How Dermatologists Can Learn and Contribute at the Leading Edge of the COVID-19 Global Pandemic | Dermatology | JAMA Dermatology | JAMA Network
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Editorial
April 30, 2020

How Dermatologists Can Learn and Contribute at the Leading Edge of the COVID-19 Global Pandemic

Author Affiliations
  • 1Department of Dermatology, University of Utah, Salt Lake City
  • 2Section Coeditor, Clinical Images, JAMA Dermatology
  • 3Society of Dermatology Hospitalists
  • 4Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 5Department of Dermatology, University of California, San Francisco
  • 6Editor, JAMA Dermatology
JAMA Dermatol. 2020;156(7):733-734. doi:10.1001/jamadermatol.2020.1438

In this issue of JAMA Dermatology, clinical cases and images of rashes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are presented.1,2 Although these early observations are not comprehensive of all skin manifestations seen, our intention in publishing them is to help dermatologists recognize emerging patterns of rashes in patients with coronavirus disease 2019 (COVID-19). The reported prevalence of cutaneous signs in association with this pandemic is conflicting; one study reported a rash in only 0.2% of a cohort of Chinese patients,3 whereas the estimated prevalence in a cross-sectional Italian study was 20.4%.4 In the latter study, performed by dermatologists, the cutaneous manifestations were most commonly described as an erythematous rash; however, a range of additional morphologic features were observed, including generalized urticaria and vesicular eruptions. A predilection for the trunk was also noted.4 It may not be possible to determine the exact prevalence of skin findings in infected patients until serologic testing is more widely available, given that some individuals may lack the typical respiratory signs of COVID-19.5

There are many important considerations in the interpretation of these early reports from a dermatologic perspective. Whether these rashes are specific manifestations of SARS-CoV-2 infection involving the skin or represent reaction patterns in association with COVID-19 is an important question to keep in mind when evaluating these images. We must be cautious in attributing all rashes seen in patients with COVID-19 to direct effects of SARS-CoV-2; rashes may develop because of co-infection with SARS-CoV-2 and another respiratory infection,6 medical complications that arise in a critically ill patient (such as fever or disseminated intravascular coagulation), or other supportive medications or empirical treatments for infection. The limited availability of SARS-CoV-2 testing, especially early in the global pandemic, further complicates the interpretation of rashes seen in diagnostically unconfirmed cases. Careful and detailed prospective study, including performing specific SARS-CoV-2 testing on skin biopsy specimens, will be needed to clarify the pathogenesis of these rashes.

Clinical Case Highlights

The case reports in this issue show 2 distinct forms of rashes seen in association with COVID-19: a petechial flexural eruption1 and a digitate papulosquamous rash.2 The timing of rash onset is strikingly variable, suggesting that skin findings may present at any stage of the infection. In cases we have seen as medical dermatologists, rashes may precede the onset of fever and other systemic features, and they may also occur late during the infection, including after other typical viral features have subsided.

Key histopathologic features vary depending on the morphologic presentation. Collaborations between dermatologists and dermatopathologists will be essential to characterize these eruptions, both to identify histopathologic features (if any) that are specific to COVID-19 and may guide the treatment of patients—who may have other potential triggers of rash, including use of certain medications—and to perform specific tests to discriminate between direct manifestations of the virus vs generic reaction patterns. In the report by Sanchez et al,2 the papulosquamous eruption has a fundamentally spongiotic pattern, including foci of spongiosis and spongiotic vesicles containing lymphocytes and Langerhans cells. Purpura revealed by a morphologic examination may result from extravasated erythrocytes, as in the article by Diaz-Guimaraens,1 in which no thrombotic vasculopathy was noted. In emerging reports posted on social media and in other journals, pernio-like lesions seen on acral sites may represent vasculitis and/or thrombosis in the cutaneous microvasculature, a critical clinicopathologic correlation and possible pathophysiologic mechanism that may be unique to COVID-19.7

