The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years ( Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219 ).

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.