key: cord-0724450-oi1h567x
authors: Luís, Helena; Barros, Carolina; André, Diogo; Malheiro, Alexandra
title: Cutaneous manifestations associated with SARS-CoV-2: an emerging topic in a pandemic era
date: 2021-09-03
journal: BMJ Case Rep
DOI: 10.1136/bcr-2021-244763
sha: 38359b3fece66057033d0e433d722d806a03956e
doc_id: 724450
cord_uid: oi1h567x

A 70-year-old man was admitted to our COVID-19 ward with thoracalgia, productive mucus cough, fatigue and erythematous–violaceous macules on the inner side of feet and interdigital regions. The patient was started on oxygen and dexamethasone. On the day of discharge, he maintained the skin changes despite the resolution of COVID-19 symptoms. A 57-year-old woman initially presented with diffuse urticarial rash on the cervical and chest region. Oral cetirizine was started, and pruritus improved. Thirty days after the discharge, the patient maintained the rash, but without pruritus. A 49-year-old man was admitted with thoracalgia, shortness of breath, dry cough and urticarial rash on the cervical and chest region. The patient was treated with cetirizine. The pruritus improved, and 5 days after discharge, the urticarial areas completely disappeared.

In December 2019, in the Chinese city of Wuhan, were reported the first cases of unexplained pneumonia, 1 caused by a new infectious pathogen named SARS-CoV-2. 2 The resulting disease was called COVID-19 3 and has become a global health threat, infecting 118 058 503 individuals, and resulting in 2 621 046 deaths by 12 March 2021. 4 With the global increase in the number of SARS-CoV-2 infections, there has been a rising frequency of cutaneous manifestations with different morphology types. Mechanisms responsible for the skin rash in SARS-CoV-2 have been formulated, including direct virus infection of an open wound of the skin, immune system responses or iatrogenic drug introduction. 5 In a prospective nationwide case collection study in Spain conducted by Galván et al, which included 375 patients, the authors described five clinical patterns associated with COVID-19. These patterns comprised acral areas of erythema-oedema with some vesicles or pustules (pseudochilblain), other vesicular eruptions, urticarial lesions, other maculopapules, and livedos or necrosis. 6 Their frequency and timing in the disease's natural course are still challenging to determine. 7 However, some authors reported maculopapular eruptions, pseudochilblain and urticarial rash to be the most common mucocutaneous manifestations in COVID-19, 8 9 developing few days before the onset of the systemic symptoms. Erythematous rash and localised or generalised urticaria appear to be the most shared cutaneous manifestations in patients with acute severe infection, although the underlying cause, such as viral infection or drug reaction may be challenging to identify. 10 For example, hydroxychloroquine, experimentally used for the treatment of COVID-19 in the early days of the pandemic, is associated with a generalised pustular rash. 8 10 Since cutaneous manifestations of COVID-19 seem to be self-resolving, the treatment recommendations support symptoms control with analgesics, corticosteroids or non-steroidal anti-inflammatory drugs. 11

A 70-year-old man with a medical history of arterial hypertension and type 2 diabetes mellitus was admitted to our COVID-19 ward. The diagnosis of SARS-CoV-2 infection by a positive nasopharyngeal swab test was made while he was asymptomatic, as he had high-risk contact with a family member who had been diagnosed with COVID-19. Subsequently, the patient began to experience thoracalgia, productive mucus cough and progressive fatigue and was admitted 8 days after the SARS-CoV-2 positive test to the hospital with bilateral pneumonia. He presented with erythematous-violaceous macules on the inner side of his feet (figure 1) and interdigital regions (figures 2 and 3).

Arterial blood gas analysis revealed pH 7.51, pCO 2 30.5 mm Hg, pO 2 59.9 mm Hg, oxygen saturation 93.7%, HCO 3 − 26.2 mEq/L and lactate 1.2 mg/ dL. Laboratory tests showed lymphopenia 800/ µL, increased D-dimers (4693 ng/mL), hyponatraemia (123 mEq/L) and hypochloraemia (90 mEq/L), increased gamma-glutamyltransferase (GGT) (88.9 U/L) and lactate dehydrogenase (LDH) (392 U/L), and elevated C reactive protein (CRP) (62.50 mg/L) and ferritin (1675 ng/mL). The platelet count and renal function were both normal. Chest radiography revealed peripheral cotton infiltrates in both lung bases with greater extension in the right base (figure 4).

According to the recommended protocol by our government's health authority, Directorate-General of Health, the patient was started on oxygen and dexamethasone. Prophylactic enoxaparin, sodium chloride, furosemide, perindopril, paracetamol and metamizole were also administered.

In the following days, the patient promptly recovered, and we have been able to gradually reduce oxygen flow. On the day of discharge, the patient maintained the skin changes despite the resolution of COVID-19 symptoms. In the re-evaluation consultation, 30 days after discharge, complete resolution of the dermatological manifestations was noted.

A 57-year-old woman with a medical history of migraine, arterial hypertension, chronic venous insufficiency, gastro-oesophageal reflux disease and obesity, initially presented with diffuse urticarial rash on the cervical and chest region (figures 5 and 6). Three days later, she developed fever, fatigue and posterior thoracalgia.

Nasopharyngeal swab for SARS-CoV-2 RNA amplification came back positive on the day of admission to our COVID-19 ward. Blood test results revealed increased D-dimers (799 ng/mL), LDH (261 U/L), CRP (48.20 mg/dL) and ferritin (439 ng/mL). The white blood cells, platelet count, kidney and liver function, and ionogram were all normal. There were no signs of pneumonia on the chest X-ray.

