Association of Facial Pustular Neutrophilic Eruption With Messenger RNA–1273 SARS-CoV-2 Vaccine | Dermatology | JAMA Dermatology | JAMA Network
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July 28, 2021

Association of Facial Pustular Neutrophilic Eruption With Messenger RNA–1273 SARS-CoV-2 Vaccine

Author Affiliations
  • 1Department of Dermatology, University of California, San Francisco
  • 2Department of Dermatology, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California
  • 3Dermatopathology Service, Departments of Dermatology and Pathology, University of California, San Francisco
JAMA Dermatol. 2021;157(9):1128-1130. doi:10.1001/jamadermatol.2021.2474

Multiple cutaneous reactions to the messenger RNA (mRNA)–1273 SARS-CoV-2 vaccine have been reported, including immediate injection site reactions,1-3 delayed injection site reactions,1-4 and localized facial/lip swelling in prior dermal filler injection sites.2,3 We report a facial eruption that developed within 24 hours after receiving the mRNA-1273 vaccine in 2 patients without a history of known allergies, rosacea, facial/dental fillers, or prior SARS-CoV-2 infection.

Report of Cases

Patient 1

A previously healthy man in his 50s presented to our department 4 days after receiving his initial dose of the mRNA-1273 vaccine. Within 24 hours after receiving his vaccination, the patient noticed chills and facial swelling that developed into painless, nonpruritic erythema. At presentation, he did not have a fever and had a leukocytosis with neutrophil predominance. On examination, there were bilateral edematous, erythematous, well-demarcated plaques of the central face and eyelids with numerous punctate monomorphic pustules and crust (Figure 1A). The clinical differential diagnosis included acute localized exanthematous pustulosis, neutrophilic dermatosis, rosacea fulminans, Demodex folliculitis, and a skin and soft tissue infection. Cephalexin and halobetasol, 0.05%, ointment was prescribed. Cephalexin use ended 3 days later when a bacterial culture from a pustule did not reveal a causative organism. Histopathology results revealed an infiltrate of neutrophils interstitially and within intact follicular epithelium with negative infectious stains. (Figure 2, A and B). The rash cleared within 7 days. The patient received the second vaccine dose as scheduled without recurrence.

Figure 1.  Clinical Images of Facial Pustular Neutrophilic Eruption Associated With Messenger RNA (mRNA)–1273 SARS-CoV-2 Vaccine
Clinical Images of Facial Pustular Neutrophilic Eruption Associated With Messenger RNA (mRNA)–1273 SARS-CoV-2 Vaccine

Edematous, erythematous, well-demarcated plaques with overlying punctate monomorphic pustules and crusting on the central face and eyelids at 4 days after administration of an mRNA-1273 vaccine in patient 1 (A) and 5 days after vaccination in patient 2 (B).

Figure 2.  Histopathologic Images of Facial Pustular Neutrophilic Eruption Associated With Messenger RNA (mRNA)–1273 SARS-CoV-2 Vaccine
Histopathologic Images of Facial Pustular Neutrophilic Eruption Associated With Messenger RNA (mRNA)–1273 SARS-CoV-2 Vaccine

Hematoxylin-eosin–stained lesional specimens from patient 1. A, Interstitial and intrafollicular infiltrate composed mostly of neutrophils with some admixed lymphocytes and plasma cells that are present in the superficial and deep dermis. There is follicular dilatation and plugging. B, High magnification demonstrating neutrophils with prominent involvement of hair follicles.

Patient 2

A previously healthy man in his 80s presented to our department 5 days after receiving his second dose of the mRNA-1273 vaccine. He had not had a reaction after the first dose. Within 24 hours of receiving his vaccination, the patient noticed swelling, predominantly of the central face and eyelids, with worsening swelling, pain, and erythema over the next several days. He had weakness, malaise, and subjective fevers. At presentation, he did not have a fever, had tachycardia, and had a leukocytosis with neutrophil predominance. On examination, there were erythematous, edematous plaques spanning the eyelids, cheeks, and nasal dorsum; during the course of 24 hours, monomorphic submillimeter follicularly based pustules and crust emerged within the erythema (Figure 1B). Given the same clinical differential diagnosis as patient 1, he was prescribed vancomycin and piperacillin/tazobactam and tacrolimus, 0.1%, ointment. His systemic symptoms resolved within 24 hours. When infectious workup results did not reveal an obvious infection, antibiotics were narrowed to doxycycline and continued for an additional 5 days while awaiting histopathology results. Bacterial culture from a pustule did not reveal a causative organism. Histopathology results showed similar findings to patient 1. The rash completely resolved 10 days later.

Discussion

The clinical presentation of a facial rash with pustules and the shared histopathologic findings of a dense neutrophilic infiltrate interstitially and within intact follicular epithelium support a facial pustular neutrophilic eruption as the reaction pattern. The differential diagnosis can be narrowed to rosacea fulminans, neutrophilic dermatosis, and skin and soft tissue infection. The abrupt onset of facial erythema, edema, and pustules may be consistent with rosacea fulminans, although the lack of nodules, papules, and cysts and occurrence in 2 older men go against this diagnosis.5 The abrupt onset of marked edema and pustules fits well for a neutrophilic dermatosis, although negative tissue cultures are a diagnostic criterion. It is unclear if this facial eruption in the setting of the mRNA-1273 vaccine represents a distinct entity or an unmasking of a dermatologic condition in a predisposed individual. It is also notable that for patient 2, the eruption occurred after the second dose only, which has been reported elsewhere.3 Reassuringly, this facial pustular neutrophilic eruption resolved within 7 to 10 days and without serious sequelae. This is consistent with evidence that most cutaneous reactions that are associated with the mRNA SARS-CoV-2 vaccines are generally self-limited and minor.3

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Article Information

Corresponding Author: Aileen Y. Chang, MD, University of California, San Francisco, Department of Dermatology, San Francisco General Hospital, 995 Potrero, Bldg 90, Ward 92, Room 216, San Francisco, CA 94110 (aileen.chang@ucsf.edu).

Published Online: July 28, 2021. doi:10.1001/jamadermatol.2021.2474

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patients for granting permission to publish this information. We also thank Hovik Ashchyan, MD, Ayan Kusari, MD, and Jason F. Wang, MD, MS (University of California, San Francisco), for their involvement in the clinical care of these patients. They were not compensated for their contributions.

Additional Information: Drs Merrill and Kashem contributed equally as co–first authors of this work.

References
1.
Baden  LR, El Sahly  HM, Essink  B,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389 PubMedGoogle ScholarCrossref
2.
US Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee meeting December 17, 2020. Accessed March 18, 2021. https://www.fda.gov/media/144434/download
3.
McMahon  DE, Amerson  E, Rosenbach  M,  et al.  Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases.   J Am Acad Dermatol. 2021;85(1):46-55. doi:10.1016/j.jaad.2021.03.092PubMedGoogle ScholarCrossref
4.
Blumenthal  KG, Freeman  EE, Saff  RR,  et al.  Delayed large local reactions to mRNA-1273 vaccine against SARS-CoV-2.   N Engl J Med. 2021;384(13):1273-1277. doi:10.1056/NEJMc2102131 PubMedGoogle ScholarCrossref
5.
Walsh  RK, Endicott  AA, Shinkai  K.  Diagnosis and treatment of rosacea fulminans: a comprehensive review.   Am J Clin Dermatol. 2018;19(1):79-86. doi:10.1007/s40257-017-0310-0 PubMedGoogle ScholarCrossref
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