Pemphigus vulgaris (PV) is a severe autoimmune blistering dermatosis associated with autoantibodies to desmoglein (Dsg)-3 and Dsg-1.1 In Central Europe, the estimated incidence rate of PV is approximately one case per million inhabitants per year.1, 2 While several drugs may trigger PV, there is limited evidence for the association of PV with anti-viral vaccines, including influenza, hepatitis B or tetanus.1, 3 We describe the striking occurrence of PV following SARS-CoV-19 vaccination.

An 89-year-old patient in good general condition developed painful oral lesions accompanied by cutaneous blisters. The first signs occurred 1 month after the second dose of the mRNABNT162b2 vaccine (Comirnaty®) and worsened following a urology procedure under general anaesthesia. The vaccination otherwise resulted in mild transitory flu-like symptoms. The patient was treated for suspected herpes varicella zoster virus infection with no improvement. On examination, he had oral erosive lesions in the buccal mucosa, palate and gingiva as well as flaccid blisters, eroded and crusted lesions on the left arm and trunk (Fig. 1). Light microscopy studies of a biopsy specimen showed a blister with suprabasal acantholysis. Direct immunofluorescence microscopy studies showed cell-surface-bound immunoglobulin IgG in the epidermis. The patient’s serum had high values of anti-Dsg-3 (200 U/mL; normal < 7 U/mL) and anti-Dsg-1 antibodies (140.5 U/mL; <14 U/mL) by ELISA (MBL). He also had IgG antibodies (75.6 AU/mL; <12.0 AU/mL) against the SARS-CoV-2 S1 receptor binding domain 2 months after the second dose, indicating that the vaccination was effective. The patient was treated with rituximab and oral prednisone with a complete control of disease activity within 10 weeks.

(a) Scattered vesicles, eroded and crusted lesions on the back. Inset: close-up view of vesicles, erosions and crusts; (b) large eroded and crusted plaque on the anterior surface of left upper arm; (c) Histopathological findings showing a suprabasal cleft with acantholysis and discrete superficial lymphohistiocytic infiltrates (original magnification × 100, haematoxylin and eosin (H&E)).

The mass vaccination campaign during the SARS-CoV-2 pandemic has shown that mRNA-based COVID-19 vaccines result in high protection rates with significant reduction of death and complications. These vaccines have different side-effects, which are almost invariably not severe.4 However, there is increasing data suggesting that SARS-COV-2 vaccines rarely cause flares or de novo development of autoimmune diseases, including haematological, neurological and rheumatic diseases.5-7 Furthermore, there have been anecdotal cases of flares of autoimmune bullous dermatoses upon vaccination.8, 9 A report described five bullous pemphigoid and PV patients showing a flare up of their disease within 2 weeks after the first vaccination with mRNA SARS-CoV vaccines.8 Our observation of PV development 1 month after mRNA BNT162b2 vaccination raises the question of a causal relationship because of the chronology, the rarity of PV in Swiss natives and its occurrence in a very elderly patient. Most PV patients are aged 40–60 years at diagnosis.1 The mean age of pemphigus patients was 62.5 years in the Swiss cohort.3 However, the development of PV after COVID-19 vaccination may be simply coincidental in our patient. The first described case of PV potentially related to COVID-19 vaccination occurred 5 days after the first dose of the mRNA vaccine BNT162b2 with worsening after the second dose.9 In the latter case, since the interval between PV occurrence and the first vaccination dose was extremely short, while the pathophysiology of PV is so complex, it is likely that the patient already had a paucisymptomatic PV form which flared after the first vaccination.1

The mechanisms underlying these autoimmune phenomena remain unclear. The mRNA vaccines appear to be able to activate Toll-like receptors and cytosolic inflammasome components.5, 6 Furthermore, the vaccine-generated spike protein may induce autoimmunity by molecular mimicry eliciting immune cross-reactivity with human tissues. Genetic susceptibility and bystander effects likely favour such dysregulation.5, 6 BNT162b2 has been shown to promote both humoral and cellular immune response with a shift in the Th profile and increased production of IFN-γ, IL-2, CD4 and CD8 cells.10

Since the vaccination is a critical public health measure to overcome the COVID-19 pandemic, the rare occurrence of autoimmune reactions should not discourage the vaccination of patients with autoimmune diseases.

The patient has provided written consent for the publication of the case.