Early-Onset IBD Linked to Greater Risk of Diseases with Possible Autoimmune Pathogenesis

Findings from a recent study are highlighting an increased risk of developing diseases with a possible autoimmune pathogenesis in children and adolescents with inflammatory bowel disease (IBD).¹

Results published in Inflammatory Bowel Diseases showed a heightened risk of psoriatic arthritis, spondyloarthritis, celiac disease, rheumatoid arthritis, as well as type 1 and type 2 diabetes among patients with early-onset IBD, with further analysis revealing only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.¹

Although the exact cause of IBD is unknown, it is widely attributed to inappropriate immune response to environmental triggers and genetic predisposition. Accordingly, it is widely speculated that IBD may share pathogenic pathways with other immune-mediated diseases and thus, patients with IBD may be at greater risk of diseases with a possible autoimmune pathogenesis. This concept is well-proved in adults, but it remains to be explored in early-onset IBD.^2,3

“The development of diseases with a possible autoimmune pathogenesis is common in adults with inflammatory bowel disease. In early onset IBD, it may differ but the evidence is sparse,” Line Riis Jølving, PhD, associate professor at Odense University Hospital in Denmark, and colleagues wrote.¹

To investigate the risk and time span from IBD diagnosis to outcomes with different associated disorders with possible autoimmune pathogenesis, investigators conducted a register-based study of Danish patients with early onset IBD (≤18 years) between 1980 and 2021, additionally including 50 matched references without IBD for each case. For each patient, they examined the risk of type 1 and type 2 diabetes, celiac disease, thyroid disease, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis.¹

In total, 6822 patients with IBD and 337,728 matched references were identified. The median age at the time of IBD diagnosis or index date for the matched references was 16 years, and the median age at the time of an outcome or at the end of follow-up was 28.1 years.¹

According to the cumulative incidence plots, psoriatic arthritis and spondyloarthritis were diagnosed approximately 10 years after the IBD onset, while the remaining outcomes were diagnosed later.¹

The adjusted hazard ratio (aHR) after full follow-up for each disease was as follows:

• 4.72 (95% CI, 3.85-5.80) for psoriatic arthritis
• 5.21 (95% CI, 4.17-6.50) for spondyloarthritis
• 2.77 (95% CI, 1.92-4.00) for celiac disease
• 2.15 (95% CI, 1.54-3.01) for rheumatoid arthritis
• 1.69 (95% CI, 1.23-2.32) for type 1 diabeters
• 1.64 (95% CI, 1.21-2.21) for type 2 diabetes

Investigators noted although the risk estimates were significantly increased for all outcomes except thyroid disease (aHR, 1.16; 95% CI, 0.97-1.40) at the end of follow-up, according to the cumulative incidence plots, only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.¹

Findings build upon prior knowledge about the development of diseases with a possible autoimmune pathogenesis in IBD, expanding this association beyond adult patients to include children and adolescents with early-onset disease.¹

References:

1. ^{Jølving LR, Zegers FD, Lund K, et al. Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis. Inflammatory Bowel Diseases. https://doi.org/10.1093/ibd/izae047}
2. ^{US Centers for Disease Control and Prevention. What is inflammatory bowel disease (IBD)? Inflammatory bowel disease (IBD). April 13, 2022. Accessed March 25, 2024. https://www.cdc.gov/ibd/what-is-IBD.htm}
3. ^{Halling ML, Kjeldsen J, Knudsen T, et al. Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases. World J Gastroenterol. 2017;23(33):6137-6146. doi:10.3748/wjg.v23.i33.6137}