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Are Chilblains Associated With COVID-19?

Reports regarding potential skin manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been circulating online and in the literature.1-3 An unusual finding being reported is the appearance of purplish red chilblain lesions on the toes and/or fingers, dubbed “COVID toes,” which some speculate may be connected to mild or asymptomatic cases of the coronavirus disease 2019 (COVID-19).4,5 However, no studies have shown a pathologic link between these lesions and COVID-19.5

Two new European studies published in JAMA Dermatology investigated the potential association between the virus and chilblains among patients with no other diagnosable condition. Both studies showed no direct link between COVID-19 and the ischemic acral cutaneous lesions.5,6 While more data are needed to refute or support these findings, both studies suggest there may be other factors at play among patients with chilblains.

Herman et al5

Anne Herman, MD, with the department of dermatology at Cliniques Universitaires Saint-Luc, and fellow researchers conducted a monocentric case series at a tertiary care hospital in Brussels, Belgium, between April 10 and April 17, 2020. A total of 31 referred patients who had recently developed chilblains were included in the study. Most of the patients were teenagers or young adults, 19 were women, and all were generally in good health.

In the study, the researchers performed real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 RNA on nasopharyngeal swabs and collected skin biopsies from 22 patients. They also tested blood samples from patients for specific SARS-CoV-2 antibodies. Histologic examinations were performed on 22 patients’ biopsy specimens, and immunofluorescence examinations were performed on 15 patients’ biopsy specimens.
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In the histopathologic analysis, the researchers confirmed the diagnosis of chilblains for all skin biopsy specimens from the 22 patients, also finding occasional lymphocytic or microthrombotic phenomena. In biopsies from seven patients, immunofluorescence analyses showed vasculitis of small-diameter vessels.

Nasopharyngeal swabs, biopsy samples, and blood samples were all negative for SARS-CoV-2 RNA and antibodies. In addition, the researchers did not find any significant abnormalities in blood test results that were suggestive of systemic disease. Antinuclear antibody titers were low in seven patients and higher in one patient, they added.

Roca-Ginés et al6

In the prospective case series, Juncal Roca-Ginés, MD, with the department of dermatology at Hospital Universitario y Politécnico La Fe, and colleagues identified 20 children and adolescents with new-onset inflammatory lesions not associated with a diagnosis in a tertiary referral hospital in Valencia, Spain, between April 9 and April 15, 2020. Of the cohort, 13 patients were male, and all patients included in the study had not been exposed to any drug or other intervention.

The researchers performed a RT-PCR for SARS-CoV-2 and a range of blood tests for possible origins of the lesions. In addition, they collected biopsies from six patients.

“Clinical findings fit into the following patterns: acral erythema (6 patients), dactylitis (4 patients), purpuric maculopapules (7 patients), and a mixed pattern (3 patients),” the researchers said. In addition, they noted that none of the patients had remarkable hematologic or serologic abnormalities, including negative SARS-CoV-2 antibodies. The biopsies from six patients showed histologic findings characteristics of perniosis, they added.

Limitations

Herman et al noted that the short time period and use of patients from a single center were limitations of the study. “Furthermore, there is still limited knowledge regarding the clinical manifestations of and detection methods for SARS-CoV-2,” they added.5

In addition, Roca-Ginés et al stated that the small sample size, which may not be representative of the general population, lack of control group, and no long-term follow up were limitations of their study.6

Conclusion

Overall, both studies found no evidence to support the association between SARS-CoV-2 infection and chilblains.5,6 The exact cause of these chilblains and their link to COVID-19 remains a mystery. Herman et al hypothesized “that these skin lesions may be caused by lifestyle changes brought on by containment and lockdown measures.”5

References

1. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020;35(5):e212-e213. doi:10.1111/jdv.16387
2. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 2020;82(5):e177. doi:10.1016/j.jaad.2020.03.036
3. Lee YJ. 'COVID toes' might be the latest unusual sign that people are infected with the novel coronavirus. Business Insider. Published April 23, 2020. Accessed July 1, 2020. https://www.businessinsider.com/covid-toes-frostbite-coronavirus-skin-lesion-discolored-swollen-feet-2020-4
4. Freeman EE, McMahon DE, Fitzgerald ME, et al. The AAD COVID-19 Registry: drowdsourcing dermatology in the age of COVID-19. J Am Acad Dermatol. Published online April 17, 2020. doi:10.1016/j.jaad.2020.04.045
5. Herman A, Peeters C, Verroken A, et al. Evaluation of chilblains as a manifestation of the COVID-19 pandemic. JAMA Dermatol. Published online June 25, 2020. doi:10.1001/jamadermatol.2020.2368
6. Roca-Ginés J, Torres-Navarro I, Sánchez-Arráez J, et al. Assessment of acute acral lesions in a case series of children and adolescents during the COVID-19 pandemic. JAMA Dermatol. Published online June 25, 2020. doi:10.1001/jamadermatol.2020.2340

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