Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic

QUESTION What are the clinical, pathologic, and laboratory characteristics of patients with chilblain-like lesions during the coronavirus 2019 (COVID-19) pandemic? FINDINGS In this series of 40 consecutive patients with chilblain-like lesions, none had positive findings on polymerase chain reaction (PCR) tests, and 12 (30%) had positive COVID-19 serologic results. Common findings included increased D-dimers, lymphocytic inflammation, vascular damage on skin biopsy results, and a significant interferon-alpha response compared with patients with PCR-positive, acute COVID-19 infection. MEANING Patients presenting with chilblain-like lesions during the COVID-19 pandemic all had negative PCR results for COVID-19 at the time of the diagnosis and developed antibodies in only 30% of cases, and had histologic and biologic patterns of type I interferonopathy. IMPORTANCE Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown. OBJECTIVE To 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 PARTICIPANTS In 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 MEASURES Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-alpha) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis. RESULTS Overall, 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-alpha production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19. CONCLUSIONS AND RELEVANCE Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.