12.5 Immune reconstitution inflammatory syndrome

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    TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can occur in a patient on antiretroviral and/or TB treatment. It is characterised by the onset of new or worsening (after initial improvement) signs and symptoms of TB resulting from the restoration of the immune system by ART.

     

    Most common signs and symptoms of TB-IRIS are fever, lymphadenopathy, pulmonary infiltrates, pleural effusion, respiratory distress, neurological signs[1]Citation 1.M. Lanzafame, S. Vento. Tuberculosis-immune reconstitution inflammatory syndrome. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, Volume 3, 2016.
    https://doi.org/10.1016/j.jctube.2016.03.002    .

     

    TB-IRIS occurs in two circumstances:

    • Paradoxical TB-IRIS: the diagnosis of active TB is made, the patient starts TB treatment, followed by ART and then signs and symptoms of TB worsen.
    • Unmasking TB-IRIS: TB is not detected, the patient starts ART and then develops signs and symptoms of TB.

     

    TB-IRIS is more common in patients with low CD4 count. It usually occurs within 3 months of starting ART, most often within the first month[2]Citation 2.World Health Organization. Operational handbook on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022.
    https://apps.who.int/iris/bitstream/handle/10665/352523/9789240046832-eng.pdf    .

     

    The following differential diagnoses should be considered before making the diagnosis of TB-IRIS:

    • New onset of opportunistic infection.
    • Other infections unmasked after immune reconstitution due to ART.
    • Failure of TB treatment due to drug resistance.

     

    TB-IRIS is considered severe in patients with neurological signs, respiratory distress, or if their condition requires hospitalisation or frequent ambulatory care.

    Treatment of severe TB-IRIS is based on corticosteroids (except in the case of Kaposi's sarcoma or cryptococcal meningitis, for which corticosteroids are contraindicated).

    Patients on corticosteroids should be monitored to detect any other opportunistic infections.

     

    In patients with non severe TB-IRIS, treatment is based on non-steroidal anti-inflammatory drugs.

     

    In case of unmasking TB-IRIS, TB treatment should be started immediately.

     

    ART should not be interrupted, except in case of life-threatening IRIS.

     

    Table 12.2 – Symptomatic treatment of TB-IRIS

    TB-IRIS

    Treatment

    Severe

     

    prednisolone PO 

    Child and adult: 1.5 mg/kg once daily (2 weeks) then 0.75 mg/kg once daily (2 weeks)[3]Citation 3.Meintjes G, Wilkinson RJ, Morroni C et al. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Aids, 24(15), 2381–2390 (2010). [PubMed: 20808204].
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940061/
     

    Non-severe

    ibuprofen PO for the shortest possible duration

    Child over 3 months: 5 to 10 mg/kg 3 to 4 times daily (max. 30 mg/kg daily)
    Child 12 years and over and adult: 200 to 400 mg 3 to 4 times daily (max. 1200 mg daily)
     
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