Infections account for majority of in-hospital deaths in childhood lupus
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Key takeaways:
- Infections are a “small but increasing” cause of hospitalization in childhood SLE, and account for most in-hospital mortality.
- Children with lupus nephritis and end-stage renal disease had an increased mortality risk.
Infections account for most in-hospital mortality in childhood systemic lupus erythematosus, with patients exhibiting lupus nephritis or end-stage renal disease at increased risk, according to data published in The Journal of Rheumatology.
“Infection is one of the most common and potentially serious complications of lupus and its treatments,” Jordan E. Roberts, MD, MPH, attending physician in pediatric rheumatology at Seattle Children’s Hospital, told Healio. “However, there was little recent data on rates of infection and mortality among children with lupus following changes in care practices, like expanded childhood vaccination, newer treatment approaches, such as use of biologic steroid-sparing medications, and the emergence of COVID-19.”
To examine the frequency of various types of infections among hospitalized children and adolescents with childhood-onset SLE, as well as determine risk factors for ICU admission and mortality, Roberts and colleagues conducted a retrospective study. The analysis included 8,588 patients with childhood-onset SLE aged 2 to 21 years (median age, 15 years), with at least one hospitalization, enrolled in the Pediatric Health Information System, a database of U.S. children’s hospitals, from 2009 to 2021.
Infections were identified with ICD codes at discharge and antimicrobial medication use during hospitalization. Meanwhile, the researchers used generalized linear mixed effects models to identify ICU admission and mortality risk factors among those hospitalized with infection.
According to the researchers, there were 26,269 hospitalizations overall, 13% of which included ICD codes for infection, with that proportion increasing over time (P = .04). The most common hospitalized infections were bacterial pneumonia (31%), sepsis (18%), cellulitis (18%) and urinary tract infection (14%).
Out of a total of 103 instances of in-hospital mortality, 60 occurred during hospitalizations for infection. The infections with the highest mortality rates were Pneumocystis jirovecii pneumonia (PJP) (21%), aspergillosis (16%) and other fungal infections (21%).
“Although PJP is very rare, we were struck by its relatively large contribution to overall mortality in this cohort,” Roberts said. “Although we were not able to assess the use of PJP prophylaxis in this study, this finding may support the use of PJP prophylaxis in children with lupus, particularly those who are highly immunocompromised.”
Among children admitted for serious infections, those with lupus nephritis (OR = 1.47; 95% CI, 1.2-1.8) and end-stage renal disease (OR = 2.4; 95% CI, 1.7-3.4) demonstrated increased odds for ICU admission. End-stage renal disease was also associated with higher mortality (OR = 2.34; 95% CI, 1.1-4.9).
Roberts and colleagues wrote that infections are a “small but increasing” driver of hospitalizations in childhood-onset SLE.
“Currently, our group is working on linking the Pediatric Health Information System used in this study with additional datasets containing outpatient data to evaluate the relative infection risk of different disease-modifying antirheumatic drug choices, adjunctive biologic medications such as rituximab (Rituxan, Genentech), and glucocorticoid dosing,” she told Healio. “We hope this work will help give clinicians more concrete guidance about the risks of different therapies.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Children and teenagers, particularly girls aged 12 to 16 years, make up 10% to 20% of all lupus cases, and tend to have more severe disease and worse prognoses compared with adults.
Adults with systemic lupus erythematosus are at high risk for infection, with an incidence rate close to 30%, due to the immune abnormalities associated with the disease and the use of immunosuppressive treatments. Meanwhile, children with childhood-onset SLE often face even more severe disease and require stronger immunomodulatory medications, including higher doses of glucocorticoids. In one study, those receiving pulse doses of methylprednisone demonstrated a 2.39-times higher risk for infection. Common infections in these cases include urinary tract infections, skin and soft tissue infections, and pneumonia.
Another study showed that sepsis occurred in 45% of ICU admissions involving any infection, with herpes simplex, influenza, herpes zoster, cytomegalovirus and SARS-CoV-2 being the most common viral infections. Fungal infections like systemic candidiasis and aspergillosis were also frequently identified. Their study further revealed that mortality occurred in cases of Pneumocystis jirovecii pneumonia, aspergillosis and other fungal infections, with adenovirus showing the highest mortality rate among viral infections.
Complications of infections in childhood-onset SLE included sepsis, macrophage activation syndrome, end organ damage and death. Infection remains a major concern in both adult and pediatric SLE, causing death in 30% of cases within the first 5 years of follow-up. However, there is hope for further advances in targeted SLE treatments that offer better disease control with less immunosuppression.
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