{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:30:22Z","timestamp":1788517822568,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition characterized by excessive activation of cytotoxic lymphocytes and macrophages, resulting in a cytokine storm, multiorgan damage, and high mortality. HLH is classified into primary (genetic) and secondary (acquired) forms, with diagnosis often challenging due to nonspecific symptoms. Macrophage activation syndrome (MAS) refers to the secondary HLH triggered by rheumatic diseases. In this study, we retrospectively analyzed the clinical and laboratory features of patients with secondary HLH to enhance understanding of this life-threatening condition and summarize emerging management strategies. Materials and Methods: This single-center retrospective study analyzed medical records of patients hospitalized with HLH at the University Hospital in Krak\u00f3w, Poland, from 2013 to 2024, based on HLH-2009 criteria and HScore &gt; 169 points. Diagnostic criteria included clinical, laboratory, and histological findings, e.g., hemophagocytosis in bone marrow, circulating cytopenia, and elevated ferritin levels. Results: A total of 21 patients met the criteria for HLH diagnosis, with a median age of 35 (range: 19\u201367) years, including 12 women (57.1%). The median HScore among the patients was 244 (range: 208\u2013304) points. Fever was the most common presenting symptom, occurring in all cases. High ferritin, hypertriglyceridemia, and hypofibrinogenemia in peripheral blood were also prevalent. Bone marrow hemophagocytosis was confirmed in 66.7% of cases (n = 12\/18 of available data). Regarding immunosuppressive therapy, glucocorticosteroids were the most frequently used (used in all cases). Four (19.0%) patients died during HLH (cases triggered by lymphoma [twice], Epstein\u2013Barr virus infection, unknown reason). Compared to survivors, these patients had lower counts of white blood cells, neutrophils, and lymphocytes at diagnosis (p &lt; 0.05 for all). Conclusions: Secondary HLH is a severe syndrome requiring rapid diagnosis and timely intervention to improve patient outcomes. Lower white blood cell, neutrophil, and lymphocyte counts present worse prognostic factors.<\/jats:p>","DOI":"10.3390\/medicina61060977","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:49:52Z","timestamp":1748234992000},"page":"977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characteristics of 21 Patients with Secondary Hemophagocytic Lymphohistiocytosis\u2014Insights from a Single-Center Retrospective Study"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-3557","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Dziedzic","sequence":"first","affiliation":[{"name":"Jagiellonian University Medical College, Doctoral School of Medical and Health Sciences, \u015bw. \u0141azarza 16, 31-530 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-0963","authenticated-orcid":false,"given":"Stanis\u0142awa","family":"Bazan-Socha","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Department of Internal Medicine, Faculty of Medicine, Jakubowskiego 2, 30-668 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-9739","authenticated-orcid":false,"given":"Mariusz","family":"Korkosz","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Department of Rheumatology and Immunology, Jakubowskiego 2, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-2253","authenticated-orcid":false,"given":"Joanna","family":"Kosa\u0142ka-W\u0119giel","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Department of Rheumatology and Immunology, Jakubowskiego 2, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4037\/aacnacc2019463","article-title":"Hemophagocytic Lymphohistiocytosis","volume":"30","author":"Skinner","year":"2019","journal-title":"AACN Adv. Crit. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1016\/S2665-9913(23)00273-4","article-title":"Diagnosis and Investigation of Suspected Haemophagocytic Lymphohistiocytosis in Adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) Consensus Guideline","volume":"6","author":"Cox","year":"2024","journal-title":"Lancet Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","article-title":"Adult Haemophagocytic Syndrome","volume":"383","author":"Khamashta","year":"2014","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/bjh.14147","article-title":"Advances in the Pathogenesis of Primary and Secondary Haemophagocytic Lymphohistiocytosis: Differences and Similarities","volume":"174","author":"Brisse","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1182\/blood.2019000936","article-title":"Pediatric Hemophagocytic Lymphohistiocytosis","volume":"135","author":"Canna","year":"2020","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.coi.2017.08.004","article-title":"Hemophagocytic Syndrome: Primary Forms and Predisposing Conditions","volume":"49","author":"Sepulveda","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1136\/annrheumdis-2015-209020","article-title":"Elevated Circulating Levels of Interferon-\u03b3 and Interferon-\u03b3-Induced Chemokines Characterise