Sex: F
Vaccine: COVID19
Symptoms: Biopsy skin, Chest X-ray, Erythema nodosum, Laboratory test
Clinical narrative: ERYTHEMA NODOSUM; This 73-year-old, Hispanic or Latino, White, female subject (US3652008) was participating in A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older (mRNA-1273-P301) and experienced the medically significant event of erythema nodosum.    The subject's medical history, as provided by the investigator, included insomnia, arthritis, seasonal allergies x2, sciatica of left side, postmenopausal, botulinum toxin (forehead), hypertension, post-nasal drip, anxiety, murmur (cardiac), intermittent neck pain (due to motor vehicle accident), snoring, and dry eyes. Concomitant medications included acetylsalicylic acid, chlorpheniramine maleate, clonazepam, escitalopram oxalate, hydrochlorothiazide, and losartan.    The subject was randomized to receive blinded intramuscular Placebo (dosed on 08 Sep 2020 and 06 Oct 2020) and was unblinded on 06 Jan 2021. The subject consented to receive mRNA-1273 for SARS-CoV-2 vaccination after being unblinded and received their first dose of mRNA-1273 on 06 Jan 2021. The subject received their second dose of mRNA-1273 on 03 Feb 2021. The subject received the booster dose of mRNA-1273 on 01 Oct 2021.   On 09 Oct 2021, the subject experienced erythema nodosum. She noted an erythematous, nodular, tender rash to her bilateral lower extremities.  On 15 Oct 2021, the subject saw her primary medical doctor who suspected erythema nodosum. Unspecified labs were drawn and a chest x-ray was performed to rule out underlying sarcoidosis or mycobacterium as an associated cause. The chest x-ray showed that the lungs were clear. There was unchanged right apical pleural thickening. There was no pleural effusion or pneumothorax. The heart size was normal, with normal mediastinal contours. There was levoconvex rotatory scoliosis of the thoracolumbar spine. Additionally, the subject denied sore throat, recent strep infection, joint pain, or abdominal pain.  On 18 Oct 2021, the subject was referred to a dermatologist, who performed a punch biopsy of the right lower leg (medial), confirming the diagnosis of erythema nodosum, early stage. Microscopic description: the biopsy showed a lymphocytic and neutrophilic infiltrate within the interalveolar septae and within the periphery of fat lobules. There was associated edema. Diapedesis of red blood cells into the septal stroma was also present. Per the investigator, the subject was currently receiving no treatment.    Action taken with study drug in response to the event was not applicable, as the subject had already received all scheduled doses.   The event, erythema nodosum, was reported as resolving.   The investigator assessed the event, erythema nodosum, as related to study drug and not related to study procedure.  Analysis of Similar Events: On 28 Oct 2021, the safety database was searched for events similar to erythema nodosum using the following search criteria: PT: Erythema nodosum, HLT: Rashes, Eruptions and exanthems NEC.   As of 28 Oct 2021, under IND 019745 for mRNA-1273, 3 similar events were retrieved in 2 cases, including the current index case. One case was retrieved under HLT: Rashes, Eruptions and exanthems NEC (MOD-2020-000753: PT: Rash vesicular and PT: Rash) and the index case was retrieved with PT: Erythema nodosum.  None of these cases reporting the following events were previously submitted as IND Safety Reports.  There was 1 case which was a non-IND Safety Report (expected and related or unexpected and unrelated or expected and unrelated to the IMP) reporting the following event: Rash vesicular and rash MOD-2020-000753. This case concerns a 48-year-old, white, male subject with medical history of left kidney stones among others who experienced the unexpected events of disseminated vesicular reaction, elevated liver transaminase level, and generalized rash skin eruption. The event of disseminated vesicular reaction occurred 2 months 8 days after the first dose of study vaccine administration and 1 month 11 days after the second dose. The events of elevated liver transaminase level and generalized rash skin eruption occurred 2 months 11 days after the first dose of study vaccine administration and 1 month 14 days after the second dose. Fibrinogen and skin punch biopsy direct immunofluorescence studies were negative for IgG, IgA, IgG, and complement component C3, and SARS-CoV-2 test resulted negative. As per medical records, the rash looked viral in nature. Treatment included oral antivirals, antihistamines and steroids and topical treatment included steroids and aluminum hydroxide/ diphenhydramine/ lidocaine/ magnesium hydroxide/ simethicone. The events were considered not related to IP in agreement with the Investigator's assessment.  There was 1 case which was a non-IND Safety Report (expected and related or unexpected and unrelated or expected and unrelated to the IMP) reporting the following event: Rash vesicular and rash MOD-2020-000753. This case concerns a 48-year-old, white, male subject with medical history of left kidney stones among others who experienced the unexpected events of disseminated vesicular reaction, elevated liver transaminase level, and generalized rash skin eruption. The event of disseminated vesicular reaction occurred 2 months 8 days after the first dose of study vaccine administration and 1 month 11 days after the second dose. The events of elevated liver transaminase level and generalized rash skin eruption occurred 2 months 11 days after the first dose of study vaccine administration and 1 month 14 days after the second dose. Fibrinogen and skin punch biopsy direct immunofluorescence studies were negative for IgG, IgA, IgG, and complement component C3, and SARS-CoV-2 test resulted negative. As per medical records, the rash looked viral in nature. Treatment included oral antivirals, antihistamines and steroids and topical treatment included steroids and aluminum hydroxide/ diphenhydramine/ lidocaine/ magnesium hydroxide/ simethicone. The events were considered not related to IP in agreement with the Investigator's assessment.  The index case concerns a 73-year-old, Hispanic or Latino, White, female subject with a history of arthritis, seasonal allergies x2, hypertension, anxiety, murmur (cardiac) and dry eyes, among others, who experienced the unexpected event of erythema nodosum. The event occurred 8 days after last dose of mRNA-1273 (booster). The subject had also received the first dose and second dose of the study vaccine administration 9 months 4 days and 8 months 6 days prior to the event, respectively. The event was reported as resolving. Even though supportive diagnostic procedures to rule out alternative etiologies were not provided at the time of this report, the event was considered related to the study vaccine in agreement with the Investigator's assessment based on close temporal association and inflammatory nature of the event.   Based on temporal association, the Sponsor cannot rule out a possible cause and effect relationship between administration of IMP and the occurrence of erythema nodosum. Other etiologies could potentially have contributed to the event, however they have not been investigated.   After review of the clinical details and investigator comments pertaining to this adverse event, and based upon experience to date, the Sponsor does not believe that changes to the conduct of this clinical trial are warranted. The Company will continue to monitor these and other serious adverse events reported in association with the IMP and will communicate any relevant changes to the protocol, Informed Consent Form, Investigator's Brochure, and/or Core Safety Information.; Reporter's Comments: This case concerns a 73-year-old, Hispanic or Latino, White, female subject with a history of arthritis, seasonal allergies x2, sciatica of left side, postmenopausal, botulinum toxin (forehead), hypertension, post-nasal drip, anxiety, murmur (cardiac), intermittent neck pain (due to motor vehicle accident), snoring, and dry eyes, who experienced the unexpected event of erythema nodosum. The event occurred 9 months 4 days after the first dose of mRNA-1273, 8 months 6 days after the second dose and 8 days after last dose of mRNA-1273 (booster). Action taken with study drug in response to the event, dechallenge and rechallenge were not applicable. The event was reported as resolving. The event was considered related to the study vaccine in agreement with the Investigator's assessment. Additional information was requested.