Ivan Bristow PhD
On behalf of the COVID-19 Committee, College of Podiatry, London
Updated 2 November 2020

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.

With the global pandemic continuing into November, data from John Hopkins University suggests nearly 30 million people globally have been infected with over 1 million deaths (Data as of 31/10/2020: https://coronavirus.jhu.edu/map.html). Research into the disease continues to be published at a significant rate. A range of skin presentations have been observed and reported.^1-4 Common lesions patterns include:

• Morbilliform (measles-like) rash
• Urticaria
• Macular erythema
• Vesicular (blistering, chickenpox-like) eruption
• Papulosquamous presentation
• Retiform (net-like) purpura
• Chilblain-like lesions

Published data from the International Registry of COVID-19 Associated Dermatologic Manifestations has been collated from 31 countries to date. Analysis shows that lesions have been reported across all continents, in a full range of skin types (including white, Asian, Black African / African American and Latin / Hispanic patients).⁵

Literature pertaining to the phenomenon of chilblain-like lesions (often labelled COVID toes) has been reviewed and circulated by the College of Podiatry to members in its regular e-bulletins.  This week, media interest in COVID toes was reignited by a presentation made at the European Academy of Dermatology in Switzerland. Dr Esther Freeman who leads the International COVID Dermatology Register presented data to dermatologists which included collected data on the phenomenon. They reported that the chilblain lesions, in line with previous research, lasted around 12 days on average however, they cited 6 patients who continued with the purple lesions on their toes lasting over 60 days in patients who tested positive for the disease with two of these showing skin lesions at 130 days after diagnostic confirmation. They conclude that such a prolonged presence of the lesions may represent a symptom of the condition termed “Long COVID” where symptoms of the disease may manifest for many weeks after the initial infection but further research is required to fully explain this.

Data published so far on COVID-19 and the skin has been analysed in a paper by Danaheshgaran et al.⁶  In their work, thirty-four papers describing nearly 1000 patients with various skin symptoms were included and demonstrated that chilblains were the most reported dermatological condition, representing 40% of all dermatological conditions in COVID patients. The average age of these patients was 23.2 years old. Lesions generally developed after the onset of the signature symptoms (persistent cough, temperature etc.,) which concurs with earlier observations that such lesions are generally a later manifestation of the disease. Although viral particles have been recovered from chilblain-like lesion biopsies,^7,8 the exact mechanism by which they develop is still requires further investigation.

References

1. Manalo IF, Smith MK, Cheeley J, Jacobs R: A Dermatologic Manifestation of COVID-19: Transient Livedo Reticularis. J Am Acad Dermatol 2020
2. Marzano AV, Genovese G, Fabbrocini G, Pigatto P, Monfrecola G, Piraccini BM, Veraldi S, Rubegni P, Cusini M, Caputo V et al: Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients. J Am Acad Dermatol 2020:early view
3. Recalcati S: Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol 2020
4. Gianotti R, Veraldi S, Recalcati S, Cusini M, Ghislanzoni M, Boggio F, Fox LP: Cutaneous Clinico-Pathological Findings in three COVID-19-Positive Patients Observed in the Metropolitan Area of Milan, Italy. Acta Derm Venereol 2020
5. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Desai SR, Harp J, Takeshita J, French LE, Lim HW et al: The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries. J Am Acad Dermatol 2020
6. Daneshgaran G, Dubin DP, Gould DJ: Cutaneous Manifestations of COVID-19: An Evidence-Based Review. Am J Clin Dermatol 2020, 21(5):627-639
7. Colmenero I, Santonja C, Alonso-Riaño M, Noguera-Morel L, Hernández-Martín A, Andina D, Wiesner T, Rodríguez-Peralto JL, Requena L, Torrelo A: SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases. Br J Dermatol 2020, n/a(n/a)
8. 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, n/a(n/a)

