Vaccines May Increase Risk for Gout Flares, But Benefits of Vaccination Outweigh Risks

Patients with gout were found to be twice as likely to experience a flare in the days following vaccination compared with periods when vaccination was not administered, according to a study published in Annals of the Rheumatic Diseases. However, the researchers cautioned that avoiding vaccinations in light of these findings is not advised.¹

Safety data on the recombinant zoster vaccine (RZV) identified a link between RZV and gout flares.² Previous research showed that the inflammatory cascade responsible for gout flares occurs following activation of the NLRP3 inflammasome and subsequent release of interleukin-1β.³ Aluminum adjuvants contained in many adult vaccines have been shown to activate the NLRP3 inflammasome.⁴ Therefore, the current study aimed to evaluate whether aluminum adjuvants in vaccines might trigger gout flares through the same mechanism.¹

To examine the possibility that vaccines other than RZV might trigger gout flares, the investigators conducted an online case-crossover study of 517 patients with gout from 2003 to 2010, prior to the introduction of RZV. Most respondents were white (89%) and male (79%), and the mean age was 55 years.

Over a one-year follow-up period, participants completed online questionnaires every 3 months. They also logged onto the study website each time they experienced a flare to answer questions about medication exposure, alcohol consumption, purine intake, and other risk factors in the 2-day hazard period.¹

The participants completed 990 hazard period questionnaires, with 28 patients reporting having undergone vaccination. They also completed 1407 control-period questionnaires, with 21 patients reporting undergoing vaccination. Using logistic regression, the researchers identified a 2-fold higher risk of flare during hazard periods. Risks were greater for men (2.4-fold). Patients aged ≤60 years, those with higher alcohol and purine consumption, those undergoing treatment with allopurinol, and those using nonsteroidal anti-inflammatory drugs and diuretics also had an increased risk, but these factors were not statistically significant.

“In conclusion, this study suggests that vaccination in the prior 2 days is associated with a twofold higher odds of gout flares compared with periods when no vaccine was administered,” the researchers said. “However, these findings must be interpreted within the context of the low frequency of gout flares in relation to vaccinations and the overwhelming benefits of vaccinations.”

References

1. Yokose C, McCormick N, Chen C, et al. Risk of gout flares after vaccination: a prospective case cross-over study. Ann Rheum Dis. 2019;78(11):1601-1604.
2. Ehrlich Agger P, Reindel R. Biologics license application clinical review memorandum: Shingrix. Silver Spring, MD: US Food and Drug Administration; 2017.
3. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-241.
4. Franchi L, Núñez G. The Nlrp3 inflammasome is crucial for aluminum hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur J Immunol. 2008;38(8):2085-2089.