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Patients with gout had twice the risk of experiencing a flare in the days immediately following vaccination, a case-crossover study found.

Compared with periods when no vaccines were administered, the crude odds ratio of a gout flare during the 2 days after vaccination was 2.16 (95% CI 1.14-4.12), according to Hyon Choi, MD, of Massachusetts General Hospital (MGH) and Harvard Medical School in Boston, and colleagues.

And after adjustment for alcohol consumption, treatment with diuretics, and purine intake, the odds ratio for flare during the 2 days after receipt of a vaccine was 1.99 (95% CI 1.01-3.89), the researchers reported online in .

Nonetheless, "the benefits of vaccinations on both individual and public health are overwhelming and cannot be emphasized enough," said the study's first author, Chio Yokose, MD, also of MGH. "In particular, patients with gout often are older and/or have multiple comorbidities, constituting subpopulations who stand to benefit the most from routine adult vaccinations," Yokose told MedPage Today.

The association between vaccination and gout was identified during the for recombinant zoster vaccine, where a 3.6-fold increased risk of gout was seen for vaccine recipients. In those studies, 27 patients given the vaccine experienced a flare during the subsequent month compared with eight patients given placebo.

Previous research has suggested that the inflammatory cascade leading to the clinical manifestations of gout occurs following activation of the NLRP3 inflammasome and the resultant release of interleukin-1β. The recombinant zoster vaccine contains a non-aluminum adjuvant that is also thought to activate the NLRP3 inflammasome through signaling in the innate immune system. Aluminum adjuvants contained in many other adult vaccines, such as tetanus/diphtheria/pertussis and the pneumococcal and hepatitis B vaccines also have been shown to activate the inflammasome pathway.

Therefore, to examine the possibility that these other vaccines could influence gout flares, the researchers recruited 517 gout patients during the years 2003 to 2010 (before the recombinant zoster vaccine was available). Participants completed online questionnaires every 3 months during a year of follow-up and logged onto the study website at the time of each gout flare, answering questions about exposures such as purine and alcohol consumption and medication or vaccine exposure in the 2-day hazard period prior to the flare.

Control periods were the 2-day periods with no flares reported in the routine 3-month questionnaires.

"The case-crossover study design allows each participant to serve as his/her own control, thereby eliminating time-fixed confounding between participants," the authors explained.

The study included 517 patients whose mean age was 55 and whose disease duration was 7.9 years. Almost 80% were men and the majority were white.

During the 1 year follow-up, participants completed 990 hazard period questionnaires, with 28 patients reporting a vaccine during the prior 2 days. Participants also completed 1,407 control period questionnaires, in which there were 21 vaccinations given, with logistic regression identifying a twofold higher risk of flare during the hazard periods compared with control periods.

Risks were further increased among men, whose adjusted odds ratio of gout flare following vaccination was 2.35 (95% CI 1.12-4.92). Greater risks also were seen for patients younger than 60, those with more alcohol and purine consumption, and those receiving diuretics, allopurinol, and nonsteroidal anti-inflammatory drugs, but these were not statistically significant.

"Our findings are novel because for the first time, we have identified a trigger for gout flares that presumably acts through the inflammasome pathway, as opposed to changes in serum urate," Yokose explained.

Nonetheless, the overall risk of gout flare was low. "Thus, we are not advocating that patients with gout opt out of vaccines recommended by their doctors based on the findings of our study," he cautioned.

"Future studies could investigate the ability of prophylactic anti-inflammatory medication use, such as with colchicine, on mitigating the risk of gout flares associated with vaccination without compromising vaccine efficacy," Yokose concluded.

Limitations of the study, the researchers said, included its reliance on self-report for exposures and vaccinations, as well as the relatively small number of flares reported.

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