Complement disorders

Question 1

What are complement disorders?

Answer 1

Complement disorders affect the complement proteins that make up the complement system, which helps destroy pathogenic cells. Complement proteins are most important in dealing with encapsulated organisms, such as:

Haemophilus influenza B
Streptococcus pneumonia
Neisseria meningitidis

Question 2

Complement deficiency consequences?
Management?

Answer 2

Deficiencies in complement proteins result in a vulnerability to certain infective organisms, leading to recurrent infections with these organisms. Complement deficiencies make children particularly susceptible to infections of the respiratory tract, ears and throat. Complement deficiencies are also associated with immune complex disorders, such as systemic lupus erythematous, as an incomplete complement cascade leads to immune complexes building up and being deposited in tissues, leading to chronic inflammation. C2 deficiency is the most common complement deficiency.

Vaccination against encapsulated organisms is very important in patients with complement deficiencies.

Question 3

Hereditary angioedema?
Features?
Treatment?

Answer 3

C1 Esterase Inhibitor Deficiency (Hereditary Angioedema)

Bradykinin is part of the inflammatory response. It is responsible for promoting blood vessel dilatation and increased vascular permeability, leading to angioedema. Part of the action of C1 esterase is to inhibit bradykinin. An absence of C1 esterase causes intermittent angioedema in response to minor triggers, such as viral infections or stress, or without any clear trigger at all.

Angioedema often affects the lips or face but can occur anywhere on the body, including the respiratory and gastrointestinal tract. The swelling can last several few days before self resolving. Angioedema can occur in the larynx and compromise the patients airway.

Patients can be treated with intravenous C-1 esterase inhibitor as prophylaxis before dental or surgical procedures or in response to acute attacks of angioedema.

TOM TIP: A key test for hereditary angioedema (C1 esterase inhibitor deficiency) is to check the levels of C4 (compliment 4). C4 levels will be low in the condition. The exam question describe a patient with episodes of unexplained lip swelling and ask what test to perform. The answer is C4 levels.

Question 4

Mannose-binding lectin deficiency?
Consequences?

Answer 4

Deficiency in mannose-binding lectin is relatively common in the general population. A deficiency leads to inhibition of the alternative pathway of the complement system. In otherwise healthy individuals, it seems to be relatively unimportant and does not seem to cause major immunodeficiency. In patients who are otherwise susceptible to infection (e.g. cystic fibrosis) this can lead to a more severe variant of their existing disease.