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Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome

Kurver, Lisa; Seers, Timothy; van Dorp, Suzanne; van Crevel, Reinout; Pollara, Gabriele; van Laarhoven, Arjan; (2024) Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome. Open Forum Infectious Diseases , 11 (4) , Article ofad697. 10.1093/ofid/ofad697. Green open access

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Abstract

Background: Tuberculosis (TB) can induce secondary hemophagocytic lymphohistiocytosis (HLH), a severe inflammatory syndrome with high mortality. We integrated all published reports of adult HIV-negative TB-associated HLH (TB-HLH) to define clinical characteristics, diagnostic strategies, and therapeutic approaches associated with improved survival.// Methods: PubMed, Embase, and Global Index Medicus were searched for eligible records. TB-HLH cases were categorized into (1) patients with a confirmed TB diagnosis receiving antituberculosis treatment while developing HLH and (2) patients presenting with HLH of unknown cause later diagnosed with TB. We used a logistic regression model to define clinical and diagnostic parameters associated with survival.// Results: We identified 115 individual cases, 45 (39.1%) from countries with low TB incidence (<10/100 000 per year). When compared with patients with HLH and known TB (n = 21), patients with HLH of unknown cause (n = 94) more often had extrapulmonary TB (66.7% vs 88.3%), while the opposite was true for pulmonary disease (91.5% vs 59.6%). Overall, Mycobacterium tuberculosis was identified in the bone marrow in 78.4% of patients for whom examination was reported (n = 74). Only 10.5% (4/38) of patients tested had a positive result upon a tuberculin skin test or interferon-γ release assay. In-hospital mortality was 28.1% (27/96) in those treated for TB and 100% (18/18) in those who did not receive antituberculosis treatment (P < .001).// Conclusions: Tuberculosis should be considered a cause of unexplained HLH. TB-HLH is likely underreported, and the diagnostic workup of patients with HLH should include bone marrow investigations for evidence of Mycobacerium tuberculosis. Prompt initiation of antituberculosis treatment likely improves survival in TB-HLH.

Type: Article
Title: Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ofid/ofad697
Publisher version: https://doi.org/10.1093/ofid/ofad697
Language: English
Additional information: © The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons. org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: anergy, bone marrow, hemophagocytic lymphohistiocytosis, mortality, tuberculosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10190290
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