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

Kyriazopoulou, Evdoxia; Leventogiannis, Konstantinos; Norrby-Teglund, Anna; Dimopoulos, Georgios; Pantazi, Aikaterini; Orfanos, Stylianos E; Rovina, Nikoletta; Tsangaris, Iraklis; Gkavogianni, Theologia; Botsa, Elektra; Chassiou, Eleftheria; Kotanidou, Anastasia; Kontouli, Christina; Chaloulis, Panagiotis; Velissaris, Dimitrios; Savva, Athina; Cullberg, Jonas-Sundén; Akinosoglou, Karolina; Gogos, Charalambos; Armaganidis, Apostolos; Giamarellos-Bourboulis, Evangelos J.
BMC Med; 15(1): 172, 2017 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-28918754

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.
Selo DaSilva