Characterization and Outcomes of Septic Shock Patients with Macrophage Activation-Like Syndrome: Prognostic Role of Hyperferritinemia and Description of Hemoadsorption in Refractory Hyperinflammatory Septic Shock.

INTRODUCTION

Sepsis is increasingly recognized as a heterogeneous syndrome encompassing distinct immune response phenotypes. Among these, macrophage activation-like syndrome (MALS) represents a severe hyperinflammatory state characterized by dysregulated cytokine release, rapid organ failure, and extremely high mortality. Hyperferritinemia has emerged as a readily available biomarker for identifying this high-risk phenotype in septic patients. The primary objective of our study was to identify and characterize differences between septic patients fulfilling MALS criteria (ferritin >4,420 ng/mL) and those who did not, with particular focus on their clinical outcomes.

METHODS

A retrospective cohort study including 437 adult patients diagnosed with sepsis or septic shock according to Sepsis-3 criteria. Serum ferritin levels were measured within the first 12-24 h after sepsis onset. MALS was defined by ferritin concentrations >4,420 ng/mL. Demographic data, clinical characteristics, laboratory parameters, organ support requirements, and outcomes were compared between patients with and without MALS. In addition, outcomes of a subgroup of patients with refractory septic shock who underwent hemoadsorption therapy as rescue treatment were analyzed.

RESULTS

MALS was identified in 56 patients (12.8%). Compared with non-MALS patients, those with MALS were younger, more frequently immunosuppressed, and had higher severity scores, greater inflammatory marker levels, and more pronounced organ dysfunction. MALS patients required invasive mechanical ventilation and continuous renal replacement therapy more frequently. Intensive care unit (ICU) mortality was significantly higher in the MALS group (75% vs. 43.3%, p < 0.001), with markedly reduced 30- and 90-day survival. Hemoadsorption therapy was applied in 14 patients with extreme hyperinflammation and multiorgan failure, but ICU mortality remained high (71.4%).

CONCLUSION

Hyperferritinemia identifies a distinct septic shock phenotype consistent with MALS, associated with catastrophic outcomes despite advanced supportive care. While ferritin measurement allows early risk stratification, current hemoadsorption strategies appear insufficient in established MALS, underscoring the urgent need for precision immunotherapy and biomarker-guided clinical trials in hyperinflammatory sepsis.