Do COVID-19 Symptoms Run Skin-Deep?

Two small studies called into question early research suggesting that so-called “COVID toes” may be tied to coronavirus infection.

In a small cohort of patients with acral lesions, no patients tested positive for SARS-CoV-2, the virus that causes COVID-19, reported Anne Herman, MD, of Université Catholique de Louvain in Brussels, and colleagues.

In another study, Ignacio Torres-Navarro, MD, of Hospital Universitario y Politécnico la Fe in Valencia, Spain, and colleagues found new onset acute acral lesions in children and teenagers, but again no evidence of SARS-CoV-2 infection.

Both studies were published in JAMA Dermatology.

An accompanying editor’s note from two of the journal’s editors, Claudia Hernandez, MD, of Rush University Medical Center in Chicago, and Anna Bruckner, MD, of University of Colorado School of Medicine in Aurora, cited prior research suggesting “pseudo-chilblains,” or purple and/or red lesions on the hands and feet, such as “COVID toes” was tied to the virus, due to a temporal appearance with the pandemic.

But this new research provides conflicting evidence, suggesting no association between the two, and the editorialists cited lack of confirmatory testing, and relying on “indirect” evidence, such as “systemic symptoms consistent with possible infection” or serologic testing results.

“It is still unclear whether a viral cytopathic process vs a viral reaction pattern or other mechanism is responsible for ‘COVID toes,'” Hernandez and Bruckner wrote. “Dermatologists must be aware of the protean cutaneous findings that are possibly associated with COVID-19, even if our understanding of their origins remains incomplete.”

Herman and colleagues examined a cohort of 31 patients in Belgium referred between April 10 and April 17, who had recently developed chilblains. They tested patients for SARS-CoV-2 via real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing and tested their blood for IgM and IgG antibodies. In addition, 22 patients had histologic analyses and 15 had immunofluorescence examinations.

Overall, 11 patients were teenagers, and 19 were girls or women. Nine patients had a history of chilblains, and four of Raynaud syndrome. Most patients had skin lesions localized to the feet and “presented as erythematous or purplish erythematous macules, sometimes with central vesicular or bullous lesions or with necrotic areas.” Twenty patients reported “mild” COVID-19 symptoms, but only three said they had contact with a person who tested positive for the virus.

Histopathologic analysis confirmed chilblains in 22 patients, with occasional signs of lymphocytic or microthrombotic phenomena, the authors said. Immunofluorescence analyses were negative in seven cases, though seven showed vasculitis of small diameter vessels.

Importantly, however, all patients tested negative for SARS-CoV-2 via RT-PCR, and IgM and IgG antibody titers were negative. In addition, the researchers reported no significant biochemical, autoimmune, hematologic or hemostatic abnormalities. They also noted that eosinopenia, lymphopenia, and hyperferritinemia, which were often reported by COVID-19 patients, were not detected.

In the study by Torres-Navarro and colleagues, patients were referred with new onset inflammatory lesions, and did not have a diagnosis. All were tested for SARS-CoV-2, and skin biopsies were done in six patients. They ranged in age from 1 to 18, and 13 were boys.

Purpuric macules were found in seven patients, acral erythema in six patients, and dactylitis in four patients. However, no patient had any clinical symptoms of COVID-19 and did not live with anyone who had symptoms. Nine had a history of vascular reactive disease of the hands.

Both studies speculated the increase in reports of chilblains in conjunction with COVID-19 may be an indirect consequence of lockdown measures. Torres-Navarro and colleagues specifically noted 15 of these children reported walking around barefoot in the house during quarantine.

Torres-Navarro’s group offered two other possible hypotheses: that patients were in early stages of the disease, explaining the negative RT-PCR results, or that these lesions were “a subacute manifestation of the infection, in which patients no longer had detectable viral particles.”

Given the conflicting evidence, Hernandez and Bruckner concluded, “testing needs to occur in larger numbers and also at different stages of the disease to determine if a low viral load, undetectable with current methods, or the inability to mount an adequate immune response accounts for the negative SARS-CoV-2 test results.”