In Reply We thank Sun and Freeman for their interest in and commentary on our article on patients with chilblains before and during the COVID-19 pandemic,1 as well as Freeman’s leadership in organizing the American Academy of Dermatology’s COVID-19 Registry. The study included many patients with confirmed COVID-19 who allowed us to compare the hot spots of COVID-19 cases with chilblains cases, but the correlation of COVID-19 cases and chilblains cases over 207 location-months was small (Spearman coefficient, 0.18; P = .01).1 The group most disproportionately affected by COVID-19 was Latinx patients, who represented nearly half of all COVID-19 cases, but that group showed rates of chilblains that were one-third that of White or Asian American patients in our study. Some of this difference may be explained by the differences in the ability to work from home and behavioral changes associated with this, such as going without shoes at home or increased care seeking.

The pathophysiology of chilblains had for years remained elusive, but the COVID-19 pandemic has illuminated it with this newly recognized chilblains trigger. Two groups have shown an increased interferon response, as evidenced by increased myxovirus resistance protein 1, an interferon-induced GTPase seen on histopathology, in both COVID-19–associated chilblains and chilblains lupus.2,3 This shows that interferons are involved in multiple causes of chilblains and not unique to COVID-19–associated chilblains. Cappel et al4 synthesized the existing data on chilblains in their article summarizing the current knowledge of the interaction of SARS-CoV-2, angiotensin-converting enzyme 2, and the immune response via interferons and the Janus kinase–single transducer and activator of transcription proteins pathway. A robust interferon response decreases viral replication, thus potentially decreasing polymerase chain reaction (PCR) and antibody positivity. Tests of lymphocyte activation may become more sensitive markers of exposure to SARS-CoV-2 than PCR or antibody testing. This remains to be confirmed, and these tests are not widely available. Sun and Freeman point out that increased antibody testing with a combination of immunoglobulin (Ig) G, IgA, and IgM antibodies increases the sensitivity of COVID-19 case identification. That was not the design of our study, and we acknowledge this limitation in the Discussion section of our article.1

When we describe a process as idiopathic, it does not mean that there is no trigger. It means that we have not been able to identify the trigger in that patient. As diagnostic tests improve in sensitivity and affordability, we will be able to better tell what triggered many reactive cutaneous processes, including chilblains. Because most chilblains cases during the pandemic have been negative by PCR,1,5 these patients are not likely to be infectious to others, although a few of them may have been exposed and fought off COVID-19 effectively with their innate immunity.

Some authors have argued that the recent increase in chilblains is associated with undetected COVID-19, and others have argued that the increase may be the results of behavioral changes. The truth likely lies somewhere in between.

Corresponding Author: Patrick E. McCleskey, MD, Senior Dermatology, Kaiser Permanente Oakland Medical Center, 3701 Broadway, 4th Floor, Oakland, CA 94611 (patrick.e.mccleskey@kp.org).

Published Online: December 22, 2021. doi:10.1001/jamadermatol.2021.4449

Conflict of Interest Disclosures: None reported.

5.Le Cleach  L, Dousset  L, Assier  H,  et al; French Society of Dermatology.  Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.   Br J Dermatol. 2020;183(5):866-874. doi:10.1111/bjd.19377PubMedGoogle ScholarCrossref