{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:55:07Z","timestamp":1791273307789,"version":"4.1.0"},"reference-count":11,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Clinical Case Reports"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a life\u2010threatening, exceedingly rare hyperinflammatory syndrome that typically presents with nonspecific symptoms such as fever and cytopenia. An early diagnosis of HLH is a significant clinical challenge, especially in children with presentations mimicking common infectious diseases. A 9\u2010year\u2010old girl came with a 2\u2010week history of intractable high\u2010grade fever, cough, and generalized weakness, unresponsive to broad\u2010spectrum antibiotics. Physical examination showed hepatosplenomegaly and pallor. Laboratory tests showed pancytopenia, significantly elevated serum ferritin (1144\u2009ng\/mL), hypertriglyceridemia (349\u2009mg\/dL), and hypofibrinogenemia (107\u2009mg\/dL). Imaging showed hepatosplenomegaly and mild brain atrophic changes. Despite treatment with multiple antimicrobial therapies, the fever persisted, and thus, suspicion of HLH arose. She met five out of eight HLH\u20102004 diagnostic criteria, and on this basis, a presumptive diagnosis was established. Treatment consisted of supportive care, antipyretics, transfusions, and continued observation. Given the complexity of her condition and failure to achieve sufficient clinical improvement, she was subsequently transferred to a higher care facility for specialist management. This case underscores the need to keep HLH in mind in children with chronic, treatment\u2010resistant febrile illness, particularly in the setting of cytopenia and organomegaly. Importantly, this case illustrates that even when basic laboratory investigations are readily available at tertiary referral centers, delayed clinical recognition of HLH remains the primary diagnostic challenge in Pakistan. The critical gap is not always the absence of tests but the absence of HLH in the differential diagnosis. Heightened physician awareness, early clinical suspicion, and timely referral are essential to improving outcomes in low and middle\u2010income country settings.<\/jats:p>","DOI":"10.1002\/ccr3.73507","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:54:05Z","timestamp":1789534445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delayed Recognition of Hemophagocytic Lymphohistiocytosis in a Child With Refractory Fever: A Case From Pakistan"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6443-5664","authenticated-orcid":false,"given":"Muhammad Taaha","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Department of Medicine Continental Medical College  Lahore Punjab Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2925-3306","authenticated-orcid":false,"given":"Nawal","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Medicine Continental Medical College  Lahore Punjab Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9152-0059","authenticated-orcid":false,"given":"Khola","family":"Qazi","sequence":"additional","affiliation":[{"name":"Department of Medicine Jinnah Sindh Medical University  Karachi Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-7333","authenticated-orcid":false,"given":"Karan Chaman","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Medicine Liaquat University of Medical &amp; Health Sciences  Jamshoro Sindh Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-8591","authenticated-orcid":false,"given":"Md. Faisal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Bangladesh Institute of Innovative Health Research  Mirpur Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.all.0000246626.57118.d9"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000936"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61048-X"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-278127"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018894618"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1237386"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCP4ZDKJ4ICOUAT"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23911"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.123562"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21423"}],"container-title":["Clinical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.73507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ccr3.73507","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.73507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:37:51Z","timestamp":1791272271000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ccr3.73507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":11,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/ccr3.73507"],"URL":"https:\/\/doi.org\/10.1002\/ccr3.73507","archive":["Portico"],"relation":{},"ISSN":["2050-0904","2050-0904"],"issn-type":[{"value":"2050-0904","type":"print"},{"value":"2050-0904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e73507"}}