Written by Joyce Smith, BS. Antibiotic prescriptions are associated with a higher risk of rheumatoid arthritis which may be due to a disrupted highly diverse microbial ecosystem or the underlying infections driving the risk.
Antibiotic use is worldwide with approximately 30% of all primary care patients in the United Kingdom receiving at least one antibiotic prescription per year 1. While they are invaluable in their ability to target a vast array of respiratory, gastrointestinal (GI) and urinary tract infections (UTIs), antibiotics may also disturb our highly diverse and dynamic microbial ecosystem that plays an essential role in human health by modulating host metabolism and immunity 2. Antibiotic treatment is a major risk factor for increasing susceptibility to infections and developing inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease 3, as well as autoimmune diseases such as type 1 diabetes, autoimmune liver diseases, and juvenile idiopathic arthritis (JIA) 4. Rheumatoid arthritis (RA) is a chronic inflammatory disease that results in reduced microbial diversity which may be linked to the use of antibiotics 5,6.
The current 15-year nested, case-controlled study 7 explored the association between antibiotic prescriptions and the onset of RA. Using data from the primary care Clinical Practice Research Datalink (CPRD) researchers compared 22,677 RA cases to 90,013 individually matched controls (approximately 5 controls per RA case) with a median follow-up of 10 years before RA diagnosis. After controlling for confounding factors, conditional logistic regression was used to determine whether previous antibiotic prescription use was linked to onset of RA.
The authors found a number of associations between use of all classes of antibiotics and rheumatoid arthritis onset. Those exposed to one or more antibiotic prescriptions were 60% more likely to develop RA than their unexposed controls. There was also a frequency-dependent association between previous antibiotic prescriptions and RA: those with more recent antibiotic exposure had a higher odds of developing RA. The research team found that a higher likelihood of an RA diagnosis was evident even after just one year of antibiotic use. Patients receiving more than 10 antibiotics in a five-year period were more than twice as likely to receive an RA diagnosis as the controls [adjusted odds ratio 2.65 (CI 2.40,2.93)]. In addition, antibiotics that were prescribed more than a decade earlier had the strongest association with a later diagnosis of rheumatoid arthritis.
A frequency- dependent association existed between the number of previous infections and the odds of developing RA. More than 87% of lower respiratory and urinary tract infections were treated with antibiotics within 30 days. This proportion was 74% lower for upper respiratory tract (URT) and 21% lower for gastrointestinal infections (21%). Those with antibiotic- treated URT infections were more likely to be RA cases. However, the association did not hold true for the number of untreated URT infections.
Also influencing the odds of developing RA was antibiotic class and mode-of-action with Clindamycin demonstrating the highest odds. Those who were prescribed antibiotics that induce a bacterial response had a 45% higher risk of developing RA compared to those who were not prescribed antibiotics. Also associated with increased RA risk were the 7% of RA cases who received at least one antiviral and the 14% of RA cases who received antifungal prescriptions.
Study limitations include a potential misclassification of actual RA cases, an underestimation of antibiotic use and other prescribed drugs such as proton pump inhibitors which could skew the observed effects on RA risk and microbiota diversity, and the inability to generalize the results to other infections.
Source: Sultan, Alyshah Abdul, Christian Mallen, Sara Muller, Samantha Hider, Ian Scott, Toby Helliwell, and Lindsay J. Hall. “Antibiotic use and the risk of rheumatoid arthritis: a population-based case-control study.” BMC medicine 17, no. 1 (2019): 154.
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/publicdomain/zero/1.0/)
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Posted November 19, 2019.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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- Maeda Y, Kurakawa T, Umemoto E, et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis & rheumatology. 2016;68(11):2646-2661.
- Sultan AA, Mallen C, Muller S, et al. Antibiotic use and the risk of rheumatoid arthritis: a population-based case-control study. BMC medicine. 2019;17(1):154.
