Department of Dermatology, Université Côte d'Azur, CHU Nice, Nice, France.
Department of Pathology, Université Côte d'Azur, CHU Nice, Nice, France.
JAMA Dermatol. 2021 Feb 1;157(2):202-206. doi: 10.1001/jamadermatol.2020.4324.
Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.
To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.
DESIGN, SETTING, AND PARTICIPANTS: In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.
Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.
Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.
Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.
ClinicalTrials.gov Identifier: NCT04344119.
在 2019 年冠状病毒病（COVID-19）大流行期间，已报告出现冻疮样病变。此类表现的病理生理学仍知之甚少。
对在 COVID-19 大流行期间出现冻疮样病变的患者队列进行系统的临床、组织学和生物学评估。
设计、地点和参与者：在法国尼斯大学医院 COVID-19 多学科咨询小组进行的这项前瞻性病例系列研究中，纳入了 40 例连续出现冻疮样病变的患者。
患者接受了全面的一般和皮肤科检查，包括皮肤活检、血管检查、生物学分析、干扰素-α（IFN-α）刺激和检测以及严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）聚合酶链反应（PCR）和血清学分析。
总体而言，纳入了 40 例连续出现冻疮样病变的患者。大多数患者为年轻人，中位（范围）年龄为 22（12-67）岁；19 名男性，21 名女性。临床表现高度重现，病变主要位于脚趾上。11 例患者出现水疱和坏死性病变。19 例（47.5%）患者出现发绀或冷脚趾。在发病前 6 周内，11 例（27.5%）患者符合 COVID-19 病例标准。所有患者的实时 PCR（rt-PCR）检测结果均为阴性。总体而言，12 例（30%）患者 SARS-CoV-2 血清学结果为阳性。24 例（60.0%）患者的 D-二聚体浓度升高。所有检测患者的冷球蛋白血症和细小病毒 B19 血清学结果均为阴性。主要组织学发现为淋巴细胞炎症和血管损伤的特征，伴有小静脉壁增厚和周细胞增生。与轻度至重度急性 COVID-19 患者相比，体外刺激后 IFN-α产生显著增加。
综上所述，我们的结果表明，COVID-19 大流行期间观察到的冻疮样病变代表了一种病毒诱导的 I 型干扰素病的表现。
ClinicalTrials.gov 标识符：NCT04344119。
