Immune-Based Cytokine Signatures of Prolonged Pandemic-Associated Chilblains.

Sangiorgio, Giuseppe; Chamberlin, Grace; Castagnoli, Riccardo; Wachter, Brianna; Dobbs, Kerry A; Fink, Danielle; Montealegre Sanchez, Gina A; Barron, Karyl et al. · J Infect Dis · 2026

case_series · Level IV

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Abstract

Most pandemic-associated chilblains (PAC) resolve spontaneously, but a subset of patients develops persistent or recurrent disease. We analyzed peripheral cytokine profiles in 17 patients with prolonged PAC and identified elevated IFN-γ, CXCL10, CX3CL1, IL-16, CCL22, and S100A8. In contrast to the transient type I interferon response described in acute PAC, prolonged disease was characterized by a type II interferon-skewed inflammatory signature with T cell activation and endothelial involvement. Frequent autoimmune comorbidities suggest baseline immune dysregulation contributing to chronicity. These findings highlight potential therapeutic targets, including JAK inhibition and IFN-γ-directed therapies.