{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:12:40Z","timestamp":1789776760175,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Adult\u2010onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D\u2010dimer, C\u2010reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D\u2010dimer); interleukin\u20101\/interleukin\u20106\/tumour necrosis factor elevation (CRP) and T cell activation (sCD25).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single\u2010center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11\u2009360\u2009\u03bcg\/L vs. 29\u2009020\u2009\u03bcg\/L, <jats:italic>p<\/jats:italic>\u2009=\u2009.01) while D\u2010dimer was not significantly different (median 5310\u2009mg\/L FEU vs. 7000\u2009mg\/L FEU, <jats:italic>p<\/jats:italic>\u2009=\u2009.3). CRP was higher (median 168\u2009mg\/L vs. 71\u2009mg\/L, <jats:italic>p<\/jats:italic> &lt;.01) and sCD25 was lower (median 2220 vs. 7280\u2009U\/mL, <jats:italic>p<\/jats:italic>\u2009=\u2009.004) in AOSD compared to HLH. The combined ROC curve using CRP &gt;130\u2009mg\/L and sCD25&lt;\u20093900\u2009U\/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93\u20130.97) with sensitivity 91% and specificity 93%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14267","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T09:49:09Z","timestamp":1720604949000},"page":"576-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>CRP<\/scp> and <scp>sCD25<\/scp> help distinguish between adult\u2010onset Still's disease and <scp>HLH<\/scp>"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3050-9292","authenticated-orcid":false,"given":"Madelaine","family":"Beckett","sequence":"first","affiliation":[{"name":"Department of Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1446-9582","authenticated-orcid":false,"given":"Caroline","family":"Spaner","sequence":"additional","affiliation":[{"name":"Department of Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-379X","authenticated-orcid":false,"given":"Mariam","family":"Goubran","sequence":"additional","affiliation":[{"name":"Department of Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Wade","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-663X","authenticated-orcid":false,"given":"Juan Antonio","family":"Avina\u2010Zubieta","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2361-7391","authenticated-orcid":false,"given":"Audi","family":"Setiadi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver Canada"},{"name":"Division of Hematopathology British Columbia Children's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-6750","authenticated-orcid":false,"given":"Lori","family":"Tucker","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, BC Children's Hospital University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-3744","authenticated-orcid":false,"given":"Kam","family":"Shojania","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Au","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Skin Science University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-2419","authenticated-orcid":false,"given":"Andre","family":"Mattman","sequence":"additional","affiliation":[{"name":"Division of Hematopathology British Columbia Children's Hospital  Vancouver Canada"},{"name":"Department of Pathology and Laboratory Medicine St. Paul's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-6681","authenticated-orcid":false,"given":"Agnes Y. Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-8184","authenticated-orcid":false,"given":"David C.","family":"Fajgenbaum","sequence":"additional","affiliation":[{"name":"Center for Cytokine Storm Treatment &amp; Laboratory University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-2951","authenticated-orcid":false,"given":"Luke Y. C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine University of British Columbia  Vancouver Canada"},{"name":"Division of Hematology, Department of Medicine Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01065-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2016.05.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/095952879708000106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.30.2.121"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0081-x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2017.07.005"},{"issue":"3","key":"e_1_2_10_8_1","first-page":"e217","article-title":"Malignancy\u2010associated haemophagocytic lymphohistiocytosis","volume":"9","author":"Setiadi A","year":"2022","journal-title":"Lancet"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00348-6"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100707"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39332"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-209020"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911326"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.750114"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01053-w"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-820852"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-018-2012-2"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02631-7"},{"issue":"5","key":"e_1_2_10_20_1","first-page":"1508","article-title":"Recommendations for the use of etoposide\u2010based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH steering Committee of the Histiocyte Society","volume":"6","author":"Ehl S","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018894618"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead461"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27929"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38690"},{"issue":"3","key":"e_1_2_10_26_1","first-page":"424","article-title":"Preliminary criteria for classification of adult Still's disease","volume":"19","author":"Yamaguchi M","year":"1992","journal-title":"J Rheumatol"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200205000-00003"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-253815"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-02-768580"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2019.12.007"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81300-w"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2023-0086"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-017-2993-y"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000019051"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPZE77UAPSMDCD"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15579"},{"issue":"8","key":"e_1_2_10_37_1","first-page":"e575","article-title":"Endotheliopathy in COVID\u201019\u2010associated coagulopathy: evidence from a single\u2010centre, cross\u2010sectional study","volume":"7","author":"Goshua G","year":"2020","journal-title":"Lancet"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045894020966547"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012764"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20319"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae179"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-012799"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.14267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T09:17:15Z","timestamp":1739783835000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.14267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/ejh.14267"],"URL":"https:\/\/doi.org\/10.1111\/ejh.14267","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]},"assertion":[{"value":"2024-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}