The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: A case series Journal Article


Authors: Magro, C. M.; Mulvey, J. J.; Laurence, J.; Sanders, S.; Crowson, A. N.; Grossman, M.; Harp, J.; Nuovo, G.
Article Title: The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: A case series
Abstract: Background: There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes. One is perniosis occurring in mildly symptomatic patients, typically children and young adults; the second is the thrombotic retiform purpura of critically ill adults with COVID-19. Objectives: To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19. Methods: We compared the light microscopic, phenotypic, cytokine and SARS-CoV-2 protein and RNA profiles of COVID-19-associated perniosis with that of thrombotic retiform purpura in critical patients with COVID-19. Results: Biopsies of COVID-19-associated perniosis exhibited vasocentric and eccrinotropic T-cell- and monocyte-derived CD11c+, CD14+ and CD123+ dendritic cell infiltrates. Both COVID-associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein A (MXA), an established marker for type I interferon signalling in tissue. SARS-CoV-2 RNA, interleukin-6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, interleukin-6 and caspase 3; SARS-CoV-2 RNA was not seen. Conclusions: COVID-19-associated perniosis represents a virally triggered exaggerated immune reaction with significant type I interferon signaling. This is important to SARS-CoV-2 eradication and has implications in regards to a more generalized highly inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID-19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response. This allows excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation. © 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists
Journal Title: British Journal of Dermatology
Volume: 184
Issue: 1
ISSN: 0007-0963
Publisher: Blackwell Publishing  
Date Published: 2021-01-01
Start Page: 141
End Page: 150
Language: English
DOI: 10.1111/bjd.19415
PUBMED: 32779733
PROVIDER: scopus
PMCID: PMC7405151
DOI/URL:
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
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  1. Joseph Justin Mulvey
    13 Mulvey