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Immune checkpoint inhibitor-related urticaria characterized by a distinct autoimmune and autoallergic signatures

Year: 2025

Type: article

Abstract: Background: Immune checkpoint inhibitors (ICI) are increasingly used and are associated with a variety of cutaneous immune-related adverse events (irAEs). While urticarial eruptions are commonly observed in clinical practice, they are rarely described as distinct entities among cutaneous irAEs. Objectives: The objective of this study was to investigate the clinical characteristics, laboratory associations, and immunological profiles in patients with ICI-related urticaria. Methods: This cohort study enrolled patients treated with ICI at a tertiary center in Taiwan during 2015–2023. Patients with urticaria following ICI were compared with matched controls without irAE. Clinical features, laboratory findings, autoantibody profiles, autologous serum basophil activation test (BAT), ex vivo anti-immunoglobulin E (IgE) inhibition assay, serum levels of cytokines, chemokines, and immune checkpoint proteins were analyzed. Results: Twenty-eight patients developed ICI-related urticaria of 1231 patients treated with ICI. Compared to 112 matched controls, the urticaria group had significantly higher rates of hypothyroidism (35.7% vs. 8.0%, P = 0.001), eosinophilia (25.0% vs. 9.8%, P = 0.032), positive antinuclear antibodies (25.0% vs. 4.5%, P < 0.001), and elevated IgE levels (39.3% vs. 2.7%, P < 0.001). Patients with ICI-related urticaria had elevated serum levels of interferon gamma-induced protein 10, interleukin (IL)-5, tumor necrosis factor-α, IL-6, IL-8, monocyte chemoattractant protein-1, and IL-10. Kaplan–Meier analysis showed longer overall survival in the ICI-related urticarial (median: 197.5 vs. 321 days, P = 0.008). Autologous serum BAT showed significant activation in ICI-related urticaria ( P = 0.008) and was ablated by anti-IgE biologics with omalizumab ( P < 0.001). Four refractory patients received omalizumab and demonstrated marked improvement. Conclusion: ICI-related urticaria is a distinct cutaneous irAE associated with autoimmune features, endocrine dysfunction, and unique immunological signatures. These patients also demonstrated better overall survival, suggesting a potentially favorable prognostic implication.

Source: Dermatologica Sinica