Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case–Control Study

Abstract

BACKGROUND AND OBJECTIVE: Recent evidence has linked childhood antibiotic use and microbiome disturbance to autoimmune conditions. This study tested the hypothesis that antibiotic exposure was associated with newly diagnosed juvenile idiopathic arthritis (JIA). METHODS: We performed a nested case–control study in a population-representative medical records database from the United Kingdom. Children with newly diagnosed JIA were compared with age- and gender-matched control subjects randomly selected from general practices containing at least 1 case, excluding those with inflammatory bowel disease, immunodeficiency, or other systemic rheumatic diseases. Conditional logistic regression was used to examine the association between antibacterial antibiotics (including number of antibiotic courses and timing) and JIA after adjusting for significant confounders. RESULTS: Any antibiotic exposure was associated with an increased rate of developing JIA (adjusted odds ratio: 2.1 [95% confidence interval: 1.2–3.5]). This relationship was dose dependent (adjusted odds ratio over 5 antibiotic courses: 3.0 [95% confidence interval: 1.6–5.6]), strongest for exposures within 1 year of diagnosis, and did not substantively change when adjusting for number or type of infections. In contrast, nonbacterial antimicrobial agents (eg, antifungal, antiviral) were not associated with JIA. In addition, antibiotic-treated upper respiratory tract infections were more strongly associated with JIA than untreated upper respiratory tract infections. CONCLUSIONS: Antibiotics were associated with newly diagnosed JIA in a dose- and time-dependent fashion in a large pediatric population. Antibiotic exposure may play a role in JIA pathogenesis, perhaps mediated through alterations in the microbiome.