Recognition and Differential Diagnosis of Hereditary Angioedema in the Emergency Department

Abstract

Background: Angioedema (AE) is a clinical syndrome marked by localized swelling of the subcutaneous layer of the skin or the submucosal layer of the respiratory or gastrointestinal tracts. While AE is commonly mediated by histamine (allergic AE), some types result from excessive bradykinin activity, including hereditary AE (HAE), acquired AE, and angiotensin-converting enzyme inhibitor-induced AE. These are less common but important to consider given different treatment requirements and potentially serious outcomes, including death from laryngeal swelling.

Objective: This review describes the pathophysiology and clinical features of AE as well as the diagnosis and treatment of AE in the emergency department (ED).

Discussion: Bradykinin-mediated AE does not respond to antihistamines and corticosteroids. By contrast, several targeted, effective therapies are available, including C1-inhibitor (C1-INH) concentrates, which replace the missing protein activity underlying some bradykinin-mediated AE, and medications that directly lessen bradykinin activity (eg, ecallantide and icatibant). Urticaria is generally absent in bradykinin-mediated AE and serves as a primary differentiating factor in the clinical diagnosis. Relevant laboratory assessments may include C1-INH levels, C1-INH function, and C4 complement. Patients with HAE or a family member can communicate their known diagnosis when presenting to the ED, and some may even bring their own medication(s) with them. Patients newly diagnosed with HAE in the ED should be referred for specialized outpatient care upon ED discharge.

Conclusions: There is a great need for ED clinicians to be aware of HAE, its differential diagnosis, and appropriate treatment to ensure that patients receive optimal and timely treatment.

Keywords: angioedema; bradykinin-mediated; diagnosis; hereditary angioedema; histamine-mediated; pathophysiology; treatment.