SARS‐CoV‐2 mRNA vaccine‐associated fixed drug eruption

Abstract

A 26-year-old, healthy, female nurse on no regular medication developed a mildly pruritic, erythematous, annular patch with faint, central clearing on her left shoulder (Fig. 1a). The patient had received the first dose of the Pfizer-BioNTech (Pfizer Inc., New York City, NY, USA) SARS-CoV-2 mRNA vaccine in the same arm 15 days prior to the development of the lesion. The injection site was 7 cm distal to the evolving patch. Over the span of 2 days, the patch developed a shallow, central erosion surrounded by a halo of erythema (Fig. 1b) and subsequently started to resolve spontaneously. The patient had also experienced facial flushing 15 minutes after the vaccine was administered. An identical erythematous patch re-emerged 14 days after the patient was administered the second Pfizer-BioNTech SARS-CoV-2 mRNA vaccine dose. This time, the patch was accompanied by prominent vesiculation within its duskier centre (Fig. 1c). The vesicles eventually ruptured and scabbed, giving the lesion a targetoid appearance (Fig. 1d). Of note, the patient had self-medicated with a stat dose of hydroxyzine an hour prior to receiving the second vaccine to abate facial flushing. She had otherwise not taken any prescribed or over-the-counter medications. Self-medication with topical 1% hydrocortisone and terbinafine applied twice daily for a couple of days on the second eruption proved ineffective. The patient was referred for a dermatological opinion. A diagnosis of fixed drug eruption (FDE) was suspected, and a diagnostic punch biopsy was carried out. Histology showed skin covered by a variably acanthotic and atrophic epidermis with overlying crust (Fig. 2a). A patchy lymphohistiocytic infiltrate was present in the upper dermis, focally extending into the mid dermis around skin adnexal structures. Eosinophils were inconspicuous. Lymphocytic infiltration of the basal layer of the epidermis was noted. This was associated with basal cell vacuolar damage, Civatte body formation and pigment incontinence (Fig. 2b). Incipient clefting at the dermal–epidermal junction was also appreciated. The overall findings were those of lichenoid interface dermatitis, consistent with a fixed drug eruption. To the best of our knowledge, this is the first reported case of SARS-CoV-2 mRNA vaccine-associated FDE. FDEs represent a cutaneous adverse drug reaction (ADR) clinically characterized by the appearance of recurrent, quasi-identical, cutaneous eruptions in the same anatomical location upon exposure and re-exposure to the offending drug. The delay between drug administration and FDE ranges from 0 to 40 days, manifesting most commonly as a single lesion with a propensity for the upper limbs.1 Intraepidermal interferon γ-secreting, CD8+ T cells are the key cellular mediators of this type IV hypersensitivity reaction.2 FDEs have been associated with other vaccines including the influenza,3 human papilloma virus4 and yellow fever vaccine.5 Of the 13 794 904 COVID-19 vaccine doses administered in the United States between December 2020 and January 2021, 6354 adverse events were reported – of which, 92.4% were non-serious.6 Injection site reactions account for up to 84% of ADRs associated with the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine,7 with erythema and oedema being the commonest reactions.8 Other described cutaneous ADRs to the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine include lichen planus,9 a morbilliform rash,10 radiation recall11 and urticaria.12 Dermatologists and clinicians alike, who have now have become experts at identifying cutaneous manifestations of COVID-19, need to be aware of possible cutaneous ADR related to SARS-CoV-2 vaccination. Notwithstanding, the authors strongly recommend the administration (and uptake) of the vaccine according to internationally established guidelines and national vaccination strategies. Dr Mintoff, Dr Pisani, Dr Betts and Dr Scerri have no conflicts of interest to declare. The patients in this manuscript have given written informed consent to publication of their case details. The authors declare no funding sources.

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