Oral cetirizine was started and the pruritus improved. Lowmolecular-weight heparin in prophylactic dose (enoxaparin) and paracetamol were also administered.

Thirty days after discharge, the patient maintained the rash, but without the pruritus (figures 7 and 8).

A 49-year-old man with a medical history of colon tubulovillous adenoma with high-grade dysplasia was admitted with thoracalgia, worsening shortness of breath and dry cough. He also had, on the cervical and chest region, urticarial rash (figure 9), which started 5 days before.

SARS-CoV-2 infection, tested for by a nasopharyngeal swab, was diagnosed. Laboratory tests showed lymphopenia (700/ µL), increased D-dimers (500 ng/mL), abnormal liver function (alanine aminotransferase 60.6 U/L, aspartate aminotransferase 115.9 U/L and GGT 108.4 U/L), elevated LDH (316 U/L), CRP (106.21 mg/L) and ferritin (2886 ng/mL). Platelet count, renal function and ionogram were normal. Chest X-ray was negative for pneumonia.

The patient was treated with prophylactic enoxaparin, cetirizine and paracetamol.

The pruritus improved, and 5 days after discharge, the urticarial areas completely disappeared.

The SARS-CoV-2 infection has caused numerous repercussions on millions of individuals worldwide, medically, financially and socially. 2 Also, it constituted a new challenge to recognise the extensive range of clinical manifestations of the disease for healthcare 

professionals. Despite all the information currently released on this virus, much remains unknown about the disease's clinical characteristics, including dermatological manifestations. Articles from the beginning of the pandemic in Wuhan described the presence of rashes in 0.2% of 1099 confirmed cases of COVID-19, 12 so they were considered of little relevance for several months. 12 13 As the infection spread, reaching Europe, there was a vast recognition and interest in these category of manifestations.

The case series published by Recalcati in Lombardy 1 was the first report of the cutaneous manifestations in COVID-19 patients during the severe acute respiratory syndrome. In this study, which included 88 patients, 20.4% (n=18) had skin lesions. The patterns described included erythematous (77.8%), urticarial (16.7%) and varicella-like eruptions (5.6%). 1 12 After this publication, similar lesions were described in multiple clinical cases and case series, and other forms, such as petechiae lesions, perniosis-type, vasculitis, polymorphic erythema, livedo reticularis and reactivation of oral herpes simplex type 1 were also described. 12 14 Although most of these rashes appear to emerge from the cytopathic effect of the virus, some cutaneous patterns may be the result of a deregulatory response by the immune and thrombogenic systems through the uncontrolled release of interferon and proinflammatory cytokines. 2 12 Acral lesions, also defined as pseudochilblain, are described as a localised inflammatory dermatological disorder presented as erythematous-violaceous or purpuric macules on fingers, elbows, toes and the lateral aspect of the feet. 6 These lesions have been observed to be more common in young adult patients with a milder disease course and manifesting after the onset of commonly COVID-19 symptoms. 2 6 However, our patient from case 1, was older and, for the presence of bilateral pneumonia requiring oxygen therapy, SARS-CoV-2 infection was considered of moderate severity. Pseudochilblain eruptions are frequently asymmetrically distributed, 15 and Galvan et al reported pain in 32% and itches in 30% of patients. 6 Our patient had these lesions on both feet and reported only pain on palpation. Despite Singh et al stating an association between these lesions and exposure to cold temperatures or damp, humid environments, 16 most studies did not confirm this relationship. 2 7 12 17 The urticarial rash was the first dermatological pattern described in patients with SARS-CoV-2 infection 12 and can appear before cough and fever. 15 In the case series published by Recalcati, 16 .7% of the 18 patients had these lesions, slightly itchy and mainly distributed over the trunk. 1 12 It is important to note that these skin changes did not correlate with the severity of the disease 12 and were described in patients with a milder clinical course and limited symptoms. 13 In the literature cases, this rash has improved with the introduction of oral antihistamines. 12 15 In our two patients with urticarial rashes, the COVID-19 had a 

► Acral areas of erythema-oedema with some vesicles or pustules (pseudochilblain), other vesicular eruptions, urticarial lesions, other maculopapules, and livedos or necrosis are the most reported cutaneous symptoms of COVID-19. ► Clinicians should be aware of the cutaneous manifestations linked to COVID-19 as they might be the presenting sign of infection in asymptomatic or minimally symptomatic patients. ► As in most of the aspects intrinsic to this new virus, much remains to be revealed concerning cutaneous manifestations, which demands further investigations.

milder course, and the introduction of cetirizine improved the associated pruritus.

Cutaneous manifestations in COVID-19: a first perspective

Cutaneous manifestations of COVID-19: an evidence-based review

Cutaneous manifestations in hospitalized patients diagnosed as COVID-19

COVID-19) Dashboard. Consulted on the 12th of

COVID-19 and cutaneous manifestations: a systematic review

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

COVID-19: cutaneous manifestations as issues related to dermatologic care

Cutaneous manifestations and considerations in COVID-19 pandemic: a systematic review

Urticaria and COVID-19: a review

Cutaneous manifestations in COVID-19: a new contribution

COVID toes and other cutaneous manifestations of COVID-19

Cutaneous manifestations in the context of SARS-CoV-2 infection (COVID-19)

Cutaneous manifestations of the coronavirus disease 2019 (COVID-19): a brief review

Cutaneous signs in COVID-19 patients: a review

Cutaneous manifestations of COVID-19: a systematic review

A comprehensive review of cutaneous manifestations associated with COVID-19

The authors are grateful to our colleagues of COVID-19