How can I differentiate between HAE and other causes of angioedema in primary care?

To differentiate hereditary angioedema (HAE) from other causes of angioedema in primary care, focus on clinical history, family history, and specific features of the swelling episodes. HAE typically presents with recurrent, non-itchy, non-pitting swelling affecting the skin, gastrointestinal tract, or upper airway, without urticaria or anaphylaxis symptoms, which are common in allergic angioedema ¹ (Gill and Betschel, 2017). A positive family history of similar episodes strongly suggests HAE, as it is an inherited condition ¹ (Johnston and Lode, 2013). The swelling in HAE often develops over hours and lasts 2–5 days, whereas allergic angioedema usually resolves more quickly and is often associated with identifiable triggers such as allergens or medications ¹ (Gill and Betschel, 2017).

Laboratory testing is essential for confirmation: C4 complement levels are typically low during and between attacks in HAE, and C1 inhibitor (C1-INH) levels or function are reduced or dysfunctional, distinguishing it from other forms of angioedema ¹ (Johnston and Lode, 2013). In contrast, allergic angioedema usually has normal complement levels. Bradykinin-mediated angioedema, such as HAE, does not respond to antihistamines or corticosteroids, unlike histamine-mediated angioedema ¹ (Gill and Betschel, 2017).

In summary, key differentiators in primary care are: recurrent angioedema without urticaria, positive family history, absence of response to antihistamines, and low C4 with abnormal C1-INH tests ¹ (Johnston and Lode, 2013; Gill and Betschel, 2017).