biostudies-literatureKurver LBiomedical Research CentreHealth Research and Developmentclinical fellowship of The Netherlands OrganizationUCLH NIHRofad697https://www.ebi.ac.uk/biostudies/studies/S-EPMC10977624biostudies-literatureUnknown11(4)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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, <i>Mycobacterium tuberculosis</i> 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 (<i>P</i> < .001).<h4>Conclusions</h4>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 <i>Mycobacerium tuberculosis</i>. Prompt initiation of antituberculosis treatment likely improves survival in TB-HLH.Open forum infectious diseasesTuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome.PMC109776249032212110006van Dorp Svan Crevel RPollara GSeers Tvan Laarhoven AKurver LfalseTuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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, <i>Mycobacterium tuberculosis</i> 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 (<i>P</i> < .001).<h4>Conclusions</h4>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 <i>Mycobacerium tuberculosis</i>. Prompt initiation of antituberculosis treatment likely improves survival in TB-HLH.2024-01-01T00:00:00Z2024 Apr2025-04-22T08:12:53.377Z2025-04-05T22:32:09.782ZS-EPMC109776243856061210.1093/ofid/ofad697