Cutaneous adverse reactions after m‐RNA COVID‐19 vaccine: early reports from Northeast Italy

Abstract

We report the first registered cases of cutaneous adverse reactions in Northeast Italy after the m-RNA COVID-19 vaccine Comirnaty®-BioNTech/Pfizer (BioNTech Innovative Manufacturing Services GmbH, Idar-Oberstein, Germany). During January 2021, in the public health jurisdiction of Trieste, a total of 19 485 individuals have been vaccinated: 13 266 (68.08%) first doses and 6219 (31.92%) completed cycles of two doses. In this population, 266 (1.36%) adverse reactions have been reported to the Pharmacovigilance Service. Notably, one or more cutaneous adverse effects were present in 44 people, accounting for 0.22% of all vaccinated individuals and 16.54% of communicated adverse effects. The reactions included both those at the injection site and more extensive manifestations (Table 1). 38 Fig. 1a–b 39 Fig. 1e 40 Fig. 1f 41 Fig. 1g Malar erythema, 12 h after the first dose; erythema of the face, trunk and thighs with fever, 3 days after the second dose 45 Fig. 1c 46 Fig. 1d Nine subjects were evaluated in a Dermatology Clinic of the Friuli Venezia-Giulia region, in North-East Italy (Table 1, patients nr. 38–46). Three of them presented with a diffuse urticaria (Fig. 1a–c), with onset of 60 h to 5 days after the first dose. For these three subjects, advise for not applying the second dose was given. Interestingly, one more patient developed an urticarial rash limited to the chest, together with chilblain-like manifestations on the first and third finger of one foot (Fig. 1d). The other cutaneous reactions observed in the remaining five patients were as follows: a malar erythema, an erythematous macular rash of the hands (Fig. 1e), a fixed drug eruption (FDE, Fig. 1f) and two cases resembling pityriasis rosea (Fig. 1g). Even if the first two reactions are not easy to interpret from a pathogenetic point of view, all five patients completed the two-dose vaccine cycle. The outlined manifestations are quite heterogeneous and occur within a time frame of 60 h to 10 days after injection. Their course was mostly mild and self-limiting. Only one patient with urticaria (nr. 45) required intravenous steroid treatment. With regard to the urticarial manifestations, Polyethylene glycol-2000 (PEG-2000), an excipient of the vaccine, may play a role. In fact, PEG contained in several drugs can produce immediate hypersensitivity reactions1 and cases of urticaria have been reported.2 Moreover, PEG is investigated as possible responsible for the rare cases of anaphylaxis induced by BioNTech/Pfizer vaccine.3, 4 The question of completing the vaccination cycle, after urticaria triggered by the first dose, remains open. We preferred to avoid exposure to the second dose, because it is currently unclear whether it should be regarded as a risk factor for anaphylaxis, although the timing of onset after exposure is not consistent with a type I Ig-E mediated reaction. Regarding the other observed reactions, it must be admitted that FDE represents a stereotypic reaction induced by drugs, but it is rarely induced by vaccines.5 Conversely, pityriasis rosea has been reported after vaccinations or drug use.6, 7 It appears remarkable that urticarial, pityriasis rosea-like rashes or chilblain-like changes have been frequently reported during or after COVID-19.8-10 For two patients (nr. 45–46), a swab and a serological test for SARS-CoV-2 resulted negative. For the remaining cases, we cannot exclude with certainty a contagion with SARS-CoV-2 shortly before or after the vaccine injection. In conclusion, cutaneous adverse reactions triggered by Comirnaty®-BioNTech/Pfizer are seldom but appear similar to those reported during SARS-CoV-2 infections. Limitations of this study include the use of self-reported data. However, the reporting subjects were largely healthcare workers, and therefore, the reliability of data can be considered high. In addition, all the reports show a temporal relation with the vaccine, but this does not allow us to conclude that a true causal link exists. The exact biological mechanisms underlying cutaneous effects after this m-RNA COVID-19 vaccine have still to be elucidated, and further studies based on larger cohorts are needed to better understand them. The persons in this manuscript have given written informed consent to publication of their case details. None. The authors have no conflict of interest.

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