Are Covid Toes Really a Thing? Probably Not

Chilblain-like lesions, aka “Covid toes,” do not appear to be associated with SARS-CoV-2 infection, according to a small case-series study of 17 teens whose Chilblain-like lesions were assessed during the first wave of the Covid-19 pandemic in Italy. Along with no signs of SARS-CoV-2 infection, the lesions occurred in the absence of other inflammatory, autoimmune, or thrombophilic phenomena.

“This case series of otherwise healthy adolescents delineated a clinical picture that emerged during the Covid-19 pandemic of chilblain-like lesions of the toes associated with microvascular remodeling with a long but benign course to self-resolution not associated with signs of SARS-CoV-2 infection,” Valentina Discepolo MD, PhD from the Department of Translational Medical Sciences, Section of Pediatrics, University of Naples, Italy, and colleagues wrote in JAMA Network Open, adding that “These skin lesions were characterized by erythematous or cyanotic acral lesions typically bilaterally localized at the distal extremities, with invariable involvement of the periungual area of the toes. The onset was often associated with pain, swelling, and pruritus.”

The study authors noted that chilblains are typically seen in “middle-aged women after exposure to cold or after a sudden temperature change,” which is why the occurrence in kids is puzzling. One hypothesis is that the lesions in children, while also occurring distally, had heel involvement, “which is absent in classic chilblains,” Discepolo and colleagues noted. “Whether walking barefoot at home, which has occurred more frequently during the Covid-19 lockdown, contributed to the development of lesions remains a hypothesis.”

Another piece of the puzzle of the erythema pernio (chilblains) in this case series was the mild histological findings, which “might have been associated with the younger age of the patients and suggest a chronic rather than an acute inflammatory process, resulting in tissue remodeling that resembles vascular stasis more than vasculitis,” the study authors wrote. They also noted that “capillaroscopy did not reveal signs of impaired microcirculation in the upper limbs, in contrast to systemic vasculitis.”

The study authors also posited that underlying conditions such as connective tissue diseases, cryopathies, neoplastic diseases, blood hyperviscosity, genetic diseases, anorexia, and malnutrition might also be associated with the occurrence of chilblains. “However, the patients in this case series did not report a personal history of autoimmunity and did not have any laboratory signs of underlying autoimmune, inflammatory, or proliferative conditions,” Discepolo and colleagues reported.

So, why the interest in these chilblains-like lesions?

Well, early in the Covid-19 pandemic researchers jumped on any anomaly in the search for answers, and these “chilblains” were “one of the most commonly reported cutaneous manifestations… these acral lesions are described as erythematous to purple purpuric macules, papules, and/or vesicles that predominantly involve the feet and, to a lesser extent, the hands. Unlike other cutaneous findings, chilblain-like lesions tend to mostly affect patients without systemic or evident Covid-19 symptoms; in fact, patients with such eruptions are less likely to have severe disease. SARS-CoV-2 infection remains unconfirmed in many patients with these lesions.”

Thus, the study authors conducted their prospective case series analysis to see if they could resolve this potential association. There were 17 adolescents, all with chilblain-like lesions, enrolled in the study from April 1 to June 30, 2020. All were enrolled at a single tertiary referral academic hospital in Italy.

The participants underwent a complete laboratory workup, dermatologic evaluation including dermoscopy, and a histopathologic analysis. Additionally, capillaroscopy was done to exclude systemic microvascular alterations. Follow-up at four weeks included clinical, lab, and dermatologic evaluation.

“All patients underwent a nasopharyngeal swab for SARS-CoV-2 molecular testing at enrollement and quantitative IgM and IgG serologic testing against SARS-CoV-2 at enrollment and follow-up to investigate the association with SARS-CoV-2 infection,” Discepolo and colleagues wrote.

Most of the participants were male, the median age was 13.2 years (12.5-14.3), and all were enrolled during the first wave of the pandemic.

Of note “16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture,” the study authors noted. “Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions.”

Bottom-line? The data don’t support so-called Covid toes as a cutaneous manifestation of SARS-CoV-2 disease.

Additionally, Discepolo and colleagues pointed out that as the pandemic continued to escalate in Campania from 10-20 cases per 100,000 to 75 cases per 100,000, there were only three new cases of chilblain-like lesions after June 2020.

“That only 3 new cases were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection; in addition, none of these patients tested positive for SARS-CoV-2,” the study authors wrote. “The fact that all 3 cases during the second wave occurred in winter months (November 2020, January 2021, and March 2021) suggests that exposure to the cold might, at least in some cases, trigger the skin lesions. In line with this hypothesis, 7 of the enrolled adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.”

The study authors acknowledge limitations of their study—namely the small sample size and that its design “did not allow risks to be calculated or case-effect relationships to be established.”

1. Chilblain-like lesions, aka “Covid toes,” do not appear to be associated with SARS-CoV-2 infection, according to a small case-series study of 17 teens whose Chilblain-like lesions were assessed during the first wave of the Covid-19 pandemic in Italy.

2. Along with no signs of SARS-CoV-2 infection, the lesions occurred in the absence of other inflammatory, autoimmune, or thrombophilic phenomena.

Candace Hoffmann, Managing Editor, BreakingMED™

Cat ID: 926

Topic ID: 79,926,730,926,138,192,927,928