Clinical Scenario:
A 6-year-old boy with HIV infection was diagnosed with drug-susceptible pulmonary tuberculosis and started on appropriate anti-tuberculous treatment. ART was initiated 10 days later. His initial CD4 count was 78 cells/mm³.
After 4 weeks of ART, his mother reports increasing fever and enlargement of previously noted cervical lymph nodes. He has been adherent to both TB treatment and ART. Examination shows enlarged, tender cervical lymph nodes, but no new respiratory symptoms. His HIV viral load has fallen substantially since starting ART.
Which of the following is the most likely diagnosis?
A. TB treatment failure
B. Drug-resistant tuberculosis
C. Paradoxical TB-IRIS
D. New bacterial infection
E. ART failure
Correct answer & Explanation:
Correct answer: C. Paradoxical TB-IRIS
Explanation
This child has paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS).
The key clues are:
- Known TB already receiving appropriate treatment
- ART started recently
- Clinical deterioration within weeks of ART initiation
- Enlargement of previously involved lymph nodes
- Very low baseline CD4 count
- Good virological response to ART
- Reported adherence to both treatments
TB-IRIS occurs when immune recovery following ART produces an exaggerated inflammatory response against mycobacterial antigens. It most commonly occurs during the first month after starting ART, although it can occur within the first 3 months.
Why the other options are incorrect
A. TB treatment failure — Incorrect:
Treatment failure should be considered, but the close temporal relationship to ART initiation and improving HIV viral load strongly support IRIS. Adherence and drug resistance should nevertheless be assessed before diagnosing IRIS.
B. Drug-resistant TB — Incorrect:
Drug resistance must be excluded in a deteriorating child, but the timing and clinical pattern are more characteristic of TB-IRIS.
D. New bacterial infection — Incorrect:
Possible in a child with HIV, but there is no clear clinical focus and the characteristic post-ART inflammatory deterioration favours IRIS.
E. ART failure — Incorrect:
The viral load has fallen substantially, indicating an effective virological response rather than ART failure.
Postgraduate Exam Clue:
There are two forms of TB-IRIS:
- Paradoxical TB-IRIS: TB was already diagnosed and treated, but the disease temporarily worsens after ART.
- Unmasking TB-IRIS: previously unrecognized TB becomes clinically apparent after ART begins.
In most cases, TB treatment and ART should be continued. Mild-to-moderate symptoms may be managed symptomatically; corticosteroids can be considered for severe TB-IRIS after alternative diagnoses, particularly drug-resistant TB, have been considered.
Reference
- World Health Organization. WHO operational handbook on tuberculosis: module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
- World Health Organization. WHO consolidated guidelines on tuberculosis: module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
