Cold and COVID: recurrent pernio during the COVID‐19 pandemic

Dear Editor, Pernio is a commonly reported cutaneous manifestation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.¹ Our international registry of COVID‐19 dermatological manifestations has collected 1176 total cases of COVID‐19 skin manifestations, including 619 cases of pernio in patients with suspected or confirmed COVID‐19.¹ Most patients with new‐onset pernio were entered into the registry after the first pandemic wave (79% in March to May 2020). Starting in September 2020, the registry received reports of a subset of these patients who developed recurrent pernio in the following months. Herein, we present the cases of the first 18 patients with recurrent pernio in the COVID‐19 dermatology registry. Patients with a prior pre‐pandemic history of pernio were excluded. The registry was reviewed by the Partners Healthcare Institutional Review Board and was determined to not meet the definition of Human Subjects Research.

These patients with recurrent pernio (n = 18) had a median age of 22 years [interquartile range (IQR) 16–37], were 72% male, and 83% white. Patients resided in the USA (n = 16) [Massachusetts (n = 7), California (n = 3), Pennsylvania (n = 2), New York (n = 1), Rhode Island (n = 1), Connecticut (n = 1) and Michigan (n = 1)], ​the Netherlands (n = 1) and the UK (n = 1). Patients were SARS‐CoV‐2 polymerase chain reaction (PCR) and antibody positive (6%), antibody‐positive only (11%), PCR‐positive only (17%), close contacts of a laboratory‐confirmed case (17%) or clinically suspected only (50%).

Of note, patient 2 was SARS‐CoV‐2 antibody‐positive 5 weeks after initial pernio lesions started, but tested negative twice for SARS‐CoV‐2 PCR including a few days after both initial pernio and recurrent pernio symptoms began. Conversely, patient 4 tested PCR positive for SARS‐CoV‐2 shortly after COVID‐19 symptoms of anosmia, dysgeusia and myalgia began, but when antibody testing became available several months later, tested antibody negative. These cases highlight the importance of the timing of testing, and also highlight how patients even with documented prior COVID‐19 may test negative on commercial antibody tests.

Overall, 17 of 18 patients initially developed pernio during March to May 2020, the first wave of the COVID‐19 pandemic in the USA and Europe (northern hemisphere spring). The pernio resolved in May–July and recurred between September and December 2020 in autumn/winter (Figure 1). The exception (patient 6) was symptomatic with PCR‐confirmed COVID‐19 in August, developed pernio in September that remitted by October, and then recurred in November 2020.

Figure 1.

Timeline demonstrating 18 patients who experienced pernio during two discrete timepoints in the setting of laboratory‐confirmed or suspected COVID‐19 infection during 2020. PCR, polymerase chain reaction; +, positive.

These cases of recurrent pernio suggest that cold temperatures, combined with a history of SARS‐CoV‐2 infection, may prompt and perpetuate the inflammatory response.² Recent data have demonstrated that patients with pernio/chilblains in the setting of acute SARS‐CoV‐2 infection have high interferon‐alpha responses,², ³ which may allow rapid control of SARS‐CoV‐2. Furthermore, not only are there similarities between patients with pernio and type I interferonopathies,³ but cold exposure has also been noted to cause pernio flares in patients with type I interferonopathies.⁴ In cases of recurrent pernio, the mechanism is not yet clear. It remains to be seen whether initial SARS‐CoV‐2 infection primes patients to be more cold sensitive and therefore prone to recurrent pernio, or whether cold temperature itself is triggering some type of secondary interferon‐alpha response without a new SARS‐CoV‐2 infection.⁵

Limitations to this case series include that only one‐third of patients had laboratory confirmation of SARS‐CoV‐2 infection, an effect heightened by lack of SARS‐CoV‐2 laboratory testing during the first wave and also noted by prior studies.¹, ⁶, ⁷ In patients without laboratory‐confirmed disease, recurrent pernio/chilblains during the pandemic may also be because of an unrelated cause. However, none of these patients experienced pernio pre‐pandemic. This finding also highlights the possibility that other cases of recurrent perniosis prior to the COVID‐19 pandemic could have been triggered by viral infection.

We do not yet know how frequently, and for how long, patients who developed pernio in the setting of the COVID‐19 pandemic will experience recurrent symptoms with subsequent cold exposure. Reports have noted ‘long‐hauler’ cutaneous manifestations of COVID‐19,⁸ and it remains to be seen how persistent and/or recurrent post‐COVID pernio will be. Future studies on recurrent pernio may enhance our understanding of the role of temperature and interferon, as well as best practices for patient management.

Author Contribution

Esther Freeman: Conceptualization (equal); Data curation (equal); Funding acquisition (equal); Methodology (equal); Project administration (equal); Resources (equal); Supervision (equal); Writing‐original draft (equal). Devon Emily McMahon: Conceptualization (equal); Formal analysis (equal); Methodology (equal); Visualization (equal); Writing‐original draft (equal). Jules Lipoff: Conceptualization; Methodology; Writing‐review & editing (equal). Misha Rosenbach: Conceptualization; Methodology; Writing‐review & editing (equal). Seemal R. Desai : Conceptualization; Methodology; Writing‐review & editing (equal). Marlys Fassett: Conceptualization; Methodology; Writing‐review & editing (equal). Lars E. French: Conceptualization; Methodology; Resources (equal); Supervision (equal); Writing‐review & editing (equal). Henry Lim: Conceptualization; Methodology; Resources (equal); Supervision (equal); Writing‐review & editing (equal). George Hruza: Conceptualization; Methodology; Supervision (equal); Writing‐review & editing (equal). Lindy Fox: Conceptualization; Methodology; Supervision (equal); Writing‐review & editing (equal).