Gaining a Better Understanding of COVID-19–Associated Skin Findings

Early reports about the cutaneous eruptions seen in patients with COVID-19 raise more questions than they provide answers. Some of the rashes we have observed are reminiscent of viral eruptions commonly seen in children, and yet it is well established that viral exanthems are rare in adults. Whether these eruptions suggest pathophysiologic mechanisms underlying rash that may be relevant to the systemic features of COVID-19, and whether these are specific to SARS-CoV-2 or to coronaviruses in general, are vital questions. Furthermore, the significance of a cutaneous eruption associated with COVID-19 remains unclear, especially as it pertains to prognosis. It will require additional study to determine if specific host or pathogen factors contribute to the likelihood of developing a rash, and especially a specific pattern of rash. As dermatologists, we are familiar with rashes that are immediately recognizable as the telltale sign of a particular infection, such as parvovirus B19–associated papular-purpuric “gloves and socks” syndrome or the “slapped cheeks” appearance in children; it remains to be seen whether this will be the case for COVID-19. Careful study, including comprehensive mucocutaneous examinations, analysis of other systemic clinical features or host characteristics, and histopathologic correlation, will be vital to understanding the pathophysiologic mechanisms of what we are seeing on the skin. Recognizing the dermatologic effect of both supportive drugs and empirical treatments for SARS-CoV-2 infection, including combinations of well-known medications and novel therapeutics such as remdesivir, will provide critical information.

How Dermatologists Can Learn and Contribute During a Pandemic

In the past few weeks, rapid implementation of teledermatology and changes in telemedicine regulation have occurred in response to the COVID-19 pandemic. Teledermatology provides patients ongoing access to dermatologic care and affords a safer way to evaluate patients, including those with confirmed or suspected COVID-19. This strategy also allows for the preservation of resources, including personal protective equipment, that may become increasingly scarce. However, will teledermatology be adequate for all patients, or sufficient for effectively evaluating clinical entities with which we are unfamiliar? Some recently published studies incorporate data (including images) from the indirect evaluation of patients or do not provide images to accompany the clinical descriptions (because of infection control regulations in hospitals). To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19.8 Clear descriptions and high-quality images will help all clinicians learn to recognize the cutaneous features of COVID-19, potentially aiding in diagnosis and treatment. It will be critical at this time for dermatologists, like other specialists, to contribute however possible, in ways large and small—including by being a presence in the hospital to provide unique expertise in the evaluation of SARS-CoV-2–infected patients with rashes. This challenging time provides opportunities to contribute and to learn. The creative strategies developed during this pandemic may prove beneficial to future patients and expand the reach of our specialty. Social media posts and online forum discussions of many deidentified clinical images of rashes in infected patients has already enabled the rapid recognition of skin signs by dermatologists; it is now time for rigorous science. We hope that dermatologists will be among those leading the global response to the COVID-19 pandemic: characterizing COVID-19–related rashes, understanding their implications, and determining best evidence for their treatment.

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Article Information

Corresponding author: Kanade Shinkai, 1701 Divisadero St, 3rd Floor, San Francisco, CA 94115 (kanade.shinkai@jamanetwork.org).

Published Online: April 30, 2020. doi:10.1001/jamadermatol.2020.1438

Conflict of Interest Disclosures: None reported.

Disclaimer: The views expressed herein are those of the authors and do not necessarily represent the perspectives of the Society of Dermatology Hospitalists.

