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Clinical features of recurrent angioedema with unknown etiology

Published online: April 28, 2018

Recurrent angioedema may be accompanied by, or occur without, wheals. Angioedema without wheals is considered a distinct disease. The classification of angioedema without wheals distinguishes three hereditary and four acquired forms. One of the latter, idiopathic non-histaminergic acquired angioedema (InH-AAE), is diagnosed by excluding other disorders associated with angioedema of known etiology and by ascertaining the failure of antihistamine therapy. Its pathophysiology has not been elucidated, nor its appropriate therapy defined. Most commonly, bradykinin release is the underlying factor in hereditary forms of angioedema (hereditary angioedema with C1-INH deficiency (C1-INH-HAE), or with a mutation of coagulation factor XII (FXII-HAE)). However, in a proportion of patients with hereditary angioedema, the causative defect cannot be identified (hereditary angioedema of unknown origin, U-HAE).

In an article recently published in The Journal of Allergy and Clinical Immunology: In Practice, Andrasi et al. explored the clinical features of 46 patients with InH-AAE, 27 patients with U-HAE and 73 patients with C1-INH-HAE, in a population managed at the Hungarian Angioedema Reference Center. Demographic data were compared among these three patient groups (such as mean age at the time of the onset of symptoms/time of diagnosis, the mean number of edematous episodes occurring over a year, and the locations of the attacks reported by the subjects).

The authors identified trends in the clinical manifestations of these three groups. Angioedema symptoms occur the earliest in C1-INH-HAE patients. U-HAE patients begin to experience symptoms during their young adulthood, and angioedema appears latest in patients with InH-AAE. With regard to the frequency of the symptoms, patients with the two idiopathic disease forms experience edema as often as do C1-INH-HAE patients. This underlines the importance of monitoring these patients, because their disease burden is similar to that of patients with C1-INH-HAE. Both in InH-AAE patients and in those with U-HAE, edema most often involved the face and the tongue. Limb and gastrointestinal edema were the most characteristic locations in C1-INH-HAE but were less typical in InH-AAE and in U-HAE.

Based on the differences between InH-AAE and C1-INH-HAE, the researchers speculate that the occurrence of edema may be attributed to different mechanisms in these forms. On the other hand, the similarities between InH-AAE and pure U-HAE in these aspects may suggest similar pathophysiological processes behind the symptoms.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.