See also

Emergency airway management 

Can't intubate can't oxygenate 

Anaphylaxis

Key points

1. Angioedema in hereditary angioedema (HAE) is non-pitting swelling not associated with urticaria, itching or redness
2. Life-threatening laryngeal oedema can occur at any age
3. Children diagnosed with HAE should have a personalised ASCIA HAE management plan explaining when and how to treat attacks
4. Early management of HAE attacks with specific treatments has been shown to improve outcomes, efficacy and quality of life. Antihistamines, corticosteroids and adrenaline have no role in the management of HAE related angioedema

Background

• HAE is a rare but potentially life-threatening autosomal dominant disorder due to absolute (HAE-C1-INH Type 1 -- 85% of cases) or functional (HAE-C1-INH Type 2) deficiency of C1-esterase inhibitor (C1-INH)
• HAE attacks are recurrent, often unpredictable, episodes of painful, non-pruritic and non-pitting angioedema (swelling)
• In an acute attack, children may develop swelling in one or more sites involving subcutaneous tissues or submucosa of the gut and upper respiratory tract
  • Cutaneous angioedema: over 90% develop non-pitting, non-pruritic swelling affecting face, limbs (especially hands and feet) and genitals. The first few attacks are usually associated with pain and dysfunction
  • Upper airway swelling: may affect oropharynx (tongue, soft palate) or larynx and can be life-threatening
  • Abdominal pain: often associated with nausea, vomiting and diarrhoea and can lead to dehydration and collapse
  • Rash: about one third develop an erythema marginatum rash either before or during an attack. This is non-pruritic and non-urticarial
• Attacks typically peak at 24 hours and resolve over 48-72 hours
• Can occur spontaneously or may be precipitated by injury (including local trauma, dental or other surgery), infection, psychological stress, medications (especially oestrogen containing and ACE inhibitors), menstruation, vigorous exercise or certain foods
• HAE symptoms typically first occur between 5-11 years of age; 40% experience a first episode by age 5
• Early symptom onset may predict a more severe disease course
• The frequency and severity of a HAE attack may worsen in adolescence, and symptoms typically persist throughout life

Assessment

History

• Family history of HAE is present in 75% of cases
• Consider trigger (stress, infection, injury)
• Prodromal symptoms: fatigue, flu-like symptoms, indigestion, tingling or rash (erythema marginatum) may precede onset of swelling

Examination

• Airway swelling: tongue, soft palate, uvula
• Laryngeal oedema: stridor, hoarseness, drooling, altered voice (ask caregivers)
• Angioedema behind teeth (eg tongue, posterior oropharyngeal, laryngeal) is more likely to progress to airway obstruction than angioedema in front of teeth
• Facial and limb swelling
• Confirm absence of redness and itching, which would otherwise suggest diagnosis other than HAE

Differential diagnoses

• Allergic reactions and anaphylaxis (see Anaphylaxis)
• Idiopathic angioedema
• Drug-induced angioedema
• Acquired angioedema (exceedingly rare in childhood)

Management

Investigations

• C4 in a suspected acute attack, if no prior HAE diagnosis

Management of acute attacks

• Children with diagnosed HAE presenting in an acute attack should have an individualised ASCIA HAE management plan
• Aims of treatment are to reduce the duration and severity of an attack, minimise functional impairment, reduce morbidity and potential mortality
• Treatment of any non life-threatening HAE attack should be at the discretion of the child and parent
• Treatments available are Icatibant (subcutaneous) or C1 esterase inhibitor concentrate (intravenous)
• Clinical response should be observed within 2 hours. If there is no response after 2 hours, reconsider diagnosis and evaluate for other causes
• If above treatments are unavailable, consider solvent/detergent treated FFP for laryngeal and/or severe abdominal attacks, though this may have a paradoxical effect and worsen angioedema
• Consult local allergy/immunology specialist as required

Acute treatment

Management of special clinical features

• Airway/laryngeal attacks: medical emergency requiring immediate treatment with Icatibant or C1-INH concentrate. Signs of impending airway obstruction should prompt senior involvement/ICU/anaesthetics, ideally with fibre optic-guided intubation and surgical airway skills (see Emergency airway management)
• Peripheral swelling: significant pain +/- significant disability and/or angioedema involving face or genitals should be treated. Mild swelling that doesn't impact function may not require treatment
• Abdominal pain: moderate to severe pain, vomiting and/or abdominal distension require C1-INH concentrate administration. If severe, consider fluid resuscitation. Mild pain can be treated with simple analgesia including NSAIDs

Consider consultation with local paediatric team when

• First episode of swelling / no previous diagnosis
• Airway / laryngeal attack
• No response to medication within 2 hours
• Relapse to first line treatment

Consider transfer when

• Airway / laryngeal attack - children will usually require observation in PICU / HDU setting
• Immediate life-threatening situation
• A child requiring care beyond the comfort level of the hospital
• Inadequate response to acute treatment

Consider discharge when

• Following successful emergency treatment, children who have started to improve with peripheral swellings and/or abdominal attacks may be discharged even if peripheral swellings have not fully resolved
• Any child diagnosed with HAE should have a consultation with an allergy/immunology specialist or clinician with expertise in managing angioedema

Additional notes

Short term prophylaxis

Long term prophylaxis

Regular medication prescribed by the child's Immunologist to prevent attacks and reduce the burden of disease. Options include oral antifibrinolytics (tranexamic acid), subcutaneous C1-INH concentrate (Berinert® SC) and advanced therapies like plasma kallikrein inhibitors (Lanadelumab) and factor XIIa inhibitors (Garadacimab)

Investigations

• In the non-acute setting, screening for HAE may be considered, in consultation with an Immunologist: serum C4 level, C1-INH blood level, C1 functional assay
  • Two sets of complement tests should be obtained, at least 3 months apart
• Genetic testing is not usually required to confirm the diagnosis
  • Both C1-INH levels and function are difficult to interpret in children <1 year of age and at least 1 set of HAE bloods should be performed after the age of 1
  • If the diagnosis is confirmed, family screening is recommended

Diagnostic testing profiles for HAE subtypes

Parent information

ASCIA HAE

ASCIA HAE Management Plan

Last updated May 2025