Angioedema

Question 1

What is angioedema?

Answer 1

This is an episodic, localised, non pitting swelling of submucous and subcutaneous tissues.

It most frequently affects the face, extremities and genitalia. Involvement of the larynz or tongue may cause light threatening respiratory tract obstruction and oedema of the intestine may cause abdominal pain and distension.

Question 2

What is the pathophysiology of angioedema?

Answer 2

In most cases, the underlying mechanism is degranulation of mast cells. Angioedema can sometimes be mediated by increased local bradykinin concentration. Differentiating the mechanism of angioedema is important in determining appropriate investigations and treatment.

Question 3

What are the different types of angioedema?

Answer 3

1) Allergic reaction to specific trigger (anaphylaxis)
2) Idiopathic angioedema
3) Hereditary angioedema
4) ACE inhibitor associated angioedema

Question 4

How does idiopathic angioedema present?

Answer 4

This is caused by non-IgE mediated degranulation of mast cells.
Histamine is a key mediator.

Clinically:

• usually associated with urticaria
• may be triggered by physical stimuli such as heat, pressure or exercise
• dermatographism is common
• occasionally associated with underlying infection or thryoid disease

Associated drug reactions - NSAIDs, opioids, radiocontrast

Question 5

What is hereditary angioedema?

Answer 5

aka inherited C1 esterase inhibitor deficiency

Autosomal dominant disorder caused by decreased production or activity of C1 inhibitor protein. This complement regulatory protein inhibits spontaneous activation of the classical complement pathway.

C1 inhibitor is also a regulatory protein for the kinin cascade, activation of which increases local bradykinin levels and gives rise to local pain and swelling.

Question 6

How does HAE present?

Answer 6

Angioedema may be spontaneous or triggered by local trauma or infection.
Multiple parts of the body are involved, especially the face, extremities, upper airway and GIT. Oedema of the intestinal walls causes severe abdominal pain.
The most important complication is laryngeal obstruction, often associated with minor dental procedures.
Episodes of angioedema are self limiting, and usually resolve within 48 hours.
HAE should be considered in cases of angioedema without urticaria.

Question 7

How is HAE diagnosed?

Answer 7

Acute episodes are always accompanied by low C4 levels and the diagnosis can be confirmed by C1 inhibitor measurement.

Between attacks C4 levels are the best screening tool.

Question 8

How is HAE treated?

Answer 8

Prevention is with modified androgens (e.g. danozol) which increase endogenous production of complement proteins.
Severe acute attacks should be treated with purified C1 inhibitor or FFP is this is not available.

Question 9

What is acquired C1 inhibitor deficiency?

Answer 9

This rare disorder is clinically indistinguishable from HAE but presents in late adulthood.

It is associated with autoimmune and lymphoproliferative diseases. Treatment is of the underlying disorder.

Question 10

How does ACE induced angioedema present?

Answer 10

This is caused by the inhibition of breakdown of bradykinin.
It is not associated with urticaria and does not cause anaphylaxis.
It usually affects the head and neck, and may cause life-threatening respiratory tract obstruction.
Can occurs years after the start of treatment.
No specific investigations.
Discontinue ACEi and avoid ARBs as well.