Patients with Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis","volume":"76","author":"Bracaglia","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1016\/j.bbmt.2009.11.014","article-title":"Histiocytic Disorders: Recent Insights into Pathophysiology and Practical Guidelines","volume":"16","author":"Filipovich","year":"2010","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/DAD.0000000000002619","article-title":"Febrile Ulceronecrotic Mucha-Habermann Disease Associated with Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature","volume":"46","author":"Chen","year":"2024","journal-title":"Am. J. Dermatopathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1111\/ped.13064","article-title":"Hemophagocytic Lymphohistiocytosis: Pathogenesis, Diagnosis, and Management","volume":"58","author":"Morimoto","year":"2016","journal-title":"Pediatr. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1136\/ard-2023-224123","article-title":"The 2022 EULAR\/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis\/Macrophage Activation Syndrome (HLH\/MAS)","volume":"82","author":"Shakoory","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1182\/asheducation-2009.1.127","article-title":"Hemophagocytic Lymphohistiocytosis (HLH) and Related Disorders","volume":"2009","author":"Filipovich","year":"2009","journal-title":"Hematology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1002\/art.38690","article-title":"Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome","volume":"66","author":"Fardet","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.5858\/arpa.2020-0802-RA","article-title":"Hemophagocytic Lymphohistiocytosis","volume":"146","author":"Ponnatt","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s12032-013-0740-3","article-title":"Hemophagocytic Lymphohistiocytosis (HLH): A Review of Literature","volume":"30","author":"Mehta","year":"2013","journal-title":"Med. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8111","DOI":"10.2147\/IJGM.S388880","article-title":"Hemophagocytic Lymphohistiocytosis in Adults: A Retrospective Study in a Belgian Teaching Hospital","volume":"15","author":"Yildiz","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_17","first-page":"330","article-title":"Outcomes of Adult Critically Ill Patients with Hemophagocytic Lymphohistiocytosis in United States-Analysis from an Administrative Database from 2007 to 2015","volume":"10","author":"Kumar","year":"2020","journal-title":"Am. J. Blood Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/bjh.12138","article-title":"Diagnostic Evaluation of Patients with Suspected Haemophagocytic Lymphohistiocytosis","volume":"160","author":"Lehmberg","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/ajh.23911","article-title":"Clinical Characteristics, Prognostic Factors, and Outcomes of Adult Patients with Hemophagocytic Lymphohistiocytosis","volume":"90","author":"Otrock","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.2174\/1381612825666190709202804","article-title":"Hyperferritinaemia: An Iron Sword of Autoimmunity","volume":"25","author":"Islam","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Karakike, E., and Giamarellos-Bourboulis, E.J. (2019). Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00055"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e277","DOI":"10.1097\/MPH.0000000000001514","article-title":"Disturbances in NK Cells in Various Types of Hemophagocytic Lymphohistiocytosis in a Population of Polish Children","volume":"41","author":"Popko","year":"2019","journal-title":"J. Pediatr. Hematol.\/Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1586\/eci.09.58","article-title":"Primary and Secondary Hemophagocytic Lymphohistiocytosis: Clinical Features, Pathogenesis and Therapy","volume":"6","author":"Gupta","year":"2010","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1007\/s00277-023-05153-1","article-title":"Risk Factors and Prognosis of Early Death in Secondary Hemophagocytic Lymphohistiocytosis","volume":"102","author":"Zhang","year":"2023","journal-title":"Ann. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e543","DOI":"10.7861\/clinmed.2021-0053","article-title":"Secondary Haemophagocytic Lymphohistiocytosis in Hospitalised COVID-19 Patients as Indicated by a Modified HScore Is Infrequent and High Scores Do Not Associate with Increased Mortality","volume":"21","author":"Stammers","year":"2021","journal-title":"Clin. Med."},{"key":"ref_26","first-page":"628","article-title":"Malignancy-Associated HLH: Mechanisms, Diagnosis, and Treatment of a Severe Hyperinflammatory Syndrome","volume":"66","author":"Witzig","year":"2024","journal-title":"Leuk. Lymphoma"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gualdoni, G.A., Hofmann, G.A., Wohlfarth, P., Winkler, H.-M., Winkler, S., Haslacher, H., Thalhammer, R., Makristathis, A., Ratzinger, F., and Burgmann, H. (2019). Prevalence and Outcome of Secondary Hemophagocytic Lymphohistiocytosis Among SIRS Patients: Results from a Prospective Cohort Study. