Negative tests for SARS-CoV-2 infection do not rule out its responsibility for chilblains: reply from the authors.

Dear Editor, With great interest, we read the comment by Battesti and Descamps on our recently published study in the BJD. Their comment is based on their findings that histological and immunostaining of skin biopsies of seven cases of ‘epidemic chilblains’ with negative SARS‐CoV‐2 reverse transcription polymerase chain reaction (RT‐PCR) testing and repeated serology was similar to those of a historical series of 11 cases of chilblains lupus, notably for high expression of CD123 and MxA [a type‐I interferon (IFN‐I)‐induced protein] in both groups. Thus, they hypothesized that chilblains observed during the COVID‐19 outbreak are linked to a high IFN response to SARS‐CoV‐2, leading to both negative RT‐PCR and serology due to this effective antiviral response and that development of chilblains is due to IFN production. Their hypothesis is notably based on recent publications showing that impaired IFN response is observed in patients who are critically ill with COVID‐19.,

Even though we agree that it cannot be absolutely excluded, there is no evidence that their reported cases without RT‐PCR or serological confirmation are really related to the infection. In our series, where most cases were negative for SARS‐CoV‐2 both by PCR and serology, it is highly unlikely that they are false‐negatives as serology was performed an average of 3 weeks after the onset of manifestation. Secondly, their hypothesis warranted further exploration, notably to confirm the high IFN production in patients with chilblains and negative serology and PCR. Testing of IFN levels was performed in blood samples in two patients in our series and showed a low level of IFN production. In addition, to extrapolate that high IFN production would lead to negative PCR and serology, starting from the findings that profoundly impaired IFN‐I response characterized by low interferon production is observed in critically ill patients, is a very speculative hypothesis. Indeed, such high IFN response could be expected to cause other clinical manifestations in addition to chilblains.

Finally, it was previously shown that CD123 immunostaining is not different between chilblain lupus erythematosus and idiopathic chilblains. So, the fact of observing this expression in ‘epidemic chilblain’ is not an argument for attributing them to SARS‐CoV‐2. We also observed in five cases a high expression of CD123 in patients with negative serology and without any associated infectious signs.

Author Contribution

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