Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Br J Dermatol. 2021 Jan;184(1):141-150. doi: 10.1111/bjd.19415. Epub 2020 Sep 15.
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.
To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19.
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.
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.
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.
COVID-19 有两种明显的肢端表现，体现出不同的临床表型。一种是发生在症状轻微的患者（通常为儿童和青年）中的冻疮样病变；另一种是 COVID-19 重症患者的血栓性网状青斑。
比较这两种不同的 COVID-19 皮肤表现的临床和病理特征。
我们比较了 COVID-19 相关冻疮与 COVID-19 重症患者血栓性网状青斑的组织学、表型、细胞因子以及 SARS-CoV-2 蛋白和 RNA 特征。
COVID-19 相关冻疮活检显示以血管为中心的、外分泌细胞亲嗜性 T 细胞和单核细胞衍生的 CD11c、CD14 和 CD123 树突状细胞浸润。COVID 相关和特发性冻疮均表现出强烈的 I 型干扰素诱导的粘病毒抗性蛋白 A（MXA）表达，这是组织中 I 型干扰素信号的一个既定标志物。SARS-CoV-2 RNA、白细胞介素-6 和半胱氨酸蛋白酶 3 的表达较少，局限于单核炎性细胞。网状青斑/血栓性青斑的活检显示，几乎没有炎症性血管血栓形成，且没有任何 MXA 染色。血管广泛沉积补体，SARS-CoV-2 蛋白、白细胞介素-6 和半胱氨酸蛋白酶 3 定位于内皮细胞；未见 SARS-CoV-2 RNA。
COVID-19 相关冻疮代表了一种由病毒触发的、具有显著 I 型干扰素信号的过度免疫反应。这对于 SARS-CoV-2 的清除非常重要，并对更广泛的高度炎症反应具有重要意义。我们假设，在 COVID-19 重症患者的血栓性网状青斑中，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，导致病毒蛋白释放，定位于肺外内皮细胞并触发广泛的补体激活。
