Negative tests for SARS-CoV-2 infection do not rule out its responsibility for chilblains.

Dear Editor, We read with great interest the report of Le Cleach et al. discussing chilblains as a manifestation of the COVID‐19 pandemic. They reported 311 patients with acral lesions occurring during the COVID‐19 lockdown in France. The most frequent clinical presentation of these acral lesions was typical chilblains. Among the 150 patients with reverse transcription polymerase chain reaction (RT‐PCR) testing and/or serology, only 10 had confirmed COVID‐19. They concluded that there is no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS‐CoV‐2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor.

We do not agree with this explanation. We recently published cases of chilblains enrolled during the COVID‐19 pandemic. We performed the same virological tests, which were also mostly negative, but our conclusion was different. We demonstrated in skin biopsies a high expression of MxA [interferon type I induced (IFN‐I) protein] and CD123 (a marker of plasmacytoid dendritic cells, known as the major producer of IFN‐I). Histochemical results were comparable to those found in our chilblain lupus erythematosus group. We concluded that chilblain was a manifestation of IFN‐I upregulation as observed in genetic interferonopathies. Active viral replication is not necessary to mount an efficient IFN response in SARS‐CoV infection. IFN‐induced transmembrane protein may inhibit coronavirus replication. This inhibition may be one of the reasons why PCR tests were negative. It was also demonstrated that high expression of IFN‐I at the onset of viral infection may induce a depletion of B cells and may explain the negativity of serologies. Moreover, subcutaneous injection of β‐interferon is known to induce vasculopathy. We concluded that chilblains reflect a strong antiviral response in patients that are potentially genetically predisposed for high production of IFN‐I.

Author Contribution

Gilles Battesti: Conceptualization (supporting). Vincent Descamps: Conceptualization (lead).