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040541"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/rheumatology\/keae391","article-title":"Current Treatment in Macrophage Activation Syndrome Worldwide: A Systematic Literature Review to Inform the METAPHOR Project","volume":"64","author":"Baldo","year":"2025","journal-title":"Rheumatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1177\/10600280221134719","article-title":"A Review of Current and Emerging Therapeutic Options for Hemophagocytic Lymphohistiocytosis","volume":"57","author":"Summerlin","year":"2023","journal-title":"Ann. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s12098-015-1877-1","article-title":"Macrophage Activation Syndrome","volume":"83","author":"Sen","year":"2016","journal-title":"Indian. J. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1136\/adc.85.5.421","article-title":"Macrophage Activation Syndrome: A Potentially Fatal Complication of Rheumatic Disorders","volume":"85","author":"Sawhney","year":"2001","journal-title":"Arch. Dis. Child."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gioia, C., Paroli, M., Izzo, R., Di Sanzo, L., Rossi, E., Pignatelli, P., and Accapezzato, D. (2024). Pathogenesis of Hemophagocytic Lymphohistiocytosis\/Macrophage Activation Syndrome: A Case Report and Review of the Literature. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115921"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s10067-013-2227-1","article-title":"Recurrent Macrophage Activation Syndrome as the Primary Manifestation in Systemic Lupus Erythematosus and the Benefit of Serial Ferritin Measurements: A Case-Based Review","volume":"32","author":"Vilaiyuk","year":"2013","journal-title":"Clin. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00296-019-04393-7","article-title":"Macrophage Activation Syndrome Complicating Rheumatic Diseases in Adults: Case-Based Review","volume":"40","author":"Gilboa","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e1141","DOI":"10.1002\/iid3.1141","article-title":"Clinical Features of Macrophage Activation Syndrome in Adult Dermatomyositis: A Single-center Retrospective Case-control Study","volume":"12","author":"Zhu","year":"2024","journal-title":"Immun. Inflam. Amp; Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1111\/1756-185X.12162","article-title":"A Fatal Case of Acquired Hemophagocytic Lymphohistiocytosis (Macrophage Activation Syndrome) in the Initial Course of Dermatomyositis with Anti-J O-1 Antibody","volume":"20","author":"Zolcinski","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00277-016-2727-6","article-title":"Prognostic Factors of Early Outcome in Pediatric Hemophagocytic Lymphohistiocytosis: An Analysis of 116 Cases","volume":"95","author":"Bin","year":"2016","journal-title":"Ann. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cyto.2017.03.013","article-title":"Prognostic Factors of Early Death in Children with Hemophagocytic Lymphohistiocytosis","volume":"97","author":"Luo","year":"2017","journal-title":"Cytokine"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Harnchoowong, S., Soponkanaporn, S., Vilaiyuk, S., Lerkvaleekul, B., and Pakakasama, S. (2022). Central Nervous System Involvement and Thrombocytopenia as Predictors of Mortality in Children with Hemophagocytic Lymphohistiocytosis. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.941318"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1651-2227.2011.02501.x","article-title":"Risk Factors for Early Death in Children with Haemophagocytic Lymphohistiocytosis","volume":"101","author":"Trottestam","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"La Marle, S., Richard-Colmant, G., Fauvernier, M., Ghesqui\u00e8res, H., Hot, A., S\u00e8ve, P., and Jamilloux, Y. (2023). Mortality and Associated Causes in Hemophagocytic Lymphohistiocytosis: A Multiple-Cause-of-Death Analysis in France. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041696"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lee, J.C., and Logan, A.C. (2023). Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis. Cancers, 15.","DOI":"10.3390\/cancers15061839"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Poto, R., Cristinziano, L., Criscuolo, G., Strisciuglio, C., Palestra, F., Lagnese, G., Di Salvatore, A., Marone, G., Spadaro, G., and Loffredo, S. (2024). The JAK1\/JAK2 Inhibitor Ruxolitinib Inhibits Mediator Release from Human Basophils and Mast Cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1443704"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Schuster, F.S., Nyvlt, P., Heeren, P., Spies, C., Adam, M.F., Schenk, T., Brunkhorst, F.M., Janka, G., La Ros\u00e9e, P., and Lachmann, C. (2022). Differential Diagnosis of Hyperferritinemia in Critically Ill Patients. J. Clin. Med., 12.","DOI":"10.3390\/jcm12010192"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/6\/977\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:40:22Z","timestamp":1760031622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/6\/977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["medicina61060977"],"URL":"https:\/\/doi.org\/10.3390\/medicina61060977","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]}}}