key: cord-0928422-g6zj0twr
authors: Padniewski, Jessica J.; Jacobson‐Dunlop, Erick; Albadri, Sam; Hylwa, Sara
title: Stevens–Johnson syndrome precipitated by Moderna Inc. COVID‐19 vaccine: a case‐based review of literature comparing vaccine and drug‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis
date: 2022-04-10
journal: Int J Dermatol
DOI: 10.1111/ijd.16222
sha: 432972d1524cd44810ba724ba70ab82d83f9209c
doc_id: 928422
cord_uid: g6zj0twr

The Moderna COVID‐19 vaccination was approved for use in the United States in December of 2020(1) and since that time massive public health efforts have been made to vaccinate patients against the COVID‐19 infection. Adverse reactions from the vaccination are well‐reported and include both local skin reactions, such as pain, swelling, and erythema at the injection site, as well as systemic reactions including fever, malaise, headache, muscle aches, drowsiness, nausea, and vomiting. While severe serious cutaneous adverse reactions, such as Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), remain rare; two cases of SJS/TEN related to COVID‐19 vaccination have been reported. We herein review the two previously reported cases of SJS/TEN and report the first case of SJS precipitated by the Moderna Inc., MRNA 1273 COVID‐19 vaccination in the United States. Although we review potential adverse reactions to vaccination, the benefits of COVID‐19 vaccination outweigh the risks based on current data. Cases should be reported to the Vaccine Adverse Event Reporting System (https://vaers.hhs.gov/) to help public health officials recognize and track these severe but rare adverse events.

The Moderna COVID-19 vaccination was approved for use in the United States in December of 2020 1 and since that time massive public health efforts have been made to vaccinate patients against COVID-19 infection. Adverse reactions from the vaccination are well-reported and include both local skin reactions, such as pain, swelling, and erythema at the injection site, as well as systemic reactions including fever, malaise, headache, muscle aches, drowsiness, nausea, and vomiting.

Rarely, anaphylaxis and myocarditis have occurred. Although serious adverse events such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are rare, two cases have now been reported after the COVID-19 vaccination. We present the third case and perform a case-based review of vaccine vs. drug-induced SJS/TEN.

A 46-year-old Ethiopian female with a medical history of diabetes mellitus type 2, hyperlipidemia, and obesity on chronic metformin and atorvastatin therapy received her first dose of COVID-19 vaccination (Moderna Inc., MRNA 1273) . She remained asymptomatic the day of vaccination but the following day developed oral discomfort and mucosal sloughing. She presented to an outside hospital 3 days after vaccination with erosions of the mucous membranes. She received cetirizine 10 mg daily and prednisone 60 mg daily and was transferred to our ª 2022 the International Society of Dermatology.

International Journal of Dermatology 2022 hospital. On arrival, she was afebrile, and her vitals were stable. Physical exam revealed: dusky, pink-purple plaques on her eyelids and cheeks; nasal and oral mucosal sloughing (Fig. 1a,b) ; small, dusky, purple papules coalescing into plaques across her trunk and arms (Fig. 2a,b) ; and violaceous annular lesions on her palms and soles (Fig. 3a,b) Biopsy of the right forearm revealed confluent and fullthickness necrosis of the epidermis with a basket weave-type stratum corneum, sparse mild perivascular infiltrate of lymphocytes in the dermis, consistent with SJS/TEN (Fig. 4a-c) . She was started on prednisone 80 mg daily and clobetasol 0.05% ointment twice daily. She began to see improvement on this regimen and after 6 days was discharged to home on a prednisone taper and continued topical clobetasol 0.05% ointment.

After obtaining written consent from the patient for publication of the case and photos, a literature review was performed. A literature review was conducted using the NCBI database (PMC and PubMed filters) using the keywords "Stevens Johnson Syndrome," "SJS," "SJS/TEN," "TEN," "bullous," and "COVID vaccination." Parameters were expanded to include literature from any date. The literature review identified two previously documented cases of SJS/TEN related to COVID vaccination.

The COVID-19 pandemic has resulted in mass fatalities while efforts for prompt, global vaccinations remain underway. Skin reactions related to COVID-19 vaccinations are uncommon. (Table 1) . 6, 7 In assessing the three cases noted in Table 1 Moderna vaccine contains none of these aforementioned inactive ingredients; moreover, none of the ingredients in the vaccine have been previously reported as causing SJS/TEN (Table 2) .

There are similarities but also notable differences between drug-induced SJS/TEN and vaccination-induced SJS/TEN. The clinical presentation of drug-induced and vaccineinduced SJS/TEN is similar with dusty red macules coalescing into patches, skin, and mucosal erosions. 9 The least common manifestation of vaccine-induced SJS/TEN is a targetoid rash. 9 Compared to drug-induced SJS/TEN where SJS is more common than TEN, in vaccine-induced, SJS and TEN appear to be equally likely to occur. 12 Perhaps the most notable difference is in the timeline of symptom development between drug-induced versus vaccineinduced SJS/TEN. Symptoms of drug-induced SJS/TEN typically begin 2-3 weeks post medication administration; however, in post-vaccine exposure, the timeline is shorter with the eruption beginning 1-8 days after administration, with 3-5 days being typical. 9, 14, 18 To date, cases reported of SJS/ TEN presented on average~3.5 days post vaccination fitting this timeline.

Lastly, patients have been reported to progress from an EMlike presentation to full TEN with vaccine-induced SJS/TEN, which is considered unlikely to occur with drug-induced SJS/ TEN. 9 We present a case of Stevens-Johnson Syndrome occurring after COVID-19 vaccination to increase awareness of this exceedingly rare potential adverse event. The benefits of vaccination outweigh risks based on current data, and patients should continue to be vaccinated. Adverse events, however, should be reported to the Vaccine Adverse Event Reporting System (https://vaers.hhs.gov/) to help public health officials recognize and track these severe but rare adverse events. 11, 14, 15 Conflict of interest None declared. Multiple dusky, pink-purple plaques on her eyelids and cheeks; nasal and oral mucosal sloughing. Fig. 1 (a,b) : small, dusky, purple papules coalescing into plaques across her trunk and arms Fig. 2 (a,b) : and violaceous annular lesions on her palms and soles Fig. 3 

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