Journal Article

Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis

Gogos, Charalambos, Armaganidis, Apostolos, Leventogiannis, Konstantinos, Norrby-Teglund, Anna, Orfanos, Stylianos E., Cullberg, Jonas-Sundén, Rovina, Nikoletta, Dimopoulos, Georgios, Giamarellos-Bourboulis, Evangelos J., Gkavogianni, Theologia, Kotanidou, Anastasia, Kyriazopoulou, Evdoxia, Chassiou, Eleftheria, Savva, Athina, Tsangaris, Iraklis, Pantazi, Aikaterini, Akinosoglou, Karolina, Botsa, Elektra, Kontouli, Christina, Chaloulis, Panagiotis, Velissaris, Dimitrios

2017

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Alpha iron / Analysis / Arthritis / Bioindicators / Biomarkers / Biomedicine / Blood / Cell activation / Cohort Studies / Cytokines / Development and progression / Diagnosis / Disseminated intravascular coagulation / Family medical history / Female / Ferritin / Ferritins - metabolism / Genetic aspects / Health aspects / Hemophagocytic syndrome / Humans / Immunology / Infections / Inflammation / Inflammatory response / Intensive care / Interferon / Interleukin 1 / Interleukin 10 / Interleukin 18 / Interleukin 6 / Interleukin-18 - metabolism / Macrophage Activation Syndrome - complications / Macrophage Activation Syndrome - pathology / Macrophages / Male / Medical prognosis / Medicine / Medicine & Public Health / Middle Aged / Mortality / Outcome / Patients / Physiological aspects / Prognosis / Prospective Studies / Proteins / Regression analysis / Reproducibility of Results / Research Article / Risk factors / Sepsis / Sepsis - etiology / Sepsis - mortality / Systemic inflammatory response syndrome / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Young Adult