Infection Reported as Leading Cause of Death in Patients with SLE

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"Infections are one of the key determinants of early morbidity and mortality of patients with SLE, strongly linked to disease activity and immunosuppression."

A nationwide analysis of the Spanish Hospital Discharge Database (SNHDD) concluded that infections are the leading cause of death in patients with systemic lupus erythematosus (SLE), according to a study published in Lupus Science & Medicine.1 Further, the highest proportion of infection-related deaths were more frequently seen in younger patients when lupus when compared with the general population in the same age range.

“Thanks to the recent advances and better management of the disease, the prognosis of patients with SLE has dramatically improved in recent decades,” investigators explained. “However, mortality is still twofold to fivefold higher in patients with SLE than in the age-matched and sex-matched population, confirming that there is still a lot of room for improvement. Infections are one of the key determinants of early morbidity and mortality of patients with SLE, strongly linked to disease activity and immunosuppression, particularly glucocorticoid (GC) use.”

Admissions and causes of death in patients diagnosed with SLE, as well as infection-related deaths of the Spanish population via the National Statistical Institute (NSI), were collected and analyzed. Data included demographic and epidemiological information, diagnosis, and life expectancy and mortality rates within the Spanish population. Only infections that were reported as the main diagnosis, defined as a severe or clinically relevant infection, were included.

The mean age of patients was 53.2 years, 83% were female, and 92% were Caucasian. Among the 18,430 admissions in patients with SLE, disease activity accounted for 19% of admissions and 15% (n = 2755) were related to infection. However, SLE activity was responsible for only 6% (n = 36) of deaths, while infection was the main cause of death in 25% of cases (p<0.001). Severe infection surpassed SLE as the cause of death in patients who died between the ages of 40-59 (23% vs 4%), 60-79 (26% vs 6%), and patients aged 80 years or older (25% vs 6%).

In the Spanish population, infection only accounted for 8% of deaths, significantly lower when compared with patients with SLE (p<0.001). Further, infections were the highest relative cause of death in patients with SLE when compared with the general population. The mean age of the deceased patients due to SLE and infection were similar (67.7 vs 62 years, respectively, p=0.144). However, the proportion of deaths due to infection in younger patients was significantly higher when compared with SLE, accounting for 40% vs 3% of patients below 20 years old, 33% vs 4% for patients between 20 and 39, 23% vs 5% for those between 40 and 59, 26% vs 5% in the 60 to 79 age group, and 25% vs 9 % for those aged 80 years or older.

Information on disease course, prednisone usage, immunosuppressive drugs, antimalarials, and microbiological isolations were not available. Selection bias may have played a role in the analysis, as data was restricted to hospital admissions. Additionally, the rate of infections could not be calculated as the prevalence of SLE could not be properly determined and only deaths could be compared between groups. However, the nationwide analysis including a large sample size and long study period strengthened the analysis.

“Since infection is the main factor accounting for the high age-standardized mortality rate identified in patients with lupus, measures mitigating its impact on this population should be reinforced, such as a rational use of immunosuppression and glucocorticoids, vaccination and prompt identification and treatment of infection,” investigators emphasized.


Moreno-Torres V, Martínez-Urbistondo M, Gutiérrez-Rojas A, et al. Impact of severe infections in SLE: an observational study from the Spanish national registry. Lupus Sci Med. 2022;9(1):e000711. doi:10.1136/lupus-2022-000711