New-Onset Pemphigus Following Drug Exposure and Vaccination: A Systematic Review of Reported Cases

Background: Although an increasing number of cases of new-onset pemphigus have been reported following drug exposure or vaccination, the available evidence remains fragmented and distinguishing true trigger-associated disease from coincidental onset continues to represent a major clinical challenge. We performed a systematic review to evaluate the available evidence on drug- and vaccine-associated new-onset pemphigus and to compare their clinical characteristics, management, and outcomes. Methods: This systematic review was conducted according to the PRISMA 2020 statement and prospec- tively registered in PROSPERO (CRD420261307622). PubMed was searched from database inception to 30 April 2026. Studies reporting individual patients with new-onset pemphigus temporally associated with drug exposure or vaccination were included. Demographic, clin- ical, immunopathological, therapeutic, and outcome data were extracted and synthesized descriptively because of the anticipated heterogeneity of the available evidence. Results: A total of 20 drug-associated and 26 vaccine-associated cases identified from primary reports were included in the descriptive synthesis. Drug-associated cases demonstrated marked heterogeneity in the implicated agents, broader clinical variability, and a longer median latency, with frequent clinical improvement following withdrawal of the suspected drug when reported. In contrast, vaccine-associated cases occurred predominantly after SARS-CoV-2 vaccination, displayed a substantially shorter latency, and were mainly rep- resented by pemphigus vulgaris and pemphigus foliaceus. Across both groups, systemic corticosteroids constituted the mainstay of treatment, with generally favorable outcomes among patients with available follow-up. However, the available evidence consisted al- most exclusively of case reports and small case series, precluding reliable assessment of incidence or causality. Conclusions: Current evidence suggests that drugs and vaccines may act as potential triggers of new-onset pemphigus in susceptible individuals; however, the strength of evidence differs substantially between the two settings. Drug-associated cases generally provide more convincing clinical support for a trigger-related mechanism, whereas vaccine-associated cases require more cautious interpretation because temporal association alone cannot establish causality. Standardized case reporting, prospective pharmacovigilance, and mechanistic studies are needed to strengthen causal inference and improve the recognition and management of trigger-associated pemphigus.