The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series.

TitleThe differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series.
Publication TypeJournal Article
Year of Publication2021
AuthorsMagro CM, Mulvey JJ, Laurence J, Sanders S, Crowson AN, Grossman M, Harp J, Nuovo G
JournalBr J Dermatol
Date Published2021 01
KeywordsAdolescent, Age Factors, Aged, Biopsy, Caspase 3, Chilblains, COVID-19, Diagnosis, Differential, Female, Foot, Hand, Humans, Interferon Type I, Interleukin-6, Livedo Reticularis, Male, Middle Aged, Myxovirus Resistance Proteins, Purpura, RNA, Viral, SARS-CoV-2, Severity of Illness Index, Skin, Spike Glycoprotein, Coronavirus

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.

Alternate JournalBr J Dermatol
PubMed ID32779733
PubMed Central IDPMC7405151
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
Related Faculty: 
Cynthia M. Magro, M.D.


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