Erythema Multiforme After Pfizer and Moderna COVID-19 mRNA Vaccines

Papers Reviewed

2023 Apr (Yousefian et al) – Occurrence of erythema multiforme following COVID-19 vaccination: a review

• Erythema multiforme (EM) is among the oral mucocutaneous side effects of COVID-19 vaccines
• Review: 90 patients with Erythema Multiforme (EM) as a side effect of COVID-19 vaccination across several studies
• EM is a skin inflammatory condition, typically caused by infections (herpes simplex virus and mycoplasma), medications and internal diseases
• to date: 984 cases of EM due to vaccinations (mumps, measles, Hep.B)
• EM minor: skin lesions < 10% of body surface with minimal or no mucosal
• EM major: skin lesions > 10% body surface with mucosal involvement
• Oral EM: oral mucosal ulcers without any skin lesions
• In this review of 90 EM patients after COVID-19 Vaccines:
  • mean age 51, women 2x than men
  • 79% of the vaccines were mRNA vaccines 47% Pfizer, 32% Moderna
  • 45% developed EM less than 3 days after jab
• EM is an acute self-limiting reaction caused by exaggerated immune response, which is characterized by targetoid skin lesions that may be associated with mucosal involvement as well.
• mRNA elicits cellular immune response to antigens through CD4 type 1 T-helper cells, and induce the release of interferon IFN-gamma and eventual activation of autoreactive system in genetically susceptible individuals.
• Treat: Corticosteroids are prescribed topically, orally (30–90 mg prednisolone daily) or intravenously (0.5–1 mg/kg body weight methyl prednisolone every 8 hours) for more severe cases

2023 Feb (Karatas et al) – Erythema multiforme reactions after Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 vaccination: A case series 

• CASE 1: 61M had 1st dose Moderna 10 days before onset of symptoms
• Physical examination (P/E) revealed scattered, non-tender, erythematous, targetoid plaques on the face, trunk, and extremities, including the palms and soles
• also had bilateral conjunctival erythema with multiple vesicles and erosions in the oral mucosa
• Diagnosis; EM major with extensive oral and nasal involvement

• CASE 2: 21F had 2nd dose of Pfizer mRNA 3 days prior
• Presented with rash on hands and feet, swelling and joint discomfort
• She was diagnosed with EM, put on steroids and rash resolved

• CASE 3: 50M had 2nd Pfizer mRNA dose 5 days prior onset of symptoms
• Presented with worsening rash and pruritus for 4 days.
• had erythematous targetoid plaques on trunk and extremities and hemorrhagic crusts on oral mucosa
• was diagnosed with EM and put on prednisone taper and also topical steroid

• CASE 4: 53F had 2nd Moderna mRNA dose 2 days prior to onset
• presented with a 3 week history of rash and pruritus on hands, arms and legs
• P/E: erythematous targetoid plaques on hands and extremities, no mucosal involvement.
• Diagnosed with EM and treated with topical steroid.

• pathogenic mechanism of EM after infection is thought to be a cell-mediated immune reaction with activation of T helper cells and cytokine production,resulting in a robust mucocutaneous inflammatory response.
• The mechanism of EM after vaccination is not entirely clear, but it is likely to be a similar mechanism

2022 Nov (Fadul et al) – Sever erythema multiforme post-COVID-19 Moderna vaccine: Case report and literature review

• 36F woman had 1st Moderna mRNA 24 hours prior to onset
• presented with sore throat, painful mouth ulcers, bilateral red and itchy eyes and itchy skin lesions that started on her chest, back and genital area and quickly spread to the rest of her body, becoming intensely itchy

2022 Mar (Petruzzi et al) – Oral erythema multiforme after Pfizer-BioNTech COVID-19 vaccination: a report of four cases

• Case Series of 4 cases post Pfizer mRNA Vaccination
• CASE 1: 55F had 1st Pfizer mRNA dose 10 days prior
• presented complaining of painful lesions on lips, oral mucosa, hands, knees, and feet

• CASE 2: 15M had 1st Pfizer mRNA dose 7 days prior
• developed oral erythema, erosions, and pseudo-membranes throughout the oral mucosa, associated with severe pain and dysphagia

• CASE 3 – 49F had 2nd Pfizer mRNA dose 24 hours prior to onset
• presented with erythematous and bullous like lesions on tongue and mouth floor

• CASE 4: 20F had 1st dose of Pfizer mRNA 18 days prior
• presented with pain and bleeding from the mouth, dysphagia and dysphonia
• P/E: erosions on the gingival and lips mucosa, squamous crusted lesions on the labial skin and vermillion

2021 Nov (Burlando et al) – Cutaneous reactions to COVID-19 vaccine at the dermatology primary care

• 21 patients were referred to Dermatology Clinic with skin reactions after COVID-19 Vaccination
• One patient our of 21 (67 year old man), 48 hours after the second dose of Moderna vaccine, developed a bullous erythema multiforme, which required hospitalization

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Dr. William Makis is a Canadian physician with expertise in Radiology, Oncology and Immunology. Governor General’s Medal, University of Toronto Scholar. Author of 100+ peer-reviewed medical publications.

Featured image is from COVID Intel