Hereditary angioedema (HAE)
A rare inherited disorder causing recurrent episodes of deep tissue swelling — of the limbs, face, gut or airway — without the itchy hives of an allergy. It doesn't respond to usual allergy treatments, and a persistently low complement C4 is a key screening clue.
What it is
Hereditary angioedema is a rare genetic condition caused, in most cases, by a deficiency or malfunction of a protein called C1 esterase inhibitor, which normally keeps part of the immune and clotting systems in check. Without it, a chemical called bradykinin builds up and makes blood vessels leak, causing episodes of swelling deep in the tissues. Attacks affect the hands, feet, face, genitals, gut (causing severe abdominal pain, cramps and vomiting that can mimic a surgical emergency) and, most dangerously, the throat and airway. Crucially, unlike allergic angioedema, it comes without itchy hives (urticaria) and does not respond to antihistamines, adrenaline or steroids — which is why recognising it matters. Attacks can be triggered by trauma (including dental work), stress, infections or certain medications, and it usually runs in the family. A persistently low complement C4 between attacks is a simple, important screening clue that prompts specific testing of C1 inhibitor.
Key lab markers
- Complement C4 — characteristically low, even between attacks; a key, simple screening clue.
- C1 esterase inhibitor level and function — the specific diagnostic tests (both quantity and activity).
- C1q — sometimes measured to distinguish inherited from acquired forms.
- Genetic testing — confirms the diagnosis in unclear cases and for family screening. Allergy tests (IgE) are typically normal — this is not an allergic condition.
Symptoms
- Recurrent episodes of swelling of the hands, feet, face, lips or genitals
- Swelling WITHOUT itchy hives (unlike an allergic reaction)
- Severe abdominal pain, cramps and vomiting during gut attacks (can mimic appendicitis)
- Throat or tongue swelling causing difficulty breathing or swallowing — the dangerous form
- Attacks building over hours and lasting a few days
- Triggers such as trauma, dental work, stress, infection, or certain medicines
- A family history of similar swelling
When to discuss with a doctor
Any swelling of the throat or tongue with difficulty breathing or swallowing is a medical emergency — call for urgent help immediately, and note that HAE attacks need specific treatments, as they do NOT respond to adrenaline, antihistamines or steroids. Recurrent angioedema without hives — especially with unexplained severe abdominal attacks, a family history, or swelling that doesn't respond to allergy treatment — should prompt a doctor to check complement C4 and refer for C1-inhibitor testing. A confirmed diagnosis is managed by an immunology or allergy specialist, with specific medicines to treat and prevent attacks and a plan for emergencies and before procedures. Mediora.AI can flag a persistently low C4 that fits this picture; the diagnosis and specialist treatment belong with immunology.