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

Dear Editor,

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).

Table 1

Summary of the total cutaneous adverse reactions reported to the Pharmacovigilance Service of Trieste (patients nr.1–44), including those evaluated at the Dermatology Clinic of Trieste (patients nr.38–44) and in other clinics of the Friuli Venezia‐Giulia region, in Northeast Italy (patients 45–46)

Patient	Sex, Age	Cutaneous adverse reaction, timing of onset (if specified)	First or Second dose
1	F, 55	Urticarial rash limited to the upper limbs	First
2	F, 27	Urticarial rash limited to the neck and chest	Not reported
3	F, 64	Itchy erythema of the neck and hands	First
4	M, 38	Itching at the inoculation site	First
5	F, 49	Erythema at the inoculation site	First
6	F, 23	Urticarial rash limited to the chest	First
7	F, 49	Itchy erythema of the palms	First
8	F, 32	Itchy dermatitis of the face with fever	First
9	F, 34	Generalized itching	First
10	F, 37	Morbilliform eruption	Not reported
11	F, 43	Painful and itchy erythematous subcutaneous nodule at the inoculation site, 3 days after the dose	First
12	F, 50	Erythema of the chest and hands	First
13	F, 34	Urticarial rash limited to the upper limbs	First
14	F, 53	Painful hardening of the skin at the inoculation site with fever	Second
15	F, 65	Swelling of the face, 18 h after the dose	First
16	F, 51	Itchy arm with axillary lymphadenopathy, 24 h after the dose	First
17	F, 57	Painful swelling and erythema of the right eyelid, 7 days after the dose	First
18	F, 52	Generalized itching	First
19	F, 46	Burning wheal at the inoculation site	First
20	F, 63	Itchy wheal at the inoculation site	First
21	M, 28	Itchy swelling at the inoculation site	First
22	F, 56	Erythematous and itchy hardening of the skin at the inoculation site with fever	Second
23	F, 34	Herpes Zoster of the scalp	First
24	F, 46	Erythema at the inoculation site, 1 day after the dose	First
25	F, 46	Urticarial rash limited to the chest and lower limbs	First
26	F, 37	Cutaneous rash of the trunk	Second
27	F, 46	Generalized itching	First
28	F, 65	Nodule following itchy erythema at the inoculation site	First
29	F, 37	Painful wheal at the inoculation site	First
30	F, 55	Erythema at the inoculation site with fever	Second
31	F, 37	Swelling of the eyelids and face with mandibular lymphadenopathy	First
32	M, 70	Erythema at the inoculation site	First
33	F, 26	Painful swelling at the inoculation site	First
34	F, 39	Wheal at the inoculation site with axillary lymphadenopathy	First
35	F, 36	Itchy erythema of the abdomen, 1 week after the dose	First
36	F, 35	Swelling at the inoculation site with fever	Second
37	F, 48	Herpes Zoster	First
38 Fig. 1a–b	F, 54	Diffuse urticaria, 5 days after the dose	First
39 Fig. 1e	F, 41	Erythematous macular rash of the hands, 8 days after the dose	First
40 Fig. 1f	F, 44	Purplish macule on the third finger of one hand (fixed drug eruption), 10 days after the dose	Second
41 Fig. 1g	F, 42	Pityriasis rosea‐like rash on the thighs and abdomen, 4 days after the dose	Second
42	M, 64	Pityriasis rosea‐like rash on the neck, upper limbs, and trunk, 5 days after the dose	First
43	M, 18	Diffuse urticaria, 60 h after the dose	First
44	F, 55	Malar erythema, 12 h after the first dose; erythema of the face, trunk and thighs with fever, 3 days after the second dose	First and second
45 Fig. 1c	F, 34	Diffuse urticaria; transient periorbital and perioral swelling, 4 days after the dose	First
46 Fig. 1d	F, 27	Chilblain‐like rash on the first and third finger of one foot accompanied by urticarial rash, 4 days after the first dose; urticarial rash, 1 day after the second dose	First and second

Data were collected during the vaccination campaign with Comirnaty®‐BioNTech/Pfizer (m‐RNA COVID‐19 vaccine) in January 2021.

Figure 1

Cutaneous adverse reactions after administration of Comirnaty®‐BioNTech/Pfizer, an m‐RNA COVID‐19 vaccine. (a–c) Diffuse urticaria. (d) Chilblain‐like rash on the first and third finger of the left foot. (e) Erythematous macular rash of the hands. (f) Purplish macule on the third finger of the right hand, consistent with the diagnosis of fixed drug eruption. (g) Pityriasis rosea‐like plaque (located on abdomen).

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 reactions and cases of urticaria have been reported. Moreover, PEG is investigated as possible responsible for the rare cases of anaphylaxis induced by BioNTech/Pfizer vaccine. ,

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. Conversely, pityriasis rosea has been reported after vaccinations or drug use. , It appears remarkable that urticarial, pityriasis rosea‐like rashes or chilblain‐like changes have been frequently reported during or after COVID‐19. , , 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.

Funding sources

None.

Conflict of interest

The authors have no conflict of interest.