Treatment of Patients with Hereditary Angioedema with Normal C1 Inhibitor: Evaluation of 295 Patients

Abstract

Hereditary angioedema (HAE) with normal C1 inhibitor (nlC1-INH) is a rare condition, with clinical features similar to those of HAE with C1-INH deficit. Hormones have a special role as triggering factor. There is no biomarker for diagnosis, requiring a compatible clinical and familial history and/or identification of associated mutation (Factor 12, Angiopoietin 1 and Plasminogen). We evaluated 295 patients (242 F: 53 M) out of 101 families with confirmed diagnosis of HAE nlC1-INH from 16 reference centers in Brazil. 72.9% (215/295) were symptomatic (194F:21M) and 27.1% (80/295) asymptomatic with age range 3 - 91 years (median: 36). Genetic evaluation showed: F12 mutation 178/245 (72.6%); angiopoietin1 in 4/245 and 63/245 had unknown mutation. Symptoms initiated between 2 - 68 years old (median=18). Main triggering factors: hormones 68.3%; stress 59.6%; trauma 47.6%; dental therapy 13.9%; unknown 13% and others 27%. Edema occurred in: face 84.6%; abdomen 75.5%; extremities 61.1%; laryngeal 36.1%; tongue 23.1% and others. Three patients died due to HAE. One third of the patients improved after contraceptive withdrawal only; 21.3% (36) treated on demand; continuous prophylaxis was used in 68.6% and 18.3% for surgical procedures; 22.5% increased doses of prophylactic medications during the attacks. Main prophylactic drug was tranexamic acid (n=45). F12 mutation was present in a high number of our patients in comparison with other reports. Symptoms persisted in the majority of patients although estrogen therapy was interrupted. Plasmin inhibitor was effective in HAE nlC1-INH.