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Cutaneous manifestations in COVID-19: Lessons learned from current evidence

2020; Elsevier BV; Volume: 83; Issue: 1 Linguagem: Inglês

10.1016/j.jaad.2020.04.094

1097-6787

Poonkiat Suchonwanit, Kanchana Leerunyakul, Chaninan Kositkuljorn,

Chemotherapy-related skin toxicity

To the Editor: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is a significant global concern. As of April 19, 2020, a total of 2,241,359 accumulated cases and 152,551 deaths have been reported worldwide.1World Health OrganizationCoronavirus disease 2019 (COVID-19) Situation Report—90. April 19, 2020.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200419-sitrep-90-covid-19.pdf?sfvrsn=551d47fd_2Date accessed: April 20, 2020Google Scholar The clinical features of COVID-19 have been described in several articles. The disease typically presents with symptoms resembling other viral respiratory infections, most commonly with fever and dry cough. Patients with severe infection may later develop acute respiratory distress syndrome that could progress to multiple organ failure with a relatively high mortality rate.2Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; https://doi.org/10.1056/NEJMoa2002032Crossref Scopus (20513) Google Scholar In addition, the disease is associated with leukopenia, thrombocytopenia, and elevated D-dimer levels that increase the risk of venous thromboembolism.3Clerkin K.J. Fried J.A. Raikhelkar J. et al.Coronavirus disease 2019 (COVID-19) and cardiovascular disease.Circulation. 2020; https://doi.org/10.1161/CIRCULATIONAHA.120. 046941Crossref Google Scholar Emerging evidence suggests that the uncontrolled release of proinflammatory cytokines resulting in cytokine storm syndrome plays an immunopathogenic role in disease progression and the development of severe disease.4Mehta P. McAuley D.F. Brown M. Sanchez E. Tattersall R.S. Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression.Lancet. 2020; https://doi.org/10.1016/s0140-6736(20)30628-0Abstract Full Text Full Text PDF Google Scholar Cutaneous manifestations are considered an infrequent presentation of COVID-19, being rarely described in the literature. They are probably under-recognized due to a lack of dermatology consultations in this group of patients. The first evidence of skin manifestations was reported in 2 patients with severe respiratory disease in a study of 1099 cases in China. However, neither characteristics nor progression of the lesions were documented.2Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; https://doi.org/10.1056/NEJMoa2002032Crossref Scopus (20513) Google Scholar Since then, subsequent case reports and case series have described COVID-19–associated skin lesions in patients with confirmed COVID-19, including clinical features that indicate viral exanthems (ie, morbilliform rash, petechial rash coexisting with thrombocytopenia, erythematous-to-purpuric coalescing macules, widespread urticaria, and varicella-like vesicles) and vasculopathy-related skin manifestations (ie, peripheral cyanosis with bullae and dry gangrene, transient unilateral livedo reticularis, and red papules on fingers resembling chilblains). Other patients with non-laboratory-confirmed COVID-19 showed urticaria and painful erythematous-to-violaceous patches evolving into tense vesicles or dark crusts. All cases reported so far are summarized in Table I.Table ISummary of reported COVID-19 cases with cutaneous manifestations between January 1, 2020, and April 19, 2020Authors∗References supporting this table are available from the corresponding author upon request.No.Age, y and sexCutaneous manifestationsExtracutaneous manifestationsLaboratory-confirmed COVID-19 caseAssociated with disease severitySkin biopsyProgressionArticle linkReported cases with skin manifestations that indicate viral exanthems Guan et al2 of 1099NANANAYesYesNoNAhttps://doi.org/10.1056/NEJMoa2002032 Joob and Wiwanitkit1NASkin rash with petechiaeFever, thrombocytopenia, respiratory symptomsYesNANoNAhttps://doi.org/10.1016/j.jaad.2020.03.036 Recalcati18 of 88NAErythematous rash (n = 14), widespread urticaria (n = 3), chickenpox-like vesicles (n = 1)NAYesNoNoNAhttps://doi.org/10.1111/jdv.16387 Hunt and Koziatek120, MDiffuse nonpruritic erythematous morbilliform rash on trunk and extremitiesFever, multifocal pneumonia with decreased oxygen saturationYesYesNoNAhttps://doi.org/10.5811/cpcem.2020.3.47349 Mahé et al164, FErythematous rash on both antecubital fossa, trunk, and axillary folds resembling symmetric drug-related intertriginous and flexural exanthemFever, cough, asthenia, bilateral pneumoniaYesNoNoImproved within 5 dayshttps://doi.org/10.1111/jdv.16471 Jimenez-Cauhe et al184, FMild pruriginous erythematous-purpuric, coalescing macules on the periaxillary areaBilateral pneumoniaYesNANoNAhttps://doi.org/10.1016/j.jaad.2020.04.016 Marzano et al228-90; 16M and 6FDiffuse/scattered papulovesicular lesions on trunk (n = 22) and extremities (n = 4), mild itch (n = 9), pain (n = 2), burning (n = 3)Fever, cough, headache, weakness, coryza, dyspnea, hyposmia, hypogeusia, pharyngodynia, diarrhea, myalgiaYesNoYes (n = 7)4-15 dayshttps://doi.org/10.1016/j.jaad.2020.04.044 Lu et al1NAUrticariaBilateral pneumonia with minimal