References
1.
Diaz-Guimaraens  B, Dominguez-Santas  M, Suarez-Valle  A,  et al.  Petechial skin rash associated with severe acute respiratory syndrome coronavirus 2 infection.   JAMA Dermatol. Published online April 30, 2020. doi:10.1001/jamadermatol.2020.1741Google Scholar
2.
Sanchez  A, Sohier  P, Benghanem  S,  et al.  Digitate papulosquamous eruption associated with severe acute respiratory syndrome coronavirus 2 infection.   JAMA Dermatol. Published online April 30, 2020. doi:10.1001/jamadermatol.2020.1704Google Scholar
3.
Guan  WJ, Ni  ZY, Hu  Y,  et al; China Medical Treatment Expert Group for Covid-19.  Clinical characteristics of coronavirus disease 2019 in China.   N Engl J Med. Published online February 28, 2020. doi:10.1056/NEJMoa2002032 PubMedGoogle Scholar
4.
Recalcati  S.  Cutaneous manifestations in COVID-19: a first perspective.   J Eur Acad Dermatol Venereol. 2020. Published online March 26, 2020. doi:10.1111/jdv.16387 PubMedGoogle Scholar
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Bai  Y, Yao  L, Wei  T,  et al.  Presumed asymptomatic carrier transmission of COVID-19.   JAMA. 2020;323(14):1406-1407. doi:10.1001/jama.2020.2565 PubMedGoogle ScholarCrossref
6.
Wu  X, Cai  Y, Huang  X,  et al.  Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China.   Emerg Infect Dis. 2020;26(6). doi:10.3201/eid2606.200299 PubMedGoogle Scholar
7.
Mazzotta  F, Troccoli  T. Acute acro-ischemia in the child at the time of COVID-19.  Dermatologia Pediatrica. March 2020. Accessed April 23, 2020. https://img.beteve.cat/wp-content/uploads/2020/04/acroischemia-ENG.pdf
8.
Wu  P, Duan  F, Luo  C,  et al.  Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China.   JAMA Ophthalmol. Published online March 31, 2020. doi:10.1001/jamaophthalmol.2020.1291 PubMedGoogle Scholar
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    1 Comment for this article
    EXPAND ALL
    A DELUGE OF DISINFECTANTS AND SKIN LESIONS DURING COVID-19 PANDEMICS
    Arturo Tozzi, pediatrician | University of North Texas
    A DELUGE OF DISINFECTANTS AND SKIN LESIONS DURING COVID-19 PANDEMICS


    Different types of skin lesions have been described during the current COVID-19 pandemic, although reports are mostly scant and anecdotic (Landa et al., 2020; Diaz-Guimaraens et al., 2020). Despite a number of patients affected by dermatologic diseases display either swab-negativity or absence of the typical signs and symptoms of COVID-19, it is tempting to hypothesize a causal relationship between systemic effects of SARS-CoV-2 and such a substantial increase of skin lesions in the countries plagued by the coronavirus.
    Nevertheless, an alternative explanation
    for the reported increase of dermatologic alterations during COVID-19 pandemic might be hypothesized. Indeed, skin lesion might be correlated with, instead of caused by, SARS-CoV-2. In the last months, routine cleaning and disinfection for households have been provided aimed at limiting the survival of the virus in the environments, together with suggestions for hand, mouth, eye, nose hygiene (CDC, 2020). For example, United States Environmental Protection Agency (2020) delivered a list of all products meeting EPA’s criteria for use against SARS-CoV-2. In particular, the List N of Disinfectants for Use Against SARS-CoV-2 includes, among others, Quaternary ammonium, Sodium hypochlorite, Phenolic, Hypochlorous acid, Hydrogen chloride, Hydrogen Peroxide, Citric acid, Peroxyacetic acid, and so on. It is noteworthy that also other substances, although less effective against SARS-CoV-2, are widely employed for cleaning purposes, such as benzalkonium chloride. The most of these products are able to cause skin lesions: to provide just an example among countless ones, benzalkonium chloride is an irritant and, to a less extent, also a sensitizer (Isaac and Scheinman, 2017). All over the world, scared people are washing hands, households, surfaces, using an unprecedented amount of disinfectants, cleaners, and so on. Therefore, it might be speculated that, among other causes, the current increase of skin lesions all over the world could at least partially explained not by the pathogenic effects of SARS-CoV-2, rather by the legitimate fear of SARS-CoV-2.



    REFERENCES
    1) CDC. 2020. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cleaning-disinfection.html
    2) Diaz-Guimaraens B , Dominguez-Santas M , Suarez-Valle A , et al. 2020. Petechial skin rash associated with severe acute respiratory syndrome coronavirus 2 infection. JAMA Dermatol. doi:10.1001/jamadermatol.2020.1741
    3) Isaac J, Scheinman PL. 2017. Benzalkonium Chloride: An Irritant and Sensitizer. Dermatitis. 2017 Nov/Dec;28(6):346-352. doi: 10.1097/DER.0000000000000316.
    4) Landa N, Mendieta-Eckert M, Fonda-Pascual P, Aguirre T. 2020. Chilblain-like lesions on feet and hands during the COVID-19 Pandemic. Int J Dermatol. 2020 Apr 24. doi: 10.1111/ijd.14937.
    5) United States Environmental Protection Agency. 2020. https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2.


    Arturo Tozzi
    Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA
    tozziarturo@libero.it
    Arturo.Tozzi@unt.edu
    CONFLICT OF INTEREST: None Reported
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