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Skin reactions to COVID-19 vaccines

Authors: Dr Sarah Elyoussfi (Dermatology Registrar) and Dr Ian Coulson (Consultant Dermatologist), Department of Dermatology, East Lancashire NHS Trust, United Kingdom. Copy edited by Gus Mitchell. December 2021. Further updated December 2022


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What are the COVID-19 vaccines?

The coronavirus disease 2019 (COVID-19) pandemic has led to the development and approval of vaccines against the responsible virus — severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 100 companies and institutions worldwide have developed vaccine candidates. 

How do the COVID-19 vaccines differ?

Current approved vaccines rely on a nucleic-acid-based vaccine platform

  • Messenger ribonucleic acid (mRNA) eg, Pfizer/BioNTech + Fosun Pharma, Moderna + National Institute of Allergy and Infectious Diseases
  • Viral vector platforms eg, AstraZeneca + University of Oxford, Janssen Pharmaceutical
  • Inactivated virus eg, Sinopharm + China National Biotec Group Co
  • Protein subunit vaccines eg, Novavax (not yet approved in any country)

What are the common types of skin reaction to COVID-19 vaccines?

The majority of current literature regarding cutaneous reactions relate specifically to mRNA COVID-19 vaccinations.

The spectrum of reported cutaneous reactions after mRNA vaccination include: 

  • Local site reaction
    • Swelling, erythema, and pain in the vaccinated arm.
    • Median onset of 1 day after vaccination.
  • Urticaria
    • Median onset reported on day 2–3 after vaccination.
    • Common sites include arms (68%), trunk (57%), and legs (46%).
  • Morbilliform eruptions
    • Median onset reported on day 2–3 after vaccination.
    • Common sites include the arm (62%), legs (27%), and trunk (42%).
  • Delayed large local reaction (“COVID arm")
    • The COVID-19 vaccines may cause a delayed localized hypersensitivity reaction presenting as a pruritic and painful erythematous reaction near the injection site.
    • Median development of 7 days after vaccine administration with a median duration of 5 days, but can persist for up to 21 days.
    • Pink plaques are variably oedematous and typically homogenous or less commonly annular.
    • Sweet syndrome-like local reactions have been reported.
    • Treatments include topical steroids, oral antihistamines, and cool compresses, but lesions are usually self-limiting
    • Eosinophilic pustular folliculitis may be triggered by Covid vaccines.

How common are cutaneous reactions after COVID-19 vaccination?

In one study, cutaneous reactions within 3 days after receiving the vaccine were reported in 1.9% of individuals after receiving their first dose of the mRNA COVID vaccine (Pfizer-BioNtech and Moderna).

The majority of cutaneous reactions after COVID-19 vaccination occur in women (around 90%). Erythema and itching (other than at the injection site) was the most common cutaneous reaction, which was reported by 1%.

In a study (May, 2021) of those with a self-reported cutaneous reaction to the first dose, 95% received their second dose. Among those who completed a symptom survey after the second dose, 83% reported no recurrent cutaneous reactions.

However, a different study (July, 2021) reported that 43% of patients receiving an mRNA COVID-19 vaccine who reported first-dose reactions, experienced a second-dose recurrence.

What are the uncommon mild skin reactions to COVID-19 vaccines?

  • Filler reactions
    • Swelling at the site of cosmetic fillers has been reported after COVID-19 vaccination. Reports have identified patients with facial swelling after both Moderna and Pfizer vaccines associated with prior use of injectable cosmetic filler.
    • May indicate delayed hypersensitivity to filler following introduction of an immunologic trigger. Similar reactions have been previously noted after other viral illnesses and influenza vaccines.
  • Erythromelalgia
    • Erythromelalgia has also been reported in response to other vaccines such as those for influenza and hepatitis B.
  • Pernio/chilblains
    • Mimics dermatologic manifestations of COVID-19 (COVID toes)
    • Potentially suggests that the host immune response to the virus is being replicated by the vaccine

What are the uncommon serious skin reactions to COVID-19 vaccines? 

