Angioedema: What We Know and What We Need to Know

Abstract

Angioedema involving airways is a life-threatening condition, which is the cause of significant morbidity, emergency room visits, and hospitalizations. The economic impact of this condition is huge. There are two major forms of angioedema—bradykininmediated angioedema and histamine-mediated angioedema. The bradykinin-mediated angioedema is popularly known as the complement-mediated angioedema. It is now clear that bradykinin is the final mediator of this illness regardless of the functional status of the C1 esterase inhibitor SERPING1. This conclusion is supported by genetic manipulation studies in the mouse model and the efficacy of bradykinin inhibitors in angioedema. Bradykinin-mediated angioedema can be caused by a functional deficiency of SERPING1 (type 1 and 2 hereditary angioedema), which blocks kallikrein and factor XII, the Hageman factor—the upstream activators of bradykinin. It can also be caused by mutation of the Hageman factor (type 3 hereditary angioedema). Unfortunately, many patients do not fall into either category, so they are labeled with idiopathic angioedema, although bradykinin remains the final common mediator. Bradykinin-mediated angioedema responds to treatment with the C1 esterase inhibitor (fresh frozen plasma, concentrate, or recombinant C1 esterase inhibitor), kallikrein inhibitors, and bradykinin receptor antagonists. Prophylaxis with anabolic androgens and anti-fibrinolytics is helpful. This condition contrasts with histamine-mediated angioedema, which is frequently associated with urticaria, and represents a spectrum of the urticarial syndrome. Histamine-mediated angioedema is more common than bradykinin-mediated angioedema. It can be extrinsic (allergic/IgE mediated and nonallergic), autoimmune, and idiopathic. This form of angioedema responds to antihistamines, glucocorticoids, and epinephrine.