COVID Toes - An Update

Iain B Mcintosh

BA(Hons) MBChB, DGMRCP.MSSCh Former Chiropody Schools Inspector

Summary

Doctors and podiatrists were puzzled at the start of the pandemic when people began reporting swelling and redness of feet, which were often chilblain-like lesions, with the condition sometimes lasting for months. The condition remains controversial despite further research into the cause and effect with further evidence of causation required from larger studies. Patient history enquiries into changed footwear and behaviour during the pandemic and particularly during lockdown and quarantine are required. Identifying environmental and behavioural factors may direct treatment to conventional chilblain management, concentrating on advice and prevention rather than covid causation.

Chilblains form after intermittent or prolonged exposure to cold or damp air. The coldness causes blood vessels near the skin surface to constrict leading to decreased oxygenation and inflammation in those exposed areas. “COVID toe” was thought to be a side effect of the body switching into attack mode to fight off the virus with the immune system overreacting in its response. Lesions occur at any age, but affect children and teenagers more commonly. For some it is painless, but the rash can be extremely sore and itchy, with tender blisters and swelling. A range of cutaneous manifestations have been described in association with SARS-CoV-2 infection during the COVID-19 pandemic [1]. Among them, chilblain-like lesions (CLL) have been occurring more frequently than expected. However, the link between SARS-CoV-2 infection and CLL is not well established. SARS-CoV-2 infection strongly triggers the expression of type I interferon (IFN)-stimulated genes, which assist in the host’s antiviral protection. Diseases mediated by type I IFN, such as monogenic autoinflammatory interferonopathies or lupus erythematosus, are characterized by micro-angiopathy leading to clinical chilblains. SARS-CoV-2 infection seems to be associated with vascular skin symptoms and has been shown to damage capillary endothelium and disrupt the thrombo-protective state of endothelial cells, likely contributing to microvascular thrombosis. Moreover, the histopathological features of COVID-19-associated CLL include endothelial damage and features of micro-angiopathic damage [2-8] . An observational study was conducted during April 2020 in France.1 All patients referred with CLL seen during this period of the COVID-19 pandemic were included except patients with a history of chilblains or chilblain lupus. to study skin, blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains, excluding chilblain lupus. Researchers pinpointed the parts of the immune system that appear to be involved. Findings, reported an activation loop in the skin associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells, leading to clinical manifestations. The conclusion was that chilblain-like lesions are characterized by immune cytotoxic infiltration, interferon polarization and endothelial alteration in the skin.

During the pandemic many often observational reports have offered circumstantial evidence pointing toward an association with SARS-CoV-2 infection, although the immunological and PCR data have been more limited, with only the minority of cases having evidence of infection [1,4–8] and some studies having none whatsoever [2, 3]. Anecdotally, post pandemic cases are being diagnosed and managed differently from idiopathic chilblains due to this presumed relationship with SARSCoV-2.

Chilblain diagnoses have increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection and a subsequent robust antiviral immune response. As a result, providers have managed cases differently than idiopathic chilblains, which are associated with cold exposure. The relationship between pandemic chilblains and SARS-CoV-2 infection, however, remains unclear as most patients do not test positive for SARS-CoV-2–specific PCR or antibodies [2].

Recent research evidence from Yale University does not support the assumption that covid is a cause of increased chilblain-like lesions [9]. In this study, there was evidence of prior SARS-CoV-2 infection in the cohort with a temporal association in local infection rate and the co-occurrence of cases from the same household, as well as a substantial fraction reporting exposure (35%) to infected individuals and symptoms indicative of infection (35%). However, only (9.5%) patients with chilblain eruptions had evidence of a prior SARS-CoV-2 infection. None of the cases within households had evidence of infection. This number approximates to the regional seroprevalence of SARS-CoV-2 at the time (8.5%), indicating that this outcome could have been expected by chance. In this detailed study of a cohort of patients with chilblain eruptions presumed to be caused by SARS-CoV-2, researchers did not find evidence supporting an association with prior infection [2] .

