@article{3108329,
    title = "Macrophage activation-like syndrome: An immunological entity associated with rapid progression to death in sepsis",
    author = "Kyriazopoulou, E. and Leventogiannis, K. and Norrby-Teglund, A. and Dimopoulos, G. and Pantazi, A. and Orfanos, S.E. and Rovina, N. and Tsangaris, I. and Gkavogianni, T. and Botsa, E. and Chassiou, E. and Kotanidou, A. and Kontouli, C. and Chaloulis, P. and Velissaris, D. and Savva, A. and Cullberg, J.-S. and Akinosoglou, K. and Gogos, C. and Armaganidis, A. and Giamarellos-Bourboulis, E.J. and on behalf of the Hellenic Sepsis Study Group",
    journal = "BMC Medicine",
    year = "2017",
    volume = "15",
    number = "1",
    publisher = "BioMed Central Ltd.",
    issn = "1741-7015",
    doi = "10.1186/s12916-017-0930-5",
    keywords = "CD163 antigen;  ferritin;  gamma interferon;  interleukin 10;  interleukin 18;  interleukin 6;  tumor necrosis factor;  ferritin;  interleukin 18, Article;  cohort analysis;  controlled study;  death;  disease association;  disseminated intravascular clotting;  early diagnosis;  ferritin blood level;  hemophagocytic syndrome;  hepatobiliary disease;  human;  immunopathology;  infection;  macrophage activation like syndrome;  major clinical study;  mortality;  mortality risk;  predictive value;  prognosis;  protein analysis;  protein blood level;  risk factor;  sensitivity analysis;  sepsis;  Swedish citizen;  systemic inflammatory response syndrome;  validation process;  adult;  aged;  complication;  female;  macrophage activation syndrome;  male;  metabolism;  middle aged;  pathology;  prospective study;  randomized controlled trial;  reproducibility;  sepsis;  young adult, Adult;  Aged;  Cohort Studies;  Female;  Ferritins;  Humans;  Interleukin-18;  Macrophage Activation Syndrome;  Male;  Middle Aged;  Prognosis;  Prospective Studies;  Reproducibility of Results;  Sepsis;  Young Adult",
    abstract = "Background: A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS). This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis. Methods: Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704). MALS was diagnosed for patients scoring positive either for the hemophagocytic syndrome score and/or having both hepatobiliary dysfunction and disseminated intravascular coagulation. Logistic regression analysis was used to estimate the predictive value of MALS for 10-day mortality in both cohorts. Ferritin, sCD163, IL-6, IL-10, IL-18, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were measured in the blood the first 24 h; ferritin measurements were repeated in 747 patients on day 3. Results: The frequency of MALS was 3.7% and 4.3% in the test and the validation cohort, respectively. In both cohorts, MALS was an independent risk factor for 10-day mortality. A ferritin level above 4420 ng/ml was accompanied by 66.7% and 66% mortality after 28 days, respectively. Ferritin levels above 4420 ng/ml were associated with an increase of IL-6, IL-18, INF-γ, and sCD163 and a decreased IL-10/TNF-α ratio, indicating predominance of pro-inflammatory phenomena. Any less than 15% decrease of ferritin on day 3 was associated with more than 90% sensitivity for unfavorable outcome after 10 days. This high mortality risk was also validated in an independent Swedish cohort (n = 109). Conclusions: MALS is an independent life-threatening entity in sepsis. Ferritin measurements can provide early diagnosis of MALS and may allow for specific treatment. © 2017 The Author(s)."
}