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Secondary hemophagocytic lymphohistiocytosis in pediatric patients with visceral leishmaniasis and Epstein-Barr virus infection

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Abstract

Visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis (VL-HLH) is indistinguishable from those of HLH of other etiologies due to the overlap symptoms, posing a serious threat to life. In this study, we aimed to provide insights for early diagnosis and improve outcomes in pediatric patients with VL-HLH. We retrospectively analyzed the clinical and laboratory data of 10 pediatric patients with VL-HLH and 58 pediatric patients with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The median time from symptom onset to cytopenia in patients with VL-HLH and EBV-HLH was 11 days (interquartile range, 7–15 days) and five days (interquartile range, 3.75–9.25 days) (P = 0.005). Both groups showed liver injury and increased lactate dehydrogenase levels; however the levels of aspartate aminotransferase, alanine aminotransferase, direct bilirubin, and lactate dehydrogenase in patients with VL-HLH were significantly lower than those in patients with EBV-HLH (P < 0.05). The fibrinogen and triglyceride levels were almost normal in VL-HLH patients but were significantly altered in EBV-HLH cases ( P < 0.05). The positive rate of first bone marrow microscopy examination, anti-rK39 IgG detection, and blood metagenomic next-generation sequencing was 50%, 100%, and 100%, respectively. After VL diagnosis, eight patients were treated with sodium stibogluconate and two were treated with liposomal amphotericin B. All the patients with VL-HLH recovered. Our study demonstrates that regular triglyceride and fibrinogen levels in pediatric patients with VL-HLH may help in differential diagnosis from EBV-HLH. VL-HLH is milder than EBV-HLH, with less severe liver injury and inflammatory responses, and timely treatment with antileishmanial agents is essential to improve the outcomes of pediatric patients with VL-HLH.

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Funding

This research did not recieve any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Yuanfang Li, Nadan Lu, Weilin Wang & Dao Wang

  2. Department of Infectious Diseases, The Sixth People’s Hospital of Zhengzhou, Zhengzhou, China

    Sanjing Li

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  1. Yuanfang Li
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  4. Weilin Wang
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  5. Dao Wang
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Contributions

Dao Wang: Conceptualization, Methodology, Supervision,

Yuanfang Li: Writing-Origial Draft, Formal analysis.

Sanjing Li: Resources, Methodology.

Nadan Lu: Investigation, Formal analysis.

Weilin Wang: Investigation, Formal analysis.

Corresponding author

Correspondence to Dao Wang.

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The authors have no competing interests to declare.

Ethics approval

The study protocol was evaluated and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (approval number 2023-KY-0730). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Li, Y., Li, S., Lu, N. et al. Secondary hemophagocytic lymphohistiocytosis in pediatric patients with visceral leishmaniasis and Epstein-Barr virus infection. Ann Hematol 103, 1541–1547 (2024). https://doi.org/10.1007/s00277-024-05695-y

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