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Patients with Newly Diagnosed SLE More Prone to Major Infections

"The high prevalence of severe infection in newly diagnosed SLE implies that infections may be related to the underlying immune disturbance of SLE itself.”

Likely due in part to underlying immune disturbance, patients with newly onset active systemic lupus erythematosus (SLE) are more susceptible to major infections. Identifying these high-risk patients using a prediction tool may eventually lead to better tailored management and better outcomes, according to a study published in Lupus Science & Medicine.1

“Short disease duration (<1 year) has been shown to be an independent risk factor associated with infections in different SLE cohorts,” investigators explained. “In patients with SLE, infections are largely considered a complication of immunosuppressive therapy; however, as high as 25.9% of severe infections are reported at the time of SLE diagnosis in the absence of immunosuppressive therapy. The high prevalence of severe infection in newly diagnosed SLE implies that infections are attributable to glucocorticoid and immunosuppressive therapy and may be related to the underlying immune disturbance of SLE itself.”

Hospitalized patients with newly diagnosed (<3 months) SLE were included in the hospitalized Systemic Lupus Inception Cohort (hSLIC) from January 2013 and November 2020. Patients were followed for at least 1 year or until death. Baseline characteristics were collected at the time of hospitalization, including demographics, clinical characteristics, and laboratory testing results. Major infection events were recorded during follow-up, defined as microbiological/clinical-based diagnosis treated with intravenous antimicrobials. The hSLIC cohort was then further divided into a training set and a testing set. Major infection predictors were identified via multivariable logistic regression analysis.

Of the 494 patients in the cohort, 67 patients (14%) reported 69 episodes of major infections during the first year of follow-up, with nearly all occurring within the first 4 months (n = 65/69, 94%). Major infections were linked to all-cause mortality. Approximately 1/3 of patients (n = 22/67; 33%) died from factors related to their infection. The mean age at enrollment was 36 years, median duration from diagnosis to admission was 9 days, and 87% (n = 432) were women.

After adjusting for glucocorticoid and immunosuppressant exposure, a data-driven risk prediction model was created to identify patients at both low risk (3%-5%; risk score ≤1) and high risk (37%-39%; risk score ≥2) of major infections within the first 4 months based on SLE Disease Activity Index (SLEDAI) >10, serum creatinine >104 µmol/L, and peripheral lymphocyte count <0.8×109/L. The most common infections were pneumonia (n = 46/69; 67%), bacteremia (n = 18/69; 26%), skin and soft-tissue infections (n = 7/69; 10%), and serous cavity infections (n = 4/69; 6%). Central nervous system infections (3%) and urinary tract infections (3%) were less common among patients.

Generalizability is an important limitation of the study. Investigators stress that the results from the hSLIC cohort should not be extrapolated to all patients with a new SLE diagnosis, in particular, those with mild disease activity and juvenile populations, as only 5% of the cohort represented patients with adolescent-onset SLE. The single-center study without external validation, the absence of vaccination status, and the lack of antibiotics prophylaxis protocol also hindered the study. These issues can be addressed in future research.

“Our data shed some light to better understand the pattern and risk factors of major infections in newly diagnosed severe SLE,” investigators concluded.

Reference:

Wang H, Zhou Y, Yu L, et al. Major infections in newly diagnosed systemic lupus erythematosus: an inception cohort study. Lupus Sci Med. 2022;9(1):e000725. doi:10.1136/lupus-2022-000725