Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo

Background: The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions. Objective: We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo. Methods: Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited. Clinical features and photographs were analyzed. For some patients, skin and blood samples were obtained. Results were compared with the vitiligo group. Results: All patients developed lesions localized on photoexposed areas with a specific depigmentation pattern consisting of multiple flecked lesions without Koebner phenomenon. In contrast to vitiligo, patients receiving anti-PD-1 therapies who developed vitiligo-like lesions did not report any personal or family histories of vitiligo, thyroiditis, or other autoimmune disorders. Analysis of blood and skin samples revealed increased C-X-C motif ligand 10 levels in serum of patients developing vitiligo-like lesions, associated with skin infiltration of CD8 T-cells expressing C-X-C motif receptor 3 and producing elevated levels of interferon-gamma and tumor necrosis factor-alfa. Limitations: This cross-sectional study concerned a single center. Conclusions: Clinical and biological patterns of vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies differ from vitiligo, suggesting a different mechanism.