Hereditary Angioneurotic Oedema (HAE)
Angioedema is a well-demarcated, localized oedema of the skin and suncutaeeous tissues (urticaria oedema involves dermis alone). There is local venodilation and perivenular infiltrates of lymphocytes, eosinophils, and neutrophils.
Introduction
- Type 1 - 85% deficiency of C1E - INH
- Type 2 - 15% enzyme normal C1E - INH dysfunctional
- 75% have family history (25% speontaneous gene mutation)
- C1E-INH is a serine protease inhibitor. It is the major inhibitor of both factors 12A and kallikrein and the only known inhibitor of activation of C1 from complement pathway
- C1E-INH regulates the activity of two plasma cascade systems. Responsible for vasodilation and vasopermeability
- HAE patients have reduced or abnormal C1E-INH causing uncontrolled activation of complement and coagulation cascade, particularly in increasing bradykinin resulting in angio-oedema
- Acute attacks are precipitated by trauma (dental), anxiety and stress
- Occasionally triggered by malignancy, glomerulonephritis, rheumatoid arthritis, thyroiditis, Sjogren's syndrome, and pernicious anaemia
- ACE inhibitors can also cause particularly in healthy people.
Clinical findings
HAE presents as
- Acute abdominal pain
- Ascites and recurrent abdominal pain
- Facial and upper airway obstruction
- Usually do not have urticaria
- Does not respond to anti-H1/steroids/epinephrine
- Prodrome ("unwell", "not right" for hrs / days)
- Longer (hrs / days) onset & offset of symptoms
- Most patients have Hx and written plan with them
Treatment
Immediate management
- Airway management
- (surgical airway early if necessary)
- IV fluids
- Analgesia
- Check C4 levels (not C1)
- plain serum sample to CUH labs
- Icatibant acetate (Firazyr®): bradykinin B2 receptor antagonist (30mg SC - from CUH pharmacy)
- C1-INH concentrate
- (usually on an individual named basis only)
- (IV only, blood product in CUH blood bank)
Long term treatment
- Do not use Firazyr in peripheral (non-airway) oedema
- FFP rarely useful as prophylaxis of HAE
- Long-term prophylaxis HAE is Danazol & Stanozolol
- androgen therapy to ↓ synthesis of CN1-INH
- Tranexamic acid also used
- Remember to check detailed family history
