To date, several individuals have received COVID-19 vaccinations; therefore, the development of adverse skin reactions is expected. We report a peculiar cutaneous eruption post anti-Covid-19 vaccination (BNT162B2/Pfizer) in a woman without comorbidities, with a previous history of Covid 19 infection. A 51-year-old female patient, in good general health, had a symptomatic Covid-19 infection in April 2020 with fever, arthralgia, loss of taste and smell for 3 months and peripheral leg neuropathy that lasted for a few days; at this time, she did not present any skin manifestation. The initial anti-spike antibody value was 70.2 AU/ml (n.v. AU <12 ml). In early January 2021, 6 h after the first dose anti-Covid-19 vaccination (BNT162B2/Pfizer), she presented edema and pain at the injection site and, the next day, arthralgia, fever, and the appearance of an itchy maculopapular rash. Initially, the eruption was localized on the upper limbs (volar surface) (Figure 1A), retro-auricular region and, 1-day later, on the trunk. Anti-spike antibody value at this time was >400 AU/ml and neutralizing antibodies titer was 1:640. Nasal swab proved negative for Sars-Cov-2 virus. Two skin biopsies for histological examination and direct immunofluorescence were done. By histology, a lymphocytic vasculitis with lymphocytes infiltrating the wall of small dermal vessels, with endothelial swelling was noticed (Figure 1B) in absence of thrombi. A predominance of T CD4+ lymphocytes (Dako) over T CD8+ cells (Dako) was noticed (Figure 1C,D); immunostaining with anti-SARS-CoV-2 nucleocapsid protein antibody (Sino Biological) did not show any specific reactivity. Direct immunofluorescence directed to IgG, IgM, IgA fibrinogen, and C3 (Dako, Denmark) did not reveal any deposits in the vessels. Further blood analyses to exclude concomitant viral reactivations (in particular HHV-6-DNA, HHV-7-DNA, EBV-DNA, and CMV-DNA) proved negative; parvovirus IgG and IgM were absent. Therapy with systemic antihistamine and local steroid led to the resolution of the manifestations within a week. Due to the high level of immunization demonstrated by the serological test, the second dose of vaccine was not carried out. Vaccination in previously infected subjects is still debated as an opportunity to strengthen the defenses against the virus; however, the possible side effects are not yet fully known.1 New scientific evidences point to the possibility to perform a single dose vaccination in those who have a history of previous Covid-19 infection.2 In particular, a single dose of mRNA vaccine elicits very rapid immune responses in seropositive individuals with post-vaccine antibody titers comparable to or exceed titers found in naïve individuals who received two vaccinations.2 By now, the cutaneous patterns of symptomatic disease are well described, and the maculopapular manifestation is one of the most frequently seen and associated with a direct effect of the virus on the skin.3 After the observation of our single case, it can be hypothesized that the immune response to the virus/vaccination is also involved in the development of skin eruptions, targeting small vessels. New insights about cross-reactivity between human tissue and SARS-CoV-2 have been recently demonstrated and the possibility of development of autoimmune disease reported.4, 5 Immune response against the viral antigen following infection or vaccination can react with human tissue because of mimicry.4 The involvement of the vessel might explain the late vascular side effect such as chilblain eruption. In fact, histologically, the presence of lymphocytic vasculitis has been found also in Covid-19 chilblain eruption that; however, has in common with our case only the benign clinical course.6-8 Lymphocytic vasculitis can be find also in lupus erythematosus; however, direct immunofluorescence and autoimmune serology proved negative in our patient. The clinical features of our patient point to a post-vaccination rash similar to a paraviral eruption, rather than an allergic vaccine rash, which usually presents with anaphylactic or urticarial features.3 The timing of the eruption favors a post-vaccine eruption rather than a delayed reaction to SARS-CoV2 infection. In summary, we describe the occurrence of a peculiar post Covid-19 vaccination maculopapular rash characterized by lymphocytic vasculitis as the main histological finding, rapidly responding to systemic antihistamine and local steroid therapy.

FIGURE 1 Open in figure viewer PowerPoint (A) An itchy maculopapular rash localized symmetrically on both arms (B) perivascular lymphocytic infiltrate with endothelial swelling of small vessels (hematoxylin and eosin, x40); (C) CD4+ lymphocytes predominate over CD8+ cells (D) in the perivascular infiltrate (x20)