symptomNoNoNoNAhttps://doi.org/10.1002/jmv.25776 Henry et al127, FGeneralized urticaria on face and extremitiesOdynophagia, arthralgia, chills, fever, chest painYesNoNoNAhttps://doi.org/10.1111/jdv.16472 Fernandez-Nieto et al132, FUrticariaNAYesNoYesImproved within 5 dayshttps://doi.org/10.1111/jdv.16470 Hoehl et al1 of 2NAFaint rashMinimal pharyngitisYesNoNoNAhttps://doi.org/10.1056/NEJMc2001899Reported cases with vasculopathy-related skin manifestations Zhang et al749-71; 4 M and 3 FFinger/toe cyanosis, skin bullae, and dry gangreneFever, cough, dyspnea, diarrheaYesYesNoNAhttps://doi.org/10.3760/cma.j.issn.0253-2727.2020.0006 Mazzotta and Troccoli113, MErythematous-violaceous rounded lesions on toes with 1-cm diameter, tense blister, blackish crusts at 7 days laterLow-grade fever, muscle pain, headacheNoNoNoRegressed in 2 weekshttp://sectcv.es/wp-content/uploads/2020/04/acroischemia-ENG.pdf Manalo et al267, MTransient nonpruritic blanching unilateral livedoid patch on right thighLow-grade fever, nasal congestion, post-nasal drip, cough, hematuriaYesYesNoResolved within 19 hourshttps://doi.org/10.1016/j.jaad.2020.04.01847, FUnilateral transient asymptomatic rash on right leg resembling livedo reticularisLow-grade fever, mild headache, sinus pressure, anosmiaYesNoNoResolved within 20 minutes Ma et al1 of 369, MDry gangrene on right index fingerFever, bilateral pneumonia, antiphospholipid syndrome with cerebral infarctsYesYesNoNAhttps://doi.org/10.1016/j.clim.2020.108408 Zhang et al1 of 369, MIschemia on both lower limbs and digits of the left handFever, bilateral pneumonia, diarrhea, headache, multiple cerebral infarcts, positive antiphospholipid antibodiesYesYesNoNAhttps://doi.org/10.1056/NEJMc2007575 Alramthan and Aldaraji227 and 35; 2 FRed-to-purple papules on the dorsal aspects of fingers (n = 2), diffused erythema in the subungual area of the right thumb (n = 1), clinical features resembling chilblainsNoneYesNoNoNAhttps://doi.org/10.1111/ced.14243 Estebanez et al128, FConfluent erythematous-yellowish papules on both heels, later developed into pruritic erythematous plaques resembling urticarial vasculitisDry cough, nasal congestion, fatigue, myalgia, arthralgia, diarrhea, ageusia, anosmiaYesNoNoNAhttps://doi.org/10.1111/jdv.16474F, Female; M, male; NA, not available.∗ References supporting this table are available from the corresponding author upon request. Open table in a new tab F, Female; M, male; NA, not available. According to pre-existing data, we can speculate that cutaneous manifestations in COVID-19 may present in 2 major groups regarding their pathomechanisms: (1) clinical features similar to viral exanthems, an immune response to viral nucleotides; and (2) cutaneous eruptions secondary to systemic consequences caused by COVID-19, especially vasculitis and thrombotic vasculopathy. Apart from the above-mentioned, patients with COVID-19 are more likely to have an increased risk of adverse drug reactions and interactions of their treatment causing secondary cutaneous reactions at any point during the course of the disease. Therefore, identifying clues that support a viral cause or drug eruption is essential. Table II summarizes cutaneous reactions reported in proposed drugs for COVID-19 treatment.5Sanders J.M. Monogue M.L. Jodlowski T.Z. Cutrell J.B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review.JAMA. 2020; https://doi.org/10.1001/jama.2020.6019Crossref PubMed Scopus (2005) Google ScholarTable IISummary of possible mucocutaneous adverse effects reported for proposed COVID-19 treatments∗References supporting this table are available from the corresponding author upon request.TreatmentMucocutaneous adverse effectsChloroquine/hydroxychloroquine†Combination treatment increases the risk of QT prolongation.•Common: itching, hair loss•Less common: morbilliform rash, erythroderma, exfoliative dermatitis, urticaria, eczematous eruption, erythema annulare centrifugum, photosensitivity•Rare: acute generalized exanthematous pustulosisAzithromycin†Combination treatment increases the risk of QT prolongation.•Rare: morbilliform rashLopinavir/ritonavir•Common: morbilliform rash•Rare: acute generalized exanthematous pustulosis, hair lossCorticosteroids•Common: skin atrophy, acneiform eruption, telangiectasia, petechiae, ecchymosis, striae, hirsutismTocilizumab•Less common: anaphylaxis•Rare: morbilliform rash, erythroderma, leukocytoclastic vasculitisConvalescent plasma•Less common: morbilliform rash, itching, evanescent red spot∗ References supporting this table are available from the corresponding author upon request.† Combination treatment increases the risk of QT prolongation. Open table in a new tab In summary, whether skin lesions in patients with COVID-19 are related with the virus remains unclear. Dermatologists should keep in mind that skin eruptions occurring in patients with COVID-19 could result from viral infections, systemic consequences, or prescribed drugs. Early recognition of cutaneous signs that are associated with severe complications and prompt management are essential to improve patient outcomes. Moreover, further clinical studies regarding skin manifestations in COVID-19 are required to comprehend the exact cutaneous features for more accurate diagnoses that may predict disease outcomes in particular patients.