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Purpuric Skin Rash in a Patient Undergoing Pfizer Communication Purpuric Skin Rash in a Patient Undergoing Pfizer-BioNTech COVID-19 Vaccination: Histological Evaluation and Perspectives Gerardo Cazzato 1,* , Paolo Romita 2, Caterina Foti 1, Antonietta Cimmino 1, Anna Colagrande 1, Francesca Arezzo 3, Sara Sablone 4 , Angela Barile 1, Teresa Lettini 1 , Leonardo Resta 1 and Giuseppe Ingravallo 1 1 Section of Pathology, Departmente of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, 70124 Bari, Italy; [email protected] (C.F.); [email protected] (A.C.); [email protected] (A.C.); [email protected] (A.B.); [email protected] (T.L.); [email protected] (L.R.); [email protected] (G.I.) 2 Department of Biomedical Science and Human Oncology, Dermatological Clinic, University of Bari, 70124 Bari, Italy; [email protected] 3 Department of Biomedical Sciences and Human Oncology, Gynecologic and Obstetrics Clinic, 70124 Bari, Italy; [email protected] 4 Section of Legal Medicine, Department of Interdisciplinary Medicine, Policlinico di Bari Hospital, University of Bari, 70124 Bari, Italy; [email protected] * Correspondence: [email protected] Abstract: The COVID-19 pandemic has affected the entire planet, and within about a year and a half, Citation: Cazzato, G.; Romita, P.; has led to 174,502,686 confirmed cases of COVID-19 worldwide, with 3,770,361 deaths. Although it Foti, C.; Cimmino, A.; Colagrande, A.; is now clear that SARS-CoV-2 can affect various different organs, including the lungs, brain, skin, Arezzo, F.; Sablone, S.; Barile, A.; vessels, placenta and others, less is yet known about adverse reactions from vaccines, although more Lettini, T.; Resta, L.; et al. Purpuric and more reports are starting to emerge. Among the adverse events, we focused particularly on Skin Rash in a Patient Undergoing skin rashes. In this short report, we describe the case of a patient vaccinated with Comirnaty, who Pfizer-BioNTech COVID-19 developed a purpuric rash resistant to oral steroid therapy after 2 weeks. To date, this is one of Vaccination: Histological Evaluation the very few cases in which skin biopsy was performed to better characterize the histopathological and Perspectives. Vaccines 2021, 9, 760. https://doi.org/10.3390/ picture of this rash. Finally, we conduct a literature review of the cases of rashes from SARS-CoV-2 vaccines9070760 vaccines described in the literature, with the aim of laying foundations for future, larger case studies. Academic Editor: Martin H. Bluth Keywords: SARS-CoV-2; COVID-19; skin; rash; purpuric; vaccines Received: 12 June 2021 Accepted: 6 July 2021 Published: 8 July 2021 1. Introduction The COVID-19 pandemic has affected the entire planet [1], and within about 1 and a half Publisher’s Note: MDPI stays neutral years, has led to 174,502,686 confirmed cases of COVID-19 worldwide, with 3,770,361 deaths [2]. with regard to jurisdictional claims in In Italy, as of 6 December 2021, about 4.24 million confirmed cases, with 3.95 million recoveries published maps and institutional affil- and 127,000 deaths, have been recorded [3]. In the last few months, the advent of vaccines iations. capable of effectively “educating” the immune system to respond to a possible COVID- 19 infection has dramatically reduced infections, hospitalizations, and deaths, allowing many nations to start easing restrictions, with different time schedules and in various ways [4]. The new vaccines exploit the emerging “mRNA” technology rather than already Copyright: © 2021 by the authors. established “vector” modes [5]. Licensee MDPI, Basel, Switzerland. Although it is now clear that SARS-CoV-2 can affect various different organs, including This article is an open access article the lungs [6], brain [7], skin [8–10], vessels [11], placenta [12,13] and others, less is known distributed under the terms and about adverse reactions from vaccines, although more and more reports are starting to conditions of the Creative Commons emerge [14,15]. Among the adverse events, we focused particularly on skin rashes. In this Attribution (CC BY) license (https:// short report, we describe the case of a patient vaccinated with Comirnaty, who developed a creativecommons.org/licenses/by/ purpuric rash resistant to oral steroid therapy after 2 weeks. To date, this is one of the very 4.0/). Vaccines 2021, 9, 760. https://doi.org/10.3390/vaccines9070760 https://www.mdpi.com/journal/vaccines Vaccines 2021, 9, x FOR PEER REVIEW 2 of 7 Vaccines 2021, 9, 760 developed a purpuric rash resistant to oral steroid therapy after 2 weeks. To date,2 of this 7 is one of the very few cases in which skin biopsy was performed to better characterize the histopathological picture of this rash. Finally, we conduct a literature review of the cases of fewrashes