{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T17:53:54Z","timestamp":1777312434857,"version":"3.51.4"},"reference-count":42,"publisher":"Hamad bin Khalifa University Press (HBKU Press)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by excessive immune activation. Children with Down syndrome (DS) (trisomy 21) are at increased risk of severe infections and immune dysregulation. Although viral infections are known triggers of secondary HLH, H1N1 influenza is an uncommon cause in this population.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Case presentation:<\/jats:bold>\n                    We report a 1.8-month-old male infant with DS and multiple comorbidities\u2014including gastroesophageal reflux disease (GERD), recurrent aspiration pneumonia, and seizures\u2014who presented with fever, hypoxemia, and splenomegaly. Laboratory investigations revealed cytopenias, hyperferritinemia (&gt;1,650 ng\/mL), and hypofibrinogenemia, fulfilling five of the HLH-2004 diagnostic criteria. H1N1 influenza was confirmed as the infectious trigger. The patient was treated with standard-dose dexamethasone and etoposide, along with oseltamivir. Despite concerns about treatment-related toxicity in DS, he tolerated the regimen without hematologic or infectious complications. He achieved clinical remission with normalization of inflammatory markers and hematologic parameters. At discharge and at three-month follow-up, he remained well with no recurrence or neurological sequelae.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion:<\/jats:bold>\n                    This case highlights the diagnostic and therapeutic challenges of managing HLH in children with DS. The use of conventional HLH therapy, including etoposide, was effective and well-tolerated despite theoretical concerns in this population. Although central nervous system symptoms were present, they resolved with treatment. H1N1 influenza should be considered a potential viral trigger in immunocompromised children presenting with HLH-like features.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    H1N1 influenza-induced HLH is exceptionally rare in infants with DS. The positive outcome in this case supports the safe use of standard HLH protocols in this vulnerable population and highlights the importance of early diagnosis and multidisciplinary management to optimize outcomes.\n                  <\/jats:p>","DOI":"10.5339\/qmj.2025.120","type":"journal-article","created":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T05:30:31Z","timestamp":1765690231000},"source":"Crossref","is-referenced-by-count":0,"title":["H1N1-associated hemophagocytic lymphohistiocytosis in a child with Down syndrome: A clinical challenge"],"prefix":"10.5339","volume":"2025","author":[{"given":"Hamza","family":"Khoursheed","sequence":"first","affiliation":[{"name":"Jordan University of Science and Technology, Irbid, Jordan*Correspondance: Hamza Khoursheed hamzeh_2002@hotmail.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aref","family":"Dawoud","sequence":"additional","affiliation":[{"name":"Jordan University of Science and Technology, Irbid, Jordan*Correspondance: Hamza Khoursheed hamzeh_2002@hotmail.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Qandeel","sequence":"additional","affiliation":[{"name":"Jordan University of Science and Technology, Irbid, Jordan*Correspondance: Hamza Khoursheed hamzeh_2002@hotmail.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hani","family":"Qteishat","sequence":"additional","affiliation":[{"name":"Jordan University of Science and Technology, Irbid, Jordan*Correspondance: Hamza Khoursheed hamzeh_2002@hotmail.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suleiman","family":"Sweedan","sequence":"additional","affiliation":[{"name":"Jordan University of Science and Technology, Irbid, Jordan*Correspondance: Hamza Khoursheed hamzeh_2002@hotmail.com"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3277","reference":[{"issue":"(24):","key":"B1","series-title":"N Engl J Med","first-page":"2344\u201352","article-title":"Down syndrome","volume":"382","author":"Bull\n \nMJ","year":"2020;"},{"issue":"(2):","key":"B2","series-title":"Clin Exp Immunol","first-page":"189\u201393","article-title":"Intrinsic defect of the immune system in children with Down syndrome: A review","volume":"156","author":"Kusters\n \nMA","year":"2009;"},{"issue":"(5):","key":"B3","series-title":"Blood Rev","first-page":"245\u201353","article-title":"Hemophagocytic syndromes","volume":"21","author":"Janka\n \nGE","year":"2007;"},{"issue":"(9927):","key":"B4","series-title":"Lancet","first-page":"1503\u201316","article-title":"Adult haemophagocytic syndrome","volume":"383","author":"Ramos-Casals\n \nM","year":"2014;"},{"issue":"(4):","key":"B5","series-title":"Ann Oncol","first-page":"325\u201341","article-title":"Etoposide: Twenty years later","volume":"6","author":"Hainsworth\n \nJD","year":"1995;"},{"key":"B6","series-title":"J Hematol Oncol","first-page":"106","article-title":"Hemophagocytic lymphohistiocytosis: Current treatment advances, emerging targeted therapy and underlying mechanisms","volume":"17","author":"Wu\n \nY","year":"2024;"},{"key":"B7","series-title":"J Blood Med","first-page":"69\u201386","article-title":"Hemophagocytic lymphohistiocytosis: Review of etiologies and management","volume":"5","author":"George\n \nMR","year":"2014"},{"issue":"(Supplement 1):","key":"B8","series-title":"Blood","first-page":"5374","article-title":"Secondary hemophagocytic lymphohistiocytosis (HLH): A systematic review of incidence and prognostic outcomes","volume":"144","author":"Hameed\n \nM","year":"2024;"},{"key":"B9","series-title":"Hematology Am Soc Hematol Educ Program","first-page":"177\u201382","article-title":"Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis","volume":"2015","author":"Allen\n \nCE","year":"2015;"},{"issue":"(6):","key":"B10","series-title":"Ann Diagn 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