• Thomas Hubiche, Nathalie Cardot-Leccia, Florence Le Duff, Barbara Seitz-Polski, Pascal Giordana, Christine Chiaverini, Valérie Giordanengo, Géraldine Gonfrier, Vincent Raimondi, Olivier Bausset, Zoubir Adjtoutah, Margaux Garnier, Fanny Burel-Vandenbos, Bérengère Dadone-Montaudié, Véréna Fassbender, Aurélia Palladini, Johan Courjon, Véronique Mondain, Julie Contenti, Jean Dellamonica, Georges Leftheriotis, and Thierry Passeron.
• Department of Dermatology, Université Côte d'Azur, CHU Nice, Nice, France.
• JAMA Dermatol. 2021 Feb 1; 157 (2): 202-206.

ImportanceChilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.ObjectiveTo perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.Design, Setting, And ParticipantsIn this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.Main Outcomes And MeasuresPatients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.ResultsOverall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.Conclusions And RelevanceTaken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.Trial RegistrationClinicalTrials.gov Identifier: NCT04344119.

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