Their hypothesis was that an immune response from an abortive infection could not rule out covid, but other explanations of how the pandemic could have triggered the rise in cases should be considered in diagnosis. They suggested that people were not wearing socks and shoes when confined to the home during lockdown and when working from home. Once “covert toes” became a well-known phenomenon, people may have erroneously begun to attribute their chilblains to the condition. They postulated the increased incidence was attributable to altered behaviour during the pandemic with people not wearing socks or shoes at home during quarantine and pandemic restrictions. Home behaviour has changed remarkably since 2020 with the discarding of office clothing-wear and this may have extended to shoe and sock allegiance and closer proximity to radiator or fire encouraging chilblain appearance. This was a small study and further research with replication is needed to lend further support to the data. During the coronavirus disease pandemic, dermatologists observed an increase in pernio-like acral eruptions. Direct causality of pernio due to COVID-19 was not established in many cases because of inconsistent testing methods (often negative results) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a form of COVID-19?associated pernio is probable because of increased occurrence, frequently in young patients with no cold exposure or a history of pernio, and reports of skin biopsies with positive SARS-CoV-2 immunohistochemistry [10] . Review of published literature suggests several unifying cutaneous and systemic mechanisms may explain COVID-19?associated pernio 11: SARSCoV-2 cell infection occurs through the cellular receptor angiotensinconverting enzyme 2 mediated by transmembrane protease serine 2, subsequently affecting the reninangiotensin-aldosterone system with an increase in the vasoconstricting, pro-inflammatory, and prothrombotic angiotensin II pathway. Severe acute respiratory syndrome coronavirus 2 cell infection triggers an immune response with robust IFN-I release in patients predisposed to COVID-19 associated pernio. Age and sex discrepancies correlated with COVID-19 severity and manifestations, including pernio as a sign of mild disease, are likely explained by age-related immune and vascular differences influenced by sex hormones and genetics. These affect susceptibility to viral cellular infection, the renin-angiotensin-aldosterone system balance, and chilblains are the most common diagnosis to explain COVID toes. Affected patients present with erythema and swelling involving acral surfaces and consistent lymphocyte-rich histopathology, fulfilling the diagnostic criteria. It remains essential to distinguish pernio from other cutaneous acral eruptions that can also be associated with COVID-19 and recognize any dermatologic findings potentially associated with SARS-CoV-2 infection, which are important cutaneous signs of COVID-19 severity [10] . Attention was drawn in Podiatric Review in 2020 to a possible relationship between chilblains and covid infection at the start of the pandemic [11]. Two years and thousands of victims later despite much more research, there remains controversy about this clinical entity. Research studies have often been small and observational, and more studies are needed to justify conclusions.

Patient Management Advice

• Resist urge to scratch-this will further damage the skin. • Use calamine lotion to soothe itching. • Lanolin rubbed into the feet, will help retain body heat. • Wear woollen or cotton socks.

• Keep whole body warm. • Take paracetamol or ibuprofen to ease pain. • Avoid cold or damp environment when possible. • Wear warm, waterproof clothing, gloves, and thick socks in cold and damp environments. • Rewarm affected skin gently, without massaging, rubbing, or applying direct heat.

• Keep affected skin dry and warm, but away from sources of heat.

Conclusion

Practitioners presented with chilblain cases should certainly consider a relationship with current or past covid infection, but not assume infection is the cause. They should extend patient history enquiries into changed footwear and behaviour during the pandemic and particularly during lockdown and quarantine. Identifying environmental and behavioural factors might direct treatment to conventional management of chilblains concentrating on advice and prevention. Nifedipine prescription may be appropriate in severe cases.

DO NOT

• Put feet or hands on a radiator or under the hot water to warm them up • Smoke – narrows peripheral blood vessels

• Have drinks with caffeine in content

• Scratch or pick at affected skin

Please see overleaf for the References for this article