Stevens–Johnson syndrome in an Asian man after receiving the third dose of COVID-19 vaccine

Dear Editor, Various cutaneous reactions to COVID-19 vaccines have been reported, including urticaria, morbilliform eruptions, acute allergic vasculitis, alopecia areata, as well as infrequently observed Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).[1-3] To date, approximately 10 cases of SJS caused by COVID-19 vaccines have been reported, with most affected individuals being first-time vaccine recipients. Here, we report a case of a 31-year-old Asian male who developed SJS after receiving the third dose of the COVID-19 vaccine. A 31-year-old man developed bilateral eye pain, oral mucosal ulceration, and painful papulovesicular rashes on the face, trunk, and upper extremities 3 weeks after receiving the messenger RNA-1273 (Moderna) COVID-19 vaccine. Associated symptoms included sore throat, fever, and respiratory distress. He visited a local clinic, where symptomatic treatment with ibuprofen, diclofenac sodium, and amoxicillin was administered. The patient had no history of drug allergies. Previously, he had received two doses of the BioNTech (BNT 162b2) COVID-19 vaccine without adverse effects. However, due to progressive symptoms after the third dose of the COVID-19 vaccine, the patient was referred to our hospital. During admission, a physical examination revealed multiple dusky red-crusted macules and patches on the trunk with severe oral mucosal erosions [Figure 1a-c]. A skin biopsy was performed, which showed interface dermatitis with epidermal necrosis and dermoepidermal detachment [Figure 1d]. The patient also suffered from eye erosion and extensive oral mucosal erosions with dysphagia. The ophthalmologist revealed bilateral keratoconjunctivitis and administered a variety of medications, including levofloxacin eyedrops, steroid ointment, erythromycin ointment, and lubricant eye drops. Due to the limited therapeutic effect, bilateral Prokera implantation was performed. During hospitalization, viral screening tests, including COVID-19, Mycoplasma, hepatitis B and C, Cytomegalovirus, Epstein–Barr virus, and herpes simplex virus, were negative, as were markers related to rheumatology. In the lymphocyte activation test (LAT), both granulysin and interferon-gamma exhibited positive reactions to excipient polyethylene glycol (PEG)-2000 and the severe acute respiratory syndrome coronavirus 2 spike protein, supporting the causal relationship between SJS and vaccination. Naranjo causality assessment also showed an association between Moderna vaccination and SJS.Figure 1: (a) Clinical manifestations of Moderna vaccine-induced dusky red macules and patches on the torso, anterior view of the upper trunk, (b) Closer view of dusky red macules on the trunk, (c) Severe oral mucosal erosions developed after the Moderna COVID-19 vaccine, (d) Punch biopsy specimen with hematoxylin and eosin staining showed interface dermatitis with epidermal necrosis and full-thickness necrosis of the epidermis with dermoepidermal detachment. The adjacent area showed hyperkeratosis, spongiosis, focal basal cell vacuolization, scattered apoptotic keratinocytes, hyperpigmentation, and perivascular lymphocytic infiltrates.SJS is primarily caused by drugs. Other factors, such as viruses, immunizations, contrast media, and external chemical exposures, are also known. Some cases of SJS caused by vaccines have been reported, such as measles, varicella, smallpox, anthrax, tetanus, and influenza vaccines.[4] Vaccine-induced SJS is rare, but its significance is increasing due to the widespread administration of COVID-19 vaccinations.[4,5] Clinical disparities between drug-induced and vaccine-induced SJS are suggested. Prior literature noted both types display red macules coalescing into patches and skin erosions. Yet, targetoid lesions are rarer in vaccine-induced SJS.[4,5] Aligned with prior observations, our patient lacked targetoid lesions, showing dark red patches and erosions. In our case, vaccine-induced SJS was diagnosed through histopathology and LAT results, revealing hypersensitivity to PEG-2000 and spike protein. Notably, symptoms emerged after the third COVID-19 vaccine dose (Moderna). An explanation is that specific T cells were primed by the initial two BNT vaccine doses.[6] The third Moderna dose could surpass the threshold and activate cytotoxic T cells (CD8+),[7] evoking SJS. Therefore, repeated exposure to the vaccine may be a risk of causing the disease despite the absence of symptoms following previous exposures. Nevertheless, further study is needed to explore the exact mechanism underlying the observation. As the coverage of the vaccination increases and the severity of COVID-19 decreases, future research can focus on developing vaccines that can produce sufficient immune responses with a single dose, reducing the need for booster shots, and potentially minimizing the risk of repeated exposure-induced allergic reactions. Ethics statement This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and its amendments. Written informed consent was obtained from the patient for the publication of this case report, including any relevant images. The patient was informed about the purpose of the report and gave consent for its dissemination in medical literature while ensuring anonymity. Data availability statement The datasets generated during and/or analyzed during the current study are publicly available. Financial support and sponsorship Nil Conflicts of interest Dr. Chun-Bing Chen and Cheng-Che Lan, editorial board members at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.