{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:46:54Z","timestamp":1753868814944,"version":"3.41.2"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":206,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>A congenital loss of cytotoxic lymphocyte activity leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis. Until recently, this disease was uniformly associated with infants or very young children, but it appears now that the onset may be delayed for decades. As a result, some adults are being mis\u2010 or under\u2010diagnosed because of their \u2018atypical\u2019 symptoms that are not recognised as immunodeficiency. The clinical picture and histopathology can overlap with those of haematologic malignancy, further complicating the diagnostic thought process. The spectrum of atypical symptoms is poorly defined, and therefore, it is important to describe these cases and the attendant immunological and cellular changes associated with familial haemophagocytic lymphohistiocytosis, in order to improve diagnosis and prevent unintended consequences of symptomatic therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 45\u2010year\u2010old patient presented with suspected T\u2010cell lymphoma and was treated with combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone) supplemented with granulocyte\u2010colony stimulating factor (G\u2010CSF). To mobilise stem cells for autologous transplantation, the patient was then treated with high\u2010dose G\u2010CSF and rapidly developed haemophagocytic lymphohistiocytosis. Symptoms resolved temporarily with intensive immunosuppression with alemtuzumab and durably with a subsequent allograft.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient was found to be a carrier of bi\u2010allelic mutations in the STXBP2 protein that is essential for cytotoxic lymphocyte function, and the initial diagnosis has been revised as familial haemophagocytic lymphohistiocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case highlights the difficulty in distinguishing atypical\/late\u2010onset familial haemophagocytic lymphohistiocytosis from a malignant process as well as a possible exacerbation of the disease with G\u2010CSF therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1320","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T12:40:20Z","timestamp":1627303220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dilemmas in the diagnosis and pathogenesis of atypical late\u2010onset familial haemophagocytic lymphohistiocytosis"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-2024","authenticated-orcid":false,"given":"Adrian","family":"Minson","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology Austin Hospital Melbourne VIC Australia"},{"name":"Peter MacCallum Cancer Centre Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilia","family":"Voskoboinik","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Grigg","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Austin Hospital Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-041610-134208"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00441"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00529"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40732"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-074468"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.12.1003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30826"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13461"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-398958"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903815106"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.073098"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.03632.x"},{"key":"e_1_2_7_16_1","first-page":"2374","article-title":"Clonal expansion of \u03b1\u03b2\u2010T lymphocytes with inverted J\u03b21 bias in familial hemophagocytic lymphohistiocytosis","volume":"94","author":"Nagano M","year":"1999","journal-title":"Blood"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199903)32:3<201::AID-MPO7>3.0.CO;2-R"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20854"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11704"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-013-0292-0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20202"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00944"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044649"}],"container-title":["Clinical &amp; 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