Hereditary Angioneurotic Oedema (HAO)



Significant tongue swelling in angio-oedema case

Angioedema is a well-demarcated, localized oedema of the skin and subcutaneous 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% spontaneous 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
  • Firazyr® (30mg SC) is available in both CUH ED (antidotes press) and from CUH pharmacy ( via night sister out of hours).
  • Firazyr® should only be used (in CUH) upon direction from either the duty EM consultant or Dr Paula O'Leary.
  • 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 (TXA) also used (TXA infusion guide)
  • Remember to check detailed family history

Firazyr (Bradykinin B2 antagonist)


Content by Dr Íomhar O' Sullivan 23/09/2002. Reviewed by Dr ÍOS on 21/02/2004, 18/07/2005, 25/05/2006, 19/01/2007, 18/01/2008. Last review Dr ÍOS 3/12/18.