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

Magro, C.; Mulvey, J.J.; Laurence, J.; Sanders, S.; Crowson, N.; Grossman, M.; Harp, J.; Nuovo, G.

BACKGROUND: There are two distinctive acral manifestations of COVID‐19 embodying disparate clinical phenotypes: one is perniosis occurring in mildly symptomatic patients, typically children; the second is the thrombotic retiform purpura of critically ill COVID19 adults. MATERIALS AND METHODS: We compare light‐microscopic, phenotypic, cytokine, and SARS‐CoV‐2 protein and RNA profiles in COVID‐19‐associated perniosis of mildly symptomatic or asymptomatic patients with the thrombotic retiform purpura of critical patients with COVID‐19. RESULTS: The 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 signaling in tissue. SARS‐CoV‐2 RNA, IL‐ 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, IL6, and caspase 3; SARS CoV‐2 RNA was not seen. CONCLUSION: The COVID‐19‐associated perniosis represents an exaggerated immune reaction to a virus with significant type‐I interferon signaling 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 allowing excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation.