Antibiotic Exposure Increases Risk of Juvenile Idiopathic Arthritis

Antibiotic use in childhood more than doubles the risk of developing juvenile idiopathic arthritis (JIA), according to work presented here at the 2014 meeting of the American College of Rheumatology.

The study found that any antibiotic use was associated with a 2.6-fold increase in JIA among those under 16 years old, compared to no antibiotic use. The risk increased with an increase in use of antibiotics.

“This is a very exciting finding, suggesting that antibiotics may be involved in this poorly understood disease,” said lead author Daniel Horton, MD, of Nemours A.I. duPont Hospital for Children in Wilmington, DE.

The findings suggest, but do not directly demonstrate, that antibiotic-induced alterations in the microbiome may contribute to disease risk, he said. Antibiotic use has been previously associated with other inflammatory conditions, including irritable bowel syndrome.

The researchers drew on the Health Improvement Network database, a population-based medical records database that covers 6% of the population in the United Kingdom. Previous work has validated the coding of JIA within the database, making it ideal for this study.

They identified 153 children with JIA, along with over 1500 controls, and assessed the number and type of antibiotic prescriptions each child received. They found that 88% of those with JIA had received antibiotics, versus 76% of controls. The odds ratio for exposure associated with JIA was 2.6 (95% CI 1.5-4.6, p=0.001). Those receiving 3 to 5 courses of antibiotics had an odds ratio of 3.8. The risk did not change significantly after adjustment for number or type of infections, age at infection, antibiotic class, or maternal autoimmune disease. Neither antivirals nor antifungals were associated with an increased JIA risk.

The data point toward a role for microbiome alteration as a potential explanation, Horton said, “but we can’t demonstrate causality.” Alternatively, he said, antibiotics could be a marker for infection, and children who develop JIA may be more prone to infections. He noted the study did rule out infection immediately prior to diagnosis as a causal factor.

Further work will be need to both replicate this association and better understand any causal link between antibiotic use, changes in gut bacteria, and development of JIA. Horton also hopes to extend the study to the United States population.

“In our clinic, one of the hardest questions we are faced with from families is ‘Why did this happen?’ We know genetics accounts for only a quarter of the risk. These results raise the possibility that there could be a modifiable risk factor for juvenile idiopathic arthritis,” Horton said.