Immune-Based Cytokine Signatures of Prolonged Pandemic-Associated Chilblains

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.