Pfizer‐BioNTech SARS‐CoV‐2 mRNA vaccine‐associated erythema multiforme

Abstract

A 38-year-old healthy gentleman was referred for a dermatology review in view of a vesicobullous eruption. General examination revealed multiple, generally distributed targetoid lesions with central bullae as well as a superficial ulcer on the hard palate (Figure 1). The lesions were tender to touch but otherwise asymptomatic. Nikolsky sign was negative. Examination of other mucosae was normal. The patient denied a history of recent illness or foreign travel and had not been on any regular or as required medication. The patient had received the first dose of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine two days prior to onset of the cutaneous eruption. The clinical impression was of bullous erythema multiforme (EM) secondary to the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. An excisional biopsy of a bulla on the left forearm was performed. Histology (Figure 2) showed centrally crusted epidermis with a predominantly basket weave keratin pattern and with central hypergranulosis. A predominantly perivascular lymphocytic and histiocytic infiltrate was present in the upper dermis. Lymphocytes extended into the basal layers of the epidermis with prominent associated basal cell vacuolar damage, Civatte body formation and pigment incontinence. Occasional apoptotic keratinocytes were also seen in all layers of the epidermis. Subepidermal clefting was also noted. These features were consistent with the clinical impression of bullous EM. The patient was treated with prednisolone 40 mg daily for five days and most lesions resolved within seven days. To date, there have been three cases of EM related to the SARS-CoV-2 vaccine, two with the Moderna vaccine and another with Coronavac vaccine.1, 2 To the best of our knowledge, this is the first case of EM associated with the Pfizer-BioNTech Covid vaccine. EM is a self-limiting, cutaneous type IV hypersensitivity reaction. Cases of bullous EM are more likely to require active treatment. Drug-associated EM accounts for <10% of cases.3 The drugs most commonly associated with EM are anti-epileptics, antibiotics (particularly cephalosporins and penicillin), anti-fungals and allopurinol. EM in the context of the MMR, Influenza, DPT and Hepatitis B vaccines has also been reported.4 Cutaneous adverse drug reactions have been reported in association with COVID mRNA vaccines. Out of 19,485 individuals vaccinated with the Pfizer-BioNTech COVID mRNA vaccine in Trieste in January 2021, 44 individuals developed a cutaneous adverse reaction.5 The commonest cutaneous reactions are localized and included erythema and oedema at the injection site. Systemic reactions including morbilliform eruptions, urticarial reactions, pruritus, fixed drug eruption and pityriasis rosea-like reactions have also been observed.1, 6 A case has been reported where the Pfizer-BioNTech COVID vaccine triggered a flare-up of erythema multiforme in a 58-year-old lady on regular famciclovir for recurrent herpes-associated EM.7 Four cases of EM-like eruptions were reported in association with COVID-19 infections. These eruptions included erythematous papules and targetoid lesions and occurred approximately 21 days after the onset of symptoms.8 Furthermore, a case of EM major affecting most mucosal surfaces has been described in a male patient with COVID-19 infection.9 The patient in this case had no signs or symptoms suggestive of active COVID19 infection. The mechanisms underlying EM, EM-like eruptions and EM flare-ups in association with COVID-19 infections and vaccinations, are postulated to be secondary to an immune response targeting the epidermis and dermo-epidermal junction.7 Clinicians should be aware of the different possible cutaneous adverse reactions associated with the SARS-CoV-2 vaccination, including erythema multiforme. The patient in this manuscript has given written informed consent to the publication of his case details. Dr Borg, Dr Mercieca, Dr Mintoff, Dr Micallef, Dr Pisani, Dr Betts and Dr Scerri have no conflicts of interest to declare. The authors declare no funding sources. The data that support the findings of this study are available from the corresponding author, LB, upon reasonable request.

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