Study objective: To review and characterize reports of vulval aphthous ulcers (VAUs) following COVID-19 vaccination in VigiBase, the World Health Organization global database of reported potential adverse effects of medicinal products, to demonstrate the importance and power of case reports for rare suspected adverse reactions and to investigate whether they suggest a potential for COVID-19 vaccination to be a trigger METHODS: Cases reporting the Medical Dictionary for Regulatory Activities' (MedDRA) preferred term "Vulvovaginal ulceration" and related preferred terms in adolescent patients aged 12-17 years in association with any COVID-19 vaccine were extracted from VigiBase. The cases were clinically reviewed, and causality was assessed by applying the Bradford Hill criteria to the obtained case series.
Results: As of June 30th, 2022, there were 444 reports for the selected Medical Dictionary for Regulatory Activities preferred terms following COVID-19 vaccination in VigiBase. Ninety-four de-duplicated reports concerned adolescent female patients. Thirty-seven cases were clinically consistent with the diagnosis of VAU. On causality assessment, the analyzed case series fulfilled 6 of the 9 Austen Bradford Hill criteria supporting a potential causal relationship.
Conclusion: VAUs can be perceived as a traumatic experience, especially in adolescent patients. There is, furthermore, a risk that the ulcers will be misdiagnosed, resulting in avoidable investigation and treatment burdens for patients. We communicate our findings to support the small number of published case reports and raise awareness of VAUs occurring in a temporal association with COVID-19 vaccination. Furthermore, our analysis supports observations about the value of case reports for the recognition and assessment of rare adverse events.
Keywords: Bradford Hill criteria; COVID-19 vaccine; Lipschütz ulcers; Vulval aphthous ulcers; adolescents; case series; patient safety; pharmacovigilance.
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