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Case reports illustrate heterogeneity of skin manifestations in COVID patients


 

Two case reports published simultaneously in JAMA Dermatology prompted an accompanying editorial calling for dermatologists to actively participate in the characterization and management of skin complications associated with COVID-19 infection.

It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.

“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,” the authors of the editorial stated.

So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.

In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.

In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.

It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.

In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.

Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.

Dr. Kanade Shinkai

Dr. Kanade Shinkai

To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.

It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.

The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”

The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”

NYU Langone Health

Dr. Kirsten Lo Sicco

“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”

While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.

In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.

“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.

One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.

Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.

One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.

Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.

“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.

These are exactly the types of issues being actively investigated at her center.

Neither the authors of the case reports nor of the editorial reported any conflicts of interest.

SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.

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