COVID-19 vaccine is a risk factor accelerating time to bullous pemphigoid onset

ABSTRACT

Bullous pemphigoid (BP) is the most common autoimmune bullous disease characterized by autoantibodies against hemidesmosomal components BP180 and BP230. Although a causal association between vaccine and BP has never been proved, since mass vaccination against COVID-19 started, more than 90 vaccine-associated BP were reported. Of note, a recent study comparing very large cohorts of vaccinated and not-vaccinated individuals found no increased incidence of BP in vaccinated people, concluding that COVID-19 vaccine does not directly cause BP. To bring to an agreement among real-life clinical observations on patients with new-onset BP after COVID-19 vaccine and recent epidemiologic data, a cohort study was performed. Fifty-nine BP patients visiting our institute in 2021 were clinically and immunologically characterized. Fourteen patients (23.7%), experiencing BP onset 1-34 days after the first or second dose, were considered vaccine-associated. Vaccine-associated and non-associated patients had the same M/F ratio (1.3) and similar disease severity (mean BPDAI 41.1 vs 38.6) and mean age (76.7 vs 79.5 years). Interestingly, BP230 reactivity was higher in vaccine-associated patients (87.5% vs 41.4%, p=0.042), while no other significant differences in autoantibodies profiles and titers were found. Noteworthy, the comparison of the monthly distribution of BP onset throughout the year before and during mass vaccination showed significant differences in 2021, BP onsets on April-May and June-July increased (p=0.009) and declined (p=0.064) compared to 2018-2020, respectively. In conclusion, our findings suggest that COVID-19 vaccine may be considered an accelerating factor rather than an inducing one vaccination, in genetically predisposed individuals with sub-clinical autoreactivity against BP antigens, of which high BP230 reactivity at diagnosis could represent an indicator, could slightly anticipate BP onset without increasing its incidence.Copyright © 2023