Abstract :

Dengue fever, a widespread arboviral infection, ranges in severity from mild febrile illness to life-threatening conditions such as dengue hemorrhagic fever and dengue shock syndrome. Rarely, dengue can precipitate hemophagocytic lymphohistiocytosis (HLH), a severe hyperinflammatory syndrome characterized by dysregulated macrophage and T-cell activation. We report a case of a 45-year-old female presenting with fever, hepatosplenomegaly, cytopenias, and hyperferritinemia, who was diagnosed with dengue-associated HLH. The diagnosis was established using clinical findings, elevated ferritin, cytopenias, splenomegaly, and hemophagocytosis in the bone marrow, fulfilling the HLH-2004 criteria. Early initiation of dexamethasone, along with supportive therapy, improved the patient’s clinical status. This case underscores the importance of increased clinical vigilance for HLH in dengue patients with rapid clinical deterioration. Early diagnosis and prompt immunomodulatory therapy can significantly improve outcomes. Further research is needed to better understand the pathophysiology, diagnostic challenges, and optimal treatment strategies for dengue-associated HLH.

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Keywords :

Dengue, Hemophagocytic lymphohistiocytosis, Hepatosplenomegaly, HLH-criteria, Hyperferritinemia, Immunomodulatory therapy.

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References :

1. Khan, M.B., Yang, Z.S., Lin, C.Y., et al. 2023. Dengue overview: an updated systemic review. Journal of Infection and Public Health, 16, 1625-42. DOI: https://doi.org/10.1016/j.jiph.2023.08.001.
2. Raza, M. and Ali, S. 2024. Hemophagocytic Lymphohistiocytosis (HLH): A Rare Complication of Dengue Hemorrhagic Fever. Cureus, 16, 10 (2024), e70895. DOI: https://doi.org/10.7759/cureus.70895.
3. Munshi, A., Alsuraihi, A., Balubaid, M., Althobaiti, M. and Althaqafi, A. 2021. Dengue-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review. Cureus, 13, 12 (2021), e20172. DOI: https://doi.org/10.7759/cureus.20172.
4. Fisman, D.N. 2000. Hemophagocytic syndromes and infection. Emerging Infectious Diseases, 6, 6 (2000), 601.
5. Ray, U., Dutta, S., Mondal, S. and Bandyopadhyay, S. 2017. Severe dengue due to secondary hemophagocytic lymphohistiocytosis: a case study. IDCases, 8 (2017), 50-3. DOI: https://doi.org/10.1016/j.idcr.2017.03.013.
6. Koshy, M., Mishra, A.K., Agrawal, B., Kurup, A.R. and Hansdak, S.G. 2016. Dengue fever complicated by hemophagocytosis. Oxford Medical Case Reports, 2016 (2016), 121-4. DOI: https://doi.org/10.1093/omcr/omw043.
7. Imashuku, S., Ueda, I., Teramura, T., et al. 2005. Occurrence of haemophagocyticlymphohistiocytosis at less than 1 year of age: analysis of 96 patients. European Journal of Pediatrics, 164 (2005), 315-9.
8. Risma, K.A., Frayer, R.W., Filipovich, A.H., et al. 2006. Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis. Journal of Clinical Investigation, 116 (2006), 182-92.
9. Katano, H. and Cohen, J.I. 2005. Perforin and lymphohistiocytic proliferative disorders. British Journal of Haematology, 128 (2005), 739-50.
10. Matangkasombut, P., Chan-In, W., Opasawaschai, A., et al. 2014. Invariant NKT cell response to dengue virus infection in human. PLoS Neglected Tropical Diseases, 8 (2014), e2955.
11. Henter, J.I., Elinder, G. and Ost, A. 1991. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. Seminars in Oncology, 18 (1991), 29-33.
12. Henter, J.I., Horne, A., Aricó, M., et al. 2006. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Molecular Diagnosis, 19, 32 (2006), 33.
13. Filipovich, A., McClain, K. and Grom, A. 2010. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biology of Blood and Marrow Transplantation, 16 (2010), S82-9. DOI: https://doi.org/10.1016/j.bbmt.2009.11.014.
14. Sharp, T.M., Gaul, L., Muehlenbachs, A., et al. 2014. Fatal hemophagocytic lymphohistiocytosis associated with locally acquired dengue virus infection – New Mexico and Texas, 2012. Morbidity and Mortality Weekly Report, 63, 3 (2014), 49-54.
15. Bergsten, E., Horne, A., Aricó, M., et al. 2017. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood, 130 (2017), 2728-38. DOI: https://doi.org/10.1182/blood-2017-06-788349.
16. Ellis, E.M., Sharp, T.M., Pérez-Padilla, J., et al. 2016. Incidence and risk factors for developing dengue-associated hemophagocytic lymphohistiocytosis in Puerto Rico, 2008-2013. PLoS Neglected Tropical Diseases, 10 (2016), e0004939. DOI: https://doi.org/10.1371/journal.pntd.0004939.
17. Raju, S., Kalyanaraman, S., Swaminathan, K., Praisid, N.A. and Raju, S. 2014. Hemophagocytic lymphohistiocytosis syndrome in dengue hemorrhagic fever. Indian Journal of Pediatrics, 81 (2014), 1381-3.
18. Jamaludin, W.F., Periyasamy, P., Mat, W.R. and Wahid, S.F. 2015. Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome. Journal of Clinical Virology, 69 (2015), 91-5.