Antibiotic Use in Childhood Linked to Increased Risk of Juvenile Idiopathic Arthritis

Young female child given an oral antibioticAntibiotic exposure in childhood was linked to a 2- to 3-fold increased risk of juvenile idiopathic arthritis in a large case-control study published online ahead of print in Pediatrics. The study authors suggested that the antibiotic exposure may play a role in the pathogenesis of this form of arthritis, possibly through alterations in the microbiome.

“However, we can’t say with certainty that it is the antibiotics that caused arthritis in these cases,” said lead author Daniel B. Horton, MD, MSCE.

“A majority of children receive antibiotics, but only about 1 in 1000 children have arthritis,” Dr. Horton said. “So, even if antibiotics do contribute to the development of arthritis, it’s clearly not the only factor. That said, we need to acknowledge that antibiotics have a long—and growing—list of potential downsides, both short-term side effects (including fever and allergic reactions) and long-term risks (such as drug resistance and possibly the development of chronic diseases). These risks need to be weighed against the potential benefits whenever antibiotics are prescribed,” Dr. Horton said.

Case-Control Study Design
The study was based on 1994-2013 data from The Health Improvement Network (THIN), which is a population-representative database of electronic medical records from more than 550 general practice offices in the United Kingdom. Each case was matched to 10 control subjects by age (rage, 1 to 15 years) and gender.

A total of 152 cases of juvenile idiopathic arthritis (JIA) were diagnosed, yielding an incidence of 4.9 per 100,000 person-years.

One Course of Antibiotics Linked to Two-Fold Increased Risk of JIA
After adjustment for matching, other autoimmune conditions, and previous

infection, children who received at least 1 antibiotic prescription had a 2-fold increased risk of developing JIA (adjusted odds ratio [OR]: 2.1).

This association was dose dependent (adjusted OR for >5 antibiotic courses: 3.0), strongest for antibiotic exposures within 1 year of JIA diagnosis, and was not altered by adjusting for the number or type of infections. Treatment with nonbacterial antimicrobial drugs was not associated with JIA.

A large case-control study from Finland also found that early and repeated exposure to antibiotics were significantly associated with the development of JIA. This study found that lincosamides (eg, clindamycin) and cephalosporins had the strongest association with JIA risk (OR, 6.6 and 1.6, respectively), as reported by Arvonen et al in The Journal of Rheumatology.

What Mechanisms May Underlie This Association?
“At this point in time, the mechanism by which antibiotics might contribute to the development of arthritis is unclear,” Dr. Horton said. “Antibiotic use has been linked to other childhood diseases, such as inflammatory bowel disease. People with inflammatory bowel disease can have abnormal populations of microbes (bacteria, viruses, etc.) in the gut that relate to abnormalities in the intestinal immune system. Whether something similar is happening for children who develop arthritis remains unclear,” Dr. Horton explained.

“We and other investigators are looking to see whether this relationship between antibiotic exposure and childhood arthritis is seen in other populations of children,” Dr. Horton said. “We also need more research about what these findings really mean—about the mechanism connecting antibiotics and juvenile arthritis. Are children who go on to develop arthritis at higher risk for serious infections earlier in life, even before they have joint disease? Do antibiotics contribute, directly or indirectly, to the derangement of the immune system and the development of joint inflammation? More work is needed to address these questions,” Dr. Horton concluded.

“Drs. Arvonen and Horton have both published interesting studies showing that antibiotic use in childhood is associated with an increased risk of subsequent development of JIA,” commented Matthew Stoll, MD, Associate Professor in Pediatric Rheumatology, University of Alabama at Birmingham. “In light of my previous research showing that children with one form of JIA have an altered microbiome, it is plausible that antibiotics may alter the microbiome so as to put children at higher risk of subsequent inflammatory arthritis,” Dr. Stoll said. 

“Both authors correctly note that the infections resulting in antibiotics prescriptions may, in fact, be the culprit, rather than the antibiotics themselves,” Dr. Stoll said. “However, I hope that general pediatricians and family practice doctors will take note of these studies and use them as added impetus to minimize unnecessary use of antibiotics,” Dr. Stoll concluded.

Updated on: 08/18/16
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