Development of pemphigus vulgaris after the second dose of the mRNA‐1273 SARS‐Cov‐2 vaccine

Abstract

Upon declarations of SARS-CoV-2 as a pandemic by the WHO in March 2020, mRNA vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/ BioNtech), and viral vector vaccines, AZD1222 (Astra Zeneca) and JNJ78436735 (Johnson & Johnson's Janssen), have been widely used in the United States with emergency use authorization, with BNT162b2 (Comirnaty) only recently carrying FDA approval. While the most common side effects have been muscle pain, redness and swelling at the injection side, and headaches, there is notable literature on rare dermatologic adverse effects presenting as vesiculobullous eruptions, which have included Stevens–Johnson syndrome (Elboraey & Essa, 2021), facial pustular neutrophilic eruptions (Merrill et al., 2021), bullous pemphigoid, and pemphigus vulgaris (PV). For the two latter, the individuals mostly suffering those side effects have a history of the condition albeit in remission (Damiani et al., 2021). Two individuals developing PV without prior history of the disease have been recently described after the second dose of the BNT162b2 (Solimani et al., 2021) vaccine and ChAdOx1n CoV-19 (Thongprasom et al., 2021). Herein, we describe another example of PV occurring in a 60-year-old man without prior history who developed oral erosions of the gingiva, soft palate, oropharynx, and buccal mucosa bilaterally (Figure 1a,b), seven days after the second dose of the mRNA-1273 vaccine. A palatal biopsy demonstrated acantholysis in the lower aspect of the spinous layer of the epithelium with suprabasal epithelial splitting and preservation of the basal cell layer, favoring a diagnosis of PV (Figure 1c). Direct immunofluorescence revealed intercellular deposition of IgG and C3, predominantly in the lower half of sampled epithelium (Figure 1d). The oral lesions have been stable for five months, and the patient has not developed cutaneous lesions to this date. Laboratory testing did not reveal increased levels of desmoglein 1 and desmoglein 3, but indirect immunofluorescence demonstrated a low intercellular ICS positive titer 1:40 and monkey esophagus IgG was positive. The patient was placed on 60 mg/day prednisone together with calcium and vitamin D3supplements, Bactrim® and fluconazole. However, the oral ulcers did not improve and two doses of rituximab (1000 mg each) were administered 2 weeks apart. The patient reported resolution of his mouth ulcers within 2 weeks of the last dose of rituximab and no further mouth ulcers at his visit 1 month later. The development of autoimmune disorders after antiviral/antibacterial vaccination is exceptionally rare. Specifically, PV has been reported in association with rabies, influenza, hepatitis B, typhoid fever, tetanus, and anthrax (Damiani et al., 2021). A plausible mechanism in the present case may relate to a T cell-dependent production of IL-17, IFN-γ, or TNF-α, which occurs in association with the mRNA-1273 vaccine as it has been shown in infant rhesus macaques immunized with SARS-CoV-2 S-2P spike protein (Garrido et al., 2021). IL-17, IFN-γ, or TNF-α have been implicated in autoimmune disorders like PV and bullous pemphigoid. For example, IL-17 correlates with desmoglein-specific autoantibody production by B cells (Holstein et al., 2021), while T helper cell 1 mediates immune response through IFN-γ, which is elevated in PV (Fang et al., 2020). While the SARS-CoV-2 mRNA vaccines have demonstrated remarkably favorable risk-benefit profiles, rare orocutaneous dermatologic and other side effects may occur. The current report documents a rare mucocutaneous side effect of mRNA vaccination for SARS-CoV-2, to increase awareness among clinicians. The authors declare no conflict of interest. Renee Good: Data curation; Writing – review & editing. Prokopios P. Argyris: Resources; Visualization; Writing – review & editing. Mark Denis P. Davis: Data curation; Writing – review & editing. Daniel D. Miller: Data curation; Writing – review & editing. The peer review history for this article is available at https://publons.com/publon/10.1111/odi.14089.

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