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June 24, 2020

Clinicopathologic Aspects of a Papulovesicular Eruption in a Patient With COVID-19

Author Affiliations
  • 1Department of Dermatology and Venereology, Geneva University Hospitals, Geneva, Switzerland
  • 2Department of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
  • 3Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland
  • 4Department of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
JAMA Dermatol. 2020;156(8):922-924. doi:10.1001/jamadermatol.2020.1966

There are reports of various skin findings associated with coronavirus disease 2019 (COVID-19).1-4 We describe a patient with a papulovesicular eruption.

Report of a Case

A man in his 60s developed asthenia, anorexia, and cough. Six days later, he was hospitalized with diffuse bilateral pneumonia and was confirmed to have COVID-19 by nasopharyngeal swab using real-time reverse transcriptase–polymerase chain reaction (RT-PCR). Piperacillin-tazobactam and lopinavir-ritonavir treatment were started. Twelve hours after treatment initiation, numerous 3- to 6-mm pseudovesicular papules with superficial crusting were noted on the trunk. The papules were asymptomatic (Figure 1). Within 48 hours the papules evolved to an extensive, but not confluent, purpuric rash. The clinical differential diagnosis was a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)–associated eruption, transient acantholytic dermatosis (Grover disease), herpes simplex virus infection, or a drug reaction. Diagnostic testing was performed on a superficial skin sample for the herpes simplex, varicella zoster, and SARS-CoV-2 viruses, and the results were negative. Histologic analysis showed extensive epidermal necrosis with acantholysis and large multinucleated keratinocytes with ballooning degeneration. A dense perivascular lymphohistiocytic infiltrate with some extravasated erythrocytes and eosinophils was observed in the superficial dermis. There were also early-stage vasculitic alterations in the form of endotheliitis, with slight endothelial swelling of the dermal vessels without fibrinoid necrosis or thrombosis (Figure 2). Immunohistochemical findings were negative for the herpes simplex and varicella zoster viruses, and testing of the fixed skin tissue using RT-PCR was negative for SARS-CoV-2. Clinicopathologic correlation suggested a viral-induced skin eruption associated with COVID-19. The patient’s respiratory condition improved, and he was discharged from the hospital after 10 days.

Figure 1.  Papulovesicular Eruption Associated With COVID-19
Papulovesicular Eruption Associated With COVID-19

Multiple papules with a pseudovesicular aspect and superficial crust are seen on the trunk of a patient with coronavirus disease 2019 (COVID-19).

Figure 2.  Histologic Analysis of the Biopsy Specimen
Histologic Analysis of the Biopsy Specimen

One of the skin lesions shows an area of extensive epidermal necrosis with acantholysis and swelling of keratinocytes due to intracellular edema (blue rectangle) (hematoxylin-eosin, original magnification ×5). Right inset: Large multinucleated keratinocytes with ballooning degeneration (white arrows) (hematoxylin-eosin, original magnification ×100). Left inset: Perivascular lymphohistiocytic infiltrate with some extravasated erythrocytes and eosinophils in the superficial dermis, where vessels display slight endothelial swelling consistent with early-stage vasculitic alterations and endotheliitis (hematoxylin-eosin, original magnification ×100).


Various types of skin lesions are now reported in patients with COVID-19, but few with such a vesicular aspect.2-4 Other patients with COVID-19 in our care have also been observed to have vesicular and necrotic lesions, similar to the patient in this case report. Our differential diagnosis included transient acantholytic dermatosis, but the clinical features differed by the presence of a much more inflammatory and purpuric aspect to the lesions. Although a pseudoherpetic variant of Grover disease has been described, histologic findings showing such extensive epidermal necrosis and dense dermal infiltrate with vasculitic changes are not usually seen in lesions associated with Grover disease.5 The endotheliitis-like changes in the skin sample of this patient with COVID-19 are notable because other studies6 have reported lymphocytic endotheliitis involving different organs (lung, heart, kidney, liver, and small intestine) in patients with COVID-19, suggesting that SARS-CoV-2 infection may facilitate the induction of endothelial inflammation in several organs as a direct consequence of viral involvement and/or the host inflammatory response. The cutaneous eruption in the current case evolved independently of medication exposures, and the differential diagnosis did not support a drug reaction. The presence of large multinucleated keratinocytes might have suggested a herpes simplex virus or varicella zoster virus infection, but this possibility was eliminated by PCR and immunohistochemical test results.

This cutaneous eruption may represent an unusual viral exanthem; direct viral persistence in the epidermis through hematogenous dissemination was not confirmed in this case by multiple tests of skin samples for SARS-CoV-2. Understanding the skin findings in patients with COVID-19 may assist physicians who suspect early-stage SARS-CoV-2 infection. The epidermal alterations and dermal vasculitic changes seen in this patient are important findings to inform our understanding of the pathophysiologic mechanism of skin lesions in patients with COVID-19.

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Article Information

Corresponding Author: Laurence Toutous Trellu, MD, Department of Dermatology and Venereology, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland (laurence.trellu@hcuge.ch).

Published Online: June 24, 2020. doi:10.1001/jamadermatol.2020.1966

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

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1 Comment for this article
Eosinophilic infiltrate
Aivlys Perez, MD | San Juan Dermatopathology
I am grateful for authors that addressed the need for published literature regarding histologic skin findings in patients with SARS-CoV-2 infection. I agree with most of the differential diagnosis. I think that hypersensitivity reactions were to early removed from the working diagnosis. Some of the changes, histologic, described here I have observed in patients with skin findings during the pandemic in skin specimens that I have been able to examine.

Eosinophils should always prompt thorough evaluation for hypersensitivity. The authors describe the skin eruption developing about 12 hours after starting Piperacillin - Tazobartan
and Lopinavir - Ritonavir, which is the correct timing for a hypersensitivity reaction in a patient that has been sensitized to one of these agents before.

The appearance of secondary skin changes in about 48 hours is common to eruptions of any etiology and a biopsy of an earlier lesion would have been more useful than the later one that was obtained to make a more accurate diagnosis.

The necrosis of the epidermis spares the basal and lower spinous layers. Damage in the upper layers should always prompt in the differential diagnosis the consideration of exposure to an exogenous agent that caused damage to the epidermis. A history of what was applied on the skin before arrival to the hospital or during his care while hospitalized could reveal irritants or other external sources of trauma to the skin that could explain some of the histological findings.