C1 Esterase inhibitor deficiency

  • (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 (12-25mg/kg/dose (max 1.5g) 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, (10mg/kg/day for 5-10 days before and 2-5 days after the procedure).
    • For emergency or high-risk procedures, C1 esterase inhibitor concentrate (25units/kg infusion given 1 hour prior to the procedure)
    • 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.

    Berinert storage at RCH

    One vial is kept in the Emergency Department vaccine fridge, and 2 spare vials in RCH pharmacy. If RCH stock is exhausted, emergency supplies may be obtained from the on-call pharmacist at the Royal Melbourne Hospital, or from CSL Blood Division. Each time Berinert is used, a Special Access Scheme (SAS) form must be completed by the prescribing physician.