Rare cutaneous adverse effects of COVID‐19 vaccines: a case series and review of the literature

Abstract

Among the vaccines against coronavirus disease 2019 (COVID-19), BNT162b2 from BioNtech-Pfizer and mRNA-1273 from Moderna are mRNA vaccines targeting the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ChAdOx1 nCoV-19 (AZD1222) from Oxford-AstraZeneca is based on adenovirus expressing the full-length spike protein. Clinical trials reported different cutaneous adverse events, mainly local injection site reactions, either immediate or delayed on/after 8 days.1-3 We conducted a retrospective observational study among patients referred to the Dermatology Department of Cochin Hospital from January 2021 to April 2021 who presented with skin manifestations induced by COVID-19 vaccines. We excluded patients with immediate and/or delayed local site injection reactions. We included 8 consecutive cases, 3 men and 5 women, aged from 44 to 80 years, with no history of prior SARS-CoV-2 infection (6 patients had negative SARS-CoV-2 serology) or prior vaccine/drug-induced manifestations (Table 1). Five, 1 and 2 patients received Pfizer, Moderna or Oxford-AstraZeneca vaccine, respectively. We observed various skin reactions on average 6 days after the first dose: 2 morbilliform exanthemas, diffuse cutaneous erythema, acute generalized exanthematous pustulosis (AGEP), localized oedematous infiltrated plaque, erythematous indurated nodules or livedo racemosa (Fig. 1, Table 1). Patient 6 developed fixed drug eruption (FDE) 2 days after the second dose without previous history of FDE. No associated systemic manifestation was observed except in Patients 7 and 8 who presented with eosinophilia and fever, respectively. Patient 5 showed a livedo racemosa mimicking erythema ab igne without history of chronic heat exposure. A skin biopsy was performed in 7 patients (Table 1). Pathological examination showed several different non-specific patterns including association of features of spongiotic and interface dermatitis. Several cases resembled cutaneous drug reactions and 2 had inflammatory infiltrate with numerous eosinophils. In one case, skin biopsy displayed a superficial and deep perivascular and perieccrine lymphocytic infiltrate similar to those of chilblains or chilblain-like lesions. Symptoms subsided within 8–30 days in 6 patients; mild symptoms persisted in 2 cases. Relapse or new skin manifestations occurred in 2 patients following the second dose without worsening of symptoms. Patient 3 relapsed 4 days after the second dose with diffuse cutaneous erythema, also treated with topical corticosteroids and UVB phototherapy. Patient 2 presented with 2 erythematous nodules 4 days after the first dose and chilblains 5 days after the second dose without nodules relapse. A serology performed 2 days after chilblains onset revealed high levels of spike-specific IgG antibodies. Patient 7 presenting with AGEP did not relapse upon second dose of Pfizer vaccine (Table 1). Various skin reactions (local site and delayed large local reaction, urticaria, morbilliform purpuric and/or oedematous rash, erythromelalgia, pernio/chilblains, vasculitis) were recently described following Pfizer or Moderna COVID-19 vaccine.3-5 We report for the first time vaccine-induced livedo, FDE, AGEP or distant localized oedematous infiltrated plaques or nodules. Relapse occurred in 2 of our patients following the second dose without worsening of symptoms. One relapsing morbilliform rash and 2 cases of recurrent chilblains were described in patients following Moderna and Pfizer vaccine.6-8 In McMahon study, 43% of patients with first-dose reactions experienced second-dose recurrence with similar, milder or more severe reactions in 28%, 28% and 45% of cases, respectively.4 Practitioners should be aware of these side-effects of COVID-19 vaccines which do not require vaccination discontinuation. Similar COVID-19-associated manifestations have been described in a registry of 716 cases: morbilliform rash (22%), pernio-like lesions (18%), urticaria (16%), retiform purpura (6.4%), and macular erythematous (13%), or vesicular (11%), or papulo-squamous lesions (9.9%).9, 10 One could hypothesize a common immune response directed against the spike RNA or protein inducing vaccine and virus-associated skin lesions. The patients in this manuscript have given written informed consent to publication of their case details in accordance with French Bioethics Law for retrospective non-interventional research studies. The authors would like to thank all members of the Dermatology medical team of Cochin Hospital. Of note, Patient 2 case report has previously been published (PMID 34396420). N.D., S.G. and B.O. designed the study. E.A. N.D., B.G., N.F., S.A., S.G. and B.O. consulted with the different patients. E.A., S.G. and B.O collected the data. P.S. performed the pathological analysis. E.A., N.D., S.G. and B.O. wrote the manuscript with the input from all the other authors. None. None.

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