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The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review

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Abstract

Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28–52). Twelve were immunocompromised before tuberculosis: untreated HIV infection (n=6), or immunosuppressive treatment (TNF-α antagonists, n=5; tacrolimus, n=1). Tuberculosis was mostly neuromeningeal (n=15), pulmonary (n=10), lymph node (n=6), and miliary (n=6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4–9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n=11), cerebral vasculitis (n=8), and lymphadenitis (n=6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n=17), thalidomide (n=6), and adalimumab (n=3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.

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Acknowledgements

The authors would like to thank the patients who participated in the study, and the health care workers who took care of them.

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Authors and Affiliations

  1. Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, F-35033, Rennes, France

    Lucas Armange, Paul Petitgas, Cédric Arvieux, Matthieu Revest & Pierre Tattevin

  2. Infectious Diseases, Saint-Pierre Hospital, Saint-Pierre, La Réunion, France

    Lucas Armange & Patrice Poubeau

  3. Infectious Diseases, General Hospital, Avignon, France

    Adèle Lacroix

  4. Microbiology, Pontchaillou University Hospital, Rennes, France

    Caroline Piau-Couapel

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  1. Lucas Armange
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  2. Adèle Lacroix
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Correspondence to Pierre Tattevin.

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Armange, L., Lacroix, A., Petitgas, P. et al. The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review. Eur J Clin Microbiol Infect Dis 42, 413–422 (2023). https://doi.org/10.1007/s10096-023-04564-2

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