Hereditary angioedema (HAE) is a rare,unpredictable,autosomal dominant disorder characterized by recurrent swelling in subcutaneous and submucosal tissue.In recent years,the pathophysiology and pathogenesis of HAE have been continuously studied and elucidated.In addition to the genes encoding complement 1 esterase inhibitors,new pathogenic variants have been identified in the genes encoding coagulation factor Ⅻ,plasminogen,angiopoietin-1,kininogen,heparan sulfate 3-O-sulfotransferase 6,and myoferlin in HAE.Moreover,different pathogenic variants have different mechanisms in causing HAE.In addition,the pathogenic genes of some patients remain unknown.This review summarizes the recent progress in the classification,epidemiology,pathophysiology,and pathogenesis of HAE,aiming to provide ideas for further fundamental research,clinical diagnosis,and drug development of HAE.
Humans ; Angioedemas, Hereditary/diagnosis* ; Angiopoietin-1/metabolism* ; Plasminogen/metabolism* ; Kininogens/metabolism* ; Complement C1 Inhibitor Protein/metabolism*

PURPOSE: Hereditary angioedema is a familial disease which is caused by a genetic deficiency or functional defect of the C1 inhibitor, and it features episodic swelling that can affect any part of the body. A great number of patients are estimated not to have an accurate diagnosis after the onset of symptoms, and close attention is required because sudden hereditary angioedema attacks can result in even death. METHODS: We sent an e-mail questionnaire to 975 members of the Korean Academy of Asthma, Allergy and Clinical Immunology. A total of 82 members replied. The questionnaire, including 15 questions about the diagnosis and management of hereditary angioedema, was developed by the anaphylaxis/urticaria, angioedema workgroup of the Korean Academy of Asthma, Allergy and Clinical Immunology. RESULTS: Forty-two percent of the respondents had experience with treatment of a suspected case of hereditary angioedema, and 15.9% made a confirmed diagnosis of hereditary angioedema. When the respondents suspected of cases, 91.4% of them performed tests for C3 and C4 concentrations and C1 inhibitor level. For maintenance treatment, most of the respondents used androgen, and only 22% found that C1 inhibitor concentrates can be prescribed through the Korea Orphan Drug Center in Korea. CONCLUSION: Allergy physicians in Korea substantially recognized the correct diagnosis and treatment of hereditary angioedema. However, there was a lack of awareness for the latest treatments, such as C1 inhibitor concentrates. Education of doctors and the public is needed.
Allergy and Immunology ; Angioedema ; Angioedemas, Hereditary* ; Asthma ; Surveys and Questionnaires ; Diagnosis ; Disease Management ; Education ; Electronic Mail ; Humans ; Hypersensitivity ; Korea ; Orphan Drug Production ; Surveys and Questionnaires

Hereditary angioneurotic laryngeal edema (HALE) is an autosomal dominant hereditary disease in which there is a decrease or defect in the C1 inhibitor (C1-INH). The pathophysiology of HALE is characterized by recurrent spontaneous episodes of transient edema of the laryngeal mucose and submucosal tissue with remission at irregular. Patients may die because of a life-threatening acute upper airway obstruction caused by laryngeal edema. HALE was diagnosed on the clinical symptoms, family history, and markedly decreased serum C1-INH activity and C1-INH protein.
Angioedemas, Hereditary ; diagnosis ; Complement C1 Inactivator Proteins ; analysis ; metabolism ; Complement C1 Inhibitor Protein ; Humans ; Laryngeal Edema ; diagnosis ; Recurrence

We report on an angioedema patient with a genetic defect in complement 1 inhibitor, manifesting migraine-like episodes of headache, effective prophylaxis with Danazol, and triptan for a treatment of acute clinical episode. The patient was 44-yr-old Korean man with abdominal pain and headache, who was brought into the Emergency Department of Seoul National University Hospital, Seoul. He suffered from frequent attacks of migraine-like headache (3-7 per month), pulsating in nature associated with nausea. Severities were aggravated by activity and his headache had shown recent progression with abdominal pain. No remarkable findings were observed on radiologic examination, brain magnetic resonance images and intracranial and extracranial magnetic resonance angiography. Danazol 200 mg every other day was subsequently used. Following administration of Danazol, symptoms showed improvement and the patient was discharged. While taking Danazol, the migraine-like episodes appeared to be prevented for about 2 yr. At the eighth month, he suffered a moderate degree of migraine-like headache; however, administration of naratriptan 2.5 mg resolved his problem. A case of genetic defect of C1-INH deficiency presented with headache episodes, and was controlled by Danazol and triptan. It suggests that pathogenic mechanism of headache in hereditary angioedema may be mediated by the neurogenic inflammatory-like physiology of migraine.
Adult ; Angioedemas, Hereditary/*complications/diagnosis/*genetics ; Brain/radionuclide imaging ; Complement C1 Inhibitor Protein/*genetics/metabolism ; Danazol/therapeutic use ; Estrogen Antagonists/therapeutic use ; Humans ; Magnetic Resonance Angiography ; Male ; Migraine Disorders/*diagnosis/drug therapy/*etiology ; Piperidines/therapeutic use ; Tryptamines/therapeutic use ; Vasoconstrictor Agents/therapeutic use

Hereditary angioedema is a rare genetic disease transmitted with a autosomal dominant trait result of a quantitative or functional defect of Cl inhibitor. We report three cases of heriditary angioedema from the same famly respectively the 35-year-old sister, the younger bn)ther of 32, and the younger sister of 20 The older sister died due to her airway being obstructel by acute laryngeal edema, and her you igirbrother and sister experienced recurrent episodes oswelling on the hand and forearm. The ore we examined the two patients serum complement levils to confirm diagnosis. In both, the r;ults showed decreased levels of Cl inhibitor and C4 which are the evidence of hereditary a giedema. The younger sister has been administered danazol (600mg/day) to prevent angioedem or 8 weeks, and we have not yet found a recurrenc of he symptoms. However, well cont ol the dosage of danazol because amenorchea has developec.
Adult ; Angioedema ; Angioedemas, Hereditary* ; Complement System Proteins ; Danazol ; Diagnosis ; Forearm ; Hand ; Humans ; Laryngeal Edema ; Siblings