Antibiotic Use Linked to Juvenile Arthritis

Jennifer Garcia

July 20, 2015

Past antibiotic exposure may be associated with newly diagnosed juvenile idiopathic arthritis (JIA), which suggests that alterations in the human microbiome may be implicated in the development of the disease. The results of the case-control study were published online July 20 in Pediatrics.

Using a population-representative electronic medical records database in the United Kingdom, researchers identified 152 children (aged 1 to 15 years) newly diagnosed with JIA between 1994 and 2013. They compared each case with 10 age- and sex-matched control subjects who did not have immunodeficiency, inflammatory bowel disease, or system rheumatic diseases.

The authors evaluated all antibiotic courses among both groups and included data on the timing, duration, and dose of antibiotic exposure.

One or more courses of antibiotic therapy was associated with an increased risk of developing JIA when compared with control subjects (adjusted odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2 - 3.5), and "[t]he magnitude of the association increased with additional antibiotic courses." This association was noted after adjusting for matching, previous infection, or other autoimmune disease.

Further, the researchers found that antibiotic prescription within 1 year of a diagnosis of JIA showed the strongest association with developing the disease, but there was no difference among antibiotic types.

To address whether infections rather than antibiotic use could be associated with an increased risk of developing JIA, the authors compared the risk among patients with treated vs untreated upper respiratory tract infections and found that those treated with antibiotics were more strongly associated with later development of JIA.

The authors, led by Daniel B. Horton, MD, MSCE, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, acknowledge limitations of the study, such as the fact that unspecified subcategories of JIA made it difficult to determine whether an association exists between antibiotic use and particular JIA categories. They also note that the relatively young patient population (median age, 3 years in both groups) limits the generalizability of these findings to older children and adolescents.

"Our study supports the hypothesis that antibiotic exposure is associated with an increased risk of developing JIA," write Dr Horton and colleagues.

"This public health finding is potentially important, considering that approximately one-quarter of antibiotics prescribed for children, and an estimated one-half of antibiotics for acute respiratory infections, may be unnecessary and potentially avoidable."

Dr. Horton and colleagues also point out that previous studies have suggested a link between disturbance of the human microbiome and inflammatory diseases, including at least one type of JIA. “Our finding that antibiotic exposure is most strongly associated with JIA within 1 year of diagnosis (and 6 months of first symptom/referral) supports the hypothesis that antibiotic-induced microbiome dysregulation could precipitate JIA in children predisposed to this disease,” they write.

In an accompanying editorial, Jennifer L. Goldman, MD, and Mary Anne Jackson, MD, from Children's Mercy Hospitals & Clinics and University of Missouri–Kansas City, note that although the study does not confirm a causal relationship between antibiotic use and the development of JIA, it underscores the need for further research into the association between antibiotic use and the development of systemic inflammation.

Dr Goldman and Dr Jackson posit that these findings "may represent the tip of the iceberg," and that "[b]oth the well-recognized and currently unknown, undesired sequelae of antibiotic prescribing should give clinicians and patients pause when an antibiotic is prescribed."

As reported previously by Medscape Medical News, Dr Horton and colleagues presented an earlier version of their study at the American College of Rheumatology 2014 Annual Meeting.

The authors and the editorialists have disclosed no relevant financial relationships.

Pediatrics. Published online July 20, 2015. Abstract


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