key: cord-291144-6p40cqvk
authors: Strom, Mark A.; Trager, Megan H.; Geskin, Larisa J.
title: Reticular skin eruption as the initial sign of coronavirus disease 2019 infection
date: 2020-06-24
journal: JAAD Case Rep
DOI: 10.1016/j.jdcr.2020.06.032
sha: 
doc_id: 291144
cord_uid: 6p40cqvk

nan

INTRODUCTION Several recent reports have described clinically significant coagulopathy associated with a spectrum of severity of coronavirus disease 2019 (COVID-19) infection. 1, 2 Although it remains unclear to what extent coagulation abnormalities play a role in COVID-19 pathogenesis and severity, 3 severe coagulation abnormalities, including disseminated intravascular coagulation are strongly associated with increased mortality. 4 Furthermore, there is some evidence to suggest that anticoagulation may improve mortality in severe cases with coagulopathy, and this is currently being tested in clinical trials. 5, 6 Skin findings may precede other manifestations of COVID-19, revealing underlying pathologic conditions early in the disease course. Here we describe a patient whose initial sign of COVID-19 infection was a reticular skin eruption, portending the discovery of hypercoagulability and development of severe disease.

A man in his 70s with well-controlled hypertension presented to the emergency department with a 4-day history of rash, and a 3-day history of progressive weakness and tachypnea. He had not started any new medications in the last month, and had not recently traveled outside of the New York City metropolitan area. Additionally, the patient had no personal or family history of any dermatologic conditions, including psoriasis, bullous disease, or cutaneous lupus erythematosus. The patient's vital signs were notable for a blood pressure of 145/85, a respiratory rate of 30, and an oxygen saturation of 88% on 4 L/min supplemental oxygen by nasal cannula. Coagulation laboratory and inflammatory markers are included in Table I . The patient's cutaneous examination was notable for reticular, partially blanching erythematous patches and plaques with nonblanching purpuric borders on the abdomen (Fig 1) and lower back. Computed tomography scan found patchy opacities of the bilateral lower lobes, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified by reverse transcription polymerase chain reaction.

The patient required intubation and was transferred to the intensive care unit (ICU) for further treatment. His skin eruption gradually improved over the initial seven days of his ICU course without any directed treatment. He completed a 5-day course of hydroxychloroquine and azithromycin per protocol. However, despite supportive care, his condition continued to deteriorate; even with maintaining blood pressure and cardiac output, the patient had ischemic renal injury requiring hemodialysis. Laboratory evidence showed worsening coagulopathy, including prothrombin time of 17.0 s, international normalized ratio of 1.4, activated partial thromboplastin time of 43.4 s, and a D-dimer of 11.84 g/mL. On day 10 of hospitalization, after the patient's initial eruption had resolved, a rotational thromboelastometry study was performed to evaluate the hemostatic properties of the patient's blood and was suggestive of a hypercoagulable state; as a result, the patient started unfractionated heparin. On day 14 of hospitalization, the patient had prominent white scars in the same location as the prior livedoid reaction on an erythematous background (Fig 2) . At this point, the dermatology department evaluated the patient by telemedicine. It was thought that the new eruption was likely an exanthem secondary to a medication the patient had received while hospitalized (potential culprits included meropenem, furosemide, hydroxychloroquine, azithromycin, and piperacillin-tazobactam), with the reticular islands of scarring theorized to be secondary to prior, COVID-induced microvascular ischemia. The eruption was not biopsied at the time because of a severe shortage of personal protective equipment in the New York City area. At the time of this writing, the patient remains admitted to the ICU for 2 months.

Reticular or livedoid dermatitis (sometimes transient) indicates small blood vessel compromise caused by vessel wall damage or occlusion, resulting in downstream ischemia. In our case, we were Table I unable to biopsy the initial reticular eruption, as the initial eruption had resolved at the time of dermatology consultation; however, the reticular patterning of his initial presentation is suggestive of underlying microvascular injury. Nonetheless, a skin biopsy would have been necessary to confirm microvascular pathology. Further case series, including classification of pathologic findings, are indicated to see if these findings are due to underlying microvascular injury. In fact, one pathologic study of 5 COVID-19 patients, 3 of whom had cutaneous signs of systemic hypercoagulability including retiform purpura and livedo racemosa, found a potential role for complement-associated microvascular injury. 7 It is notable that our patient's skin findings preceded other symptoms of COVID-19 and may have heralded the development of coagulopathy. Reticular skin findings are increasingly described in patients with COVID-19, although they appear less frequently than other cutaneous manifestations. One study in Spain examined a series of 375 patients with cutaneous symptoms and suspected or confirmed COVID-19. They described numerous morphologies, including maculopapular eruptions, pseudochilblain, urticarial lesions, and vesicular eruptions; notably, 6% of patients with cutaneous manifestations were described as having a livedoid pattern. 8 Most appeared at the same time as other symptoms, whereas only 5% of the livedoid patterns developed earlier. A recent report from the United States found transient livedo reticularis pattern in 2 patients recovering from COVID-19 who were asymptomatic at the time. 9 Another large study of 277 COVID-19esuspected patients in France found livedo reticularis in 4 patients (1%). 10 Future large cohort studies and evidence may shed light on the prognostic implications of livedo on the course of COVID-19

infection. Additional clinical trials may identify whether anticoagulation may hasten the resolution of such livedoid findings and improve overall outcomes. Dermatologists should be aware of this potential initial manifestation of COVID-19, even if a patient presents without other symptoms.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Coagulopathy and antiphospholipid antibodies in patients with Covid-19

Hypercoagulability of COVID-19 patients in intensive care unit. A Report of thromboelastography findings and other parameters of hemostasis

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Thromboinflammation and the hypercoagulability of COVID-19

Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases

A dermatologic manifestation of COVID-19: transient livedo reticularis

Chilblains are a common cutaneous finding during the COVID-19 pandemic: a retrospective nationwide study from France