Macrophage activation syndrome in systemic lupus erythematous and Still's disease: distinct phenotypes shaped by the underlying diseases.

OBJECTIVES

Macrophage activation syndrome (MAS) is a severe complication of Still's disease (SD-MAS), but may also, albeit rarely, complicate SLE (SLE-MAS). The clinical profile of SLE-MAS compared with SD-MAS remains unclear, as do the optimal treatment strategies.

METHODS

A retrospective multicentre cohort of adults with a history of SLE-MAS or SD-MAS was gathered from eight tertiary referral centres. MAS clinical/laboratory features, treatments and outcomes were compared; 'inaugural MAS' was defined if occurring within 6 months from the onset of the underlying disease. Exploratory multivariable profiling assessed for disease-specific features. The SLE-MAS group was also compared with large historical SLE cohorts to identify candidate risk signals.

RESULTS

While SD-MAS aligned with the prototypical hyperinflammatory pattern (more marked hyperferritinemia, very high CRP, organomegaly and liver injury; 100% meeting 2016 ACR/EULAR/PRINTO criteria), SLE-MAS (92% meeting criteria) more often featured CNS dysfunction, less liver injury, greater degree of cytopenias including anaemia, with a strong signal of autoimmune haemolysis (73% direct Coombs [DCT] positivity). Therapeutically, IL-1 antagonism was used in seven SLE-MAS with mixed results without any rapid MAS resolution. Mucocutaneous disease, autoimmune haemolysis, CNS involvement, less pronounced female preponderance and much higher DCT positivity dominated the SLE-MAS phenotype compared with historical SLE cohorts comprising 1000, 2228 and 2055 cases each.

CONCLUSIONS

SLE-MAS diverged from SD-MAS with less organomegaly and liver injury but more pronounced CNS involvement and hematological involvement, the latter strongly linked to red blood cell directed autoantibodies. These findings indicate that SLE-MAS pathogenesis may be divergent and require distinct therapeutic approaches beyond extrapolation from SD-MAS.