{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:59:10Z","timestamp":1790830750919,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) and related cytokine storm syndromes are life\u2010threatening hyperinflammatory disorders that frequently intersect with pediatric critical care. Critically ill children may present with fever, shock, cytopenias, liver dysfunction, coagulopathy, hyperferritinemia, respiratory failure, neurologic deterioration, and multiple organ dysfunction, creating substantial overlap with severe sepsis. Traditional diagnostic criteria remain foundational but do not identify the dominant mechanism or optimal therapy for an individual child. In this review, precision immunomodulation is defined operationally as matching the suspected trigger and clinical phenotype with pathway\u2010informed biomarkers when available, drug\u2010delivery feasibility during organ failure, and the plan for definitive disease control. Interferon\u2010gamma activity may be supported by CXCL9; interleukin (IL)\u20101\/IL\u201018 biology may support anakinra in macrophage activation syndrome; broader cytokine signaling may support Janus kinase inhibition in selected refractory HLH; and IL\u20106\u2010directed therapy is primarily syndrome\u2010 and grade\u2010directed in immune effector cell cytokine release syndrome. These markers are supportive rather than validated treatment thresholds. Targeted therapy must proceed alongside antimicrobial therapy, source control, organ support, infection surveillance, and early hematopoietic stem cell transplantation planning when indicated. This review provides a bedside framework for phenotype assignment, biomarker interpretation, intensive care unit\u2010focused targeted therapy, extracorporeal bridge strategies, and reassessment at 24\u201372\u00a0h.<\/jats:p>","DOI":"10.1002\/ped4.70087","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:52:01Z","timestamp":1789465921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision immunomodulation for pediatric hemophagocytic lymphohistiocytosis in intensive care"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3199-9446","authenticated-orcid":false,"given":"Weerapong","family":"Lilitwat","sequence":"first","affiliation":[{"name":"Department of Pediatrics Texas Tech University Health Sciences Center  Lubbock Texas 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