Clinical Immunology Review Series: An approach to the patient with angio-oedema

Abstract

Angio-oedema is a common reason for attendance at the accident and emergency department and for referral to immunology/allergy clinics. Causative factors should always be sought, but a large proportion of patients have the idiopathic form of the disease. A minority of patients represent a diagnostic and treatment challenge. Failure to identify the more unusual causes of angio-oedema may result in life-threatening situations. Common and rare causes of angio-oedema will be discussed in this article, as well as the diagnostic and treatment pathways for the management of these patients. A comprehensive history and close monitoring of response to treatment are the most cost-effective diagnostic and treatment tools.

Fig. 1

Following contact activation of Factor XII by exposure to a negatively charged surface, kallikrein catalyses the production of bradykinin from high molecular weight kininogen. Contact system activation also enhances complement activation. Bradykinin binding to B2-receptors on the vascular endothelium causes local oedema. Bradykinin is metabolized by a variety of enzymes, including angiotensin converting enzyme (ACE). C1 inhibitor (C1INH) regulates the contact and classical complement pathways by inhibition at a variety of points, shown in yellow.

Fig. 2

(a) Swollen left hand in patient with hereditary angio-oedema (HAE). (b) Mild oedema of left eye in patient with HAE. Symptoms resolved after 500 units of C1 inhibitor given by slow intravenous injection. Delay in treatment typically results in more severe swelling requiring 1000 units of C1 inhibitor for relief.

Fig. 3

Diagnostic algorithm for the patient with recurrent angioedema.