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

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 22 August 2025Updated: 22 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

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 and are supported by recent literature emphasizing the importance of recognising hereditary angioedema even in patients with normal C1-esterase inhibitor levels . 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 .

Educational content only. Always verify information and use clinical judgement.