{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:24:16Z","timestamp":1772166256954,"version":"3.50.1"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diagn Pathol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died.<\/jats:p>\n                    <jats:p>The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as\u00a0highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13000-021-01075-6","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T10:07:24Z","timestamp":1614247644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["From SARS-CoV-2 hematogenous spreading to endothelial dysfunction: clinical-histopathological study of cutaneous signs of COVID-19"],"prefix":"10.1186","volume":"16","author":[{"given":"Angela","family":"Patr\u00ec","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Buonanno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carmela","family":"Annunziata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Russo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Staibano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Servillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Fabbrocini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"1075_CR1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jdermsci.2020.04.007","volume":"98","author":"R Gianotti","year":"2020","unstructured":"Gianotti R, Zerbi P, Dodiuk-Gad RP. Clinical and histopathological study of skin dermatoses in patients affected by COVID-19\u00a0infection in the Northern part of Italy. J Dermatol Sci. 2020;98:141\u20133.","journal-title":"J Dermatol Sci"},{"key":"1075_CR2","doi-asserted-by":"crossref","unstructured":"Diaz-Guimaraens B, Dominguez-Santas M, Suarez-Valle A, Pindado-Ortega C, Selda-Enriquez G, Bea-Ardebol S, et al. Petechial Skin Rash Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection [published online ahead of print, 2020 Apr 30]. JAMA Dermatol. 2020;10.1001\/jamadermatol.2020.1741.","DOI":"10.1001\/jamadermatol.2020.1741"},{"key":"1075_CR3","doi-asserted-by":"crossref","unstructured":"Zengarini C, Orioni G, Cascavilla A, Horna Solera C, Fulgaro C, Misciali C, et al. Histological pattern in Covid-19\u00a0induced viral rash [published online ahead of print, 2020 May 2]. J Eur Acad Dermatol Venereol. 2020;10.1111\/jdv.16569.","DOI":"10.1111\/jdv.16569"},{"key":"1075_CR4","doi-asserted-by":"crossref","unstructured":"Jimenez-Cauhe J, Ortega-Quijano D, Carretero-Barrio I, Suarez-Valle A, Saceda-Corralo D, Moreno-Garcia Del Real C, et al. Erythema multiforme-like eruption in patients with COVID-19\u00a0infection: clinical and histological findings [published online ahead of print, 2020 May 9]. Clin Exp Dermatol. 2020;10.1111\/ced.14281.","DOI":"10.1111\/ced.14281"},{"key":"1075_CR5","doi-asserted-by":"crossref","unstructured":"Robustelli Test E, Vezzoli P, Carugno A, Raponi F, Gianatti A, Rongioletti F, et al. Acute Generalized Exanthematous Pustulosis with Erythema Multiforme-Like lesions in a COVID-19 woman [published online ahead of print, 2020 May 9]. J Eur Acad Dermatol Venereol. 2020;10.1111\/jdv.16613.","DOI":"10.1111\/jdv.16613"},{"key":"1075_CR6","doi-asserted-by":"publisher","first-page":"e227","DOI":"10.1016\/j.jaad.2020.03.098","volume":"82","author":"A Patr\u00ec","year":"2020","unstructured":"Patr\u00ec A, Gallo L, Guarino M, Fabbrocini G. Sexual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A new possible route of infection? J Am Acad Dermatol. 2020;82:e227.","journal-title":"J Am Acad Dermatol"},{"key":"1075_CR7","doi-asserted-by":"crossref","unstructured":"Smadja DM, Guerin CL, Chocron R, Yatim N, Boussier J, Gendron N, et al. Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients [published online ahead of print, 2020 May 27]. Angiogenesis. 2020;10.1007\/s10456-020-09730-0.","DOI":"10.1007\/s10456-020-09730-0"}],"container-title":["Diagnostic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13000-021-01075-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13000-021-01075-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13000-021-01075-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T09:02:41Z","timestamp":1625994161000},"score":1,"resource":{"primary":{"URL":"https:\/\/diagnosticpathology.biomedcentral.com\/articles\/10.1186\/s13000-021-01075-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":7,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1075"],"URL":"https:\/\/doi.org\/10.1186\/s13000-021-01075-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-50000\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-50000\/v1","asserted-by":"object"}]},"ISSN":["1746-1596"],"issn-type":[{"value":"1746-1596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]},"assertion":[{"value":"27 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Informed consent for the study and for the publication of the photos was obtained from the patients. The study complied with the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent for the study and for the publication of the photos was obtained from the patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16"}}