Chilblains After SARS-CoV-2 Vaccination: Coincidence or Real Association?

To the Editor:

We read with great interest the article of Meara et al1 in your journal describing a case of chilblain-like lesions after vaccination against SARS-CoV-2. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, millions of vaccine doses have been administered and their safety has been generally confirmed. However, case reports and small case series indicate that vaccination against COVID-19 might be associated with autoimmune adverse reactions,2 although a causal relationship cannot be easily established. Along these lines, a few cases of chilblains development after anti-SARS-CoV-2 vaccination have been reported.1,3,4 Interestingly, COVID-19 itself can be also complicated by chilblain-like rash appearance.5

Over the last few months, an unusual number of patients presented in our outpatient rheumatology clinics complaining of chilblains. This observation, in relation to the above-mentioned evidence, prompted us to report these findings, in which we speculate that these lesions could be related to vaccination against SARS-CoV-2. In total, out of the 359 patients attending for the first time our outpatient rheumatology clinics between October 2021 and February 2022, the presenting symptom in 25 (7.0%) patients was chilblain-like lesions (ie, erythematous to violaceous macules, papules, plaques, or nodules), accompanied or not by dactylitis and/or arthritis (Table). The majority (22/25, 88%) were female and their mean age was 39.25 (SD 15.6) years. Three patients had a history of autoimmune rheumatic disease (ARD) and 4 also had a history of chilblains. None of them had a history of infection with SARS-CoV-2.

Table.

Characteristics of patients that developed chilblain-like lesions after anti-SARS-CoV-2 vaccination.

The mean time to chilblain appearance after last vaccine dose was 2.88 (SD 1.53) months, either after the first (n = 1), second (n = 12), or third (n = 12) dose with mRNA vaccines. No treatment was given in 15/25 patients. Ten patients received glucocorticoids (GCs; 6 topical, 2 oral, 2 intramuscular). Most cases followed a benign course, resolving completely in 18/25 (72%) patients within 2 months (mean 32.6 [SD 31.1] days) from onset. However, 4 patients who received no treatment and 1 who received intramuscular GCs experienced persistent (lesions still active after 3 months) and ongoing (improvement but symptomatology is ongoing after 30 days) chilblains, respectively; 2 patients who received oral or topical GCs and nonsteroidal antiinflammatory drugs (Table) exhibited relapsing/remitting symptoms.

Several skin reactions, including injection-site reactions, urticaria, erythema multiforme-like, pityriasis rosea–like lesions, and leukocytoclastic vasculitis have been described after COVID-19 vaccination,6 whereas vaccine-related chilblain-like rash is also increasingly recognized.1,4,6 Chilblains are erythematous or violaceous skin lesions that develop in extremities after exposure to cold. These lesions are often painful,1,4 making it difficult to differentiate them from frank arthritis.

The possible pathogenetic mechanisms linking chilblains with COVID-19 vaccines are unknown; however, endothelial dysfunction and immune activation, especially type I interferon (IFN-I) response, might be involved.3 Of note, in a recent post vaccine pernio-like case by Lesort et al, blood IFN signature was enhanced.4 A robust IFN-I pathway activation has been reported in mild COVID-19 infection and was associated with chilblain-like lesion development,7 while strong IFN-I response has been observed shortly after vaccination with mRNA anti–SARS-CoV-2 vaccination.8 Of note, all cases reported to date occurred after vaccination with mRNA vaccines.1,4

Similar to the published case reports so far, most of the patients in our study were women and developed chilblains shortly after vaccination.1,4 Also, in line with other post vaccine autoimmune events, the course of symptoms for most individuals who developed chilblains was benign and self-limited.2,6 Considering that most of our cases were reported during the winter period, it is plausible that exposure to cold and vaccination against SARS-CoV-2 might have acted synergistically in the development of chilblains.

Our study has certain limitations. First, we cannot prove a causal relationship between SARS-CoV-2 vaccination and chilblains. However, the self-limiting nature of symptoms in addition to the temporal proximity between the events supports our argument. Importantly, in examining the frequency of chilblain-like lesions as a presenting symptom during the same time period 1 year ago (October 2020 to February 2021), we found only 2/154 (1.3%, P = 0.008 vs 2021–2022) patients fulfilling these criteria. Notably, vaccination in our country for the general population started in March 2021. Second, 3 of our patients had an underlying rheumatic disease, so we cannot exclude that this might have contributed to some extent in the appearance of chilblains. Of note, in 2 of these individuals, chilblains resolved without treatment after 4 to 7 days. In the rest of the patients, antinuclear and extracted nuclear autoantibodies as well as rheumatoid factor were negative, whereas complement levels were within normal range.

In conclusion, we report an increased frequency of new chilblains as a presenting manifestation in a rheumatology outpatient setting during the last 5 months. We speculate that this may be related to vaccination against SARS-CoV-2. Rheumatologists should be alert for this condition, as the clinical picture can easily resemble symptoms seen in ARDs.

Copyright © 2022 by the Journal of Rheumatology

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