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.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
Two recent publications have brought attention to COVID-19–associated cutaneous manifestations.4 , 5 Joob and Wiwanitkit4 reported on a dengue-like petechial rash in a patient with COVID-19 from Thailand. Recalcati5 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 I.
Demographic and clinical data of patients with varicella-like exanthem associated with COVID-19
| ID | Sex | Age, years | Hometown | Systemic symptoms' onset | Positive result on nasopharyngeal swab | Skin lesions | Skin symptoms | Latency time, days | Duration, days | Localization | Systemic symptoms | Negative result on nasopharyngeal swab | Course |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 75 | Rome | February 19, 2020 | March 4, 2020 | Diffuse papulovesicular lesions (predominance of papules) | No itching | 12 | 5 | Trunk | Fever, asthenia, hypogeusia, hyposmia | Yes | Resolution |
| 2 | M | 57 | Milan | February 20, 2020 | February 22, 2020 | Diffuse papulovesicular lesions (predominance of vesicles) | Mild itching | 5 | 4 | Trunk | Fever, cough, coryza, headache, hyposmia, hypogeusia, weakness | Yes | Resolution |
| 3 | M | 59 | Milan | February 28, 2020 | March 2, 2020 | Scattered papulovesicular lesions (predominance of papules) | Mild itching | 7 | 15 | Trunk | Fever, cough, pharyngodynia, headache, weakness | Yes | Resolution |
| 4 | F | 56 | Brescia | February 28, 2020 | March 2, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | Pain | 3 | 15 | Trunk | Fever, cough, coryza, headache, weakness | Yes | Resolution |
| 5 | M | 28 | Bologna | March 1, 2020 | March 10, 2020 | Diffuse papulovesicular lesions started (predominance of papules) | Itching | 4 | 7 | Trunk | Fever, cough | Yes | Resolution |
| 6 | M | 45 | Biella | March 1, 2020 | March 6, 2020 | Scattered papulovesicular lesions (predominance of papules) | No itching | 6 | 10 | Trunk | Fever, diarrhea, nausea | Yes | Resolution |
| 7 | M | 72 | Brescia | March 1, 2020 | March 14, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | No itching | Unknown | NA | Trunk, limbs | Fever, cough, coryza, headache, dyspnea | No | Active disease |
| 8 | M | 83 | Cremona | March 2, 2020 | March 10, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | No itching | 2 | 5 | Trunk | Fever, dyspnea | No | Active disease∗ |
| 9 | M | 61 | Milan | March 2, 2020 | March 5, 2020 | Diffuse papulovesicular lesions (predominance of vesicles) | Mild itching | 2 | 4 | Trunk | Fever, cough, dyspnea, coryza, headache, weakness | // | Death |
| 10 | M | 29 | Brescia | March 3, 2020 | March 10, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | Mild itching | 1 | 12 | Trunk | Fever, cough, weakness | Yes | Resolution |
| 11 | M | 65 | Brescia | March 3, 2020 | March 16, 2020 | Scattered papulovesicular lesions (predominance of papules) | Burning | 2 | 13 | Trunk | Fever, cough, dyspnea, coryza, headache, weakness | No | Active disease |
| 12 | M | 44 | Brescia | March 8, 2020 | March 16, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | Burning, itching | 3 | 8 | Trunk | Fever, cough, coryza, headache, weakness | No | Resolution |
| 13 | M | 75 | Cremona | March 8, 2020 | March 16, 2020 | Scattered vesicular lesions (predominance of vesicles) | No itching | 0 | 8 | Trunk, limbs | Fever, dyspnea | // | Death |
| 14 | F | 51 | Brescia | March 8, 2020 | March 17, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | Pain | 4 | 8 | Trunk | Fever, cough, dyspnea, coryza, headache, weakness | No | Active disease |
| 15 | F | 62 | Brescia | March 9, 2020 | March 18, 2020 | Scattered papulovesicular lesions (predominance of papules) | Burning | 2 | 11 | Trunk | Fever, cough, coryza, headache, weakness | No | Improvement |
| 16 | M | 25 | Siena | March 10, 2020 | March 17, 2020 | Diffuse papulovesicular lesions (predominance of vesicles) | Itching | 5 | 6 | Trunk, limbs | Cough, hyposmia, hypogeusia | No | Resolution |
| 17 | F | 90 | Cremona | March 12, 2020 | March 20, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | No itching | 1 | 6 | Trunk | Fever, cough, dyspnea, coryza, headache, weakness | No | Active disease |
| 18 | F | 69 | Brescia | March 12, 2020 | March 20, 2020 | Scattered papulovesicular lesions (predominance of papules) | No itching | Unknown | NA | Trunk | Fever, cough, dyspnea, coryza, hyposmia, hypogeusia, headache, weakness | No | Active disease |
| 19 | M | 65 | Naples | March 13, 2020 | March 20, 2020 | Diffuse papulovesicular lesions (predominance of papules) | Mild itching | -2 | 9 | Trunk | Fever, cough | No | Improvement |
| 20 | M | 80 | Brescia | March 14, 2020 | March 22, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | No itching | Unknown | NA | Trunk, limbs | Fever, dyspnea | // | Death |
| 21 | M | 43 | Milan | March 15, 2020 | March 23, 2020 | Scattered papulovesicular lesions (predominance of vesicles) | Mild itching | 0 | 11 | Trunk | Fever, myalgia | No | Active disease |
| 22 | F | 8 | Milan | March 15, 2020 | March 24, 2020 | Scattered papulovesicular lesions (predominance of papules) | No itching | 3 | 7 | Trunk | Fever, cough | No | Resolution |
F, Female; ID, identification; M, male; NA, not available; //, not applicable.
Patient with acute respiratory distress symptoms in intensive care unit.
Fig 1.
A-D, Papulovesicular exanthem on the trunk in 4 patients with COVID-19. A-C, In 3 patients, predominance of papules is seen. D, In another patient mainly presenting with vesicles, exanthem resolution with crusts is evident; E, Basket-wave hyperkeratosis; slightly atrophic epidermis; and vacuolar degeneration of the basal layer with multinucleate, hyperchromatic keratinocytes and dyskeratotic cells. Note the absence of inflammatory infiltrate. (Hematoxylin-eosin stain; original magnification: ×4.) F, Close-up image with atrophic epidermis, vacuolar alteration with disorganized keratinocytes lacking orderly maturation, and enlarged and multinucleate keratinocytes with dyskeratotic (apoptotic) cells. (Hematoxylin-eosin stain; original magnification: ×20).
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.5 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.
Acknowledgments
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.
Footnotes
Funding sources: None.
Conflicts of interest: None disclosed.
IRB approval status: Because of the retrospective nature of the study, only a notification to the ethical committee of the principal investigator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) was requested. All patients gave written informed consent for publishing the clinical images.
References
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