C1-inhibitor deficiency and angioedema.
C1-inhibitor deficiency can be inherited or acquired; both conditions lead to recurrent angioedema that can be life threatening when the larynx is involved (hereditary angioedema, HAE; acquired angioedema, AAE). The genetic defect is due to the heterozygous deficiency of C1-Inh that is transmitted as an autosomal dominant trait. Mutations causing HAE have been found distributed over all exons and splice sites of C1-Inh structural gene: only a few of them have been found more than once. Depending on DNA defect, C1-Inh is not transcribed, or not translated or not secreted. Finally, in 15% of HAE patients, an antigenically normal, but non-functional C1-Inh is present in serum (HAE type II). C1-Inh deficiency can be acquired, due to an accelerated consumption. Such an accelerated consumption can depend on circulating autoantibodies that bind C1-Inh causing its inactivation and catabolism; or to associated diseases, usually lymphoproliferative diseases, that consume C1-Inh with different mechanisms. Effective therapies can prevent or revert angioedema symptoms in C1-Inh deficiency, the main problem of this condition remaining misdiagnosis. The common knowledge that angioedema is an allergic symptom frequently prevents a correct diagnostic approach: C1-Inh deficiency goes unrecognized and the disease can still be lethal. Correct prophylactic treatment is based on attenuated androgens in HAE and on antifibrinolytic agents in AAE. Life threatening laryngeal attacks and severe abdominal attacks are effectively reverted, in both conditions, with C1-Inh plasma concentrate. A special remark to this treatment should be made for autoantibody-mediated AAE where very high doses can be needed depending on the rate of C1-Inh consumption.
Carugati
A
A
Department of Internal Medicine, University of Milan, IRCCS Ospedale Maggiore, Via Pace 9, 20122 Milan, Italy.
Pappalardo
E
E
Zingale
L C
LC
Cicardi
M
M
D000799:Angioedema / Q000209:etiology* / Q000235:genetics* / Q000628:therapy; D001323:Autoantibodies; D001327:Autoimmune Diseases; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology
D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins