Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome

Definition and Context

MAS is a specific subtype of secondary HLH that occurs exclusively in patients with underlying autoimmune/autoinflammatory diseases, while HLH is the broader umbrella term encompassing both primary and secondary forms triggered by infections, malignancies, or autoimmune conditions 1, 2, 3, 4
The American College of Rheumatology and other guideline societies imply that MAS and HLH share a common terminal pathway of hyperinflammation but have different pathogenetic roots 1, 2, 3, 4

Free IL-18 levels are significantly higher in MAS associated with Still's disease compared to other forms of HLH, though IL-18BP levels do not differ between MAS and other HLH forms 5, 6, 7
S100A12 can differentiate MAS from both primary and secondary HLH with high sensitivity and specificity, particularly helpful when MAS presents at disease onset before the underlying autoimmune diagnosis is clear 5, 6, 7

The American College of Rheumatology suggests that MAS treatment typically starts with high-dose corticosteroids as first-line therapy, with second-line options including cyclosporine A, anakinra, or tocilizumab—agents specifically targeting the autoimmune/autoinflammatory pathways 1, 2, 3, 4
Other secondary HLH forms may require more aggressive immunosuppression with etoposide-containing regimens, particularly when triggered by malignancies or severe infections 1, 2, 3, 4

The term MAS should be reserved specifically for HLH in the context of autoimmune/autoinflammatory diseases, not for infection- or malignancy-triggered secondary HLH 1, 2, 3, 4