PMID- 33128796
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20220202
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 203
IP  - 2
DP  - 2021 Feb
TI  - The role of interleukin-18 in the diagnosis and monitoring of hemophagocytic 
      lymphohistiocytosis/macrophage activation syndrome - a systematic review.
PG  - 174-182
LID - 10.1111/cei.13543 [doi]
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory 
      disorder, characterized by multiorgan failure, fever and cytopenias. The 
      diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a 
      challenge. Interleukin 18 (IL-18) is emerging as a potential biomarker for 
      HLH/MAS but is currently not a part of diagnostic criteria. This systematic 
      review aimed to assess the potential role of IL-18 in the diagnosis and 
      monitoring of HLH and MAS, and was performed according to the Preferred Reporting 
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and 
      Embase were searched on 30 January 2020. Studies included all subtypes of HLH and 
      a range of underlying disorders in both children and adults. A total of 14 
      studies were included. Generally, serum IL-18 was elevated in both primary and 
      secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with 
      healthy individuals; thus, serum IL-18 may be able to discriminate between HLH 
      and other inflammatory conditions. Significantly increased IL-18 (> 10 000 pg/ml) 
      was also consistently described in MAS compared with other subtypes of HLH. The 
      ability of IL-18 to distinguish MAS from systemic juvenile idiopathic arthritis 
      (JIA) is less unambiguous, as IL-18 levels > 100 000 pg/ml were described in sJIA 
      patients both with and without MAS. IL-18 may help to differentiate between HLH 
      subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, 
      only few and relatively small studies exist on the subject. Larger, prospective 
      multi-center studies are called for to assess the diagnostic precision of IL-18 
      for HLH and MAS.
CI  - (c) 2020 British Society for Immunology.
FAU - Krei, J M
AU  - Krei JM
AD  - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
FAU - Moller, H J
AU  - Moller HJ
AD  - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
AD  - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
FAU - Larsen, J B
AU  - Larsen JB
AUID- ORCID: 0000-0002-2978-5185
AD  - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
LA  - eng
SI  - ClinicalTrials.gov/NCT03113760
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20201123
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Animals
MH  - Diagnosis, Differential
MH  - Humans
MH  - Interleukin-18/*immunology
MH  - Lymphohistiocytosis, Hemophagocytic/*diagnosis/immunology
MH  - Macrophage Activation
MH  - Macrophage Activation Syndrome/*diagnosis/immunology
MH  - Macrophages/*immunology
MH  - Monitoring, Immunologic/*methods
MH  - Phenotype
PMC - PMC7806447
OTO - NOTNLM
OT  - hemophagocytic lymphohistiocytosis
OT  - interferon gamma-inducing factor
OT  - interleukin-18
OT  - macrophage activation syndrome
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2020/11/01 06:00
MHDA- 2021/08/07 06:00
PMCR- 2022/02/01
CRDT- 2020/10/31 17:08
PHST- 2020/07/14 00:00 [received]
PHST- 2020/09/30 00:00 [revised]
PHST- 2020/10/21 00:00 [accepted]
PHST- 2020/11/01 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2020/10/31 17:08 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - CEI13543 [pii]
AID - 10.1111/cei.13543 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2021 Feb;203(2):174-182. doi: 10.1111/cei.13543. Epub 2020 Nov 
      23.