Background/Purpose:

Macrophage activation syndrome (MAS) is an uncommon but potentially fatal complication of SLE. We conducted a case-control study comparing hospitalized adults with SLE with and without MAS to better understand risk factors associated with development of MAS.

Methods:

Within our large academic hospital lupus registry (n= 2094 SLE patients with ≥ 4 ACR criteria, 1970-2016), we identified patients ≥ age 18 with a hospital admission. We identified SLE patients with MAS among them by screening for a ferritin > 5,000 ng/ml during a hospital admission, excluding patients with end stage renal disease, iron overload and cirrhosis, and confirming MAS diagnosis by medical record review. For each case, we chose 4 hospitalized SLE patients without MAS, matched on dates of SLE diagnosis (± 1 year) and hospital admission (± 1 year). We collected demographic and clinical factors from the medical records. We employed conditional logistic regression models to identify factors associated with MAS.

Results:

We identified 21 SLE patients hospitalized with MAS and matched them to 84 adults hospitalized with SLE but without MAS. The most common causes of admission among SLE controls were lupus flare (48%; 30% with nephritis) and infection (30%). Cases and controls had similar age at SLE diagnosis (29 vs. 30 years), proportion of females (76 vs. 85%), median area-level income ($52,122 vs. $64,178), racial distribution, and length of time between SLE diagnosis and hospitalization (2,010 vs. 1,849 days) (all p-values >0.05). Among cases, mean SLE Disease Activity Index (SLEDAI) scores at admission (31 vs. 21, p=0.002) and length of stay (17 vs. 3 days, p<0.0001) were higher than among controls. Mortality was 19% among cases and 1% among controls (p=0.01). In multivariable models, the presence of prior arthritis (OR 0.09, 95%CI 0.01-0.62) and hydroxychloroquine use on admission (OR 0.21, 95%CI 0.05-0.94) were associated with decreased MAS risk, while higher SLEDAI scores were associated with increased MAS risk (OR 1.11, 95% CI 1.03-1.19) (Table). There were no differences in other ACR criteria or medication use at time of admission. 

Conclusion:

The finding that hydroxychloroquine was associated with a reduced risk of MAS among hospitalized SLE patients is novel. Hydroxychloroquine is a SLE-stabilizing medication associated with reducing SLE flares and organ complications. In addition, the presence of arthritis may signify a distinct SLE phenotype with a decreased risk of hematologic manifestations, or reflect that patients with arthritis are more likely to receive hydroxychloroquine. Although the comparison group in this study was seriously ill SLE patients admitted to the hospital with mean SLEDAI score of 21, the association of highly elevated SLEDAI on admission with increased MAS risk is important for clinicians, as SLE patients with extremely active disease may be at highest MAS risk.