A meta-analysis of contemporary non-academic and academic literature related to the skin condition called COVID toe.
Viral infections are often known to be associated with distinctive skin rashes. It is not uncommon to see skin rashes cases of viral pneumonia and more communicable diseases such as Fifth Disease or Hand, Foot and Mouth Disease. Rashes that result from a condition like viral infections are difficult to study due to their geographic diversity and variation in patient demographics. But when a viral pandemic occurs, the opportunity for studying disease and it’s trends change dramatically. The number of cases of the novel coronavirus in healthcare facilities around the world has enabled clinicians and researchers to be able to aggregate data in ways that are only typically seen in wartime. One trend specific to the novel corona virus is a skin condition called Covid toe.
When studying a disease, medical researchers and clinicians always lean into trends and patterns to find answers. What trends and patterns can we find? What associations to other aspects of the patient’s medical care or personal life can we identify? And more importantly, how can we duplicate these trends and patterns in other patients? Trends and patterns are what guide our diagnostic testing and our therapeutic modalities. In this latest pandemic, it is very interesting in diversity of providers that are involved in patient care. COVID-19 is obviously a respiratory virus (1), but we’ve seen numerous COVID-19 patients who have had associated issues related to heart disease (2), acute kidney disease (AKD), renal failure (3) and skin rashes. (4) One of the more common skin issues seen in COVID-19 patients is a rash referred to as Covid toe. This means lower extremity health professionals are a significant part of the team diagnosing and treating COVID-19 and its multi-system manifestations.
Cutaneus manifestations of COVID-19
A study published on April 4, 2020 in the British Journal of dermatology describes the five most common skin manifestations found in COVID-19 patients. (5) In this article, Casas and colleagues describe the findings of 375 COVID-19 patients treated in Spain as follows;
“Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings.”
- Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%)
- Other vesicular eruptions (9%)
- Urticarial lesions (19%)
- Maculopapular eruptions (47%)
- Livedo or necrosis (6%).
Cases and colleagues describe prodromal symptoms found acral (extremities, toes and fingers) to include small blisters (vesicles) and erythema (redness). While vesicular eruptions are found prior to pulmonary symptoms, mottled discoloration of the foot and toes, which resembles Chilblains, occurs in a later stage of the disease often following the onset of pulmonary symptoms.
The French National Union of Dermatologists and Venereologists released a publication where they classify the dermatological manifestations of COVID-19 as acrosyndromes. (5) The terms acrosyndromes is used to describe the symptoms seen in arterial occlusive disease that limit circulation to acral areas (toes, fingers). Acrosyndromes also describe the findings seen in frostbite or Raynaud’s Disease. These localized lesions as described by Casas show erythema (redness) and vesicles (small fluid filled bumps). (6)
What causes Covid toe?
There is no consensus in the literature that describes the etiology of the characteristic rashes found in early, mid-stage and late stage COVID-19 infections. Varga et al, describe a mechanism of injury to the peripheral vascular system that involves angiotensin converting enzyme 2 (ACE2) receptors. (6) ACE2 receptors are found in the lung, heart, kidney and intimal lining of peripheral arteries. COVID-19 virus appears to attach to ACE2 receptors, causing acute inflammatory change and blockage of the artery. This acute inflammatory reaction results in pulmonary, cardiac, renal and peripheral vascular disease and even death.
In addition to the theory of COVID-19 virus attacking the intimal lining of the peripheral artery, another theory describes damage caused by the virus to the heme molecules in red blood cells (RBC). In an article by Wenzhong, he and his colleagues describe evidence of a coordinated attack by the COVID-19 virus on the hemoglobin molecule resulting in an oxidized hemoglobin molecule. Oxidized hemoglobin is far less capable of carrying oxygenated RBC’s to peripheral cells, including the toes. (7)
Where are the patterns and trends that might help clinicians and researchers better understand COVID-19 diagnosis and treatment? The consensus notes that the acrosyndromes of COVID-19 all relate to a hypercoaguable state in which localized arterial supply is disrupted. It appears that COVID-19 is not due to a single event but rather due to a number of related vascular factors. To use a plumbing analogy, both the pipe that carries the fluid (artery) and the fluid in the pipe (plasma portion of the blood) are doing a poor job of delivering the end product. The result can be minor localized problems, serious isolated system disease (pulmonary, renal or cardiac disease) or death.
Join the discussion on Covid toe.
- Xu Z, Shi L, Wang Y, Zhang J et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet. Feb 18, 2020
- Mehra M, Desai S, Kuy S, Henry T, Patel A. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 , New England Journal of Medicine. May 1, 2020
- Durvasula R, Wellington T, McNamara E, Watnick S. COVID-19 and Kidney Failure in the Acute Care Setting: Our Experience From Seattle. American Journal of Kidney diseases. April 8, 2020.
- Darlenski R, Tsankov N. Covid pandemic and the skin – what should dermatologists know. Clinics in dermatology. March 28, 2020.
- Mazzotta F, Troccoli T. Acute acro-ischemia in the child at the time of COVID-19. International Federation of Podiatrists. March 2020.
- La Revue du Praticien. Covid revealing acrosyndromes. April 2020.
- Liu W, Hualan L. COVID-19 Attacks the 1-Beta Chain of Hemaglobin and Captures the Porphyrin to Inhibit Human HEME metabloism. ChemRxiv April 24, 2020