key: cord-0925669-d696ji6o
authors: Baeck, M.; Herman, A.
title: Chilblains and COVID‐19: can recent epidemiological data shed light on the aetiological debate?
date: 2021-03-03
journal: Clin Exp Dermatol
DOI: 10.1111/ced.14586
sha: 9c2cecdc81030c69927478819b773e1bf5156e6d
doc_id: 925669
cord_uid: d696ji6o

In March and April 2020, at the peak of the COVID-19 pandemic, several countries imposed lockdown measures. Concurrently, a significant number of chilblains were observed in otherwise healthy adolescents and young adults. The physiopathology of these chilblains has not been completely elucidated and their direct link to COVID-19 remains unconfirmed and debated1 . RT-PCR on nasopharyngeal swabs and anti-SARS-CoV-2 antibodies were negative in most patient series reported2 . Lifestyle changes associated with lockdown - notably increased sedentariness and prolonged barefoot exposure to cold floors - in predisposed subjects (high number of patients with antinuclear antibodies positivity and low BMI) could be a possible explanation for the outbreak of chilblains3,4 . The underreporting of chilblain "outbreaks" in Nordic countries, where strict confinement was not imposed, could also indirectly point towards a link between confinement and chilblains5 .

doi: 10.1111/ced.14586

In March and April 2020, at the peak of the COVID-19 pandemic, several countries imposed lockdown measures. Concurrently, a significant number of chilblains were observed in otherwise healthy adolescents and young adults. The physiopathology of these chilblains has not been completely elucidated and their direct link to COVID-19 remains unconfirmed and debated. 1 Reverse transcription (RT)-PCR on nasopharyngeal swabs and anti-SARS-CoV-2 antibodies were negative in most patient series reported. 2 Lifestyle changes associated with lockdown, notably increased sedentariness and prolonged barefoot exposure to cold floors, in predisposed subjects (a high number of patients with antinuclear antibodies positivity and low body mass index) could be a possible explanation for this outbreak of chilblains. 3, 4 The under-reporting of chilblain 'outbreaks' in Nordic countries, where strict confinement was not imposed, could also indirectly point towards a link between confinement and chilblains. 5 An analysis of recent Belgian epidemiological data may shed additional light on the aetiological debate surrounding these lesions. Belgium began experiencing a second wave of SARS-CoV-2 infections from July 2020 and especially from September 2020 (Fig. 1a) . Although testing strategies varied, the number of SARS-CoV-2 infected patients during this second wave seems to have exceeded the first.

These new infections were mainly observed in younger subjects (peak in the 10-39 years age group), compared with the March-April wave, which preferentially involved older patients (peak in the 50-90 years age group) (Fig. 1b,c) . The demographic characteristics of subjects infected by SARS-CoV-2 in the second wave were therefore similar to those of patients in whom chilblains were previously reported. 3 A major factor differentiating the two populations is that from July to November, the population was no longer confined indoors. Although a resurgence of chilblain-like lesions would have been expected in this second wave in parallel with the increase in the number of SARS-CoV-2 infections, especially in the age group concerned, no new cases of chilblains were observed in Belgium during this period, to our knowledge [data from the National Data Collection of skin manifestations associated with COVID-19 (DERMCovid e-registry), along with data from dermatologist, paediatrician and general practitioner networks and our own clinic]. Furthermore, the delay since the new rise of SARS-CoV-2 infections is sufficient to account for late symptom onset.

Interestingly, new cases of chilblains were observed from the beginning of December 2020 (14 patients in our centre), following the implementation of more stringent containment measures in Belgium (closure of sports/fitness centres, increased remote working and increased home schooling for teenagers) and the return of colder temperatures. Although we cannot formally exclude that the apparent absence of chilblains during the summer and early autumn could be partially explained by people possibly self-diagnosing using the information about 'COVID toes' available to the public, this seems improbable given that new cases are again being observed. Furthermore, those patients presenting recently seemed unaware of the nature of their lesions and of a possible association with COVID-19.

The clinical (Fig. 2) and histological presentations of these new cases of chilblains were similar to those observed during the first wave. SARS-CoV-2 RT-PCR on nasopharyngeal swabs was negative for all these patients. Serological tests performed with two different techniques (Elecsys Anti-SARS-CoV-2 Kit and Cobas e602 Analyzer; both Roche Diagnostics GmBH, Mannheim, Germany) and an in-house ELISA developed in Universit e Catholique de Louvain Lab Research (Institut de Duve) were negative except in one patient who reported having had typical COVID-19 symptoms with anosmia and agueusia, as well as positive RT-PCR 2 months before the emergence of chilblains. Other causes of chilblains such as parvovirus infection, coagulopathy or systemic diseases were excluded. The lesions quickly improved with the application of topical corticosteroids and the reinforcement of protective measures against cold.

Several of the patients with lesions also had chilblains during the first wave, and some of these were included in our first study series. 3 Moreover, patients from the first study series were re-contacted and 17 of the 54 patients reported the reappearance of chilblains. SARS-CoV-2 reinfection is an unlikely explanation as this recurrence of chilblains already largely exceeds the isolated reported cases of SARS-CoV-2 re-infections. 6 Clinical and Experimental Dermatology In our opinion, these epidemiological data argue in favour of the aetiological hypothesis associating these chilblain-like lesions with lockdown-induced lifestyle changes and against a direct association with SARS-CoV-2 infection.

Marie Baeck and Anne Herman: Substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work; Drafting the work or revising it critically for important intellectual content; Final approval of the version to be published; Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. 

Emerging evidence of the direct association between COVID-19 and chilblains

Do we have serological evidences that chilblain-like lesions are related to SARS-CoV-2? A review of the literature

Evaluation of chilblains as a manifestation of the COVID-19 pandemic

Major cluster of paediatric 'true' primary chilblains during the COVID-19 pandemic: a consequence of lifestyle changes due to lockdown

Why are chilblains underreported in Nordic countries during the COVID-19 pandemic? An analysis of google trends

COVID-19 reinfection: prolonged shedding or true reinfection?

M. Baeck 1 and A. Herman 1 Department of Dermatology, Cliniques Universitaires Saint-Luc, Universit e Catholique de Louvain (UCLouvain), Brussels, Belgium E-mail: marie.baeck@uclouvain.be Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 28 January 2021