Global burden of vaccine-associated cutaneous immune-related adverse events, 1968–2024: An international pharmacovigilance study

Objective: Since vaccines stimulate the immune system, monitoring immune-related adverse events is critical. This study focuses on the global incidence of cutaneous immune-related adverse events (cirAEs), the most common type of immune-related adverse events, and their associations with different vaccine types. Methods: This study is based on the global pharmacovigilance database VigiBase from 1968 to 2024. We analyzed the incidence rate of cirAEs based on vaccination status, stratified by sex and age. The information component (IC) and reporting odds ratio (ROR) were calculated using the Bayesian method for report–non-report analysis. Results: Out of 8,562,584 cases, 220,299 reports of all-cause cirAEs were included in this study. Among these, 8,354 reports (male, n=4,083 [48.87%]) were identified as vaccine-associated cirAEs. Most of the cases were reported in the region of the Americas (62.37%) and in the age group between 0–11 years (46.65%). Although COVID-19 mRNA vaccines accounted for the highest incidence rate (28.01%), the strongest associations with cirAEs were observed in some viral vaccines (ROR, 3.94 [95% CI, 3.30–4.71]; IC, 1.95 [IC0.25, 1.65]) followed by anthrax (ROR, 2.66 [95% CI, 1.96–3.62]; IC, 1.38 [IC0.25, 0.86]), hepatitis B (ROR, 2.24 [95% CI, 2.02–2.47]; IC, 1.15 [IC0.25, 0.99]), MMR (ROR, 2.15 [95% CI, 2.01–2.30]; IC, 1.10 [IC0.25, 0.98]), hepatitis A (ROR, 2.08 [95% CI, 1.82–2.39]; IC, 1.05 [IC0.25, 0.82]). Conclusions: Vaccines are among the most effective tools for preventing infectious diseases globally. However, safety concerns remain, particularly regarding immune-related adverse events. Given that vaccines work by engaging the immune system, it is crucial for clinicians to pay close attention to potential immune reactions, such as cirAEs, to ensure vaccine safety.