ABSTRACT

The majority of angioedema cases encountered in clinical practice are histamine-mediated (allergic); however, some cases are bradykinin-related (non-allergic) and do not respond to standard anti-allergy medications. Among bradykinin-related angioedema, hereditary angioedema (HAE) is a rare, but chronic and debilitating condition. The majority of HAE is caused by deficiency (type 1) or abnormal function (type 2) of the naturally occurring protein, C1-inhibitor (C1-INH)—a major inhibitor of proteases in the contact (kallikrein-bradykinin cascade), fibrinolytic pathway, and complement systems. Failure to recognize HAE and initiate appropriate intervention can lead to years of pain, disability, impaired quality of life (QoL) and, in cases of laryngeal involvement, it can be life-threatening. HAE must be considered in the differential diagnosis of non-urticarial angioedema, particularly for patients with a history of recurrent angioedema attacks, family history of HAE, symptom onset in childhood/adolescence, prodromal signs/symptoms before swellings, recurrent/painful abdominal symptoms, and upper airway edema. Management strategies for HAE include on-demand treatment for acute attacks, short-term prophylaxis prior to attack-triggering events/procedures, and long-term or routine prophylaxis for attack prevention. Patients should be evaluated at least annually to assess need for routine prophylaxis. HAE specific medications like plasma-derived and recombinant C1-INH products, kallikrein inhibitors, and bradykinin B2 receptor antagonists, have improved management of HAE. While the introduction of intravenous C1-INH represented a major breakthrough in routine HAE prophylaxis, some patients fail to achieve adequate control and others have psychological barriers or experience complications related to intravenous administration. Subcutaneous (SC) C1-INH, SC monoclonal antibody (mAb)-based therapies, and an oral kallikrein inhibitor offer effective alternatives for HAE attack prevention and may facilitate self-administration. HAE management should be individualized, with QoL improvement being a key goal. This can be achieved with broader availability of existing options for routine prophylaxis, including greater global availability of C1-INH(SC), mAb-based therapy, oral treatments, and multiple on-demand therapies.

摘要

临床实践中遇到的大多数血管性水肿病例是组胺介导的（过敏性）；然而，有些病例与缓激肽有关（非过敏性）并且对标准抗过敏药物没有反应。在缓激肽相关的血管性水肿中，遗传性血管性水肿 (HAE) 是一种罕见但慢性且使人衰弱的疾病。大多数 HAE 是由天然蛋白质 C1-抑制剂 (C1-INH) 的缺乏（1 型）或功能异常（2通路和补体系统。未能识别 HAE 并启动适当的干预可能会导致多年的疼痛、残疾、生活质量 (QoL) 受损，并且在喉部受累的情况下，可能会危及生命。在非荨麻疹性血管性水肿的鉴别诊断中必须考虑 HAE，特别是对于有复发性血管性水肿发作史、HAE 家族史、儿童/青春期症状发作、肿胀前有前驱症状/症状、复发/腹部疼痛症状、和上呼吸道水肿。HAE 的管理策略包括急性发作的按需治疗、发作触发事件/程序之前的短期预防以及长期或常规预防发作预防。应至少每年对患者进行一次评估，以评估是否需要常规预防。HAE 特定药物，如血浆衍生和重组 C1-INH 产品、激肽释放酶抑制剂和缓激肽 B2 受体拮抗剂，已改善了 HAE 的管理。虽然静脉注射 C1-INH 的引入代表了常规 HAE 预防的重大突破，但一些患者未能达到足够的控制，而另一些患者则存在心理障碍或经历与静脉给药相关的并发症。皮下 (SC) C1-INH、基于 SC 单克隆抗体 (mAb) 的疗法和口服激肽释放酶抑制剂为预防 HAE 发作提供了有效的替代方法，并可能促进自我给药。HAE 管理应该是个性化的，QoL 的改进是一个关键目标。这可以通过现有常规预防选择的更广泛可用性来实现，包括 C1-INH(SC)、基于 mAb 的疗法、口服治疗和多种按需疗法的更大全球可用性。一些患者无法获得足够的控制，而另一些患者则有心理障碍或经历与静脉给药相关的并发症。皮下 (SC) C1-INH、基于 SC 单克隆抗体 (mAb) 的疗法和口服激肽释放酶抑制剂为预防 HAE 发作提供了有效的替代方法，并可能促进自我给药。HAE 管理应该是个性化的，QoL 的改进是一个关键目标。这可以通过现有常规预防选择的更广泛可用性来实现，包括 C1-INH(SC)、基于 mAb 的疗法、口服治疗和多种按需疗法的更大全球可用性。一些患者无法获得足够的控制，而另一些患者则有心理障碍或经历与静脉给药相关的并发症。皮下 (SC) C1-INH、基于 SC 单克隆抗体 (mAb) 的疗法和口服激肽释放酶抑制剂为预防 HAE 发作提供了有效的替代方法，并可能促进自我给药。HAE 管理应该是个性化的，QoL 的改进是一个关键目标。这可以通过现有常规预防选择的更广泛可用性来实现，包括 C1-INH(SC)、基于 mAb 的疗法、口服治疗和多种按需疗法的更大全球可用性。和口服激肽释放酶抑制剂为预防 HAE 发作提供了有效的替代方法，并可能促进自我给药。HAE 管理应该是个性化的，QoL 的改进是一个关键目标。这可以通过现有常规预防选择的更广泛可用性来实现，包括 C1-INH(SC)、基于 mAb 的疗法、口服治疗和多种按需疗法的更大全球可用性。和口服激肽释放酶抑制剂为预防 HAE 发作提供了有效的替代方法，并可能促进自我给药。HAE 管理应该是个性化的，QoL 的改进是一个关键目标。这可以通过现有常规预防选择的更广泛可用性来实现，包括 C1-INH(SC)、基于 mAb 的疗法、口服治疗和多种按需疗法的更大全球可用性。