Stevens-Johnson Syndrome Following ChAdOx1 nCoV-19 Vaccination (AstraZeneca)

Dear Editor:

The pandemic caused by SARS-CoV-2 continues, and by June 30, 2021, 182 million people worldwide have been infected with COVID-19, with 3.9 million deaths. Various types of vaccines have been developed to combat this pandemic infectious disease. As of July 1, 2021, 15 million people in Korea had received the first vaccination, of which 10 million received the University of Oxford/AstraZeneca non-replicating chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine that delivers the spike antigen protein of SARS-CoV-2 using adenoviruses1. Due to the short history of this type of vaccine, its safety remains unknown. Steven Johnson Syndrome (SJS) is a rare, potentially life-threatening skin disorder usually caused by an immune-mediated reaction to drugs2. Vaccineassociated SJS, however, is rare2.

A healthy 59-year-old female presented with bullae on the trunk and both extremities. She had no previous history of medication or hypersensitivity reactions to any drugs. She had received the first dose of ChAdOx1 nCoV-19 vaccine 3 weeks prior. The patient reported fever and chills that started the day after vaccination, and a skin rash developed a few days later. On physical exam, multiple, variable-sized, erythematous patches and hemorrhagic bullae were located on the lips, dorsum of the right hand, trunk, and extremities (Fig. 1). The laboratory tests were normal, other than slightly elevated erythrocyte sedimentation rate and C-reactive protein. The histologic findings of skin biopsy showed subepidermal blister, full thickness epidermal necrosis, and diffuse intraepidermal deposition of immune-reactants on direct immunofluorescence those were consistent with SJS (Fig. 2).

Fig. 1
A 59-year-old female presented with asymptomatic, multiple, variable-sized, erythematous patches and hemorrhagic bullae on the lip (A), dorsum of the right hand (B), trunk (C), and both extremities (D) for several days. We received the patient’s consent form about publishing all photographic materials.

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Fig. 2
Subepidermal blister and full thickness epidermal necrosis with necrotic keratinocytes and edema of the papillary dermis (A: H&E, ×100; B: H&E, ×200). Direct immunofluorescence showing diffuse granular staining for immunoclobulin G (C), complement 3 (D), and fibrinogen (E) in the epidermis.

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The patient was treated with triamcinolone 4 mg, prednisolone 2.5 mg, and topical methylprednisolone 0.1% cream for 7 days. The skin lesions cleared, but the patient refused to receive the second dose of the vaccine.

In this report, we describe SJS after ChAdOx1 nCoV-19 vaccination. In the phase 2/3 trial of ChAdOx1 nCoV-19, serious adverse events did not occur1. In an interim analysis of 4 randomized controlled trials, angioedema and cellulitis were reported as adverse events related to skin and subcutaneous tissue disorders during 74,341 person-months of safety follow-up3. Recently, a case of SJS induced by the ChAdOx1 nCoV-19 vaccine was reported in India4. The Janssen Ad26.COV2. S COVID-19 vaccine has a mechanism similar to that of the ChAdOx1 nCoV-19 vaccine, and one case of a severe cutaneous adverse reaction after Janssen Ad26.COV2.S COVID-19 vaccination has been reported5.

SJS after vaccination is rare2. The injected vaccines most commonly associated with SJS/toxic epidermal necrolysis are measles, mumps, and rubella; combined diphtheria, tetanus, and acellular pertussis; varicella; and pneumococcal conjugate vaccines. Reported times from vaccination to onset of SJS ranged from a median of 10 days to a median of 3 weeks2.

Contraindications to ChAdOx1 nCoV-19 vaccination are anaphylaxis at the time of the first vaccination or allergy to polysorbate 801. Severe adverse cutaneous reactions to COVID-19 vaccines, however, have not been established.

Here, we present the first Korean case of ChAdOx1 nCoV-19 vaccine-induced SJS. This case represents a rare complication of the vaccine, and the benefits of vaccination against COVID-19 outweigh the risks.