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Urticaria 12 Days After COVID-19 mRNA Booster Vaccination

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A healthy 27-year-old woman received a COVID-19 mRNA booster vaccine (Moderna) on December 7, 2021. She had not experienced adverse effects after the first 2 vaccine doses on January 17 and February 5, 2021. Twelve days after the booster vaccination, she developed pruritic wheals on her face and bilateral, transient eyelid swelling. Over the next week, a pruritic rash spread over her neck, chest, trunk, and arms; each lesion faded without scarring within 24 hours. She did not experience lip, tongue, or neck swelling; shortness of breath; wheezing; chest pain; or palpitations. Application of pressure to her forearm in a circular motion using a pen cap elicited wheal and flare lesions (Figure, left panel). On physical examination, performed 17 days after the onset of rash, her vital signs were normal. She had no tongue, lip, or throat swelling, and her lungs were clear to auscultation bilaterally. Wheal and flare lesions developed on her upper eyelids during the examination and resolved after approximately 30 minutes (Figure, right panel). Light pressure applied to her skin with a tongue depressor elicited wheal and flare lesions within 3 to 5 minutes.

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Inducible urticaria (symptomatic dermatographism) and acute urticaria

C. Prescribe a nonsedating antihistamine at a standard dose and increase to high-dose antihistamine if symptoms persist.

The key to the correct diagnosis is recognition of urticaria and dermatographism, an exaggerated wheal and flare response that occurs within minutes of skin being stroked, scratched, or having pressure applied to it.1 Advising the patient against future COVID-19 mRNA vaccination (choice A) is incorrect because she did not have a vaccine allergy. An immediate allergic reaction occurs within 4 hours of vaccination; vaccine anaphylaxis typically occurs within 30 minutes of vaccination, is rapidly progressive, and includes systemic signs such as hypotension or hypoxemia.2,3 A preloaded epinephrine autoinjector (choice B) is not indicated for acute urticaria or angioedema, unless there is a strong suspicion of anaphylaxis.4 Systemic glucocorticoids (choice D) are not recommended for most patients with acute urticaria with or without angioedema.1,4 Moreover, glucocorticoids may alter the immunologic response to COVID-19 vaccination.4,5

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Article Information

Corresponding Author: Kimberly G. Blumenthal, MD, MSc, The Mongan Institute, Massachusetts General Hospital, 100 Cambridge St, 16th Floor, Boston, MA 02114 (e-kblumenthal@mgh.harvard.edu).

Published Online: April 14, 2022. doi:10.1001/jama.2022.5247

Conflict of Interest Disclosures: Dr Freeman reported receiving grants from the International League of Dermatologic Societies COVID-19 Dermatology Registry and National Institutes of Health (NIH) (K23); receiving royalties from UpToDate; and receiving in-kind support from the American Academy of Dermatology for the COVID-19 Dermatology Registry. Dr Blumenthal reported receiving grants from the Massachusetts General Hospital Transformative Scholar Award, Executive Committee on Research, COVID-19 Junior Investigator Support Initiative, Agency for Healthcare Research and Quality (R01HS025375), and NIH (R01 AI150295); receiving royalties from UpToDate; and receiving personal fees from Weekley, Schulte, Valdes, Murman, and Tonelli; Vasios, Kelly, and Strollo; and Piedmont Liability Trust. No other disclosures were reported.

Additional Information: We thank the patient for providing permission to share her information.

Zuberbier  T , Abdul Latiff  AH , Abuzakouk  M ,  et al.  The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.   Allergy. 2022;77(3):734-766. doi:10.1111/all.15090PubMedGoogle ScholarCrossref
Klein  NP , Lewis  N , Goddard  K ,  et al.  Surveillance for adverse events after COVID-19 mRNA vaccination.   JAMA. 2021;326(14):1390-1399. doi:10.1001/jama.2021.15072PubMedGoogle ScholarCrossref
Blumenthal  KG , Robinson  LB , Camargo  CA  Jr ,  et al.  Acute allergic reactions to mRNA COVID-19 vaccines.   JAMA. 2021;325(15):1562-1565. doi:10.1001/jama.2021.3976PubMedGoogle ScholarCrossref
Macy  E .  Practical management of new-onset urticaria and angioedema presenting in primary care, urgent care, and the emergency department.   Perm J. 2021;25(4):104-110. doi:10.7812/TPP/21.058PubMedGoogle ScholarCrossref
Deepak  P , Kim  W , Paley  MA ,  et al.  Effect of immunosuppression on the immunogenicity of mRNA vaccines to SARS-CoV-2: a prospective cohort study.   Ann Intern Med. 2021;174(11):1572-1585. doi:10.7326/M21-1757PubMedGoogle ScholarCrossref
Folci  M , Ramponi  G , Brunetta  E .  A comprehensive approach to urticaria: from clinical presentation to modern biological treatments through pathogenesis.   Adv Exp Med Biol. 2021;1326:111-137. doi:10.1007/5584_2020_612PubMedGoogle ScholarCrossref
Taşkapan  O , Harmanyeri  Y .  Evaluation of patients with symptomatic dermographism.   J Eur Acad Dermatol Venereol. 2006;20(1):58-62. doi:10.1111/j.1468-3083.2005.01372.xPubMedGoogle ScholarCrossref
Kadali  RAK , Janagama  R , Peruru  S ,  et al.  Non-life-threatening adverse effects with COVID-19 mRNA-1273 vaccine: a randomized, cross-sectional study on healthcare workers with detailed self-reported symptoms.   J Med Virol. 2021;93(7):4420-4429. doi:10.1002/jmv.26996PubMedGoogle ScholarCrossref
Robinson  LB , Fu  X , Hashimoto  D ,  et al.  Incidence of cutaneous reactions after messenger RNA COVID-19 vaccines.   JAMA Dermatol. 2021;157(8):1000-1002. doi:10.1001/jamadermatol.2021.2114PubMedGoogle ScholarCrossref
Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States. Accessed March 13, 2022. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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