Macrophage activation syndrome in systemic lupus erythematosus: risk factors and outcomes

To identify risk factors and outcomes of macrophage activation syndrome (MAS) in febrile patients with systemic lupus erythematosus (SLE), and to compare clinical characteristics between MAS occurring at initial SLE diagnosis and during established disease.

We retrospectively reviewed medical records of SLE patients admitted to Seoul St. Mary's Hospital between 1990 and 2025 and identified those with MAS. Age- and sex-matched febrile SLE patients without MAS were selected as controls in a 1:3 ratio. Clinical and laboratory variables were compared, and logistic regression analysis was performed to determine factors associated with MAS.

Among 1,512 febrile SLE patients, 54 (3.6%) developed MAS. Hypoalbuminemia was independently associated with MAS occurrence (OR 29.86, 95% CI 1.58-564.22; P = 0.024), while renal involvement was inversely associated (OR 0.01, 95% CI 0.00-0.24; P = 0.004). MAS occurred as initial presentation of SLE in 28 patients (51.9%) and during established disease in 26 patients (48.1%), but outcomes did not differ significantly by onset timing. The in-hospital mortality rate of MAS patients was 11.1%, and overall survival did not differ significantly across treatment modalities.

MAS is a rare but life-threatening complication of SLE. Its presentation is nonspecific, and prognosis appears independent of onset timing or treatment approach. Further large-scale, prospective studies are needed to validate these findings and better delineate clinical and laboratory features of MAS in SLE. Key Points • Hypoalbuminemia was identified as a potential predictor of SLE-associated MAS, independent of proteinuria or lupus nephritis. • Clinical features and survival outcomes were comparable between MAS presenting at initial SLE diagnosis and during established disease. • Early recognition of MAS remains critical, given its severe and potentially life-threatening course in SLE.