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19 例意大利儿科患者类冻疮样皮损的临床、组织病理学和实验室研究:与 COVID-19 感染关系的明与暗。

A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection.

机构信息

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Virology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

出版信息

J Eur Acad Dermatol Venereol. 2020 Nov;34(11):2620-2629. doi: 10.1111/jdv.16682. Epub 2020 Jul 2.

Abstract

BACKGROUND

Acral chilblain-like lesions are being increasingly reported during COVID-19 pandemic. However, only few patients proved positivity for SARS-CoV-2 infection. The relationship between this skin manifestation and COVID-19 infection has not been clarified yet.

OBJECTIVE

To thoroughly characterize a prospective group of patients with chilblain-like lesions and to investigate the possible relationship with SARS-CoV-2 infection.

METHODS

Following informed consent, patients underwent (i) clinical evaluation, (ii) RT-PCR and serology testing for SARS-CoV-2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy.

RESULTS

Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu-like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS-CoV-2 and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS-CoV-2 spike protein was positive in 6 patients and borderline in 3.

CONCLUSIONS

Chilblain-like lesions during COVID-19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS-CoV-2 infection in our patients, history data and the detection of anti-SARS-COV-2 IgA strongly suggest a relationship between skin lesions and COVID-19. Further investigations on the mechanisms of SARS-CoV-2 infection in children and pathogenesis of chilblain-like lesions are warranted.

摘要

背景

在 COVID-19 大流行期间,越来越多的患者出现肢端冻疮样病变。然而,仅有少数患者的 SARS-CoV-2 感染检测结果呈阳性。这种皮肤表现与 COVID-19 感染之间的关系尚未明确。

目的

全面描述一组肢端冻疮样病变患者,并探讨其与 SARS-CoV-2 感染之间的可能关系。

方法

患者签署知情同意书后,我们对其进行了(i)临床评估、(ii)SARS-CoV-2 的 RT-PCR 和血清学检测、(iii)指/趾甲襞的数字视频毛细血管镜检查、(iv)自身免疫性疾病和凝血异常筛查的血液检测、(v)组织病理学、直接免疫荧光检查,以及在某些情况下进行电子显微镜检查。

结果

共纳入 19 例患者,均为青少年(平均年龄 14 岁)。19 例患者中有 11 例(58%)及其同居者在皮肤表现出现前 1-2 个月有流感样症状。病变局限于脚趾,也可累及脚跟和脚底。视频毛细血管镜检查显示,在大多数患者的手指和脚趾中均存在毛细血管周围水肿、扩张和异常毛细血管、微出血。主要的组织病理学发现包括表皮基底层空泡化、乳头真皮水肿和红细胞外渗、血管周围和毛囊周围真皮淋巴细胞浸润以及真皮和皮下组织的黏蛋白沉积;两例患者还观察到真皮血管血栓。血液检查正常。鼻咽拭子 SARS-CoV-2 检测和 SARS-CoV-2 核衣壳蛋白 IgG 血清学检测均为阴性。重要的是,6 例患者的 SARS-CoV-2 刺突蛋白 S1 结构域 IgA 血清学检测为阳性,3 例患者的 SARS-CoV-2 刺突蛋白 S1 结构域 IgA 血清学检测为临界阳性。

结论

COVID-19 大流行期间的肢端冻疮样病变具有特定的流行病学、临床、毛细血管镜和组织病理学特征,可将其与特发性冻疮相区别。尽管我们无法在患者中明确证实 SARS-CoV-2 感染,但病史资料和抗 SARS-CoV-2 IgA 的检测强烈提示皮肤病变与 COVID-19 之间存在关联。需要进一步研究 SARS-CoV-2 在儿童中的感染机制和肢端冻疮样病变的发病机制。

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