hereditary angioedema (HAE)

see also:

• allergy and hypersensitivity reactions
• angioedema
• anaphylaxis
• RCH guideline - angioedema - C1 esterase inhibitor deficiency
• Western Health patient list of HAE patients - intranet accessible only and requires password to access
• Western Health guideline on use of Berinert (pdf) - intranet only
• Western Health use of Berinert process and flow chart (docx) - intranet only
• at Western Health, icatibant is available after hours in the night store and accessible by the AHA

• hereditary angioneurotic oedema is an autosomal dominant condition caused by either a reduced (type I) or dysfunctional (type II) C1-esterase inhibitor (C1-INH) which is a blood protein enzyme which normally inhibits the kallikrein-mediated cleavage of HMW kininogen to bradykinin
• the uncontrolled production of bradykinin results in angioneurotic oedema.
• bradykinin is normally cleaved to inactive fragments with a half life of 15secs by kinase I and II which is angiotensin converting enzyme - obviously, the half life will be prolonged in patients on ACE inhibitors.
• the angioedema often affects the lips, tongue, pharyngeal structures or larynx with potentially life threatening airway compromise.
• may also:
  • affect the bowel wall causing abdominal pain.
  • be associated with bronchospasm, vasodilatation, hypotension, reflex teachycardia.
• an attack usually lasts 2-5 days
• 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.
• it is thought to affect some 500 patients in Australia.

• HAE is diagnosed by the finding of low C1 esterase inhibitor level or function.

• 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
• consider GA with endotracheal intubation for oropharyngeal procedures

• danazol is the first choice of prophylactic agent
• 10mg/kg/day for 5-10 days before and 2-5 days after the procedure

• 25 units/kg infusion given 1 hour prior to procedure

• supportive care and close observation, preferably in an area with resuscitation facilities
• antihistamines and corticosteroids have no role in the management of HAE related angioedema.
• adrenaline may have a role in Rx as for anaphylaxis
• C1 esterase inhibitor concentrate infusion (Berinert) may be indicated for severe cases (dose as for prophylaxis above)

• introduced in Australia in 2010
• much more effective than 3 day course of tranexamic acid (12-25mg/kg/dose (max 1.5g) 3-4 times per day)
• dose: 30mg slow s/cut. injection into abdominal wall
• most cases respond to a single dose, but a 2nd dose may be given in 6 hours if inadequate relief, or recurrence of symptoms
• no more than 3 doses in a 24 hour period should be given
• expensive: ~$AU40 per dose on PBS

• hypersensitivity to Firazyr
• ischaemic heart disease - theoretical risk of decrease in coronary blood flow from B2 antagonism
• stroke in the past few weeks - theoretical possibility that antagonism may attenuate the late phase neuroprotective effects of bradykinin.
• pregnancy (category C)
• lactation as it it excreted in milk - thus recommended to discard milk within 12 hours of injection
• children - no experience as yet
• elderly - limited data on its safety
• concomitant use of ACE inhibitors - patients with HAE should not be on ACEI's anyway.

• injection site reactions - pain, burning, swelling, erythema
• raised CK level
• prolonged prothrombin time
• dizziness, headache
• asthma, cough, nasal congestion, urticaria, muscle spasms and hot flushes were uncommonly reported