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 NICE CG134 Gill & Betschel 2017. A positive family history of similar episodes strongly suggests HAE, as it is an inherited condition NICE CG134 Johnston & 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 NICE CG134 Gill & 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 NICE CG134 Johnston & 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 NICE CG134 Gill & 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 NICE CG134 Johnston & Lode 2013Gill & Betschel 2017.