Hereditary Angioedema with Normal C1 Inhibitor: Clinical Symptoms and Course

PurposeA new type of hereditary angioedema was described recently. It was characterized by recurrent bouts of angioedema in various organs and normal C1 inhibitor and was observed mainly in women. Our aim was to conduct a detailed study of the clinical features of this condition.MethodsA total of 138 patients with hereditary angioedema and normal C1 inhibitor who belonged to 43 unrelated families were examined through the use of standardized questionnaires.ResultsA majority of patients with hereditary angioedema and normal C1 inhibitor had skin swellings (92.8%), tongue swellings (53.6%), and abdominal pain attacks (50%). Laryngeal edema (25.4%) and uvular edema (21.7%) also were frequent, whereas edema episodes of other organs were rare (3.6%). Facial swellings and tongue involvement occurred considerably more frequently compared with hereditary angioedema caused by C1 inhibitor deficiency. The number of patients with recurrent edema of only 1 organ was higher than in classic hereditary angioedema. The number of patients with disease onset in adulthood was significantly higher in hereditary angioedema with normal C1 inhibitor compared with classic hereditary angioedema. Erythema marginatum was not observed. A subgroup of patients from families with coagulation factor XII mutations showed the same symptoms as the other patients.ConclusionsHereditary angioedema with normal C1 inhibitor levels shows a characteristic pattern of clinical symptoms. The main clinical features include skin swellings, tongue swellings, and abdominal pain attacks. There are many differences in the clinical symptoms and course of disease between this type of hereditary angioedema and classic hereditary angioedema caused by a genetic C1 inhibitor deficiency.