{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:44Z","timestamp":1787026664968,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was conducted on 110 children initially diagnosed with sHLH at our hospital between January 1, 2018, and June 30, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio (59.1%). Regarding therapy, 44.5% of patients received the HLH-94\/04 chemotherapy protocol, among these, 75.5% had EBV infection, with a chemotherapy remission rate of 91.9%. The overall in-hospital mortality was 13.6%, with MODS accounting for 73.3% of fatalities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1753930","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:40:55Z","timestamp":1777009255000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling pediatric secondary hemophagocytic lymphohistiocytosis: a comprehensive analysis of etiology, diagnosis, and treatment"],"prefix":"10.3389","volume":"17","author":[{"given":"Ping","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Laboratory, Children\u2019s Hospital Affiliated to Shandong University","place":["Jinan, China"]},{"name":"Clinical Laboratory, Jinan Children\u2019s Hospital","place":["Jinan, 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