A 42-year old Bengali man with a history of hyperlipidemia presented to the Emergency Department with facial swelling, diffuse rash, renal insufficiency and proteinuria after receiving his COVID-19 vaccine (Moderna) booster dose. There were no adverse events with the first two doses of the vaccine except for mild transient sore throat and cough after the 2nd dose. Within a few hours after the booster dose, the patient noted a pruritic rash initially on his scalp, that then spread to his torso associated with facial swelling, fever, and chills. He presented to his primary care physician three days later. At that time, laboratory workup showed proteinuria, elevated C-reactive protein (65.2), and an elevated serum creatinine (2.84 mg/dl). He was advised to go to the Emergency Department.
General: He was in no distress; his vital signs were normal.
Skin: While the facial swelling had improved, the rash had progressed to involve the entire body. There were multiple skin lesions with raised borders, and central clearing (Figures 1 and 2); no mucosal involvement was noted.
The rest of his physical exam including lung, cardiac, gastrointestinal, and neurological examinations were normal.
Laboratory workup in the ED revealed resolution of proteinuria with serum creatinine returning to normal baseline value (0.89 mg/dl).
The patient’s rash is a classic erythema multiforme (EM) rash. The mRNA COVID-19 vaccine is a lipid nano particle-encapsulated, nucleoside-modified mRNA vaccine that encodes the perfusion spike glycoprotein of the SARS-CoV-2 virus. Local reactions include mild to moderate pain at the injection site, and systemic effects including fatigue, fever, and headache, commonly appearing within 2-5 days after the second dose. Erythema multiforme has been reported as a cutaneous reaction after the COVID-19 mRNA vaccine. As per the vaccine adverse event reporting system (VAERS) from the Centers for Disease Control and Prevention, to date, there have been 284 reported cases of EM after the Moderna COVID-19 vaccine and 500 cases reported after the Pfizer vaccine. The exact pathogenesis of EM after the vaccine is unclear. This delayed hypersensitivity reaction is likely from sensitization to a vaccine component. It appears to be a T-cell mediated response making CD4+ helper T-1 cells, release of gamma-interferon, and then recruitment of auto-reactive T-cells. It should be differentiated from immediate IgE-mediated hypersensitivity reactions such as flushing, urticaria, angioedema, and hypotension that usually appear within minutes of administering the vaccine.
While immediate hypersensitivity is a contraindication for further doses, erythema multiforme and other such delayed manifestations should not discourage the use of additional COVID-19 mRNA doses if appropriate.
Take-Home Points
- Erythema multiforme is a delayed hypersensitive reaction that may occur after COVID-19 mRNA vaccine.
- This type of delayed hypersensitivity reaction, likely from sensitization to vaccine component, is not a contraindication to further COVID-19 boosters.
- Su JR, Haber P, Ng CS, Marquez PL, Dores GM, Perez-Vilar S, Cano MV. Erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis reported after vaccination, 1999-2017. Vaccine. 2020 Feb 11;38(7):1746-1752. doi: 10.1016/j.vaccine.2019.12.028. Epub 2019 Dec 20. PMID: 31870573; PMCID: PMC7008074.
- Vaccine Adverse Events Reporting System [Internet]. CDC. 2022. Available from: https://vaers.hhs.gov/data.html.
Vijaya Arun Kumar MD, MPH
Department of Emergency Medicine
Wayne State University
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