(Hereditary Angioedema, HAE)
HAE causes recurrent episodes of angioedema in the upper
respiratory, gastrointestinal tract or in subcutaneous tissues.
Acute episodes of angioedema may be triggered by infection,
stress, menstruation, surgery, dental work, trauma and some
medicines (including oestrogen-containing contraceptives and
ACE-inhibitors) or may have no clear trigger.
HAE is a rare autosomal dominant condition in which C1 esterase
inhibitor levels are reduced (HAE type I) or poorly functional (HAE
type II). HAE is diagnosed by the finding of low C1 esterase
inhibitor level or function. C4 level is also low during episodes
of angioedema.
Assessment
Clinical features include:
- Angioedema without pruritis and without urticaria
(hives)
- Abdominal pain (+/- nausea/vomiting) due to intestinal
oedema
- Laryngeal oedema
Angioedema episodes usually take several hours to develop, and
if untreated last 1-5 days.
Mild/moderate angioedema episodes
Present with:
- Swelling of the peripheries
- Mild/moderate abdominal pain
Severe angioedema episodes
Present with:
- Stridor or respiratory distress due to laryngeal oedema
- Other signs of potential airway compromise eg hoarse voice,
persistent cough, dysphagia or tongue swelling
- Severe abdominal pain or vomiting
Management
Mild/moderate angioedema episodes
Treatment is conservative:
- Hospital admission is not usually required
- Other causes of abdominal pain may need to be excluded, and
abdominal ultrasound may help by showing intestinal wall oedema or
ascites in HAE-related angioedema.
- A 3 day course of tranexamic acid may be considered to shorten
the duration of symptoms (12-25 mg/kg/dose (max 1.5 gm) 3-4 times per
day)
Severe angioedema episodes
Severe angioedema episodes can be fatal. Management
includes:
- Hospital admission for all severe angioedema episodes
- If upper airway obstruction is present, notify a senior staff
member experienced in endotracheal intubation
- Intravenous C1 esterase inhibitor concentrate should be
administered (see below for dosing)
- Notify the on-call Allergy/Immunology Consultant in all
cases
Planned surgery or Oropharyngeal procedures
Surgery or any traumatic procedure of the oropharyngeal area
such as dental work should be carefully planned. The use of a
prophylactic agent prior to such procedures reduces the risk of
precipitating angioedema.
- Consult with an Immunologist and ICU before the procedure
- For planned procedures, danazol is the first choice of
prophylactic agent, (10 mg/kg/day for 5-10 days before and 2-5 days
after the procedure).
- For emergency or high-risk procedures, C1 esterase inhibitor concentrate (25 units/kg
infusion given 1 hour prior to the procedure) - see Notes below
- Due to the risk of precipitating laryngeal oedema,
oropharyngeal procedures should usually involve general anaesthesia
with endotracheal intubation
Notes
Antihistamines and corticosteroids
Antihistamines and corticosteroids have no role in the
management of HAE related angioedema. The role of adrenaline in the
treatment of HAE is not well established. There are anecdotal
reports of efficacy using nebulised or intramuscular adrenaline to
treat upper airway angioedema, however C1 esterase inhibitor is the
treatment of choice for airway angioedema caused by HAE.
C1 Esterase
inhibitor concentrate (Berinert)
This is not TGA approved, and approval is required to use it on
an individual patient basis. Consultation with the on-call
immunologist is important. 25 units/kg (rounded to nearest 500
units) is infused over 1-2 minutes. 70% of angioedema episodes
respond within 30 minutes of infusion, and 95% within 4 hours. If
there is no response within 4 hours alternative diagnoses should be
considered, but the dose may be repeated at this stage after
further discussion with the on-call immunologist.