[Hereditary angioedema: new mechanisms and therapeutic options].
Hereditary angioedema (HAE) is a rare genetic disorder, manifested by recurrent bouts of swelling in various tissues. The biochemical basis leading to HAE manifestations is either a quantitative or qualitative deficiency in plasma C1 esterase inhibitor (C1-INH). Its proposed physiological role is regulation of vascular permeability, by inhibiting certain steps in the complement, coagulation and the fibrinolytic pathways. Recent evidence implies that bradykinin, a plasma kinin, is the main mediator of HAE, Leading to vasodilatation and hyperpermeability of small vessels. Bradykinin receptors have been recently identified, Leading to significant progress in our understanding of the physiologic mechanisms leading to edema. HAE is characterized by edema of the extremities, face, tongue, Larynx, genitalia and severe abdominal pains. Edema of the tongue and Larynx are life-threatening, and fataloutcomes have been described. Diagnosis of HAE is frequently missed, due to the rarity, non-specific symptoms and lack of awareness of physicians to the diagnosis and treatment. In this review, the authors describe the mechanisms of HAE and the clinical approach to diagnosis and management, according to accepted international guidelines. Furthermore, new treatment modalities that have recently been developed are presented: novel molecules targeting bradykinin, either by inhibiting its generation from plasma kininogens or by direct inhibition of its specific receptors on blood vessels, replacement therapy with human recombinant C1-INH produced in transgenic rabbits. HAE is a chronic disabling diseasewith serious consequences for the patients and their families, severely affecting the quality of life. Recently, new clinical guidelines were published and treatment centers, specializing in the management of HAE were established. The authors are convinced that the increased awareness of the medical staff, in addition to new data and novel treatments, will reduce the burden of the disease, improve its grim prognosis and enable a better quality of life for HAE patients.
Reshef
Avner
A
Allergy and Clinical Immunology and the Angioedema Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. areshef@sheba.health.gov.il
Leibovich
Iris
I
Goren
Avner
A
Kidon
Mona
M
D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D030801:Animals, Genetically Modified; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency; D003937:Diagnosis, Differential; D006801:Humans; D017410:Practice Guidelines as Topic; D011817:Rabbits
D003174:Complement C1 Inactivator Proteins