Global burden of vaccine-associated Raynaud's phenomenon, 1968-2024: A comprehensive analysis of the pharmacovigilance database.

Purpose: Reports of Raynaud's phenomenon following vaccination have been steadily increasing; however, research on vaccine-associated Raynaud's phenomenon remains limited. This study aims to provide a comprehensive analysis of the association between Raynaud's phenomenon and various vaccines.

Method: This study used data from international pharmacovigilance, which contains over 35 million adverse event cases from more than 140 countries. Two established pharmacovigilance indicators, the information component (IC) and reporting odds ratio (ROR), were employed in the analysis with 95% confidence interval (CI). The IC was derived using a Bayesian methodology to compare the reporting and non-reporting groups, while the ROR, a frequentist measure of association, was calculated using contingency tables based on the number of adverse events.

Results: The signal with Raynaud's phenomenon was highest for papillomavirus vaccines (ROR: 11.49 [95% CI, 9.66-13.67]; IC: 3.45 [IC, 3.16]), followed in order by typhoid (5.86 [2.93-11.72]), hepatitis B (5.63 [4.25-7.45]; 2.42 [1.95]), COVID-19 mRNA (5.00 [4.70-5.31]; 2.00 [1.91]), and hepatitis A vaccines (4.35 [2.87-6.62]; 2.02 [1.30]). The signal was higher in females (ROR: 3.74 [95% CI, 3.54-3.95]; IC: 1.67 [IC, 1.59]) compared to males (3.44 [3.12-3.78]; 1.57 [1.43]), and it increased monotonically with age (0-11 years: IC [IC] 0.03 [-0.56]; 12-17 years: 1.54 [1.25]; 18-44 years: 1.64 [1.52]; 45-64 years: 2.00 [1.87]; ≥ 65 years: 2.12 [1.91]).

Conclusion: This study suggests the potential signal association between various vaccines and Raynaud's phenomenon. Although our study does not imply causality, we propose the need to strengthen post-vaccination monitoring and establish support policies to address such adverse events.