key: cord-272321-znnipzym
authors: Verheyden, M.; Grosber, M.; Gutermuth, J.; Velkeniers, B.
title: Relapsing symmetric livedo reticularis in a patient with COVID‐19 infection
date: 2020-06-25
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.16773
sha: 
doc_id: 272321
cord_uid: znnipzym

During the Coronavirus 2019 (COVID‐19) pandemic, several associated skin conditions were reported in infected patients, including; urticaria [1], exanthema [1], erythema multiforme [2], chickenpox‐like vesicles [1], pityriasis rosea [3], herpes simplex reactivation [4], erythema nodosum like Sweet’s syndrome [5], Symmetrical Drug‐Related Intertriginous and Flexural Exanthema [6], petechial rash [7], vasculitic purpura [7], acro‐ischemia/necrosis [8], Kawasaki disease [2] and chilblain lesions [9].

The patient in this manuscript has given written informed consent to the publication of his case details including the clinical pictures.

During the Coronavirus 2019 (COVID-19) pandemic, several associated skin conditions were reported in infected patients, including; urticaria [1] , exanthema [1] , erythema multiforme [2] , chickenpox-like vesicles [1] , pityriasis rosea [3] , herpes simplex reactivation [4] , erythema nodosum like Sweet's syndrome [5] , Symmetrical Drug-Related Intertriginous and Flexural Exanthema [6] , petechial rash [7] , vasculitic purpura [7] , acro-ischemia/necrosis [8] ,

Kawasaki disease [2] and chilblain lesions [9] .

This article is protected by copyright. All rights reserved

We present a 57-year old man with cough, dyspnea, headache, myalgia arthralgia, fever up to 38.7°C and abdominal pain worsening over 8 days. Extensive, symmetric livedo reticularis (LR) was present on trunk and thighs. Lab testing showed elevated C-reactive protein, ferritin, D-dimers and lymphopenia. Nasopharyngeal PCR detected SARS-CoV-2 and chest CT showed multifocal ground glass opacities, suggestive for COVID-19. Because of the unusual sudden onset of symmetric LR in a middle-aged man, an additional work-up for underlying conditions was performed. While antineutrophilic cytoplasmic antibodies, platelets, INR/APTT, rheumatoid factor, cryoglobulins and antiphospholipid antibodies were negative, antinuclear factor (ANA) was positive with nuclear pattern (titer 1/320, but without ENAblot specificity). The patient's previous ANA titer was unknown and so far, it has not been investigated whether COVID-19 can induce such antibodies (as described in other viral disease [10] ). Infectious causes of livedo including HIV, Mycoplasma pneumonia, Syphilis, Legionella pneumophila, Influenza A/B, RSV, Hepatitis B/C were negative. During 8 days, oxygen, acetaminophen, hydroxychloroquine and low-molecular-weight-heparin in preventive dosing were administered. After discharge, livedo fluctuated, but progressively weaned. At three-weeks follow-up, inflammatory parameters were normal (besides insignificantly elevated ferritin), while the patient still experienced slight dyspnea on exertion.

LR describes a regular, lace-like network of non-fixed, dusky patches forming complete rings surrounding a pale centre [11] . This clinical picture is caused by constriction of central arterioles and subsequent peripheral venodilation [11] . LR is rarely associated with underlying diseases. It is mostly seen in healthy young woman as a physiological reaction triggered by cold-induced vasospasms and is then named cutis marmorata [11] . When LR is not influenced by cold exposure it is called primary LR [11] . A congenital form is referred to as cutis marmorata telangiectatica congenita [11] . When livedo presents as a nonsymmetric, localized, mostly unilateral and irregular network with broken rings it is named livedo racemosa (LRC) [11] LRC is associated with more significant reduction of blood flow caused by protracted arteriolar vasospasm, thrombosis, and/or hyperviscosity. LRC is always a red flag for an underlying pathology, such as vasculitis, auto-immune disease, infection, systemic disorders, neoplasia) [11] .

This article is protected by copyright. All rights reserved Our patient had a first occurrence of a symmetric, fluctuating, unsuspicious-looking LR in the context of COVID-19, without other causes. Livedo was not blanching on pressure and typical clinical signs of vasculitis, like purpura, (asymmetric) LRC or skin necrosis were absent. COVID-19 can cause a procoagulant state [12] , with small blood vessel occlusion.

However, the absence of purpura and skin necrosis together with normal coagulation parameters make thrombi unlikely as cause of the observed LR. This suggests the presence of low-grade vascular inflammation and vasodilation caused by direct SARS-CoV-2-infection of endothelial-cells or vessel-associated smooth muscle-cells. Both cell types express angiotensin-converting enzyme 2-receptor on their surface, the target of SARS-CoV-2-spike protein [13] .

In addition to previously reported two cases of asymmetric/unilateral and transient livedo [14] , our case identifies a symmetric, fluctuating, relapsing, non-blanching LR as a warning sign for COVID-19. If symmetric LR occurs for the first time in patients without any risk factors, it warrants the search for underlying pathology, including COVID-19.

Bibliography

Cutaneous manifestations in COVID-19: a first perspective

Erythema multiforme and Kawasaki disease associated with COVID-19 infection in children

Pityriasis rosea as a cutaneous manifestation of COVID-19 infection

Diversity of clinical appearance of cutaneous manifestations in the course of COVID-19

COVID-19 Presenting with Atypical Sweet's Syndrome

A distinctive skin rash associated

Symmetric cutaneous vasculitis in COVID-19 pneumonia

Late onset of acral necrosis after SARS-CoV-2 infection resolution

Vascular skin symptoms in COVID-19: a french observational study

Antinuclear antibodies in infectious diseases

Braun-Falco's Dermatologie, venerologie und Allergologie

The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome

FACT SHEET: COVID-19 disease (SARS-CoV-2 virus), Version 2