A flare of pre‐existing erythema multiforme following BNT162b2 (Pfizer–BioNTech) COVID‐19 vaccine

Dear Editor,

The coronavirus disease (COVID)‐19 pandemic has resulted in significant morbidity and mortality worldwide. The emergency use authorization of COVID‐19 vaccinations in December 2020 has led to renewed optimism of reducing the prevalence and burden on healthcare systems. Three vaccines have now been granted temporary authorization in the UK: BNT162b2 (Pfizer–BioNTech), ChAdOx1 (Oxford–AstraZeneca) and mRNA‐1273 (Moderna).

While urticarial and allergic reactions have been reported post COVID‐19 vaccination, de novo cutaneous eruptions, or flare of pre‐existing cutaneous disorders postvaccination, are scarce.¹ We report a patient developing a flare of biopsy‐proven, erythema multiforme (EM) following COVID‐19 vaccination with BNT162b2.

A 58‐year‐old woman presented with a 7‐day history of a painful eruption on her hands and feet. A similar eruption had occurred in 2018, with the clinical suspicion of EM being confirmed by a subsequent diagnostic biopsy. The patient experienced recurrent episodes of herpes labialis, with clinical improvement after taking antiviral medication. The EM had been quiescent for 5 months on oral famciclovir. Within 12 h of receiving the first BNT162b2 vaccine, the patient developed a cutaneous eruption consisting of erythematous concentric targetoid plaques on the palms of her hands and soles of the feet bilaterally (Fig. 1). There was no mucous membrane involvement. Prior to the vaccination the patient had been systemically well, with no recent flare of herpes labialis and no recent illness. Her medical history included rheumatoid arthritis for which she was taking abatacept), endometriosis, hypertension and a multinodular thyroid goitre. Her medication was unchanged with no new medication intake around the time of vaccination. A similar eruption occurred 24 h after receiving the second BNT162b2 vaccine (Fig. 2).

Figure 1.

Erythema multiforme manifesting as erythematous concentric targetoid plaques on the palm of the hand.

Figure 2.

Erythema multiforme on the right second finger after receiving the second BNT162b2 vaccine.

Clinical improvement of the EM was obtained with topical clobetasol ointment.

Erythema multiforme is an immune‐mediated chronic inflammatory disease affecting the skin and/or mucous membranes, which has been reported in association with COVID‐19, predominantly in the paediatric population. This is believed to occur either due to the prothrombotic state or due to immune dysregulation.²

To our knowledge, there have been no cases of EM occurring post COVID‐19 vaccination; however, there are reports of EM occurring after other vaccinations.³ The hypotheses for EM following infection and vaccines share a similar aetiology. EM associated with herpes simplex virus (HSV) infection is thought to be due to a cell‐mediated immune reaction. Following HSV infection, the viral DNA undergoes phagocytosis by macrophages and other antigen‐presenting cells. The viral DNA is transported to the skin and is expressed on basal keratinocytes, which leads to activation of T‐helper cells and consequent production of cytokines such as interferon‐γ, which are responsible for the pathological inflammatory response leading to EM.⁴ Similarly, the reason for vaccine‐induced cutaneous hypersensitivity reactions is thought to be due to antigens present in the vaccine being expressed on the surface of keratinocytes, leading to a T‐lymphocyte immune response against the cells of the epidermis, and ultimately cell death and detachment at the dermoepidermal junction. At present, the specific vaccine antigen component that promotes this reaction is unknown.⁵

New reports of cutaneous manifestations related to COVID‐19 continue to emerge. As more people receive the COVID‐19 vaccinations, it is possible that de novo cutaneous eruptions or flares of pre‐existing cutaneous diseases will.