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

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

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.

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.

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.