What clinical features should prompt me to suspect hereditary angioedema (HAE) in a patient?

Clinical features that should prompt suspicion of hereditary angioedema (HAE) include:

• Recurrent episodes of non-itchy, non-pitting swelling affecting the skin, particularly of the face, extremities, genitalia, and airway.
• Recurrent abdominal pain with associated nausea, vomiting, or diarrhoea due to submucosal oedema in the gastrointestinal tract.
• Absence of urticaria or typical allergic features during swelling episodes, distinguishing HAE from allergic angioedema.
• A family history of similar episodes of angioedema, although sporadic cases can occur.
• Onset often in childhood or adolescence but can present at any age.
• Episodes may be triggered by minor trauma, stress, infection, or hormonal changes.
• Swelling episodes that do not respond to standard treatments for allergic angioedema, such as antihistamines, corticosteroids, or adrenaline.

These features align with UK clinical guidance on angioedema assessment and referral ¹ and are supported by recent literature emphasizing the importance of recognising hereditary angioedema even in patients with normal C1-esterase inhibitor levels (Jones et al., 2023). The literature highlights that normal C1-inhibitor HAE can present similarly, reinforcing the need to consider HAE in recurrent angioedema without urticaria and poor response to conventional allergy treatments (Jones et al., 2023).

Key References

• CG134 - Anaphylaxis: assessment and referral after emergency treatment
• CG116 - Food allergy in under 19s: assessment and diagnosis
• (Jones et al., 2023): Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor.