Title: Varicella-like exanthem as a specific COVID-19–associated skin manifestation: Multicenter case series of 22 patients
Abstract: To 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.1Zhu N. Zhang D. Wang W. et al.China novel coronavirus investigating and research teamA novel coronavirus from patients with pneumonia in China, 2019.N Engl J Med. 2020; 382: 727-733Crossref PubMed Scopus (18375) Google Scholar The COVID-19 outbreak emerged in Wuhan, China, and rapidly spread to Europe, particularly to Italy,2Livingston E. Bucher K. Coronavirus disease 2019 (COVID-19) in Italy [Epub ahead of print].JAMA. 2020; https://doi.org/10.1001/jama.2020.4344Crossref Scopus (761) Google Scholar where, as of April 27, 2020, a total of 199,414 people have tested positive.3Dipartimento della Protezione Civile. Comunicato stampa: Coronavirus: la situazione dei contagi in Italia, Available at: http://www.protezionecivile.gov.it/media-comunicazione/comunicati-stampa/-/content-view/view/1265583. Accessed April 27, 2020.Google Scholar Two recent publications have brought attention to COVID-19–associated cutaneous manifestations.4Joob B. Wiwanitkit V. COVID-19 can present with a rash and be mistaken for Dengue.J Am Acad Dermatol. 2020; 82: e177Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar,5Recalcati S. Cutaneous manifestations in COVID-19: a first perspective [Epub ahead of print].J Eur Acad Dermatol Venereol. 2020; (Accessed April 27, 2020)https://doi.org/10.1111/jdv.16387Crossref Scopus (913) Google Scholar Joob and Wiwanitkit4Joob B. Wiwanitkit V. COVID-19 can present with a rash and be mistaken for Dengue.J Am Acad Dermatol. 2020; 82: e177Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar reported on a dengue-like petechial rash in a patient with COVID-19 from Thailand. Recalcati5Recalcati S. Cutaneous manifestations in COVID-19: a first perspective [Epub ahead of print].J Eur Acad Dermatol Venereol. 2020; (Accessed April 27, 2020)https://doi.org/10.1111/jdv.16387Crossref Scopus (913) Google Scholar described 18 out of 88 patients with COVID-19 hospitalized in Lecco Hospital (Lombardy region, Italy) who developed erythematous rash (n = 14), widespread urticaria (n = 3), or varicella-like vesicles (n = 1). During the Italian outbreak, we have observed a varicella-like papulovesicular exanthem as a rare but specific COVID-19–associated skin manifestation. Eight Italian dermatology units collected clinical data from patients with COVID-19 (microbiologically proven by nasopharyngeal swab) and no history of new medications in the previous 15 days who developed varicella-like lesions. Demographic and clinical features of the 22 patients are summarized in Table I. The median age was 60 years, and 72.7% of patients (n = 16/22) were male. Most patients (n = 17/22; 77.3%) came from Lombardy, currently the worst-hit region in Italy, and the remaining patients came from Piedmont (n = 1), Emilia-Romagna (n = 1), Toscana (n = 1), Lazio (n = 1), and Campania (n = 1). The median latency time from systemic symptoms to exanthem was 3 days (range, -2 to 12 days). The median duration of skin manifestations was 8 days (range, 4-15 days). Lesions were scattered in most patients (n = 16; 72.7%), and they were diffuse in 6 (27.3%) patients. Predominance of vesicles was observed in 12 (54.5%) patients. No variations in the papulovesicular presentation were observed in our case series. The trunk was always involved, in some cases in association with the limbs (n = 4; 18.2%) (Fig 1, A-D). No facial or mucosal involvements were scored. Itching, which was generally mild, was reported in 9 (40.9%) patients. In all patients who underwent skin biopsy (n = 7), histologic findings were