Wells' syndrome following Oxford-AstraZeneca COVID-19 vaccination.

Abstract

Dear Editor, Coronavirus disease 2019 (COVID-19) vaccination is expected to play a crucial role in improving global health outcomes during the COVID-19 pandemic. Various COVID-19 vaccine-related adverse events have been reported, including cutaneous reactions.1 Most cases of cutaneous adverse reactions have involved administration of mRNA vaccines such as the Pfizer/BioNTech (BNT162b2) and Moderna (mRNA 1273) vaccines. However, only a few cases of cutaneous adverse events have been reported after the administration of an adenoviral vector vaccine such as the Oxford–AstraZeneca (ChAdOx1 nCOV-19) vaccine.2 Wells’ syndrome manifests as a rare inflammatory dermatitis that resembles cellulitis. Its pathogenesis remains unclear; however, several reports suggest that it might be triggered by vaccination.3, 4 Herein, we report the first case of Wells’ syndrome, a new post-vaccination adverse event, after Oxford–AstraZeneca COVID-19 vaccination. An otherwise healthy 63-year-old woman presented with a 3-day history of multiple 5-cm-sized, scattered, ill-defined, oedematous, erythematous patches on her extremities (Fig. 1). She complained of pruritus at the lesion sites but had no other symptoms. She had no experience of local injection site reaction after both doses of injection. One week prior to symptom onset, she had received her second dose of the Oxford–AstraZeneca COVID-19 vaccine. She reported no recent history of infection or medication use and no any cutaneous reaction after the first dose of Oxford–AstraZeneca COVID-19 vaccine. Punch biopsy of a calf lesion was performed. Histological findings showed superficial and deep perivascular and interstitial inflammatory cell infiltration, eosinophilic predominance and flame figures, which was suggestive of Wells’ syndrome (Fig. 2). The patient was treated with oral prednisolone 10 mg daily. The prednisolone dose was gradually tapered over 3 weeks, and the patient completely recovered. Wells’ syndrome is a rare inflammatory dermatitis that was first described by Wells in 1971 as recurrent granulomatous dermatitis with eosinophilia.5 Wells’ syndrome is diagnosed based on histological findings of eosinophilia and characteristic flame figures.5 Fortunately, it responds well to systemic glucocorticoids, and there is no residual scarring.6 However, since recurrence is quite common and may occur for several years, the underlying conditions and triggering factors must be evaluated. Insect bites, infections, drugs and vaccines have been reported as factors that trigger Wells’ syndrome.6 Vaccine-related Wells’ syndrome has rarely been reported, and most cases occur in children.3 Only two cases have been reported in adults: after tetanus vaccination in a 69-year-old woman and after influenza vaccination in an 86-year-old man.4, 7 This is the first report of an adult presenting with Wells’ syndrome after COVID-19 vaccination. Koh et al. reported a case of Wells’ syndrome diagnosed by patch testing following the thimerosal-containing vaccine administration and suggested a delayed type IV hypersensitivity reaction to be the mechanism.8 Type IV hypersensitivity reactions to non-thimerosal agents such as neomycin and aluminium hydroxide have been noted on patch testing in patients with Wells’ syndrome.3 The aetiology is still unknown; one study revealed that CD4-predominant T cell was infiltrated into a skin biopsy tissue of Wells’ syndrome patient.9 CD4+ T cells are considered to play an important role in the mechanism of type IV hypersensitivity; thus, we suggested that delayed type IV hypersensitivity reaction associated with Wells’ syndrome might be related to the activity of CD4+ T cells. Although the COVID-19 vaccine does not contain these ingredients, polyethylene glycol, which is present in the two mRNA vaccines, and polysorbate 80, which is found in the Oxford–AstraZeneca vaccine, have been reported as potential causes of delayed-type hypersensitivity.1 Delayed hypersensitivity reaction-mediated local cutaneous reactions have been reported following Oxford–AstraZeneca vaccination.10 Based on these findings, we hypothesize that delayed-type hypersensitivity reaction associated with polysorbate 80 can contribute to the occurrence of Wells’ syndrome. Further studies involving patch test for polysorbate 80 are necessary to confirm Oxford–AstraZeneca vaccine-induced delayed hypersensitivity reaction as the underlying mechanism. In conclusion, the development of Wells’ syndrome and Oxford–AstraZeneca COVID-19 vaccination may be related, with delayed-type hypersensitivity reaction as a possible mechanism. We believe that this rare case will broaden the understanding of Wells’ syndrome and raise awareness of the cutaneous side-effects of the Oxford–AstraZeneca COVID-19 vaccine. The patient in this manuscript has given written informed consent to the publication of their case details. Yul Hee Kim and You Chan Kim declare to have no conflicts of interest to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request.