Even though tremendous effort has been undertaken within the past 40 years, both sepsis incidence and mortality remain high. The concept of various immune responses in sepsis, ranging from immune paralysis to severe hyperinflammation, has gained more and more attention. As such, the hyperinflammatory phenotype macrophage activation-like syndrome (MALS) became the cornerstone in the latest intervention trials. Our study sought to systematically investigate MALS patients, including their definitions, respective bone marrow markers and monocytic HLA-DR expressions.

In this secondary analysis of a retrospective observational study, we included all patients aged ≥18 years and admitted to any adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018, who had hyperferritinemia (≥500 μg/L) and sepsis, but no diagnosis of hemophagocytic lymphohistiocytosis. For diagnosis of MALS, we used the latest definition of ferritin ≥4420 µg/L.

1629 patients were included, of whom 322 were diagnosed with MALS (19.8%). In-hospital mortality was 62.4% in MALS patients compared to 30.5% in those without MALS. MALS patients had increased macrophage counts and higher rates of activated macrophages in bone marrow biopsies. HLA-DR expression did not differ significantly between the groups. In multivariable logistic regression analysis, MALS showed the highest odds ratio associated with in-hospital mortality. Different definitions of MALS identified largely distinct patient populations.

MALS increased in-hospital mortality in sepsis patients. Our results underscore the urgent need for targeted research and therapeutic strategies. While promising insights into immune modulation have emerged, further studies are essential to refine treatment approaches and improve outcomes in this vulnerable patient population.