ArticleFrontiers in immunology2026
Unveiling pediatric secondary hemophagocytic lymphohistiocytosis: a comprehensive analysis of etiology, diagnosis, and treatment.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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6 authors.
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Abstract
Objective: To describe the etiological spectrum, treatment approaches, clinical and laboratory characteristics in pediatric secondary hemophagocytic lymphohistiocytosis (sHLH) to improve awareness of this severe illness and summarize evolving management strategies. Methods: A retrospective analysis was conducted on 110 children initially diagnosed with sHLH at our hospital between January 1, 2018, and June 30, 2025. Results: Among 110 sHLH patients, the median age at diagnosis was 2.67 years (1.17, 5.96), and 52.7% were under 3 years old. Infection-associated HLH accounted for 78.2%, with Epstein-Barr virus (EBV) as the most common trigger (57.3%). The remaining cases were attributed to rheumatic or malignant diseases. The main clinical manifestations included fever (99.1%), lymphadenopathy (83.6%), splenomegaly (77.3%), and hepatomegaly (66.3%). Respiratory system involvement was observed in over half of the patients, while central nervous system involvement (CNSI) and multiple organ dysfunction syndrome (MODS) occurred in 22.7% and 12.8% of cases, respectively. Characteristic laboratory abnormalities were highly prevalent, including pancytopenia (especially thrombocytopenia), hyperferritinemia, hypofibrinogenemia, and elevated soluble interleukin-2 receptor (sCD25). Most patients showed varying degrees of hepatic dysfunction, mainly with elevated enzymes (LDH, AST, ALT, HBDH). Characteristic immunological abnormalities included a decreased NK cell proportion (75.5%) and a reduced CD4 Conclusions: Pediatric sHLH is a severe, multisystem inflammatory disorder that predominantly affects infants and young children, with EBV infection as the primary etiological trigger. In addition to the classic HLH-2004 criteria, abnormal liver function indicators, imbalanced lymphocyte subsets and respiratory system involvement were frequent salient features, suggesting their potential utility as auxiliary diagnostic indicators. Furthermore, our findings further emphasize the importance of etiology-based individualized treatment.
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