Mucocutaneous reactions, such as pruritus, urticaria, and angioedema, may occur after COVID-19 messenger RNA (mRNA) vaccination. To our knowledge, the incidence of these reactions and recurrence with subsequent vaccination has not been described. Cutaneous reactions may contribute to unnecessary avoidance of future vaccination doses.

Methods

We prospectively studied Mass General Brigham employees who received an mRNA COVID-19 vaccine (first dose: December 16, 2020, to January 20, 2021; follow-up through February 26, 2021; eMethods in the Supplement). Institutional review board approval was provided by the Mass General Brigham human research committee with a waiver of informed consent. For 3 days after vaccination, employees completed daily symptom surveys through a multipronged approach, including email, text message, phone, and smartphone application links. Cutaneous reactions included rash or itching (other than the injection site), hives, and/or swelling of the lips, tongue, eyes, or face (eAppendix in the Supplement).

We calculated the number and frequency of self-reported cutaneous reactions with 95% confidence intervals using symptom survey respondents by dose as the denominator. We compared frequencies using χ2 tests. Statistical analyses were conducted using SAS, version 9.4 (SAS Institute), and statistical significance was set at P < .05.

Results

Of 49 197 employees who received the first dose of a COVID-19 vaccine, 12 464 (25%) received the Pfizer-BioNtech vaccine and 36 733 (75%) received the Moderna vaccine. At least 1 symptom survey was completed by 40 640 (83%) after the first dose of the vaccine.

Cutaneous reactions were reported by 776 respondents after dose 1 (1.9%; 95% CI, 1.8%-2.1%; Table and Figure). Rash and itching (other than at the injection site) was the most common cutaneous reaction, which was reported by 559 (1%; 95% CI, 1.8%-2.1%). The mean (SD) age of those reporting cutaneous reactions was 41 (14) years. Cutaneous reactions were more common in women (656 [85%]) than men (120 [15%]; P < .001) and differed by race (62% White individuals, 7% Black individuals, and 12% Asian individuals; P < .001]). More than one-third of employees who reported cutaneous reactions were physicians or nurses (285 [37%]).

Of those with self-reported cutaneous reaction to the first dose, 741 (95%) received their second dose. Among the 609 who completed a symptom survey after the second dose, 508 (83%) reported no recurrent cutaneous reactions.

Among those with no cutaneous reaction to the first dose, 765 (2.3%) reported cutaneous reactions after the second dose. Rash and itching (other than the injection site) was the most common (546 [1.6%]; 95% CI, 1.5%-1.8%).

Discussion

In this prospective cohort of almost 50 000 health care employees, 1.9% self-reported cutaneous reactions after receiving the first dose of an mRNA COVID-19 vaccine. With more than 600 employees with first-dose cutaneous reactions included, 83% did not have recurrent cutaneous reactions. An additional 2.3% reported cutaneous reactions only after the second dose of the vaccine.

Cutaneous reactions were more commonly reported among women, which was similar to reported local injection site reactions and anaphylaxis after mRNA COVID vaccinations.1,2 To our knowledge, the underlying cause for this difference is not yet known, although drug allergies are more common in women.3

The limitations of this study include the use of self-reported data. However, many employees were clinicians; thus, the data may be more reliable. Self-reported reactions may contribute to vaccine hesitancy. This study captures cutaneous reactions that occurred within 3 days after vaccination and thus cannot assess for delayed cutaneous reactions.2

Cutaneous reactions, including itching, rash, hives and swelling, occurred in more than 4% of those who received the 2-dose mRNA COVID-19 vaccines. The spectrum of reported cutaneous reactions after mRNA vaccination include large local reactions, urticaria, and morbilliform reactions.2,4 Unlike anaphylaxis, cutaneous reactions alone are not a contraindication to revaccination.5 In this cohort, most individuals received the second dose without recurrent reactions. Referral to an allergist or dermatologist is not necessary for most reactions but should be considered for patients who experience immediate or severe reactions.6 These data are reassuring for the millions of Americans who may develop cutaneous reactions after vaccination in the coming year.

Back to top Article Information

Accepted for Publication: May 3, 2021.

Published Online: June 23, 2021. doi:10.1001/jamadermatol.2021.2114

Corresponding Author: Lacey B. Robinson, MD, MPH, Massachusetts General Hospital, 55 Fruit St, Cox 201, Boston, MA 02114 (lbrobinson@mgh.harvard.edu).

Author Contributions: Drs Robinson and Blumenthal had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Robinson, Blumenthal.

Acquisition, analysis, or interpretation of data: Robinson, Hashimoto, Wickner, Shenoy, Landman, Blumenthal.

Drafting of the manuscript: Robinson, Blumenthal.

Critical revision of the manuscript for important intellectual content: Robinson, Hashimoto, Wickner, Shenoy, Landman, Blumenthal.

Obtained funding: Blumenthal.

Administrative, technical, or material support: Hashimoto, Wickner, Shenoy, Landman, Blumenthal.

Supervision: Blumenthal.

Conflict of Interest Disclosures: Dr Blumenthal reports grants from the American Academy of Allergy Asthma and Immunology Foundation, CRICO, and Massachusetts General Hospital outside the submitted work. Dr Landman reports personal fees from Abbott Medical Device Cybersecurity Council outside the submitted work. Dr Wickner reports employment with CVS Health outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by National Institutes of Health (NIH) grant K01 AI125631 and the Massachusetts General Hospital (MGH) DOM Transformative Scholar Program.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank many colleagues in the Mass General Brigham health system for the design and implementation of the COVID-19 vaccination program, including Paul D. Biddinger, MD, Thomas D. Sequist, MD, MPH, Upeka Samarakoon, MS, PhD, MPH, Rajesh Patel, MD, MPH, Leeann Ouimet, MBA, Allen Judd, AB, Aleena Banerji, MD, Anna R. Wolfson, MD, Rebecca Saff, MD, PhD, Aidan A. Long, MD, Lily Li, MD, Tanya M. Laidlaw, MD, David I. Hong, MD, Anna M. Feldweg, MD, Katrin Stinson, MPH, Amanda J. Centi, PhD, Lynn Simpson, MPH, Nahal Beik, PharmD, BCPS, Christian M. Mancini, BS, Amelia S. Cogan, MPH, and Aubree E. McMahon, BA. No compensation was received.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, Mass General Brigham, nor MGH.