The article below was written by myself as an update published by the College of Podiatry on behalf of the COVID-19 Working Group, 26th June 2020.
Since the first reports of chilblain-like lesions on the feet of children and young adults the number of publications has been escalating within the medical literature. As of the middle of June there are around 18 papers published, reviewing hundreds of cases, which refer to chilblains potentially in association with COVID-19. Some histological evidence now exists but this has shed little light on the exact aetiology [1]. The consensus from much of this work is that their appearance is more than coincidental [2-4], particularly considering the time of year is not conducive to chilblain development, and lesions appearing in those without a previous history of the problem. However, there is still doubt from some researchers [5-7] as many of the patients in these reports were either not tested for COVID-19 or the results frequently returned were negative.
Chilblains in suspected COVID-19 patients
Source: Mazzotta F, Bonifazi E. A new vasculitis at the time of Covid-19.
Dermatologia Pediatrica 2020.
Of most recent interest has been a hypothesis put forward which may bring together some of these inconsistencies and explain the relationship between COVID-19 and chilblains. Writing in the journal “Medical Hypotheses”, Lipsker [8] stated that despite lack of absolute consistency, many features of the reported chilblain cases are similar in that:
1. Lesions were of sudden onset in young patients - without a previous history of chilblains in most of them and that they were not necessarily triggered by exposure to cold.
2. Many of the young patients were asymptomatic or had few symptoms (only a few had mild clinical signs compatible with COVID-19).
3. None of them had pneumonia or severe manifestations of COVID-19.
4. Many of the reports highlight clinical signs of COVID-19 or contact with infected persons occurred a few days to one month before chilblains.
5. COVID-19 Infection could be demonstrated by nasopharyngeal swab or by serology only in a limited number of patients.
He suggests that in children and young adults with COVID-19, the infection triggers a strong release of type 1 interferons (IFN-1). IFN-1 has been shown previously to be an early defence mechanism to viral invasion as part of the innate immune systems response to presence of virus infection [9]. When IFN-1 is released, chilblains are a known cutaneous side effect – recognised earlier in patients with disorders of IFN-1 release [10]. IFN-1 is able to rapidly clear the virus, without the adaptive immune system getting involved, and before significant systemic symptoms ensue. This theory concurs with another study examining these lesions in suspected COVID-19 patients [11]. Lack of adaptive immune system involvement would also explain why tests both for current infection and antibodies (suggesting previous infection) would come back with a negative result.
The hypothesis is certainly the most tenable to date, but as things have shown already, this is a fast-moving situation with new findings being reported on a weekly basis.
References
1. Kanitakis J, Lesort C, Danset M, Jullien D. Chilblain-like acral lesions during the covid-19 pandemic (“covid toes”) : Histologic, immunofluorescence and immunohistochemical study of 17 cases. J Am Acad Dermatol 2020.
2. Colonna C, Genovese G, Monzani NA, Picca M, Boggio F, Gianotti R, Marzano AV. Outbreak of chilblain-like acral lesions in children in the metropolitan area of Milan, Italy, during the COVID-19 pandemic. J Am Acad Dermatol 2020.
3. Rodríguez-Sanz D, Tovaruela-Carrión N, López-López D, Palomo-López P, Romero-Morales C, Navarro-Flores E, Calvo-Lobo C. Foot disorders in the elderly: A mini-review. Dis Mon 2018, 64;64-91.
4. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Takeshita J, French LE, Thiers BH, Hruza GJ, Fox LP. Pernio-like skin lesions associated with COVID-19: a case series of 318 patients from 8 countries. J Am Acad Dermatol 2020.
5. Docampo-Simón A, Sánchez-Pujol MJ, Juan-Carpena G, Palazón-Cabanes JC, Vergara-De Caso E, Berbegal L, Poveda-Montoyo I, Pastor-Tomás N, Mataix-Díaz J, Terencio-Alemany C, et al. Are chilblain-like acral skin lesions really indicative of COVID-19? A prospective study and literature review. J Eur Acad Dermatol Venereol 2020, n/a.
6. Piccolo V, Neri I, Manunza F, Mazzatenta C, Bassi A. Chilblain-like lesions during the COVID-19 pandemic: should we really worry? Int J Dermatol 2020.
7. Iria N, Annalucia V, Ilaria C, Alba G, Tiziana L, Liliana G, Cosimo M, Annalisa P, Marcello L. Major cluster of pediatric " true " primary chilblains during the COVID-19 pandemic: a consequence of lifestyle changes due to lockdown. J Eur Acad Dermatol Venereol 2020.
8. Lipsker D. A chilblain epidemic during the COVID-19 pandemic. A sign of natural resistance to SARS-CoV-2? Med Hypotheses 2020, 144;109959.
9. Perry AK, Chen G, Zheng D, Tang H, Cheng G. The host type I interferon response to viral and bacterial infections. Cell Res 2005, 15;407-422.
10. Volpi S, Picco P, Caorsi R, Candotti F, Gattorno M. Type I interferonopathies in pediatric rheumatology. Pediatr Rheumatol Online J 2016, 14;35-35.
11. Kolivras A, Dehavay F, Delplace D, Feoli F, Meiers I, Milone L, Olemans C, Sass U, Theunis A, Thompson CT, et al. Coronavirus (COVID-19) infection induced chilblains: A case report with histopathologic findings. JAAD case reports.