Cutaneous reactions after COVID-19 vaccination: an update

Cutaneous reactions after vaccination for COVID-19 do not only occur immediately but can be seen up to 11 days after the first shot. They are most common in patients vaccinated with Moderna.

“First reports of unusual COVID-19 vaccine skin reactions came through social media rather than classic media,” explained Prof. Esther Freeman (Harvard Medical School, MA, USA) [1]. The first publication included 12 case reports in the New England Journal of Medicine this year [2]. Of note, all reactions appeared near the injection site after complete resolution of the initial local and systemic symptoms associated with vaccination. These delayed large reactions were evident at day 7 or 8 after the first shot with various morphologies. Biopsies revealed a basic lymphocytic infiltrate. These large local reactions were mainly seen after vaccination with Moderna. A possible cause might be a reaction to polyethylene glycol. “We have seen few reactions with the other mRNA vaccine; the reasons are still not clear. However, it is reassuring that the reaction was either less severe or did not recur after the second dose of the vaccine,” Prof. Freeman stated. The reactions were seen sooner after the second vaccination – around day 2 or 3. As there is no infection, there is no indication for antibiotics.

Fortunately, anaphylaxis to mRNA vaccines is rare. Allergic reactions to mRNA vaccines were assessed in a prospective cohort of 64,900 healthcare employees in the USA [3]. For 3 days after vaccination, employees completed symptom surveys and were asked for symptoms of acute allergic reactions including itch, rash, hives, swelling, and/or respiratory symptoms. In this cohort, 40% received the Pfizer-BioNTech vaccine and 60% the Moderna vaccine. Most participants (98%) reported not having any symptoms of an allergic reaction after receiving an mRNA COVID-19 vaccine. Some allergic symptoms were reported by 2%, but severe reactions consistent with anaphylaxis were rare: they occurred at a rate of 2.47 per 10,000 vaccinations. Moreover, all individuals with anaphylaxis recovered without shock or endotracheal intubation. “This study shows us that anaphylaxis is extremely rare with mRNA vaccines,” Prof. Freeman said.

The latest phase 3 trial published on the Pfizer-BioNTech vaccine showed no serious cutaneous reactions, only injection-site reactions [4]. In the phase 3 trials with Moderna, no serious cutaneous reactions were reported, but there were delayed injection-site reactions with an onset on or after day 8. These reactions were observed in 0.8% of patients after the first dose and 0.2% of patients after the second dose [4]. “They were really rare, but I suspect this was underreported in the trial,” Prof. Freeman said. There were also cutaneous reactions reported in the Johnson & Johnson vaccine trials (phase 1/2a). Reported cutaneous reactions in the overall vaccinated cohort were erythema (in 7%), swelling (in 5%), and pain (in 49%).

“The trial data did not give us much – I think we need to look at the real-world data,” Prof. Freeman said. This year, a registry-based study was published covering cases of cutaneous reactions after Moderna and Pfizer-BioNTech vaccination [5]. In this study, cases of cutaneous manifestations after COVID-19 vaccinations were collected from December 2020 to February 2021. Patients (n=414) reported one or more cutaneous reactions to Moderna (83%) or Pfizer-BioNTech (17%). The most common reactions were delayed large local reactions, local injection-site reactions, urticaria, and morbilliform eruptions. These reactions followed a typical timeline after the vaccination: local site reactions happened directly after the vaccination. Urticaria was seen around day 3, and 89% of cases were women. Morbilliform eruptions were seen 3–7 days after the first vaccination, most frequently on arms. Delayed large local reactions appeared 7–11 days after the first vaccination. “They were observed in >200 cases, 94% of those were vaccinated with Moderna,” Prof. Freeman said. These large local reactions were also seen after the second vaccination but on day 3. Other less common reactions included pernio and cosmetic filler reactions. The latter are not specific for COVID-19 and also occur in patients after influenza shots.

“Patients who have massive reactions after the first vaccine often do not want their second shot, but overall, we can be reassuring.” Prof. Freeman concluded that only 43% of patients with first-dose reactions experienced a recurrence after the second vaccination, and there was not a single case of anaphylaxis [5].

1. Freeman E. COVID-19 vaccine & the skin. Session S028: COVID-19 symposium. AAD VMX 2021, 23-25 April.
2. Blumenthal KG, et al. New Engl J Med 2021;384:1273-7.
3. Blumenthal KG, et al. JAMA 2021;325(15):1562-5.
4. Polack FP, et al. N Engl J Med 2020;383(27):2603-15.
5. McMahon D, et al. J Am Acad Dermatol 2021; Apr 7;S0190-9622(21)00658-7.

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Posted on 7 June 20217 June 2021