Generalized bullous fixed drug eruption after Oxford–AstraZeneca (ChAdOx1 nCoV‐19) vaccination

Abstract

A 74-year-old Thai man presented with a rash that had appeared 25 h after he had received his first dose of the adenoviral-vectored COVID-19 vaccine, ChAdOx1 nCoV-19 (Oxford–AstraZeneca). The lesions had appeared abruptly without any accompanying symptoms. The patient's medical history included end-stage renal disease, atrial fibrillation and ischaemic stroke. The patient denied taking any new drugs, supplements or foods prior to this cutaneous eruption. Physical examination revealed multiple, well-defined, round to oval, erythematous to violaceous plaques with central dusky appearance and bullous formation on the trunk and both extremities (Fig. 1). There was no mucosal involvement. A punch biopsy was taken, and histopathology findings were consistent with bullous fixed drug eruption (BFDE) (Fig. 2). Laboratory investigations did not show any definite internal organ involvement. Given the clinical and histological features, a diagnosis of generalized BFDE (GBFDE) was made. Fixed drug eruption (FDE) (not bullous or generalized) typically presents within 1–2 weeks after the initial exposure, and in < 2 days for subsequent episodes, whereas GBFDE occurs with more sudden onset and typically within 24 h.1 Based on the temporal relationship, the ChAdOx1 nCoV-19 vaccine was considered as the eruption trigger, with a score of 5 (probable) on the Naranjo Adverse Drug Reaction Probability Scale. Several vaccines have been implicated in triggering FDE, including the combined pentavalent DTaP-IPV-Hib (6-in-1) vaccine, yellow fever, influenza, human papillomavirus, recombinant adjuvant varicella zoster vaccine, and COVID-19 vaccines.2-5 Whereas FDE is usually self-limiting and has a favourable prognosis, GBFDE is considered a severe cutaneous adverse reaction (SCAR) with a high mortality rate among elderly patients.1 Despite the wide use of the COVID-19 vaccinations, only eight cases of SCAR associated with these vaccines have been documented (Table 1). Viral vector vaccine (Janssen, Ad26.COV2.S) Blood test: leucocytosis with neutrophilia and eosinophilia, normal creatinine level and liver enzymes Histology: epidermal spongiosis with subcorneal neutrophilic pustules and dermal neutrophilic inflammation with eosinophils. DIF: negative Viral vector vaccine (Oxford-AstraZeneca, ChAdOx1) Viral vector vaccine (Oxford-AstraZeneca, ChAdOx1) mRNA vaccine (Pfizer/BioNTech, BNT162b2) Blood test: marked neutrophilia Histology: supportive of the diagnosis of AGEP Viral vector vaccine (Oxford-AstraZeneca, ChAdOx1) mRNA vaccine (Pfizer/BioNTech, BNT162b2) mRNA vaccine (Pfizer/BioNTech, BNT162b2) mRNA vaccine (Moderna, mRNA-1273) Blood test: anti-BP180 negative (8), anti-BP230 negative (< 2) Histology: full-thickness epidermal necrosis and a very sparse lymphocytic inflammatory infiltrate 9 (our case) Viral vector vaccine (Oxford-AstraZeneca, ChAdOx1) Histology: subepidermal separation with superficial and deep perivascular mixed inflammatory cells infiltration composing lymphohistiocytes and numerous eosinophils, melanophages were seen in the upper dermis IFN-γ ELISpot assay: negative for polysorbate 80 The treatment for GBFDE treatment is cessation of the causative agents and supportive care.1 We treated our patient with topical 0.25% desoximetasone cream. The lesions gradually resolved within 2 weeks, leaving postinflammatory hyperpigmentation. Use of patch testing on an area of residual hyperpigmentation after FDE resolution was considered as a method to confirm the culprit drug; unfortunately, testing could not be performed due to limited access to the vaccine and hospital areas during the COVID-19 pandemic. As an alternative, an interferon (IFN)-γ ELISpot assay was undertaken. This technique assesses the amount of IFN-γ production from peripheral blood mononuclear lymphocytes after stimulation with the suspect agents. In this case, the vaccine excipient, polysorbate80 (dilutions of 1 : 2000 and 1 : 10 000), was tested and yielded negative results. Our patient also reported receiving an annual influenza vaccination, which contains a similar excipient (polysorbate), without any adverse reactions. This indicated that the GBFDE was a result of a hypersensitivity reaction to the ChAdOx1 nCoV-19 vaccine rather than the excipient. To our knowledge, this is the first report of ChAdOx1 nCoV-induced GBFDE. Because of the potential recurrence of SCAR, the patient was advised to switch to a different COVID-19 vaccine platform. We thank the patient for providing informed consent for publication of their case details and images. We also thank the Skin and Allergy Research Unit for their support.

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