  • Bullous pemphigoid
    • Relapses of autoimmune bullous disease have been reported
    • Onset within 3 days – 2 weeks following vaccination.
  • Exacerbation of underlying skin condition
    • COVID-19 vaccination may trigger exacerbation of a pre-existing inflammatory skin condition such as psoriasis and atopic dermatitis
  • Lichen planus
    • The vaccine leads to increased levels of IL-2, TNF-α, and IFN-γ — the exact cytokines involved in the development of lichen planus. Reports of this condition following vaccination have been made.
  • Erythema multiforme
    • Linked to the first dose of Moderna COVID-19 vaccine.
    • It should be noted that major-type EM is considered to be a continuous spectrum with life-threatening toxic anti-epithelial reactions (e.g., Stevens–Johnson syndrome, toxic epidermal necrolysis).
  • Anaphylaxis
    • Rare even with rates of 4.7 cases/million doses of the Pfizer-BioNTech and 2.5 cases/million doses of the Moderna vaccine
    • Anaphylaxis to vaccines generally is usually due to individual vaccine components, such as egg protein, gelatin, and other additives. However, the cause of vaccine anaphylaxis with the COVID-19 vaccine cases is unclear, but polyethylene glycol (PEG 2000) is a candidate allergen.
    • Common signs and symptoms include generalised urticaria, angioedema, and respiratory and airway obstruction symptoms.
    • Onset is typically within minutes to hours of administration.

Although the Pfizer/BioNTech vaccine contains a number of excipients, PEG 2000 is the only one reported to cause anaphylaxis. The Oxford-AstraZeneca vaccine does not contain PEG 2000 so is an alternative for people with a history of allergy to PEG 2000. However, there is occasional cross-reactivity between PEG and polysorbate 80, an ingredient in the Oxford-AstraZeneca vaccine. Evaluation by an allergy specialist may be advisable before vaccination in anyone with a suspected PEG allergy.

Contraindications for receipt of the mRNA COVID-19 vaccines include:

  • Known history of a severe allergic reaction to any vaccine component, including the excipient PEG 2000
  • An allergic reaction to a previous dose of an mRNA vaccine.

Identification of risk factors for allergy symptoms after COVID-19 vaccination will guide safe vaccination practices for individuals at the highest risk.

How are the COVID-19 skin reactions treated?

Severe cutaneous adverse reactions are very rare. The established vaccines have a satisfactory safety profile. Management should be directed at the presenting skin condition, however most of the encountered skin reactions are self-limiting.

Anaphylaxis requires prompt treatment with intramuscular adrenaline and oxygen.

Unlike anaphylaxis, cutaneous adverse reactions alone are not a contraindication to re-vaccination. The available evidence supports that cutaneous reactions to COVID-19 vaccination are generally minor, self-limiting, and should not discourage vaccination.

 

Bibliography

  • Al-Jighefee HT, Najjar H, Ahmed MN, Qush A, Awwad S, Kamareddine L. COVID-19 Vaccine Platforms: Challenges and Safety Contemplations. Vaccines (Basel). 2021;9(10):1196. doi: 10.3390/vaccines9101196. PubMed Central
  • Busto-Leis JM, Servera-Negre G, Mayor-Ibarguren A, et al. Pityriasis rosea, COVID-19 and vaccination: new keys to understand an old acquaintance. J Eur Acad Dermatol Venereol. 2021;35(8):e489–e491. doi:10.1111/jdv.17301. PubMed Central
  • Hiltun I, Sarriugarte J, Martínez-de-Espronceda I, et al. Lichen planus arising after COVID-19 vaccination. J Eur Acad Dermatol Venereol. 2021;35(7):e414–e415. doi:10.1111/jdv.17221. PubMed Central
  • Johnston MS, Galan A, Watsky KL, Little AJ. Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series. JAMA Dermatol. 2021;157(6):716–20. Journal
  • Joseph AK, Chong BF. Subacute cutaneous lupus erythematosus flare triggered by COVID-19 vaccine. Dermatol Ther. doi: 10.1111/dth.15114. Journal
  • Lospinoso K, Nichols CS, Malachowski SJ, Mochel MC, Nutan F. A case of severe cutaneous adverse reaction following administration of the Janssen Ad26.COV2.S COVID-19 vaccine. JAAD Case Rep. 2021;13:134–7. doi:10.1016/j.jdcr.2021.05.010. PubMed Central
  • 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.2021.03.092. PubMed Central
  • Niebel D, Novak N, Wilhelmi J, et al. Cutaneous Adverse Reactions to COVID-19 Vaccines: Insights from an Immuno-Dermatological Perspective. Vaccines (Basel). 2021;9(9):944. doi:10.3390/vaccines9090944. PubMed Central
  • Robinson LB, Fu X, Hashimoto D, et al. Incidence of Cutaneous Reactions After Messenger RNA COVID-19 Vaccines. JAMA Dermatol. May 2021;157(8):1000–2. doi:10.1001/jamadermatol.2021.2114. Journal
  • Sellaturay P, Nasser S, Islam S, Gurugama P, Ewan PW. Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID-19 vaccine. Clin Exp Allergy. 2021;51(6):861–3. doi: 10.1111/cea.13874. Journal
  • Shimabukuro TT, Cole M, Su JR. Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US-December 14, 2020-January 18, 2021. JAMA. 2021;325(11):1101–2. doi:10.1001/jama.2021.1967. Journal

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