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 inv olved (hereditary angioedema, HAE; acquired angioedema, AAE). The genetic d efect is due to the heterozygous deficiency of C1-Inh that is transmitted a s an autosomal dominant trait. Mutations causing HAE have been found distri buted 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 accelera ted consumption. Such an accelerated consumption can depend on circulating autoantibodies that bind Cl-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 rever t angioedema symptoms in C1-Inh deficiency, the main problem of this condit ion remaining misdiagnosis. The common knowledge that angioedema is an alle rgic symptom frequently prevents a correct diagnostic approach: C1-Inh defi ciency goes unrecognized and the disease can still be lethal. Correct proph ylactic treatment is based on attenuated androgens in HAE and on antifibrin olytic agents in AAE. Life threatening laryngeal attacks and severe abdomin al attacks are effectively reverted, in both conditions, with Cl-Inh plasma concentrate. A special remark to this treatment should be made for autoant ibody-mediated AAE where very high doses can be needed depending on the rat e of Cl-Inh consumption. (C) 2001 Elsevier Science Ltd. All rights reserved .