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who performed a systematic literature review of the highly variable cutaneous manifestations of coronavirus disease 2019 (COVID-19). Since the global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dermatologists have mobilized to identify, catalog, and disseminate potential cutaneous manifestations of SARS-CoV-2 infection. Lack of widespread testing and potential limitations in assays that detect acute and previous infections underscore the utility of identifying skin manifestations of COVID-19.
These limitations, however, make it difficult to definitively conclude that skin manifestations of COVID-19 are due to SARS-CoV-2. In fact, the most commonly reported cutaneous manifestation, pernio-like lesions (so-called COVID toes),
On the other hand, patients who have confirmed SARS-CoV-2 infection have been reported to develop a wide variety of cutaneous manifestations, including morbilliform eruption, urticaria, petechiae, retiform purpura, periorbital erythema, vesicular, livedo reticularis, digitate papulosquamous, erythema multiforme, pernio-like lesions, and androgenic alopecia
(Fig 1). It remains to be determined which skin manifestations are a sign of SARS-CoV-2 infection due to direct tissue injury from viral tropism or to sequela of infection such as coagulopathy and immune injury.
We recommend caution when concluding that cutaneous findings are specifically due to SARS-CoV-2. Without question, SARS-CoV-2 is a unique and devastating virus with multiple tissue tropism and heterogeneous immune activation. With further clinical studies, more widespread testing, and a better understanding of the natural course of the virus, these skin manifestations will likely settle into 2 types: virus-specific and nonspecific. To determine virus-specific mechanisms, direct detection of viral particles within cutaneous lesions is needed.
Furthermore, these studies should use control tissue of similar lesions (eg, perniosis) that occurred before the pandemic.
In the absence of direct viral detection, unique immune signatures identified within patients with COVID-19 should be investigated in patients who develop skin manifestations. Cutaneous lesions that are nonspecific should be grouped into those that are suggestive of COVID-19 vs those that are not. The COVID-19 Dermatology Registry will be critical to identifying which cutaneous manifestations are most suggestive of COVID-19.
The difficulty in classifying the cutaneous manifestations of a systemic, complex, and heterogenous immune-mediated disease is reminiscent of systemic lupus erythematosus (SLE). Although distinct in etiology, disease course, and treatment, the lessons learned from studying SLE may be applied to understanding the cutaneous manifestations of COVID-19. In 1992, Dr Robert A. Greenwald commented that “anything happening to a patient with SLE which is not immediately otherwise explicable will automatically be blamed on the lupus, regardless of pathophysiologic validity.”
This became known as Greenwald's law of lupus. Subsequently, Dr Richard Sontheimer provided a corollary to Greenwald's law that anything happening to patient with a positive anti-nuclear antibody will be blamed on lupus.
Funding sources: Dr Vesely is supported by the Dermatology Foundation , the Melanoma Research Alliance , and National Institutes of Health National Center for Advancing Translational Sciences ( KL2-TR-001862 ).
To the Editor: We read with interest the letters from the New York City report regarding the absence of COVID toe lesions on their patients and the recommendation of caution when concluding that cutaneous findings are specifically due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1,2 Since the global pandemic of SARS-CoV-2, the University of São Paulo Medical School Hospital—a reference center and one of the largest university hospitals in Latin America—reorganized its structure, offering about 300 intensive care units and 500 nursery beds fully dedicated to SARS-CoV-2.