High Rates of Serious Infections in Childhood IBD

Abstract

Source: Ludvigsson JF, Sachs MC, Järås J, et al. Serious infections in pediatric inflammatory bowel disease 2002-2017-a nationwide cohort study. J Pediatr. 2021 Nov;238:66-73.e1; doi:10.1016/j.jpeds.2021.06.076Investigators from multiple institutions conducted a retrospective study to assess the risk of serious infections in children with inflammatory bowel disease (IBD) compared to the general population. For the study, children <18 years old, diagnosed with IBD between 2002–2017 were identified through the Swedish Patient Registry using ICD codes or by reviewing colorectal histopathology data from a national registry. Children with IBD were further classified as having ulcerative colitis (UC), Crohn’s disease (CD), or IBD unclassified (IBD-U) based on ICD codes. Using data in the Swedish Total Population Register, each child with IBD was matched on age, sex, birth year, and place of residence with up to 10 controls without IBD.The primary study outcome was serious infection, defined as an infection requiring inpatient hospital care and identified using ICD codes. Infections were divided into several categories, including location (respiratory, gastrointestinal, urinary tract, other), sepsis, opportunistic, organism (eg, Clostridium difficile), and vaccine-preventable. Occurrence of serious infection in the year following bowel and perianal surgery also was assessed. Children with IBD and controls were followed from time of diagnosis until diagnosis of first serious infection, emigration, death, their 18th birthday, or end of the study period. Cox regression was used to compare the risk (hazard ratio [HR]) of serious infection in those with IBD to that of controls, after adjusting for matching variables. Multiple subgroup analyses also were performed.Data were analyzed on 5,766 children with IBD (2,364 with CD, 2,287 UC, and 1,115 IBD-U) and 58,418 controls. Median age at diagnosis of IBD was 15 years, with 5.3% diagnosed before 6 years of age. A total of 672 serious infections occurred in IBD patients (38.6/1,000 person-years) compared to 778 infections in controls (4.0/1,000 person years; HR, 9.46; 95% CI, 8.53, 10.50). The risk of infection was increased in those with UC (HR, 8.48; 95% CI, 7.21, 9.98), CD (HR, 9.3; 95% CI, 7.86, 11.00), and IBD-U (HR, 12.1; 95% CI, 9.66, 15.10). Overall, the risk of serious infection in children with IBD was highest in the first year of follow-up (HR, 12.6), falling to a 4.8-fold increased risk beyond 10 years of follow-up. Risk of serious infection was also high following bowel or perianal surgery (HR, 17.1 and 10.6, respectively). The risk of serious infection in those with IBD was significantly higher than that of controls in each location assessed, especially gastrointestinal (HR, 31.8; 95% CI, 25.6, 39.3). Opportunistic (HR, 11.8), sepsis (HR, 26.1), C. difficile (HR, 42.2), and vaccine-preventable (HR, 23.6), infections were all significantly more common in children with IBD.The authors conclude that children with IBD were at increased risk for serious infections requiring hospitalization.Dr Rosenthal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Utilizing the Swedish Patient Registry, the authors demonstrated that children with IBD had a greater than 9-fold increased risk of serious infections compared to reference individuals in the same Swedish population. In adults with IBD, investigators have reported an increased mortality from infections.1 Children with IBD are also at increased risk of cancer and death.2 Knowing that more children with IBD are receiving immunosuppressive therapy, the authors were interested in assessing the risk of serious infection and how these differ by IBD characteristics (IBD-subtype, sex, age of onset, length of follow-up, primary sclerosing cholangitis, and surgery). HRs for serious infections were increased for UC, CD, and IBD-U. Higher rates of serious infection occurred during the first year of follow-up. Particularly high HRs for serious infections were seen in children with IBD undergoing surgery (bowel or perianal). Not surprisingly, children with IBD had a high risk of gastrointestinal infections including C. difficile, high risk of serious infections at all other locations, opportunistic infections, and sepsis. Childhood IBD also was associated with an increased risk of vaccine-preventable diseases such as hepatitis A, hepatitis B, and influenza.Unfortunately, the Swedish Patient Registry does not capture laboratory, radiologic, or endoscopic findings to assess the effect on gastrointestinal infections in children with IBD. Further, the risks of infection with various immunosuppressants were beyond the scope of the current investigation. The researchers were unable to assess the response to various vaccines, genetic factors, and nutrition, all of which have been associated with infections in IBD.What does this all mean to the practicing physician caring for these children? It is important to recognize that children with IBD have a substantially increased risk of serious infections, especially during the first year of follow-up and following surgery. This information allows vigilance and early intervention for potentially serious infections in these children.Children with IBD are at significantly increased risk for serious infections requiring hospitalization compared with the general population.