cases described in which in skin the biopsy literature was performed after vaccines to better for characterizeother viruses the and histopathological for SARS-CoV-2, withpicture the aim of this of rash.laying Finally, foundations we conduct for future a literature larger review case ofstudies. the cases of rashes described in the literature after vaccines for other viruses and for SARS-CoV-2, with the aim of laying 2. Materialsfoundations and for Methods future larger case studies. Case Presentation 2. Materials and Methods CaseWe Presentation present the case of a 43-year-old man who presented to the Dermatology and VenereologyWe present Complex the case Operative of a 43-year-old Unit for manthe a whoppearance presented of an to unspecified the Dermatology rash. andAt der- matologicalVenereology examination, Complex Operative the patient Unit showed for the a appearancepurpuric rash of anon both unspecified lower limbs rash. (Figure At 1A–C),dermatological which had examination, appeared about the patient 15 days showed after a the purpuric second rash administration on both lower of limbs the Co- mirnaty(Figure mRNA1A–C), whichvaccine. had The appeared patient about had normal 15 days blood after the tests, second apart administration from a slight of rise the in D- Dimer.Comirnaty A swab mRNA tested vaccine. with Real The patientTime-Polymerase had normal bloodChain tests, Reaction apart from(RT-PCR) a slight was rise negative, in D- andDimer. a serological A swab testedpanel withwas Realalso Time-Polymerasenegative. His clinical Chain history Reaction did (RT-PCR) not feature was any negative, allergies or anddiseases a serological of note. panel With was the also patient’s negative. consent, His clinical a 3.5 history mm punch did not biopsy feature anyfor in-depth allergies or diag- nosticsdiseases was of note.decided With upon, the patient’s to allow consent, the most a 3.5 mmappropriate punch biopsy therapy for in-depth to be instituted. diagnostics The was decided upon, to allow the most appropriate therapy to be instituted. The biopsy biopsy specimens obtained were fixed in formaldehyde, buffered at 20% and sent to the specimens obtained were fixed in formaldehyde, buffered at 20% and sent to the U.O.C. of U.O.C. of Pathology. After appropriate sampling, processing, inclusion in paraffin, and Pathology. After appropriate sampling, processing, inclusion in paraffin, and microtome microtomecutting, histological cutting, histological sections about sections 5 microns abou thickt 5 microns were obtained thick were for hematoxylin obtained for and hema- toxylineosin (H&E)and eosin staining. (H&E) For staining. immunohistochemistry For immunohistochemistry purposes (IHC-P), purposes other sections (IHC-P), were other sectionsincubated were with incubated SARS-CoV-2 with spikeSARS-CoV-2 protein S1sp antibodyike protein (MA5-36247), S1 antibody rabbit (MA5-36247), monoclonal, rabbit monoclonal,isotype: IgG, isotype: at a concentration IgG, at a concentration of 0.2 µg/mL, of revealed 0.2 µg/mL, with revealed heat-mediated with heat-mediated antigen in antigencitrate in buffer citrate at pHbuffer 6. RT-PCR at pH 6. was RT-PCR performed. was performed. FigureFigure 1. (A 1.–C(A).– CClinical). Clinical spectrum spectrum of ofthe the purpuric purpuric rash rash in the lowerlower limbslimbs of of the the patient patient described. described. Note Note the differentthe different distributiondistribution of the of thelesions. lesions. TheThe subsequent subsequent review review of of the the literature literature wa wass conducted conducted on on cases cases of of patients patients who who pre- sentedpresented skin manifestations skin manifestations after after different different vaccination vaccination schedules. schedules. We We referred referred to to the the elec- tronicelectronic databases databases PubMed PubMed and and Web Web of Science of Science from from the the beginning beginning of thethe administrationadministration of of vaccines until 6 December 2021, using the terms “COVID-19 vaccines” or “nCov-19 vaccines until 6 December 2021, using the terms “COVID-19 vaccines” or “nCov-19 vac- vaccines” in combination with “skin” or “cutaneous manifestations”, or “eruption”, “rash” cines”and “biopsy”,in combination or “histopathology”, with “skin” or or “cutaneous “dermatopathology”, manifestations”, to see if or any “eruption”, other cases “rash” of andskin “biopsy”, manifestations or “histopathology”, subjected to biopsy or “derma for histologicaltopathology”, analysis to hadsee if been any reported other cases in of skinthe manifestations literature. subjected to biopsy for histological analysis had been reported in the literature. Vaccines 2021, 9, x FOR PEER REVIEW 3 of 7 Vaccines 2021,
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