Hereditary Angioedema

Question 1

What is the defective gene?

What does type 1 and type 2 mean?

Answer 1

SERPING1 gene

Type 1 - low levels of C1 inhibitors

Type 2 - Normal levels - functional defect

C1 inhibitors reduces the amount of bradykinin produced.

This is the key chemical which causes angioedema.

Question 2

Clinical presentation:

Where can it occur?

What is one place it can occur which is an emergency?

When does it usually peak?

Answer 2

Face
Extremities
Genitals
Intestines - they get ABDO PAIN - could lead to unnecessary surgeries

LAYNGEAL OEDEMA - EMERGENCY

36 hrs peak

Question 3

Recognised triggers:

What hormone could increase the risk?

Trauma, infection and stress can also increase the risk!

Answer 3

Oestrogen - may present at puberty or with COCP/HRT

Question 4

Layngeal oedema - emergency:

Usually happens in 3rd decade of life

Lifetime incidence of 70%

Retrospective review - 40% lost family member to asphyxiation

Labs:

What would you measure?

Management:

For airway?

Steroids and antihistamines don’t work

Nebulised adrenaline / adrenaline may decrease the vascular component of oedema but doesn’t change the underlying process.

What is the specific treatment for the cause?

Answer 4

Retrospective review - 40% lost family member to asphyxiation

Layngeal oedema - emergency:

Usually happens in 3rd decade of life

Lifetime incidence of 70%

C1 inhibitor levels

OR

Low function - C1 esterase inhibitor

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Endotracheal tube (ETT) intubation
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C1 inhibitor or Bradykinin inhibitor

Question 5

Intestinal oedema:

Rx for vomiting + diarrhoea that can occur?

Answer 5

Fluids
Anti-emetics - non-sedating - domperidone
Loparemide if acute abdomen ruled out
Pain meds

Question 6

Pharmacological Treatment:

Acute attack - C1 inhibitor concentrate

Prophylactics - androgen derivatives + antifibrnolytic agents

Answer 6

Pharmacological Treatment:

Acute attack - C1 inhibitor concentrate

Prophylactics - androgen derivatives + antifibrnolytic agents

Question 7

C1 inhibitor concentrate:

2 types?

Bradykinin inhibitors - Icatibant:
- Route?

Prophylactic therapies:

• Why is Danazol not well tolerated in women?
• Antifibrinolytics - Tranexamic acid - not effective in most patients.

What can be given as prophylaxis twice weekly?

Answer 7

Recombinant - Rabbit milk

Plasma derived - IV infusion

SC
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It is androgenic - hirtuitism

C1 inhibitor twice weekly for prevention as well