Angio-oedema - allergic, ACE-inhibitor and hereditary

angioedema · angio-oedema · HAE · hereditary angioedema · ACE inhibitor angioedema · bradykinin-mediated angioedema

Deep swelling that can obstruct an airway - and the mechanism matters, because adrenaline does not work on bradykinin.

ADMITBand A

Red flags

Any voice change, stridor, drooling, dysphagia or tongue swelling - a threatened airway, call for anaesthetic and ENT help immediately
Rapid progression of facial or oral swelling
Hypotension, wheeze or urticaria with swelling - manage as anaphylaxis
A known hereditary angio-oedema patient with any attack involving the face, neck or abdomen - give their specific treatment, and early

Recognise

On light skin

Non-pitting asymmetrical swelling, often with normal or slightly red overlying skin; where urticaria coexists, red raised weals appear alongside it.

On brown and black skin

The swelling is the diagnosis and it is tone-independent, so recognition is generally not the problem here. Accompanying urticaria is the part that is missed: weals in brown and black skin are often skin-coloured or paler than the surrounding skin rather than red, and are more easily felt than seen. Palpate for raised weals and ask about itch instead of looking for redness - because their presence or absence is precisely what separates a histamine-mediated from a bradykinin-mediated mechanism, and therefore what determines whether adrenaline will work.

In any skin tone

Deep, non-pitting, asymmetrical swelling rather than a surface rash
Urticaria and itch present - suggests a histamine-mediated cause, which responds to adrenaline. Note what Resuscitation Council UK actually says: an antihistamine is reasonable for an allergic rash alone, but antihistamines are not recommended for treating airway, breathing or circulation problems in anaphylaxis, and steroids such as hydrocortisone are no longer recommended for its routine treatment
Urticaria and itch absent - suspect bradykinin-mediated angio-oedema from an ACE inhibitor or hereditary angio-oedema, which responds poorly to adrenaline and needs specific treatment. This changes what you add, not whether you give adrenaline to a threatened airway
Onset over hours rather than minutes, and a slower resolution over days, also point to bradykinin
Ask directly about ACE inhibitors, including one taken uneventfully for years, because onset can be delayed by months
Ask about previous episodes, a family history, and recurrent unexplained abdominal pain - all suggest hereditary angio-oedema

Distribution

Deep, asymmetrical swelling of the face, lips, tongue, periorbital tissue, genitalia or extremities; may involve the larynx and the bowel wall.

Photographs

Angio-oedema of the tongue. This is the presentation that takes the airway, and the swelling is asymmetrical and deep rather than an all-ove — Angio-oedema of the tongue. **This is the presentation that takes the airway**, and the swelling is asymmetrical and deep rather than an all-over enlargement. A tongue that will not sit back in the mouth, a muffled voice, drooling or any difficulty swallowing saliva is an immediate call for senior anaesthetic and ENT help and a plan made before the airway is lost, not after.
Fitzpatrick I-III (Fitzpatrick type estimated from the photograph, not stated by the source) · James Heilman, MD · Wikimedia Commons - angioedema of the tongue · CC BY-SA 3.0

Facial angio-oedema: deep, non-pitting swelling of the eyelids, cheeks and lips. There are no weals and the swelling is not itchy - that com — Facial angio-oedema: deep, non-pitting swelling of the eyelids, cheeks and lips. **There are no weals and the swelling is not itchy** - that combination points to a bradykinin-mediated cause such as an ACE inhibitor or hereditary angio-oedema rather than an allergic one. Expect less benefit from adrenaline, antihistamine and steroid in that group, but **that is a reason to add specific treatment, never a reason to withhold adrenaline** from a threatened airway; the mechanism cannot be settled at the bedside.
Fitzpatrick I-III (Fitzpatrick type estimated from the photograph, not stated by the source) · Ravn · Wikimedia Commons - angioedema of the face · CC BY-SA 3.0

Provenance for every photograph in this library: image licences. How much of the corpus still has no darker-skin photograph: skin tone coverage.

Mimics

Erythroderma — Facial oedema with widespread erythema may be DRESS or erythroderma rather than isolated angio-oedema
DRESS - drug reaction with eosinophilia and systemic symptoms — Facial oedema is a hallmark of DRESS; the difference is the fever, the systemic features and the eosinophilia
Acute urticaria — Weals with the swelling point to a histamine-mediated mechanism; their absence points to bradykinin - so look for urticaria deliberately, and by palpation in brown and black skin

What to do in the ED

Assess the airway first and repeatedly; involve anaesthetics and ENT early for any oral, tongue or laryngeal involvement
Decide the mechanism: look and feel for urticaria, ask about itch, review the drug history for an ACE inhibitor, and ask about previous attacks and family history
If there is any suggestion of anaphylaxis, give intramuscular adrenaline and manage per the Resuscitation Council UK anaphylaxis guideline - do not withhold it while deliberating mechanism
For bradykinin-mediated angio-oedema, expect adrenaline to be of little or no benefit - but this is a reason to add specific treatment, never a reason to withhold adrenaline. The mechanism cannot be determined reliably at the bedside, and a threatened airway is treated as anaphylaxis until proven otherwise. Stop the ACE inhibitor permanently and never re-challenge
For known or suspected hereditary angio-oedema, give the patient's specific therapy - a C1 inhibitor concentrate or icatibant - without delay, and discuss with immunology; take a C4 and C1 inhibitor level but do not wait for results
Observe for a period appropriate to the mechanism and the site, because bradykinin-mediated swelling progresses over hours
Document the mechanism and the culprit prominently, and refer to immunology or allergy for anything recurrent or unexplained

Disposition

ADMIT

Any airway involvement means resuscitation area with anaesthetic and ENT presence, then critical care. Isolated peripheral or lip swelling in a patient with a clear histamine-mediated cause and a secure airway may be observed and discharged with allergy follow-up.

Safety-netting

If discharged: return immediately for any change in voice, difficulty swallowing or breathing, or tongue or throat swelling. Avoid the identified trigger absolutely. If an ACE inhibitor was stopped, that class must never be restarted. Angiotensin-II receptor antagonists should also be avoided where possible, because they can trigger angio-oedema too - so switching to one is not a safe default. Make sure both points reach the GP as well as the hospital notes.

Local variation

Availability of C1 inhibitor concentrate and icatibant, and whether they are held in the ED or in pharmacy, varies by site. Find out before a hereditary angio-oedema patient arrives, not during the attack.

Sources

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