A Dermatologic Manifestation of COVID-19: Transient Livedo Reticularis

Case 1: A 67-year-old Caucasian male was hospitalized for COVID-19 (nasopharyngeal swab PCR-confirmed) management. His symptoms began 10 days prior with low-grade fever, nasal congestion, post-nasal drip, and cough without shortness of breath. Seven days into his symptoms, he noted a transient non-pruritic blanching unilateral livedoid patch on the right anterior thigh resembling LR (Figure 1). The eruption lasted for 19 hours and resolved by the time dermatology evaluated the patient; thus no biopsy was taken. Concurrent with the lacy patches on the leg, the patient also noted gross hematuria and generalized weakness. In concert with the netlike exanthem, the hematuria resolved within 24 hours. He was eventually discharged home stable on supplemental oxygen. Case 2: A 47-year-old Caucasian female with history of Celiac disease, Hashimoto’s thyroiditis, and portal vein thrombosis in 2017 with negative work-up for a hypercoagulable state (attributed to a long plane flight combined with prior oral contraceptive) tested COVID-19-positive. Symptoms began with a mild headache, sinus pressure, anosmia, and fever, with highest recorded temperature of 37.9°C. Ten days after testing positive, and with complete clinical convalescence of COVID-19 symptoms, she was sitting outside in long pants under direct sunlight for approximately 20-30 minutes. A unilateral asymptomatic rash on her right leg resembling LR was noticed incidentally immediately upon moving indoors (Figure 2) despite an equal amount of sun exposure on both legs. The rash lasted approximately 20 minutes and did not recur upon re-challenge with sun exposure the following day. Discussion Livedo reticularis is caused by conditions, including disseminated intravascular coagulation (DIC), that reduce blood flow through the cutaneous microvasculature system leading to deoxygenated blood accumulation in the venous plexus.3 We hypothesize that the microthromboses that manifest in other organs (e.g. cardiopulmonary)4 and as DIC2,5 in critically ill COVID-19 patients are the most plausible etiology to our patients' LR presentations. We postulate that manifestations can vary from transient LR in mild-moderate cases to acrocyanosis in critically ill patients. Because our patients were not critically ill, perhaps they had transient low-grade DIC, and the concurrent hematuria in Patient 1 could be explained by a possible micro-embolic event causing glomerulonephritis or cystitis. However, due to the evanescent nature of their LR-like eruptions, they were not biopsied. Interestingly, exanthems have not been described for other coronaviruses such as SARS-CoV and MERS-CoV. In the future, histopathology of active exanthema may be helpful in elucidating the underlying pathology of the cutaneous and perhaps systemic manifestations of COVID-19 infection. Additionally, platelet count, coagulation studies, and fibrin degradation products assessments in these patients would be enlightening.病例1： 一名67岁高加索男性因新型冠状病毒肺炎（COVID-19，经鼻咽拭子PCR检测确认）住院治疗。患者10天前出现症状，初始表现为低热、鼻塞、鼻后滴漏及咳嗽，无呼吸困难。症状发作7天后，其右侧前大腿出现一过性、非瘙痒性、单侧苍白网状青斑样斑块，形态类似网状青斑（livedo reticularis, LR）（图1）。该皮损持续19小时，于皮肤科会诊时已消退，故未行活检。与此同时，患者还出现肉眼血尿及全身乏力。伴随腿部网状皮损出现的血尿，在24小时内自行缓解。患者最终在辅助吸氧状态下病情稳定，出院回家。 病例2： 一名47岁高加索女性，既往有乳糜泻（Celiac disease）、桥本甲状腺炎（Hashimoto’s thyroiditis）病史，2017年曾发生门静脉血栓，当时高凝状态相关检查结果为阴性，病因归因于长途飞行合并既往服用口服避孕药，本次新型冠状病毒肺炎检测呈阳性。初始症状为轻度头痛、鼻窦压迫感、失嗅及发热，最高体温达37.9℃。核酸检测阳性10天后，患者新冠症状已完全临床缓解，当时身着长裤在户外直射阳光下停留约20~30分钟。返回室内后偶然发现右侧腿部出现单侧无症状皮疹，形态类似LR（图2），但双侧腿部日晒时长一致。该皮疹持续约20分钟，次日再次日晒后未再复发。 讨论 网状青斑（livedo reticularis, LR）可由多种疾病引发，包括弥散性血管内凝血（disseminated intravascular coagulation, DIC），此类疾病会降低皮肤微血管系统的血流量，导致静脉丛内脱氧血液淤积。我们推测，重症新冠患者体内其他器官（如心肺）出现的微血栓4，以及并发的DIC2,5，是本病例患者出现LR表现的最合理解释。我们认为，其临床表现可从轻中度患者的一过性LR，到重症患者的肢端发绀不等。由于本研究中的两名患者均非重症，推测其可能仅存在一过性轻度DIC；病例1患者同时出现的肉眼血尿，可由可能的微栓塞事件引发肾小球肾炎或膀胱炎来解释。不过，由于患者的LR样皮损具有一过性特征，故未行活检。值得注意的是，目前尚未见严重急性呼吸综合征冠状病毒（SARS-CoV）、中东呼吸综合征冠状病毒（MERS-CoV）等其他冠状病毒引发皮疹的相关报道。未来，对活动性皮疹进行组织病理学检查，将有助于阐明新冠感染皮肤乃至全身表现的潜在病理机制。此外，对这类患者进行血小板计数、凝血功能检测及纤维蛋白降解产物评估，也将为研究提供更多有价值的信息。