Skin reactions to COVID-19 vaccines

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

• Pityriasis rosea

  • Reported with both COVID-19 infection and COVID-19 vaccines.

• Varicella zoster and herpes simplex flares

  • Case reports have documented flares following COVID-19 vaccination.

• Raynaud phenomenon

  • A case has been reported occurring 2 weeks after the COVID-19 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.

• Subacute cutaneous lupus erythematosus

  • Induction and flares have been reported.
  • Onset days to 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. However, a recent study involving over 2000 individuals did not show that vaccination statistically significantly exacerbated either atopic eczema or psoriasis.

• 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).

• Neutrophilic and Pustular Drug Reactions

  • Both acute generalised exanthematous pustulosis (AGEP) and a pustular flare of psoriasis associated with an inactivated viral vector COVID-19 vaccine have been published.
  • A further case report was classified as an overlap between AGEP and drug reaction with eosinophilia and systemic symptoms (DRESS) associated with COVID-19 vaccination.

• 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.