New insights in COVID-19–associated chilblains: A comparative study with chilblain lupus erythematosus

Perniosis during the COVID‐19 pandemic: Negative anti‐SARS‐CoV‐2 immunohistochemistry in six patients and comparison to perniosis before the emergence of SARS‐CoV‐2

“…The lack of SARS-CoV-2 nucleocapsid staining, the older average age of patients in this cohort, the absence of a history of autoimmune disease, and the fingers being affected more than the toes would all support that these cases represent a manifestation of idiopathic perniosis rather than perniosis secondary to direct infection of the skin by SARS-CoV-2. This conclusion is in line with the absence of detectable SARS-CoV-2 by PCR testing of lesional PDC tissue 14,15 and negative IgM and IgG SARS-CoV-2 serologic studies in this series and others, [1][2][3][4]22 but conflicts with reports of positive immunohistochemical staining for the spike protein in PDC. 16,17 IgM and IgG serologies may not be the best way to test for COVID -19, with evidence that IgA serologies may be better in detecting relatively asymptomatic patients in later stages of the disease.…”

“…Polymerase chain reaction (PCR) testing of skin lesions has not detected SARS-CoV-2, supporting the latter two possibilities. 14,15 In contrast, positive IHC for the spike protein (SARS-CoV/SARS-CoV-2 spike 1A9, GeneTex, Inc, Irvine, CA 16,17 ) in endothelial cells and eccrine glands of perniosis-like lesions suggests that virus is present in the skin. Given the conflicting data, we stained six consecutive cases of PDC with an antibody against SARS-CoV-2 nucleocapsid protein and compared and contrasted eight cases with perniosis-like histopathologic findings received in the first half of 2019. the antibody cross-reacts with both SARS coronaviruses but not human coronaviruses 229E and OC43.…”

“…PDC could be (a) a manifestation of direct infection of skin with SARS‐CoV‐2, 8 (b) an inflammatory reaction secondary to viral host response, 1 or (c) a coincidental rise of true idiopathic and autoimmune‐associated perniosis. Polymerase chain reaction (PCR) testing of skin lesions has not detected SARS‐CoV‐2, supporting the latter two possibilities 14,15 . In contrast, positive IHC for the spike protein (SARS‐CoV/SARS‐CoV‐2 spike 1A9, GeneTex, Inc, Irvine, CA 16,17 ) in endothelial cells and eccrine glands of perniosis‐like lesions suggests that virus is present in the skin.…”

COVID toes: where do we stand with the current evidence?

“…For a viral associated phenomenon, the strikingly low rate of testing positivity raises questions. Some authors hypothesize that chilblains could be the cutaneous expression of a strong type I interferon (IFN-I) response ( Lipsker, 2020 , Battesti et al, 2020 , Damsky et al, 2020 , Rodríguez-Villa Lario et al, 2020 ). A high production of IFN-I is suggested to be associated with early viral control and mild course of SARS-CoV-2 infection.…”

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 1 on our recently published study in the BJD 2 . 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 3 . 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.…”