{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:02:14Z","timestamp":1784894534565,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematol. Rep.","Hematology Reports"],"abstract":"<jats:p>Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive activation of the immune system. Case Presentation: We present the case of an eight-month-old infant with influenza A(H1N1) who presented with seizures, hepatosplenomegaly, cytopenias, and markedly elevated levels of ferritin, IL-18, and CXCL9, raising concern for HLH. Despite initiation of HLH-directed and antiviral therapy, she succumbed to cardiorespiratory failure. Genetic testing revealed heterozygous variants in LYST and NLRC4, suggesting a potential genetic predisposition. Conclusions: This case underscores the challenge of distinguishing primary from secondary HLH and highlights the importance of balancing aggressive immunosuppression with infection control. Early genetic and cytokine profiling may assist in guiding personalized treatment strategies, enabling targeted interventions that avoid excessive immunosuppressive treatment in cases of reactive hyperinflammation while facilitating timely escalation of therapy in true or refractory HLH.<\/jats:p>","DOI":"10.3390\/hematolrep18040051","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:38:41Z","timestamp":1784889521000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Complexities in the Diagnostic Evaluation and Treatment of Infant Hemophagocytic Lymphohistiocytosis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8336-8766","authenticated-orcid":false,"given":"Reeja","family":"Raj","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oklahoma University Health Sciences Center, 1100 N Lindsay Ave., Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8002-1455","authenticated-orcid":false,"given":"Carlos","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Children\u2019s Hospital, 6701 Fannin St., Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4796-185X","authenticated-orcid":false,"given":"Muhammad","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, McGovern Medical School, UTHealth, 64313 Fannin St., Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8204-9769","authenticated-orcid":false,"given":"Gopi","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-9670","authenticated-orcid":false,"given":"David","family":"McCall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9146-4702","authenticated-orcid":false,"given":"Amber","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Cuglievan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Nunez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Bray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McGovern Medical School, UTHealth, 64313 Fannin St., Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-2267","authenticated-orcid":false,"given":"Miriam B.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1487, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1056\/NEJMra2314005","article-title":"Hemophagocytic lymphohistiocytosis","volume":"392","author":"Henter","year":"2025","journal-title":"N. 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