US Study Finds No Association With 'COVID Toes' and COVID-19

Amy Reyes

June 23, 2021

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A large retrospective U.S. study published June 23 in JAMA Dermatology finds that chilblains, an inflammatory skin condition marked by erythema and also known as 'COVID toes,' is likely not associated with a COVID-19 diagnosis, despite an unprecedented number of new chilblain cases reported in 2020.

This study follows a report published almost 2 weeks earlier, of 17 adolescents in Italy with chilblain lesions of the toes. That report indicated that the lesions were not related to current or past infections, and that lifestyle changes may have been a contributing factor.

Early last year, clinicians in Europe and the United States began reporting an unusually high number of chilblain cases, but few of the patients described in the cases were positive for SARS-CoV-2 or its antibodies. The possible connection was explored in studies and featured extensively in the lay press. After all, viral infections, including SARS-CoV-2, are known to be associated with skin rashes. Plus, SARS-CoV-2 infections are known to exhibit a number of dermatological manifestations, such as urticarial and morbilliform eruptions, and vesicular eruptions. More than 150 papers have been published on the spectrum of cutaneous reactions to this virus.

In the new study, led by Patrick E. McCleskey, MD, a dermatologist with Kaiser Permanente Oakland (Calif.) Medical Center, a review of chilblain cases from six Bay Area counties in Northern California found a weak correlation confirming 2% of chilblain cases as potentially secondary to COVID-19.

"While chilblains do seem to follow COVID-19 infection in some cases, most cases of chilblains in our study were not shown to be related to SARS-CoV-2 infection," McCleskey said in an interview.

"We think the increase in cases probably had more to do with changes in behavior as children and adults were at home instead of work and school. The highest incidence in chilblains were seen in children ages 13-19, who were staying home from school. Only 6% in our study said they wear shoes at home, and half of our patients don't have home heating in northern California," he said.

The condition of chilblains primarily affects the dorsal feet or hands and is almost uniquely associated with spending an inordinate amount of time in damp and cold conditions. There are some medical conditions associated with chilblains, such as Raynaud's disease, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, hyperhidrosis, and lymphomas and leukemias. And, as with COVID-19, chilblains affect more women than men.

Northern California Study

The retrospective cohort study evaluated 780 patients (464 female; mean age 36.8 years) from six Bay Area counties in Northern California, who were treated for chilblains between April and December 2020 when stay-at-home orders were in effect in California. Of the 780 patients, 456 were tested for SARS-CoV-2, and 17 patients (3.7%) tested positive for the virus. In nine patients (2%), a COVID-19 infection was preceded by 6 weeks of chilblains. By September, testing for the COVID-19 virus was more reliable. Testing showed that of 97 chilblains cases, 1% were positive for the virus.

"The finding that some patients with COVID-19 developed chilblains at the same time, or subsequent to the infection, is suggestive of secondary chilblains due to COVID-19," McCleskey said.

The 2020 cases were compared with 539 patients (mean age 44.7 years) with chilblains who were treated during the same period in 2016, 2017, 2018 and 2019. During these years, the annual incidence of chilblains was 5.2 (95% confidence interval, 4.8-5.6) per 100,000 person years, compared with 28.6 (95% CI, 26.8-30.4) in 2020, during the pandemic.

Possible Explanations

The authors suggest there are several explanations for the increased reports of chilblains in 2020. First, the lack of shoes: During the pandemic, children between the ages of 13 and 19 years had more cases of chilblains than any other age group despite the fact that teenagers have a low-risk of contracting SARS-CoV-2. Six percent of teenagers with newly diagnosed chilblains wore shoes at home during the study period in 2020.

Chilblains was almost three times more common in Asian American (42.5; 95% CI, 37.7-47.8) and White individuals (35.7; 95% CI, 32.6-39.1), compared with Black (11.6; 95% CI, 7.8-17.3) and Latinx (12.5; 95% CI, 10.1-15.4) individuals. But the authors noted that the Latinx community had the highest number of COVID-19 cases (62.5; 95% CI, 61.9-63.1), three times more than Asian Americans (19.0; 95% CI, 18.6-19.3) and White individuals (17.9; 95% CI, 17.7-18.2) and two times more than in Black individuals (29.2; 95% CI, 28.4-29.9).

"Latinx patients had the highest rates of COVID-19 infections in our population, but the lowest rates of chilblains. Groups in Northern California who were more likely to stay home during the pandemic because they could work from home – White and Asian American and White patients – had much higher rates of chilblains than groups who were more likely to have to work outside the home – Latinx and African American patients," McCleskey said.

A report by the Bay Area Council in December 2020 found that Asian Americans and Whites were more likely to work from home during the pandemic (52% and 50% respectively) compared with Black and Latinx workers (33% and 30% respectively). While Latinx individuals made up 46% of all COVID-19 cases, they accounted for 9% of chilblain cases in 2020 (but cases may have been underreported), the authors wrote.

And while there may have been more cases of chilblains during the pandemic in 2020, they did not occur in cities with higher rates of COVID-19. "If chilblains were occurring in the same communities where COVID-19 cases were occurring, the Spearman coefficient would be closer to 1," wrote the authors, referring to the measure used to rank correlation in the study. In this case, the Spearman coefficient was 0.18.

Another explanation for the increase in chilblain cases could be that more patients sought care in response to news reports about "COVID toes."

"The exact cause of chilblains is still elusive. Some publications coming out of the pandemic suggest an interferon response is part of the pathophysiology of chilblains, but this was not the focus of our research," McCleskey said.

The authors hypothesized that in affected individuals, particularly younger patients, the immune response to SARS-CoV-2 contributed to chilblains in asymptomatic individuals. "It is possible that some patients with chilblains were exposed to SARS-CoV-2 but produced such a robust innate immune response that it was later difficult to find any evidence of infection," they wrote.

They suggested that better testing may help identify past exposure to SARS-CoV-2 and secondary chilblains.

The strengths of this study included its size, community base, a control group dating back to 2016, validation by medical records review, and the ability to control for geographic variation allowing investigators to track weather, which can be a factor in chilblain cases. The authors noted several limitations to the study, including the lack of reliable antibody testing early in the year and the lack of IgA antibody testing.

The authors had no disclosures. The study was funded by The Permanente Medical Group Delivery Science and Applied Research initiative.

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