Updated 11 December 2020

Further to previous updates for College of Podiatry members circulated in November, new published cases and research have appeared in the medical literature regarding the phenomenon colloquially known as “COVID toes” – chilblain like lesions arising in children and young adults with suspected or confirmed COVID-19 infection. Last month, three CPD articles were published in the British dermatology journal Clinical and Experimental Dermatology.^1-3 The first of these papers examined⁽²⁾ COVID toes summarising what has been reported to date in terms of the presentation and prognosis. The authors also include various hypotheses as to why they may arise in children, including the idea that children at the beginning of infection are able to release large amounts of interferon to attenuate viral replication. A side effect of this release is the development of chilblains, but further work is required to fully explain and understand the phenomenon. All three papers are currently free to access (links given below) and offer a good means to update podiatrists on the current knowledge around COVID toes along with other skin manifestations in children.

In another recently published paper  on the subject,⁴ the authors have highlighted how the majority of published photos of COVID toes have been in patients with Fitzpatrick skin types 1 or 2. In addition they suggest that lesions in darker skin types may be more difficult to recognise resulting in delays in diagnosis and treatment.  Consequently, they have presented seven cases of COVID toes in patients with Fitzpatrick skin types 3 – 5 to assist clinicians. The full paper, including the images can be downloaded from the link given below.

References

1. Andina D, Belloni-Fortina A, Bodemer C, Bonifazi E, Chiriac A, Colmenero I, et al. Skin manifestations of COVID-19 in children: Part 3. Clin Exp Dermatol. https://doi.org/10.1111/ced.14481
2. Andina D, Belloni-Fortina A, Bodemer C, Bonifazi E, Chiriac A, Colmenero I, et al. Skin manifestations of COVID-19 in children: Part 1. Clin Exp Dermatol. 2020. https://doi.org/10.1111/ced.14482
3. Andina D, Belloni-Fortina A, Bodemer C, Bonifazi E, Chiriac A, Colmenero I, et al. Skin manifestations of COVID-19 in children: Part 2. Clin Exp Dermatol. 2020. https://doi.org/10.1111/ced.14483
4. Daneshjou R, Rana J, Dickman M, Yost JM, Chiou A, Ko J. Pernio-like eruption associated with COVID-19 in skin of color. JAAD case reports. 2020;6(9):892-7. https://doi.org/10.1016/j.jdcr.2020.07.009

Updated 23 March 2021

The story of COVID toes continues to unfold as covered in my previous blogs (see below). I recently attended the PCDS Spring Meeting (online, of course) and was interested to see the presentation by Dr George Kravvas, a dermatologist from Bristol, discussing the dermatological manifestations of COVID-19.¹ He opened the talk discussing the phenomenon we now know as COVID toes – chilblain like lesions (pseudo-chilblains) which have frequently been observed over the pandemic. Of course, a question which has hung over the diagnosis has been are they really chilblains or a sign of COVID-19 exposure? Dr Kravvas suggested that chilblains occurring over the warmer periods were certainly suspicious, particularly in those without a previous history of chilblains. He suggested a COVID test would be appropriate, even though frequently these tests are negative. Treatment is not needed in most cases, but topical steroids and analgesia may help for troublesome lesions. Typically, they heal within 14 days.

He went onto discuss a similar presentation which had been alluded to in the recent literature by Mehta and colleagues.² They report a subset of patients (both adult and children), who appear to have more persistent digital lesions. This was first reported last year in a small group of six patients whose chilblains lasted over 60 days - see COVID Toes - November 2020 Update. The lesions resemble the vasculopathy sometimes observed in rheumatological diseases. Where lesions persist for more than a month, they recommend further investigations to rule out other causes, which may possibly have been triggered initially by the COVID-19 infection. Routine blood screening can be helpful here including anti-nuclear antibodies (ANA), extracted nuclear antigen (ENA) and antineutrophil cytoplasmic antibodies (ANCA). Typically, patients present with chilblain like lesions on a dusky blue background similar to acrocyanosis. Limbs typically may be described by patients as burning hot forcing them to immerse them in cold water. This can be counterproductive as it may exacerbate the condition further.

