Reply to “Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients”: To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out
Authors: Mar Llamas-Velasco, Pedro Rodríguez-Jiménez, Pablo Chicharro, Diego De Argila, Patricia Muñoz-Hernández, Esteban Daudén
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: We have read with great interest the article by Marzano et al1Marzano A.V. Genovese G. Fabbrocini G. et al.Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients.J Am Acad Dermatol. 2020; 83: 280-285Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar considering varicella-like papulovesicular exanthem as a rare but specific coronavirus disease 2019 (COVID-19)–associated skin manifestation. They included patients with a COVID-19–positive nasopharyngeal swab and no medications in the previous 15 days with varicella-like lesions.1Marzano A.V. Genovese G. Fabbrocini G. et al.Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients.J Am Acad Dermatol. 2020; 83: 280-285Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar A previous case report of COVID19-related varicella-like vesicles had also been published by Recalcati2Recalcati S. Cutaneous manifestations in COVID-19: a first perspective.https://doi.org/10.1111/jdv.16387Date accessed: April 20, 2020Google Scholar for the very first time. However, only the Marzano et al1Marzano A.V. Genovese G. Fabbrocini G. et al.Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients.J Am Acad Dermatol. 2020; 83: 280-285Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar article included scarce clinical images due to safety or logistic concerns. In these past few weeks we have been living in an epidemic situation in Spain, considered by the World Health Organization as an area of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) of community transmission, especially in Madrid.3World Health OrganizationNovel coronavirus situation reports.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reportsDate accessed: April 20, 2020Google Scholar Since then, we began to observe different skin manifestations in patients with COVID-19 infection. We encountered 3 in-ward patients during the last few weeks, all with microbiologically proven COVID-19 by nasopharyngeal swab, and all of them presenting with vesicles (Table I, Figs 1 and 2).Table ISummary of patients with coronavirus disease 2019 (COVID-19) positivity and cutaneous scattered vesiclesPatientSexAge, yPast relevant medical historyCOVID symptomsChest x-rayTotal number of days since onset of symptomsMedicationsLymphocyte count∗Lower count of lymphocytes of the patient during the follow-up of COVID-19 infection.1Female59NoneFeverDry coughDyspneaBilateral interstitial pneumonia25HydroxychloroquineLopinavir/ritonavirCeftriaxone620/mm32Male69NoneFeverDry coughDyspneaMyalgiasBilateral interstitial pneumonia43HydroxychloroquineLopinavir/ritonavirAmoxicillin/clavulanic acid820/mm33Male79Parkinson diseaseMelanomaFeverSkin rashNormal21None710/mm3∗ Lower count of lymphocytes of the patient during the follow-up of COVID-19 infection. Open table in a new tab Because the COVID-19 infection mechanism to produce vesicles is not known, we performed a herpesvirus family microarray polymerase chain reaction of the vesicle fluid, and we demonstrated a combination of herpes simplex-1 virus, herpes simplex-6 virus, and Epstein-Barr virus in patient 1, herpes simplex-1 virus and herpes simplex-7 in patient 2, and varicella zoster virus in patient 3. We could not simultaneously perform SARS-COV-2 polymerase chain reaction in the vesicle fluid, so we cannot completely rule out its additional involvement. Marzano and colleagues did not mention in their article whether they ruled out a herpes virus infection in every case; one might assume they did, and therefore used the term varicella-like exanthem. COVID-19 infection characteristically produces lymphopenia, and we have previous evidence of lymphopenia, which is a known factor favoring herpesvirus recurrences, in our 3 patients. We would like to know whether the patients in the Marzano et al1Marzano A.V. Genovese G. Fabbrocini G. et al.Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients.J Am Acad Dermatol. 2020; 83: 280-285Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar report also had this characteristic sign in their blood tests. Finally, we agree with the idea of further studying this recently described varicella-like exanthem to clarify how we can distinguish it from other dermatosis and use it to identify otherwise asymptomatic patients to test them earlier. But even today, when it seems that all of our patients are affected by COVID-19 and all the skin diseases may be related to COVID-19, we must keep in mind that other dermatologic diseases still exist. That is why we think that when we face a patient presenting with a varicella-like rash, we should perform Tzanck smear, virus culture, polymerase chain reaction on the vesicle fluid, or skin biopsy, or a combination of these, to rule out disseminated forms of other common viral infections. Varicella-like exanthem as a specific COVID-19–associated skin manifestation: Multicenter case series of 22 patientsJournal of the American Academy of DermatologyVol. 83Issue 1PreviewTo the Editor: COVID-19, an infection due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may cause interstitial pneumonia and respiratory failure, has currently taken on pandemic proportions.1 The COVID-19 outbreak emerged in Wuhan, China, and rapidly spread to Europe, particularly to Italy,2 where, as of April 27, 2020, a total of 199,414 people have tested positive.3 Full-Text PDF Response to: "Reply to 'Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients': To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out"Journal of the American Academy of DermatologyVol. 83Issue 3PreviewTo the Editor: We would like to thank Llamas-Velasco et al1 for their interest in our research letter "Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients."2 They emphasize the need to use Herpesviridae family microarray polymerase chain reaction (PCR) on the vesicle fluid of patients with coronavirus disease 2019 (COVID-19) with papulovesicular eruptions to define the etiology of the exanthem by giving the example of 3 patients with laboratory-confirmed COVID-19. Full-Text PDF Comment on: "To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out. Characterization of herpetic lesions in hospitalized COVID-19 patients"Journal of the American Academy of DermatologyVol. 83Issue 3PreviewTo the Editor: We have read with great interest the articles by Llamas-Velasco et al1 and Marzano et al2 about the current controversy regarding coronavirus disease 2019 (COVID-19) vesicular exanthems and the role of herpesvirus in the etiology of these lesions. Llamas-Velasco et al1 report 3 cases of vesicular lesions in patients hospitalized with COVID-19, suggesting that complementary tests, such as Tzanck smear, virus culture, polymerase chain reaction (PCR), or skin biopsy should be performed to rule out other viral infections. Full-Text PDF