COVID toes - the mystery unravels....
The connection between COVID-19 infection and chilblains in younger adults and children was raised early on in the coronavirus pandemic with many published papers reporting their appearance and postulating that the that two were associated (1-4). Colloquially, the phenomenon was labeled “COVID toes” or “Chilblain Like Lesions”. Naturally, to establish an association between the virus and chilblains evidence was required of this using available tests such as nasal and throat swabbing. However, consistently, this has returned the verdict that few patients with chilblains have tested positive for COVID-19 (5). The largest dermatological surveys to date reflected this with only a small minority of patients showing positive results when tested (6-8). However, these surveys have indicated that the appearance of such lesions was associated with a mild form of the disease with fewer symptoms. The lesions were most common on the feet and typically remained for around two weeks before resolving. Hypotheses have been put forward suggesting how the viral infection may lead to the development of chilblains and evade standard swab testing (9, 10) but despite an increase in chilblain reports, lack of positive test results has cast a shadow over this association with some medical reports suggesting the association should be treated with caution (11, 12).
Most recently, however, new research has uncovered strong evidence of the coronavirus in the aetiology of chilblains in children during the pandemic (13). Seven biopsies were taken from chilblains on the feet of children – all of whom who were negative for COVID-19 using a nasal-pharyngeal swab test. Histological and serological examination of the biopsies demonstrated a localised lymphocytic vasculitis consistent with chilblains. Moreover, immunochemistry revealed the presence of SARS-CoV-2 (COVID-19) within the tissue. This work concurs with an earlier, single case study that found similar viral proteins in a lesion taken from a patient who was negative for the infection (14). As the authors point out, this work demonstrates a causal association between the virus and chilblains, but further work is needed to fully uncover how this is occurring.
1. Basatneh R, Vlahovic TC. Addressing the Question of Dermatologic Manifestations of SARS-CoV-2 Infection in the Lower Extremities: A Closer Look at the Available Data and its Implications. J Am Podiatr Med Assoc. 2020
2. Gianotti R, Veraldi S, Recalcati S, Cusini M, Ghislanzoni M, Boggio F, et al. Cutaneous Clinico-Pathological Findings in three COVID-19-Positive Patients Observed in the Metropolitan Area of Milan, Italy. Acta Derm Venereol. 2020
3. Alramthan A, Aldaraji W. A case of COVID-19 presenting in clinical picture resembling chilblains disease. First report from the Middle East. Clin Exp Dermatol. 2020;n/a(n/a).
4. Landa N, Mendieta-Eckert M, Fonda-Pascual P, Aguirre T. Chilblain-like lesions on feet and hands during the COVID-19 Pandemic. Int J Dermatol. 2020;59(6):739-43.
5. Feito-Rodríguez M, Mayor-Ibarguren A, Hijón C, Montero-Vega D, Servera-Negre G, Ruiz-Bravo E, et al. CHILBLAIN-LIKE LESIONS AND COVID-19 INFECTION: A PROSPECTIVE OBSERVATIONAL STUDY AT SPAIN´S GROUND ZERO. J Am Acad Dermatol. 2020
6. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Desai SR, et al. The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries. J Am Acad Dermatol. 2020
7. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Takeshita J, et al. Pernio-like skin lesions associated with COVID-19: a case series of 318 patients from 8 countries. J Am Acad Dermatol. 2020;83(2):486-92.
8. Le Cleach L, Dousset L, Assier H, Fourati S, Barbarot S, Boulard C, et al. Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing. Br J Dermatol. 2020
9. Battesti G, El Khalifa J, Abdelhedi N, Ferre V, Bouscarat F, Picard-Dahan C, et al. New insights in COVID-19-associated chilblains: a comparative study with chilblain lupus erythematosus. J Am Acad Dermatol. 2020.
10. Lipsker D. A chilblain epidemic during the COVID-19 pandemic. A sign of natural resistance to SARS-CoV-2? Med Hypotheses. 2020;144:109959.
11. Denina M, Pellegrino F, Morotti F, Coppo P, Bonsignori IM, Garazzino S, et al. All that glisters is not COVID: low prevalence of seroconversion against SARS-CoV-2 in a pediatric cohort of patients with Chilblain-like lesions. J Am Acad Dermatol. 2020.
12. Vesely MD, Perkins SH. Caution in the time of rashes and COVID-19. J Am Acad Dermatol. 2020
13. Colmenero I, Santonja C, Alonso-Riaño M, Noguera-Morel L, Hernández-Martín A, Andina D, et al. SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases. Br J Dermatol. 2020
14. Santonja C, Heras F, Núñez L, Requena L. COVID-19 chilblain-like lesion: immunohistochemical demonstration of SARS-CoV-2 spike protein in blood vessel endothelium and sweat gland epithelium in a polymerase chain reaction-negative patient. Br J Dermatol. 2020