Five cases of new‐onset pemphigus following vaccinations against coronavirus disease 2019

Abstract Pemphigus is a group of blistering disorders characterized by the formation of intraepithelial blisters in skin and mucous membranes induced by the binding of circulating autoantibodies to intercellular adhesion molecules. The pathogenesis is complex and not fully understood; however, genetic predisposition and various triggers are widely accepted as key factors in pemphigus development. A few cases of new‐onset pemphigus following coronavirus disease 2019 (COVID‐19) vaccination have already been published. The present paper reports a total of two cases of pemphigus foliaceous and three cases of pemphigus vulgaris that occurred following vaccinations against COVID‐19, with anamnestic, clinical, and diagnostic data collection suggesting assumptions over a possible causal correlation.


| Case 2
An 80-year-old White man developed an acute cutaneous eruption 17 days after his booster dose with the BNT162b2 vaccine.
The patient had his first two doses 8 months (21 days apart) before the booster, which were both well tolerated. The patient had arterial hypertension and gastroesophageal reflux, for which he was under chronic therapy with amiloride, hydrochlorothiazide, and esomeprazole. Physical examination revealed diffuse erythematoussquamous patches with scaly and crusted erosions involving the face and the trunk, following a seborrheic distribution (Figure 1d,e).
Histopathological examination revealed subcorneal acantholysis with neutrophilic infiltration within the blister. DIF was negative, while IIF showed intercellular IgG deposits. ELISA was positive for anti-DSG1 antibodies (149 IU/mL), allowing for the diagnosis of PF.

| Case 3
A

| Case 4
A 73-year-old White woman came to our attention for severe oral pain that occurred about 1 month after the booster dose of the ELISA was positive for anti-DSG3 antibodies (70 IU/mL). A diagnosis of PV was made.

| Case 5
A 63-year-old White woman presented with painful oral erosions involving mainly the oral cavity and the skin of the face and trunk.   other studies in the literature, the Comirnaty vaccine seems to present the higher rate of association with onset of AIBDs, but this may probably be explained by the wider use of the BNT162b2 vaccine compared with the others in Western populations. 2 In a recent paper describing autoimmune skin disease flares following COVID-19 vaccine, full immunization with mRNA-1273 showed a higher likelihood of association with worsening of preexistent disease than BNT162b2, but the difference was not significant. 3 The pathogenesis of autoimmune disorders following antiviral vaccinations is still under debate. One of the suggested mechanisms is immune cross-reactivity caused by molecular mimicry. 4,5 In fact, this phenomenon was advocated to explain several cases of pemphigus developed following exposure to bacterial and viral antigens, as well as pharmacological agents. 6  Moreover, the onset of immune-mediated diseases seems to occur more frequently in individuals with a preexisting rheumatic or autoimmune background, thus supporting the importance of individual predisposition. 9 The role of personal susceptibility is even more supported by the fact that autoimmune bullous diseases with higher incidence in their idiopathic form, such as bullous pemphigoid, also seem to be more frequently triggered or boosted by COVID-19 vaccines. 10  An innate inflammatory process is triggered by both BNT162b2 and ChAdOx1 vaccines caused by adjuvant function of mRNA itself and adenoviral proteins, respectively, which binds to different toll-like receptors, enhancing the production of type I interferon and several proinflammatory cytokines. 11 Type I interferon is well-known for its role in stimulating antigen presentation, B-cell differentiation, and IgG secretion. [12][13][14] However, a clear link between the vaccine's mechanism of action and pemphigus development is still far from being elucidated. In our case series, the timing of pemphigus onset is the only element that may suggest a causal relationship. The presence of a correlation between these events should be supported by

ACK N OWLED G M ENT
The patients in this manuscript have given written informed consent to the publication of their case details. Open Access Funding provided by Universita degli Studi di Firenze within the CRUI-CARE

Agreement. Open Access Funding provided by Universita degli Studi
di Firenze within the CRUI-CARE Agreement.

CO N FLI C T O F I NTE R E S T
The authors declare no conflicts of interest.