Differential Diagnosis of Hyperferritinemia in Critically Ill Patients.

critically ill patients differential diagnosis ferritin hematological malignancy hemophagocytic lymphohistiocytosis (HLH) hemophagocytic syndrome (HS) liver disease macrophage activation syndrome (MAS) sepsis

Journal

Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588

Informations de publication

Date de publication:
27 Dec 2022
Historique:
received: 22 11 2022
revised: 16 12 2022
accepted: 24 12 2022
entrez: 8 1 2023
pubmed: 9 1 2023
medline: 9 1 2023
Statut: epublish

Résumé

Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.

Sections du résumé

BACKGROUND BACKGROUND
Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH.
METHODS METHODS
In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients.
RESULTS RESULTS
A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis.
CONCLUSIONS CONCLUSIONS
Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.

Identifiants

pubmed: 36614993
pii: jcm12010192
doi: 10.3390/jcm12010192
pmc: PMC9821140
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Charité - Universitätsmedizin Berlin
ID : Digital Clinician Scientist Program
Organisme : Charité - Universitätsmedizin Berlin
ID : Clinician Scientist Program

Références

Br J Cancer. 1973 Mar;27(3):212-7
pubmed: 4511989
Autoimmun Rev. 2022 Oct;21(10):103166
pubmed: 35932955
Shock. 2018 Aug;50(2):149-155
pubmed: 30010630
Annu Rev Pharmacol Toxicol. 2010;50:323-54
pubmed: 20055707
Microorganisms. 2020 Apr 18;8(4):
pubmed: 32325688
Pediatr Blood Cancer. 2007 Feb;48(2):124-31
pubmed: 16937360
Int J Lab Hematol. 2015 May;37 Suppl 1:25-30
pubmed: 25976957
BMC Med. 2013 Aug 22;11:185
pubmed: 23968282
Lancet. 2014 Apr 26;383(9927):1503-1516
pubmed: 24290661
Nephrol Dial Transplant. 2018 Dec 1;33(12):2234-2244
pubmed: 30010940
Can J Gastroenterol. 2006 Jul;20(7):467-70
pubmed: 16858498
Isr Med Assoc J. 2014 Jul;16(7):439-43
pubmed: 25167691
Trop Doct. 2017 Jul;47(3):217-221
pubmed: 28689489
Immunol Res. 2020 Aug;68(4):213-224
pubmed: 32681497
J Clin Rheumatol. 2013 Sep;19(6):324-8
pubmed: 23965472
Blood. 2015 Mar 5;125(10):1548-52
pubmed: 25573993
J Chin Med Assoc. 2019 Feb;82(2):99-104
pubmed: 30839498
Crit Care. 2020 May 24;24(1):244
pubmed: 32448380
Diabetes Metab Syndr Obes. 2020 Sep 24;13:3239-3248
pubmed: 33061489
Int J Pediatr Adolesc Med. 2020 Sep;7(3):112-115
pubmed: 33094138
BMC Complement Altern Med. 2018 Jun 7;18(1):176
pubmed: 29879960
Biochim Biophys Acta. 2013 Dec;1836(2):245-54
pubmed: 23891969
South Med J. 2015 Sep;108(9):574-8
pubmed: 26332484
Med Oncol. 2014 Sep;31(9):149
pubmed: 25108598
Hematology. 2018 Dec;23(10):817-822
pubmed: 29914346
Compr Physiol. 2013 Jan;3(1):315-30
pubmed: 23720289
Metallomics. 2014 Apr;6(4):748-73
pubmed: 24549403
Shock. 2020 Jun;53(6):701-709
pubmed: 31626037
Lupus. 2013 Nov;22(13):1327-35
pubmed: 24036580
J Clin Med. 2022 Sep 16;11(18):
pubmed: 36143085
Crit Care Med. 2020 Apr;48(4):459-465
pubmed: 32205591
Ren Fail. 2017 Nov;39(1):566-569
pubmed: 28741986
Nutrients. 2018 Aug 27;10(9):
pubmed: 30150549
Mol Cell Biol. 2000 Aug;20(16):5818-27
pubmed: 10913165
Gut. 2011 Oct;60(10):1309-16
pubmed: 21561874
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Jun;18(3):671-4
pubmed: 20561425
Liver Int. 2019 Jul;39(7):1325-1334
pubmed: 30851216
Mediators Inflamm. 2022 Jul 23;2022:6077570
pubmed: 35915740
Ann Hepatol. 2020 Nov - Dec;19(6):697
pubmed: 32866690
BMC Med. 2017 Sep 18;15(1):172
pubmed: 28918754
Am J Clin Pathol. 2016 May;145(5):646-50
pubmed: 27247369
Int Immunol. 2017 Nov 1;29(9):401-409
pubmed: 28541437
J Clin Lab Anal. 2020 Oct;34(10):e23618
pubmed: 33078400

Auteurs

Friederike S Schuster (FS)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.

Peter Nyvlt (P)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.

Patrick Heeren (P)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.

Claudia Spies (C)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.

Moritz F Adam (MF)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.

Thomas Schenk (T)

Department of Hematology and Oncology, Universitätsklinikum Jena, 07743 Jena, Germany.

Frank M Brunkhorst (FM)

Department of Anesthesiology and Intensive Care Medicine, Center for Clinical Studies, Universitätsklinikum Jena, 07743 Jena, Germany.

Gritta Janka (G)

Clinic of Pediatric Hematology and Oncology, University Medical Center Eppendorf, 20246 Hamburg, Germany.

Paul La Rosée (P)

Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, 78052 Villingen-Schwenningen, Germany.

Cornelia Lachmann (C)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany.

Gunnar Lachmann (G)

Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany.

Classifications MeSH