consistent with viral infection (Fig 1, E and F).Table IDemographic and clinical data of patients with varicella-like exanthem associated with COVID-19IDSexAge, yearsHometownSystemic symptoms' onsetPositive result on nasopharyngeal swabSkin lesionsSkin symptomsLatency time, daysDuration, daysLocalizationSystemic symptomsNegative result on nasopharyngeal swabCourse1M75RomeFebruary 19, 2020March 4, 2020Diffuse papulovesicular lesions (predominance of papules)No itching125TrunkFever, asthenia, hypogeusia, hyposmiaYesResolution2M57MilanFebruary 20, 2020February 22, 2020Diffuse papulovesicular lesions (predominance of vesicles)Mild itching54TrunkFever, cough, coryza, headache, hyposmia, hypogeusia, weaknessYesResolution3M59MilanFebruary 28, 2020March 2, 2020Scattered papulovesicular lesions (predominance of papules)Mild itching715TrunkFever, cough, pharyngodynia, headache, weaknessYesResolution4F56BresciaFebruary 28, 2020March 2, 2020Scattered papulovesicular lesions (predominance of vesicles)Pain315TrunkFever, cough, coryza, headache, weaknessYesResolution5M28BolognaMarch 1, 2020March 10, 2020Diffuse papulovesicular lesions started (predominance of papules)Itching47TrunkFever, coughYesResolution6M45BiellaMarch 1, 2020March 6, 2020Scattered papulovesicular lesions (predominance of papules)No itching610TrunkFever, diarrhea, nauseaYesResolution7M72BresciaMarch 1, 2020March 14, 2020Scattered papulovesicular lesions (predominance of vesicles)No itchingUnknownNATrunk, limbsFever, cough, coryza, headache, dyspneaNoActive disease8M83CremonaMarch 2, 2020March 10, 2020Scattered papulovesicular lesions (predominance of vesicles)No itching25TrunkFever, dyspneaNoActive disease∗Patient with acute respiratory distress symptoms in intensive care unit.9M61MilanMarch 2, 2020March 5, 2020Diffuse papulovesicular lesions (predominance of vesicles)Mild itching24TrunkFever, cough, dyspnea, coryza, headache, weakness//Death10M29BresciaMarch 3, 2020March 10, 2020Scattered papulovesicular lesions (predominance of vesicles)Mild itching112TrunkFever, cough, weaknessYesResolution11M65BresciaMarch 3, 2020March 16, 2020Scattered papulovesicular lesions (predominance of papules)Burning213TrunkFever, cough, dyspnea, coryza, headache, weaknessNoActive disease12M44BresciaMarch 8, 2020March 16, 2020Scattered papulovesicular lesions (predominance of vesicles)Burning, itching38TrunkFever, cough, coryza, headache, weaknessNoResolution13M75CremonaMarch 8, 2020March 16, 2020Scattered vesicular lesions (predominance of vesicles)No itching08Trunk, limbsFever, dyspnea//Death14F51BresciaMarch 8, 2020March 17, 2020Scattered papulovesicular lesions (predominance of vesicles)Pain48TrunkFever, cough, dyspnea, coryza, headache, weaknessNoActive disease15F62BresciaMarch 9, 2020March 18, 2020Scattered papulovesicular lesions (predominance of papules)Burning211TrunkFever, cough, coryza, headache, weaknessNoImprovement16M25SienaMarch 10, 2020March 17, 2020Diffuse papulovesicular lesions (predominance of vesicles)Itching56Trunk, limbsCough, hyposmia, hypogeusiaNoResolution17F90CremonaMarch 12, 2020March 20, 2020Scattered papulovesicular lesions (predominance of vesicles)No itching16TrunkFever, cough, dyspnea, coryza, headache, weaknessNoActive disease18F69BresciaMarch 12, 2020March 20, 2020Scattered papulovesicular lesions (predominance of papules)No itchingUnknownNATrunkFever, cough, dyspnea, coryza, hyposmia, hypogeusia, headache, weaknessNoActive disease19M65NaplesMarch 13, 2020March 20, 2020Diffuse papulovesicular lesions (predominance of papules)Mild itching-29TrunkFever, coughNoImprovement20M80BresciaMarch 14, 2020March 22, 2020Scattered papulovesicular lesions (predominance of vesicles)No itchingUnknownNATrunk, limbsFever, dyspnea//Death21M43MilanMarch 15, 2020March 23, 2020Scattered papulovesicular lesions (predominance of vesicles)Mild itching011TrunkFever, myalgiaNoActive disease22F8MilanMarch 15, 2020March 24, 2020Scattered papulovesicular lesions (predominance of papules)No itching37TrunkFever, coughNoResolutionF, Female; ID, identification; M, male; NA, not available; //, not applicable.