The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series
The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series
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DOI：
10.1111/bjd.19415
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发表时间：
2020-09-15
影响因子：
10.3
通讯作者：
Nuovo, G.
中科院分区：
文献类型：
--
作者：
Magro, C. M.;Mulvey, J. J.;Nuovo, G.
背景COVID-19有两种不同的肢端表现，体现了不同的临床表型。一种是羊粪病，发生在症状轻微的患者，通常是儿童和年轻人；二是重症成人COVID-19的血栓性视网膜紫癜。目的比较新冠肺炎两种不同皮肤表现的临床和病理特点。方法比较COVID-19危重患者与血栓性视网膜性紫癜的光镜、表型、细胞因子、SARS-CoV-2蛋白和RNA谱。结果新冠肺炎相关性腐殖病活检表现为血管中心性和嗜肾性t细胞和单核细胞来源的CD11c（+）、CD14（+）和CD123（+）树突状细胞浸润。covid - 19相关和特发性羊粪病均表现出I型干扰素诱导的黏液病毒抗性蛋白A （MXA）的显著表达，MXA是组织中I型干扰素信号传导的既定标志物。SARS-CoV-2 RNA、白细胞介素-6和半胱天冬酶3的表达极少，且局限于单核炎症细胞。活体/网状紫癜活检显示炎性血管血栓形成，无MXA修饰。血管表现出广泛的补体沉积，内皮细胞定位SARS-CoV-2蛋白、白细胞介素-6和caspase 3；未见SARS-CoV-2 RNA。结论covid -19相关性腐殖病是一种病毒引发的夸大免疫反应，具有显著的I型干扰素信号。这对根除SARS-CoV-2很重要，并对更广泛的高度炎症反应有影响。我们假设在COVID-19危重患者的血栓性视网膜紫癜中，皮肤和其他器官系统的血管血栓形成与最小的干扰素反应有关。这允许过度的病毒复制和释放病毒蛋白，这些病毒蛋白定位于肺外内皮，并引发广泛的补体激活。
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.