大分子接触而被激活，导致凝血因子 XII 的结合和自身激活、凝血因子 XIIa 激活前激肽原转化为激肽、激肽酶裂解高分子量激肽原释放出强效血管扩张剂缓激肽。目前已描述了三种 HAE 形式。I 型和 II 型 HAE 是罕见的常染色体显性遗传病，是由于 C1 抑制剂基因（SERPING1）的突变引起的。导致 I 型 HAE 的 C1 抑制剂突变发生在整个基因中，导致截短或错误折叠的蛋白，抗原性和功能性 C1 抑制剂水平降低。导致 II 型 HAE 的突变通常涉及活性部位附近或邻近的外显子 8，导致抗原性完整但功能失调的突变蛋白。相比之下，III 型 HAE（也称为雌激素依赖性 HAE）的 C1 抑制剂活性正常。HAE 的诊断提示阳性家族史、无伴随瘙痒或荨麻疹、反复发作的绞痛性胃肠道发作以及喉水肿发作。雌激素可能会加重发作，在一些患者中，发作是由创伤、炎症或心理压力引起的。对于 I 型和 II 型 HAE，C4 浓度降低高度提示诊断。进一步的实验室诊断取决于在大多数家族中证明 C1 抑制剂抗原缺乏（I 型），但一些家族具有抗原性完整但功能失调的蛋白（II 型），需要功能测定来确立诊断。III 型 HAE 无特殊的实验室发现。预防性给予 17α-烷基化雄激素或合成抗纤维蛋白溶解剂已被证明可减少发作的频率或严重程度。血浆衍生的 C1 抑制剂浓缩物、重组 C1 抑制剂、ecallantide（DX88；血浆激肽释放酶抑制剂）和icatibant（缓激肽 B2 受体拮抗剂）已被证明在治疗急性发作方面具有显著疗效，而 C1 抑制剂浓缩物作为长期预防也具有显著益处。然而，这些药物并非在所有国家都获得许可，并不总是容易获得。
