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In Reply We thank Freeman et al for their comment in reference to our recently published article in JAMA Dermatology.1 The authors rightly point out the limitations of this study in 31 patients with regard to early antibody testing and the imperfect sensitivities and specificities of these tests. However, we later reported updated data, including an additional 23 patients with chilblains.2 In this total series of 54 patients, only 2 had positive serum anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (12.75 and 135.5 AU [absorbance units]/mL, respectively). Moreover, repeated serologic testing 3 weeks after the first (39 patients) ruled out late seroconversion. Therefore, SARS-CoV-2 infection can be excluded with relative certainty, even after accounting for possible lower immunization in mildly symptomatic or asymptomatic patients and for some differences in sensitivity/specificity between the tests used.
Furthermore, it is epidemiologically predictable to find several patients presenting with chilblains with positive anti–SARS-COV-2 antibodies. This has been observed in most series reported,3 but always in a minority of patients, and in our opinion, this is not evidence of an association with coronavirus disease 2019 (COVID-19). In addition, IgA accounts for a non-negligible proportion of positive antibodies, although their sensitivity/specificity is questioned.4
We respectfully disagree with the authors’ suggestion that our series should not have included the 9 patients with a history of chilblains. Given that a direct association has not been formally established nor excluded between chilblains and COVID-19, presuming a priori that chilblains in these patients were not associated with SARS-CoV-2 and thereby excluding them would have introduced a selection bias.
We agree that a considerable body of literature has been published on this subject; however, to our knowledge, no conclusive evidence demonstrates a direct association between chilblains and SARS-CoV-2. We recently commented that positive anti–SARS-CoV/SARS-CoV-2 immunostaining on skin biopsy results of chilblains lack specificity and must be interpreted with caution.5 Moreover, the presence of coronavirus on electron microscopy images has been disputed.5,6
The outbreak of chilblains during the COVID-19 pandemic is a striking coincidence, and an association with the virus initially seemed like a logical conclusion. However, there is current conflicting evidence regarding the pathophysiology of these chilblains, and although the direct involvement of SARS-CoV-2 cannot be formally ruled out, it also cannot be confirmed. Therefore, although the absence of evidence is not the same as evidence of absence, the absence of evidence is also not the same as evidence of the presence of an association between COVID-19 and chilblains.
Corresponding Author: Marie Baeck, MD, PhD, Department of Dermatology, Cliniques Universitaires Saint-Luc (UCL), Avenue Hippocrate 10, B-1200 Brussels, Belgium (email@example.com).
Published Online: December 23, 2020. doi:10.1001/jamadermatol.2020.4655
Conflict of Interest Disclosures: None reported.
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Baeck M, Herman A. Emerging Evidence of the Direct Association Between COVID-19 And Chilblains—Reply. JAMA Dermatol. 2021;157(2):239–240. doi:10.1001/jamadermatol.2020.4655
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