SLR - February 2021 - Thomas Ehlers

Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic

Reference: Hubiche T, Cardot-Leccia N, Le Duff F, Seitz-Polski B, Giordana P, Chiaverini C, Giordanengo V, Gonfrier G, Raimondi V, Bausset O, Adjtoutah Z, Garnier M, Burel-Vandenbos F, Dadone-Montaudié B, Fassbender V, Palladini A, Courjon J, Mondain V, Contenti J, Dellamonica J, Leftheriotis G, Passeron T. Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatol. 2020 Nov 25:e204324. doi: 10.1001/jamadermatol.2020.4324. Epub ahead of print. PMID: 33237291; PMCID: PMC7689569.

Level of Evidence: 4

Scientific Literature Review

Reviewed By: Thomas Ehlers, DPM
Residency Program: Highlands/Presbyterian-St. Lukes – Denver, CO

Podiatric Relevance: During the COVID-19 pandemic, there has been an increased number of reports of chilblain-like lesions on patients’ toes, which has been dubbed “Covid toes”. Little had been known about this aberrant presentation of chilblains that seemed to be associated with the novel coronavirus infection, however, these authors elucidate the connection between the two. Their conclusion lead them to believe that these chillblains lesions were secondary to a virus induced type I interferonopathy, more commonly seen in younger and healthier patients. This is relevant to podiatrists across the world, as patients who may be suffering from COVID-19 may present with these lesions and look to their local foot and ankle specialist for an explanation of how a respiratory virus can cause painful toes.

Methods: At a hospital specifically dedicated to treating COVID-19 patients, those who presented with skin manifestations that were suspicious for association with COVID-19 were evaluated for chilblains. Those who were identified underwent significant clinical and laboratory testing and workup. Patients were also tested for the virus using polymerase chain reaction on nasopharyngeal swabs, stool samples, and serum analysis was performed.

Results: Of the 40 patients who were seen with chilblain like lesions, their clinical symptoms were all remarkably similar and reproducible, with pruritis and pain followed by violaceous purpuric lesions with bullae. Thirthy-five of the patients had contact with possible COVID-19 cases and 11 had possible infection within the 6 preceding weeks prior to the chilblains presentation. All patients tested negatively for COVID-19 via PCR, however, this is likely due to the robust immune response associated with type I interferons, which are necessary to clear the virus as well as induce the dermatological pathology on the digits. This was confirmed via the significant increase of interferon alpha production in the chilblain population compared to patients with PCR positive acute COVID-19, which was typically more severe. All cases of chilblains resolved without intervention and complete healing of all lesions.

Conclusions: The authors concluded that “COVID toes” is a real condition and it is likely a type I interferonopathy that causes mild vasculitis in the extremities, not dissimilar to auto-immune induced chilblains. Their conclusion was based on the fact that younger patients, who typically suffer a milder course of the disease, often presented with chilblains, likely due to their more robust immune response, specifically against viral infections via the interferon pathways, which have been linked to chilblains in other auto-immune conditions. I think the study design was adequate given all of the unknowns that are still present regarding the COVID-19 disease. While testing for the disease is still unfortunately offering modest at best results, however, they explain using various biochemical markers to identify those who were likely infected and why they would test negatively. This investigation  provides clarity to patients when asking about “COVID toes” or regarding the increase in chilblains seen in younger and healthier patients. The patients can be assured that this pathology is likely self-limiting and possible positive prognostic factor for the COVID-19 disease.

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