Table I.
Summary of key data supporting and rejecting the association of COVID toes with COVID-19 infection
| Variable | Evidence of association with COVID-19 | No evidence of association with COVID-19 |
|---|---|---|
| Clinical | ||
| Temporal association of an outbreak of CBLLs with the arrival of COVID-19 | Reports from Europe documented increased cases of CBLLs concurrent with a surge of COVID-19.2, 3, 4 | Studies from other heavily impacted areas, such as New York City and Sao Paolo, found no increased incidence or paucity of cases of CBLLs concurrent with similar surges of COVID-19.5, 6, 7 |
|
Geographic and racial distribution of cases of CBLLs |
CBLLs were the most common cutaneous manifestation associated with COVID-19 in Europe and the United States, with cases overwhelmingly reported in Caucasian patients.8, 9, 12 | Conspicuously few cases of CBLLs have been documented in Asia, and there is a paucity of cases identified in patients with skin of color.5, 6, 7, 11, 12 |
|
Clinical presentation suggestive of COVID-19 infection in patients with CBLLs |
Reports of patients with CBLLs having concurrent and/or prior upper respiratory infection symptoms or illness suggestive of COVID-19.17, 18, 44 Skin and acral rashes were predictive of COVID-19 infection in a large survey study.17 |
Patients with CBLLs often report no prior systemic symptoms and are commonly asymptomatic at the time of infection, clinically, not suggestive of a concurrent or prior infectious process.13, 19 |
| Biological | ||
| Laboratory evidence of COVID-19 infection coincident with the presentation of CBLLs | CBLLs have been identified after PCR-diagnosed infection due to SARS-CoV2.44 | RT-PCR for active COVID-19 infection (nasopharyngeal swab) is commonly negative in patients with CBLLs at the time of presentation, and many patients with CBLLs never tested positive for the virus.19 |
| Immunologic/serologic | ||
| Evidence of prior COVID-19 infection | Development of anti-SARS-CoV-2 IgA in up to 20% of cases of CBLLs.18,20,21 | Commercially available antibodies indicative of prior COVID-19 infection (IgG and IgM) are often undetectable in cases of CBLL.19 |
| Histologic | ||
| Immunostaining | A monoclonal antibody against the spike protein of SARS-CoV-2 detected the virus in biopsied samples of CBLLs.22 | Biopsies of CBLLs stained with antibodies against the nucleocapsid protein of SARS-CoV-2 failed to detect the virus.23 |
| Genomic evidence of COVID-19 in the skin | SARS-CoV-2 was detectable at low copy numbers using PCR on a biopsied rash from the flank of an adult woman with symptoms suspicious for COVID-19.25 | SARS-CoV-2 RNA has been undetectable using RT-PCR and in situ hybridization in biopsied samples of CBLLs.19,24 |
| Theories of pathogenesis | ||
| Type I IFN immune response/viral reactivation | IFN-α levels were significantly elevated in some patients with CBLLs, all of whom had mild disease.13, 18, 24, 26 | An increased IFN response has also been observed in patients with chilblains lupus, and the induction of type I IFN is an important part of the host’s innate immune response to common viral infections such as EBV, which is also linked to the development of chilblains.31,32 |
CBLL, Chilblain-like lesion; EBV, Epstein-Barr virus; IFN, interferon; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; PCR, polymerase chain reaction; RT-PCR, reverse transcriptase polymerase chain reaction.