Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis in a Tertiary Hospital in the Philippines: A Case Series and Review of Literature
Article Sidebar
Main Article Content
Abstract
Background and objectives: Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by uncontrolled immune activation leading to multiorgan dysfunction. It poses significant diagnostic and therapeutic challenges due to its nonspecific presentation and overlap with other systemic diseases. Among infectious triggers, Mycobacterium Tuberculosis (MTB)—endemic in the Philippines—remains a rare but serious cause of secondary HLH. This report aims to describe the clinical presentation, diagnostic challenges, management, and outcomes of patients diagnosed with Tuberculosis-Associated HLH (TB-HLH) in a tertiary hospital in the Philippines.
Methods/Case Summary: We report four adult cases of HLH secondary to confirmed MTB infection. Three of four patients met the HLH-2004 diagnostic criteria, all had a high Hscore, and TB was identified through microbiologic, molecular, or histopathologic evidence. Clinical features, laboratory findings, treatment regimens, and outcomes were reviewed.
Discussion and Conclusion: Patients presented with prolonged fever, cytopenia, unexplained hepatosplenomegaly, and elevated inflammatory markers. Diagnosis was often delayed due to overlapping features of disseminated TB and HLH. The patients received concurrent Anti-Tuberculosis Therapy (ATT) and immunomodulatory treatment, with variable clinical responses and outcomes. TB-HLH represents a diagnostic and therapeutic emergency that requires early recognition and simultaneous management of both the infection and the hyperinflammatory response. In endemic settings such as the Philippines, clinicians should maintain a high index of suspicion for HLH in patients with severe or disseminated TB. This report presents, to our knowledge, the first documented case series of TB-HLH in the country, underscoring the need for increased awareness and multidisciplinary care.
Downloads
Article Details
Copyright (c) 2025 Balane JAL, et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Kaushansky K, Lichtman M, Prchal J. Williams Hematology, 10th edition. Available from: https://accessmedicine.mhmedical.com/book.aspx?bookid=2962
Fauchald T, Blomberg B, Reikvam H. Tuberculosis-associated hemophagocytic lymphohistiocytosis: A review of current literature. J Clin Med. 2023:18;12(16):5366. Available from: https://doi.org/10.3390/jcm12165366
Janka G, Lehmberg K. Hemophagocytic lymphohistiocytosis: pathogenesis and treatment. Hematology Am Soc Hematol Educ Program (2013). 2013: (1): 605–611. Available from: https://doi.org/10.1182/asheducation-2013.1.605
La Rosèe P, Horne A, Hines M. von Bahr Greenwood T, Machowicz R, Berliner N. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019:133(23):2465–2477. Available from: https://doi.org/10.1182/blood.2018894618
World Health Organization Global Tuberculosis Report 2023. Available from: https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports/global-tuberculosis-report-2023
Department of Health. 2019 Philippines TB joint program review. Manila: Department of Health. 2019. Available from: https://ntp.doh.gov.ph/download/joint-program-review-2019-report/
Padhi S, Ravichandran K, Sahoo J, Varghese RG, Basheer A. Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis. Lung India 2015: 32. 593–601. Available from: https://doi.org/10.4103/0970-2113.168100
Kurver L, Seers T, van Dorp S van Crevel R, Pollara G, van Laarhoven A. Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome. Open Forum Infec Dis. 2024: 11(4). Available from: https://doi.org/10.1093/ofid/ofad697
Fardet L, Galicier L, Lambotte O Marzac C, Aumont C, Chahwan D, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol Hoboken NJ 2014;66(9):261320. Available from: https://doi.org/10.1002/art.38690
Jordan MB, Allen CE, Weitzman S Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011; 118(15):4041-4052. Available from: https://doi.org/10.1182/blood-2011-03-278127
Allen CE, Yu X, Kozinetz CA. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;50(6):1227-1235. Available from: https://doi.org/10.1002/pbc.21423
Fatma A, Raida B, Mourad CIkram D, Zouheir B, Henda E. Performance of the H score and the HLH 2004 score in the positive diagnosis of secondary hemophagocytic lymphohistiocytosis. Curr Res Transl Med. 2024; 72(2):103430. Available from: https://doi.org/10.1016/j.retram.2023.103430
Empeño E, Gauiran D. Clinical profile and management outcomes of adult Filipino patients with hemophagocytic lymphohistiocytosis in a tertiary hospital. PCHTM. Available from: https://registry.healthresearch.ph/index.php/registry?view=research&layout=details&cid=5640
Al-Mashdali A, Al Samawi M. Disseminated tuberculosis complicated by hemophagocytic. Lymphohistiocytosis in an immunocompetent adult with favorable outcomes: A case report. IDCases. 2022; 27: e01370. Available from: https://doi.org/10.1016/j.idcr.2021.e01370
Tang Y, Xu X, Song H, Yang S, Shi S, Wei J, et al. Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome. Br J Haematol. 2008; 143(1):84-91. Available from: https://doi.org/10.1111/j.1365-2141.2008.07298.x
Trovik L, Sandnes M, Blomberg B. Holmaas G, Ahmed AB, Tvedt THA, et al Hemophagocytic lymphohistiocytosis and miliary tuberculosis in a previously healthy individual: a case report. J Med Case Rep. 2020; 14: 217. Available from: https://doi.org/10.1186/s13256-020-02555-x
Gautam D, Dadheech M, Ingle V Jayashankar E, Purwar S, Maurya AK. Disseminated tuberculosis in rare association with hemophagocytic lymphocytosis- A case report from central India. Heliyon. 2023: 20;9(4):e15646. Available from: https://doi.org/10.1016/j.heliyon.2023.e15646
Hansen S, Alduaij W, Biggs C Belga S, Luecke K, Merkeley H, Ruxotinib as adjunctive therapy for Secondary hemophagocytic lymphohistiocytosis: A case series. Eur J Haematol. 2021: 106(5):654-661. Available from: fhttps://doi.org/10.1111/ejh.13593