∗ Patient with acute respiratory distress symptoms in intensive care unit. Open table in a new tab F, Female; ID, identification; M, male; NA, not available; //, not applicable. The most common systemic symptom was fever (n = 21/22; 95.5%), followed by cough (n = 16; 72.7%), headache (n = 11; 50%), weakness (n = 11; 50%), coryza (n = 10; 45.5%), dyspnea (n = 9; 40.9%), hyposmia (n = 4; 18.2%), hypogeusia (n = 4; 18.2%), pharyngodynia (n = 1; 4.5%), diarrhea (n = 1; 4.5%), and myalgia (n = 1; 4.5%). Death occurred in 3 (13.6%) patients. Ours is the first series on this varicella-like exanthem as a specific COVID-19–associated cutaneous picture, unlike the nonspecific cutaneous manifestations such as erythematous rash or urticaria reported by Recalcati.5Recalcati S. Cutaneous manifestations in COVID-19: a first perspective [Epub ahead of print].J Eur Acad Dermatol Venereol. 2020; (Accessed April 27, 2020)https://doi.org/10.1111/jdv.16387Crossref Scopus (913) Google Scholar Its typical features are frequent trunk involvement, usually scattered distribution, and mild/absent pruritus, the latter being in line with most viral exanthems but unlike true varicella. Lesions generally appear 3 days after systemic symptoms and disappear by 8 days, without leaving scarring. A limitation of our study was missing histologic evaluation in some cases. Moreover, demonstration of SARS-CoV-2 presence by polymerase chain reaction in lesional skin was not possible because of specific primer unavailability. If further studies validate our findings, this early skin manifestation will represent a useful clue for suspecting COVID-19 in asymptomatic/paucisymptomatic patients. The authors wish to thank the following collaborators for their help in data collection and patient treatment: Marica Annunziata, Cristiana Colonna, Massimo Ghislanzoni, Raffaele Gianotti, Chiara Moltrasio, Gianluca Nazzaro, Emanuela Passoni, Marina Picca, Gaetano Rizzitelli, and Diego Tosi. Reply to "Varicella-like exanthem as a specific COVID-19–associated skin manifestation: multicenter case series of 22 patients": Discussing specificityJournal of the American Academy of DermatologyVol. 83Issue 1PreviewTo the Editor: We read with interest the article by Marzano et al1 addressing the specificity of varicella-like exanthem to diagnose coronavirus disease (COVID-19). Although this type of COVID-19–associated rash is rare, the authors claim that it is more specific than others without having performed a diagnostic accuracy study.2 This type of study would calculate the association of COVID-19 status (yes/no) with the type of exanthem (varicella-like/non–varicella-like) in a predetermined number of patients (to ensure sufficient statistical power) and in a defined population with a known prevalence of COVID-19 disease. Full-Text PDF 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 outJournal of the American Academy of DermatologyVol. 83Issue 3PreviewTo the Editor: We have read with great interest the article by Marzano et al1 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.1 A previous case report of COVID19-related varicella-like vesicles had also been published by Recalcati2 for the very first time. However, only the Marzano et al1 article included scarce clinical images due to safety or logistic concerns. Full-Text PDF