French protocol for the diagnosis and management of hereditary angioedema

Recurrent isolated angioedema (AE) is a diagnostic and therapeutic challenge. Only a rigorous clinical approach can rule out the most obvious diagnoses. The recent international classification recognizes 7 subgroups: mast cells induced AE (spontaneous, allergic), Bradykinin mediated AE (Hereditary or acquired C1Inh; kallikrein-kinin mutations), HAE due to vascular endothelium dysfunction, drug induced AE and AE of unknow origin. Bradykinin-mediated hereditary angioedema (BK-HAE) are rare conditions. The currently accepted incidence of HAE-C1INH is approximately 1 in 50,000 inhabitants per year. Bradykinin is released following activation of the kallikrein/kinin pathway in the vascular lumen and is rapidly degraded by kininases, the main one being angiotensin-converting enzyme. The disease manifests as subcutaneous or submucosal edema. When an attack occurs in the pharynx/larynx area, there is a high risk of asphyxia (25% in the absence of specific treatment). This risk is unpredictable and exists throughout the patient's life. AE can be localized in the abdomen and resemble a surgical emergency. The disease is more symptomatic in women, as estrogen is an aggravating factor. In AE due to C1INH deficiency, the diagnosis is based on the search for a weight and/or functional deficiency in C1 inhibitor. In the forms with normal C1 inhibitor, the diagnosis is solely genetic, such as F12, PLG, or KNG1 mutations. The prognosis for these rare diseases has changed considerably in recent years with the arrival of new, highly effective specific drugs. Patient education is an important part of management. We present here the French protocol for the diagnosis and management of bradykinin-mediated hereditary AE.