Dermoscopy can also be helpful in these cases. By studying the nailfold capillaries (also known as capillaroscopy) can demonstrate any changes. A study by Natallelo and colleagues³ of the nailfolds of COVID patients (acute and recovered) demonstrated that during acute disease showed microhaemorrhages and capillary oedema compared to the recovered patient who mainly demonstrated swollen capillaries in reduced numbers. Treatment for long COVID chilblains to date has been suggested as topical steroids, oral aspirin and vaso-dilators such as nifedipine.²

References

1. Kravvas, G. Skin manifestations of COVID 19. in Primary Care Dermatology Society Spring Meeting. 2021. Online: PCDS.
2. Mehta, P., et al., Chilblain-like acral lesions in long COVID-19: management and implications for understanding microangiopathy. The Lancet Infectious Diseases, 2021.
3. Natalello, G., et al., Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement. Microvascular Research, 2021. 133: p. 104071.

Ivan Bristow PhD
On behalf of the COVID-19 Committee, College of Podiatry, London
3 November 2020

COVID toes - now be on the lookout for COVID nails

Over the last few months, during the global pandemic, we saw a rise in publications reporting the effects of the infection on the skin. Initially, under-reported it became evident that COVID-19 had the potential to cause a range of skin symptoms including erythema, urticaria, livedo reticularis, petechiae and chilblain-like lesions (1-5). It was the latter, of course, that became the focus of the podiatrist’s attention as the developing evidence of its possible association with COVID-19 was initially difficult to prove. Latterly, as I covered in a recent blog (https://www.foot.expert/post/covidtoes2), tissue samples from chilblain lesions in children and young adults showed markers of SARS-COV-2 infection finally confirming the connection.

Since then, reports have continued to be published on this but most recently in the International Journal of Dermatology, a paper discusses the case of a 37-year-old woman who developed COVID-19 symptoms which coincided with unusual nail changes. The paper by Mendez-Flores et al., (6) describes how the patient lost her sense of smell and taste and developed the classic dry cough and fever associated with the infection. A nasal swab proved positive for COVID-19. Two days later she noticed a red-violet band or flare developing in her fingernails, just distal to the lunula. This lasted a week and then disappeared.

So, what could this mean? Effectively, this is a single case study suggesting an association and it concurs an earlier publication which reported a similar finding in the fingernails of a 60-year-old patient (7). In proving a link with COVID-19 there is still a long way to go. More cases would be needed to corroborate these early findings. Then, tissue samples would be needed to demonstrate the pathology and establish the presence of the infection. Of course, the main barrier is the fact a nail biopsy in this area risks permanent nail changes and so it would be unlikely this would happen, particularly considering the phenomenon is only transient with no lasting effect as far as we know at the moment. Only time will tell and subsequent papers reporting this may lead to further developments.

References

1. Almutairi N, Schwartz RA. COVID-19 with dermatologic manifestations and implications: An unfolding conundrum. Dermatol Ther. 2020;n/a(n/a):e13544.
2. Colonna C, Genovese G, Monzani NA, Picca M, Boggio F, Gianotti R, et al. 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;37(3):437-40.
3. De Giorgi V, Recalcati S, Jia Z, Chong W, Ding R, Deng Y, et al. Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): A prospective study from China and Italy. J Am Acad Dermatol. 2020:S0190-9622(20)30941-5.
4. 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.
5. Zhao Q, Fang X, Pang Z, Zhang B, Liu H, Zhang F. COVID-19 and cutaneous manifestations: a systematic review. J Eur Acad Dermatol Venereol. 2020;n/a(n/a).
6. Méndez-Flores S, Zaladonis A, Valdes-Rodriguez R. COVID-19 and nail manifestation: be on the lookout for the red half-moon nail sign. Int J Dermatol. 2020;59(11):1414-.
7. Neri I, Guglielmo A, Virdi A, Gaspari V, Starace M, Piraccini BM. The red half-moon nail sign: a novel manifestation of coronavirus infection. J Eur Acad Dermatol Venereol. 2020;n/a(n/a).