Antibiotics in Children Increase Risk for Juvenile Arthritis

Pam Harrison

November 18, 2014

Exposure to antibiotics during childhood significantly increases the risk for juvenile idiopathic arthritis in a dose-dependent manner, say investigators reporting at the American College of Rheumatology 2014 Annual Meeting in Boston.

They suggest that alterations in the human microbiome might be implicated in the development of the disease.

"The more we learn about the microbiome, the more it appears that it plays an important role in a variety of different diseases, such as autoimmune diseases — and that includes inflammatory bowel disease and rheumatoid arthritis and perhaps psoriatic arthritis — all of which have some common features with juvenile arthritis," said Daniel Horton, MD, from the University of Pennsylvania in Philadelphia.

"We found that antibiotic exposure was associated with an increased risk of developing juvenile arthritis, at an adjusted odds ratio of 2.6, and that the risk increased with each additional prescription," he told Medscape Medical News.

The nested case–control study "adds to a growing literature on the potential harms of antibiotic use in children," Dr Horton reported.

Investigators used the Health Improvement Network, a population-based medical records database in the United Kingdom that contains comprehensive diagnostic and outpatient prescription data, to identify people younger than 16 years of age who were newly diagnosed with arthritis.

The 153 children with juvenile arthritis were matched, for age and sex, with 1530 control subjects from general practices in the United Kingdom.

The risk increased with each additional prescription.

On conditional logistic regression, the risk of developing arthritis was found to increase as exposure to antibiotics increased.

For children exposed to 1 or 2 courses of antibiotics, compared with no exposure, the odds ratio for arthritis was 3.1. For children exposed to 3 to 5 courses of antibiotics, the odds ratio was 3.8.

The association between antibiotic exposure in childhood and newly diagnosed juvenile arthritis was similar for different classes of antibiotics. However, there was no association between the development of arthritis and exposure to nonbacterial antimicrobial agents, including antifungal and antiviral drugs.

After adjustment for the number and type of infections children had, the associations did not change significantly. The age at which children were exposed to antibiotics also had no significant effect on the associations.

The fact that antimicrobial agents had a smaller effect on the development of arthritis could be because fungi and viruses are part of the human microbiome, Dr Horton told Medscape Medical News.

"This could support the hypothesis that it's the antibacterial drugs that are contributing to the development of disease," he explained.

However, Dr Horton pointed out that they couldn't rule out the possibility that the infection itself might have contributed to the development of disease, or that children who developed it early in life have a higher risk for infection, or at least more severe infection.

Another Reason to Avoid Antibiotics?

"It's always good to find another reason not to prescribe antibiotics inappropriately to children, but the fact is that antibiotics can be very useful drugs in certain situations," Dr Horton said.

Still, the reasons certain children develop arthritis remain poorly understood, he observed, and genetics explains less than half of the cases that do occur.

"If the link between antibiotics and juvenile arthritis can be confirmed, antibiotic avoidance in the right clinical situation might be one of the few ways we have to prevent this life-changing disease," Dr Horton said.

Alterations in the gut microbiota caused by antibiotic use is a plausible contributor to the development of juvenile arthritis, said Matthew Stoll, MD, from the University of Alabama at Birmingham, who was not involved in the study.

"If you have altered microbiota, there are some bacteria that appear to have proinflammatory effects, while others have anti-inflammatory effects. If you are changing the nature of the microbiota to the point where you have a lot more proinflammatory bacteria, that could potentially lead to arthritis and other autoimmune diseases," Dr Stoll told Medscape Medical News.

He said he agrees with Dr Horton that there is every reason to be cautious about prescribing antibiotics to children.

"There were reasons to be cautious about prescribing antibiotics to children even before this study came out. If a child doesn't have a bacterial infection and you give an antibiotic, you are exposing the child to unnecessary medicines. And there is a higher risk of generating antibiotic resistance when you do this," Dr Stoll said.

"Now there are potentially other reasons to be cautious about giving antibiotics to children, and this is another good one," he said.

This study is based on the Health Improvement Network in the United Kingdom. Dr Horton and Dr Stoll have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2014 Annual Meeting. Abstract 929. Presented November 16, 2014.


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