Complement deficiencies — branching viva

Opening question

Take me through your framework when a child presents with recurrent invasive meningococcal disease and you suspect a complement deficiency. What are the three clinical fingerprints that earn a complement work-up? [1] [9]

Branch 1 — the likely diagnosis

The boy is otherwise completely well, with normal growth and no other infections, but has had two episodes of invasive meningococcal disease and a family history of male meningitis deaths. His CH50 is undetectable with a normal AP50. What is the most likely category of diagnosis, why is he "otherwise well", and which pathway is affected? [9] [10]

Branch 2 — confirming the defect

How will you confirm this diagnosis, and why does a normal C3 and C4 not exclude it? What does the absent CH50 with a normal AP50 tell you that the C3/C4 alone does not? Which second-line tests identify the missing component, and how does genetic testing inform family screening? [1] [5]

Branch 3 — long-term management and family screening

Outline the principles of long-term management: meningococcal vaccination, antibiotic prophylaxis, the emergency antibiotic supply, and the prognosis. Why is the protection imperfect despite vaccination? Which family members need screening, and why does the X-linked pattern of properdin deficiency change the screening question? [9] [10]

Branch 4 — the contrasting case (the trap)

Now picture a twelve-year-old with angioedema of the tongue, no urticaria, a family history of facial swelling, and no response to adrenaline, antihistamines or corticosteroids. What is the diagnosis, why did the anaphylaxis regimen fail, and what is the correct acute therapy? How does the management of hereditary angioedema differ from the infection-defence complement deficiencies? [7] [8]

Closing — the general rule

In one sentence, what is the single rule that decides the screening test for a suspected complement deficiency, and what is the single rule that decides the acute therapy for angioedema without urticaria? Why do the two commonest errors — sending a lone C3/C4, and treating hereditary angioedema with anaphylaxis drugs — persist? [1] [8]