Oral mucous membrane pemphigoid after SARS‐CoV‐2 vaccination

To the Editor,

The vaccination campaigns against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have played an undisputed role in controlling the spread and severity of COVID‐19 disease worldwide (Mohammed et al., 2022). Nonetheless, a variety of mucocutaneous SARS‐CoV‐2 vaccine‐related adverse reactions have been constantly reported (Seirafianpour et al., 2022), including several cases of autoimmune mucocutaneous blistering diseases (Calabria et al., 2022; Maronese et al., 2022). Here, we present a case of mucous membrane pemphigoid (MMP) arising after the administration of the third dose of mRNABNT162b2 vaccine (Comirnaty®/Pfizer/BioNtech).

A 72‐year‐old female patient was admitted to the Oral Surgery and Pathology Unit of the University of Catanzaro Magna Graecia, Italy, complaining of painful oral lesions lasting over 6 months. She reported that the oral lesions appeared 9 days after receiving the third dose of the mRNABNT162b2 vaccine (Comirnaty®/Pfizer/BioNtech). Prior to our consultation, her general physician and dentist attempted to treat her condition with courses of antibiotics and antifungal medications without achieving remission of the lesions.

Moreover, her medical records revealed a previous history of breast cancer on maintenance therapy with an aromatase inhibitor and of severe osteoporosis treated with denosumab. Upon intraoral examination, generalized bullous and erythematous areas along with ulcerations at the upper and lower gingivae extended bilaterally to the vestibular fornix and to the right buccal mucosa were present (Figure 1a, b). Other mucosal membranes and skin were unremarkable. A perilesional biopsy of the bullous lesions at the upper right gingiva was taken. Histopathology demonstrated the presence of a subepithelial detachment, while the direct immunofluorescence microscopy showed the linear deposition of IgG (Figure 1c) and IgA antibodies at the basement membrane zone and prevalent granular deposition of C3 at the same sites. The ELISA test performed on the patient's serum, detected high level of anti‐BP‐180 antibodies (116 U/mL; normal <20 U/mL), while the anti‐BP‐230 antibodies titer was within the limits (5 U/mL; normal <20 U/mL). Therefore, on account of the timing of the bullous lesions onset, a diagnosis of mucous membrane pemphigoid (MMP) localized at the oral mucosa after SARS‐CoV‐2 vaccination was made. The patient was firstly treated with topical betamethasone sodium phosphate tablets 0.5 mg diluted in water as mouthwash three times per day for 3 weeks without response. Therefore, 0.5 mg/kg of systemic prednisone (25 mg/day) was prescribed for 1 week with progressively tapered dosage achieving a complete clinical remission in 3 weeks (Schmidt et al., 2021; Figure 1d). The patient is currently on follow‐up visit every 2 weeks in our department.

FIGURE 1.

(a, b) Intraoral photograph showing blisters of the upper and lower gingivae; (c) direct immunofluorescence microscopy demonstrated linear staining of IgG antibodies at the basement membrane zone; (d) complete clinical remission of the bullous lesions.

Potential pathogenic mechanisms underlying the occurrence of adverse events in COVID‐19 vaccinated patients are far to be clarified, and only a temporal correlation may be suggested. To date, a number of orofacial manifestations COVID‐19 vaccine‐related have been reported, ranging from erythema multiforme‐like reactions, oral lichenoid lesions, and oral mucositis (Di Spirito et al., 2022). While the majority of the orofacial reactions are mild‐to‐moderate and self‐limiting, severe cases of oropharyngeal pemphigus vulgaris have also been reported (Koutlas et al., 2022; Thongprasom et al., 2022). For this reason, it is of upmost relevance to increase the awareness among oral healthcare providers on the possible development of autoimmune bullous diseases with exclusive oropharyngeal involvement in order to provide the early diagnosis of these potentially life‐threatening diseases.

AUTHOR CONTRIBUTIONS

Elena Calabria: Conceptualization; investigation; writing – original draft; methodology. Alessandro Antonelli: Investigation; writing – original draft; methodology. Annamaria Lavecchia: Methodology. Amerigo Giudice: Conceptualization; investigation; validation; methodology; supervision.

FUNDING INFORMATION

This research has not been supported by any private or corporate financial institutions nor has any grant been received for this study.

CONFLICT OF INTEREST

The authors have no conflict of interest to disclose.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.