Chilblain-like lesions have characteristics of viral-induced type I interferonopathy
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Chilblain-like lesions experienced during the COVID-19 pandemic, often referred to as “COVID toes,” may represent manifestations of a viral-induced type I interferonopathy, according to a study.
“A range of cutaneous manifestations, including chilblain-like lesions, have been described in association with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection during the coronavirus 2019 (COVID-19) pandemic,” Thomas Hubiche, MD, and colleagues wrote in JAMA Dermatology. “Chilblain-like lesions have been occurring more frequently than expected, and studies have begun to explore the potential link with SARS-CoV-2 infection vs. other plausible etiologies.”
A prospective case series included 40 outpatients with chilblain-like lesions at Nice University Hospital between April 9 and April 17, 2020. Clinical, vascular and laboratory evaluations were conducted on each patient, which included white blood cell counts, liver and kidney function tests, prothrombin time and antibody tests, among others.
Contact with possible COVID-19 cases was reported in 24 patients (60%), while 11 (27.5%) met the definition of COVID-19 within 6 weeks before chilblains presented. All patients who were tested had negative SARS-CoV-2-rt-PCR results. SARS-CoV-2 serology tests showed 12 patients (30%) tested positive for IgM, IgA or IgG antibodies.
Skin biopsies of 19 patients showed pattens of lymphocytic inflammation and vascular damage similar to those in lupus-like chilblain lesions.
“An important finding of this study is that the clinical, biologic and histologic findings were suggestive of virus-induced type I interferonopathy,” the authors wrote. “Indeed, chilblains are one of the hallmarks of the clinical presentation of genetic type I interferonopathies.”
Interferon-alpha response was significantly higher in patients with chilblains compared with those with moderate or severe COVID-19.
“Although the causative link between SARS-CoV-2 infection and the occurrence of chilblain-like lesions still needs to be demonstrated, these results suggest that the type of immune response is a key factor explaining the diversity of clinical manifestations observed in COVID-19 infection,” the authors wrote.
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In this excellent study by Hubiche and colleagues, a cohort of 40 patients with pernio/chilblains during the COVID-19 pandemic, who were all PCR negative at time of testing, were evaluated for antibody and interferon-alpha production. Antibody positivity was noted in 30% of patients, primarily IgA, which is not routinely available in commercial antibody tests. Most notable is that the study authors found a significant increase of IFN-alpha production (in vitro) in the chilblain population compared with patients with PCR-positive acute COVID-19, suggesting that this COVID-19 skin manifestation is a virally induced type I interferonopathy.
This study has several important implications. The elevated type I interferon response in patients with pernio/chilblains and relatively mild COVID-19 is in direct contrast to patients with severe COVID-19 without chilblains, in which there is a defective type I interferon response. Therefore, this finding supports the idea that “COVID toes” are an outward manifestation of a robust and effective host immune response. Also, elevated interferon may explain the relatively low antibody conversion seen in patients with COVID toes because these patients may be able to clear SARS-CoV-2 rapidly without producing antibodies.
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