Background/Purpose: Infections are an important cause of mortality and morbidity in systemic lupus erythematosus (SLE) patients. Bloodstream infections (BI), which are especially severe and relatively common in these patients, are associated with a high mortality rate, both during the infectious episode and during follow-up. Whereas there is evidence that bacterial infections can trigger autoimmunity, the relationship between BI and severe lupus flares has not been fully addressed. The aim of this study was to assess whether BI are a risk factor for severe lupus flare.

Methods: We performed a retrospective cohort study comparing 107 SLE patients with an episode of BI and 107 hospitalized or ambulatory SLE patients without BI. All subjects satisfied the ACR classification criteria and none of them had severe lupus flare at baseline. Time zero was considered as: a) The episode of BI in the first group b) Hospitalization for another cause, or the medical assessment prior to the last follow-up visit as an ambulatory patient in the non-BI group. Patients were followed for three months. The primary outcome was severe lupus flare according to SELENA-SLEDAI criteria. Differences between groups were assessed by Student’s t test. Cox proportional hazards model was used to estimate the relative risk of severe flare, along with 95% confidence interval. 

Results: Thirty patients (14%) developed the primary outcome (severe flare) during follow-up; 25 (83.3%) of them had an episode of BI in the previous three months, compared with 5 (16.6%) without a history of BI (p<0.001). A high percentage of patients with severe lupus flare had a SLEDAI score >12 (36.6%). Among these flares, severe thrombocytopenia (33.3%) and renal flare (43.3%) were the most frequent. There was no difference in prednisone, cyclophosphamide and mycophenolate mofetil dose between patients who presented severe lupus flare and those who did not. Nevertheless, the basal SLEDAI, C3, C4, anti-dsDNA and azathioprine dose were significantly higher in the former group.  After multivariate analysis, the presence of BI (HR 6.24, 95% CI 1.405-27.725, p=0.016), low C4 levels (HR 3.2, 95% CI 1.272-8.078, p=0.014) and lymphopenia <1000 cells/ml (HR 5.02, 95% CI 1.137-22.23, p=0.033) remained independently associated with severe lupus flare.

Interestingly, while only 10.3% of BI episodes were caused by S. pneumoniae, 54.5% of patients infected by that microorganism developed a severe SLE flare. Noteworthy, infection by S. pneumoniae remained as an independent risk factor for lupus flare in the BI group (HR 2.75, 95% CI 1.406-5.403, p=0.019). 

Conclusion: SLE patients with BI have an increased risk for severe disease flare. Also, lymphopenia and low C4 were significant predictors in our cohort. Among patients with BI, when S. pneumoniae was the causing agent, the risk of severe SLE flare augmented significantly. High mortality associated with BI in SLE patients may not only be related to the infection per se, but also to the development of severe disease activity. Patients with an episode of BI, and specifically those who fulfill the other aforementioned characteristics, should be followed up closely in order to detect and treat flares in a timely manner.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bloodstream-infections-in-systemic-lupus-erythematosus-patients-are-associated-with-severe-lupus-flares/