Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients.

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. The COVID-19 outbreak emerged in Wuhan, China, and rapidly spread to Europe, particularly to Italy, where, as of April 27, 2020, a total of 199,414 people have tested positive.

Two recent publications have brought attention to COVID-19–associated cutaneous manifestations. , Joob and Wiwanitkit reported on a dengue-like petechial rash in a patient with COVID-19 from Thailand. Recalcati 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. 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.