Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease.

Vitiligo is an autoimmune disease of the skin that results in the destruction of melanocytes and the clinical appearance of white spots. Disease pathogenesis depends on IFN-γ and IFN-γ-induced chemokines to promote T-cell recruitment to the epidermis where melanocytes reside. The skin is a complex organ, with a variety of resident cell types. We sought to better define the microenvironment and distinct cellular contributions during autoimmunity in vitiligo, and we found that the epidermis is a chemokine-high niche in both a mouse model and human vitiligo. Analysis of chemokine expression in mouse skin showed that CXCL9 and CXCL10 expression strongly correlate with disease activity, whereas CXCL10 alone correlates with severity, supporting them as potential biomarkers for following disease progression. Further studies in both our mouse model and human patients showed that keratinocytes were the major chemokine producers throughout the course of disease, and functional studies using a conditional signal transducer and activator of transcription (STAT)-1 knockout mouse showed that IFN-γ signaling in keratinocytes was critical for disease progression and proper autoreactive T-cell homing to the epidermis. In contrast, epidermal immune cell populations including endogenous T cells, Langerhans cells, and γδ T cells were not required. These results have important clinical implications, because topical therapies that target IFN-γ signaling in keratinocytes could be safe and effective new treatments, and skin expression of these chemokines could be used to monitor disease activity and treatment responses.

Confetti-like depigmentation: A potential sign of rapidly progressing vitiligo.

BACKGROUND: Confetti-like depigmentation was noted in patients reporting recent worsening of vitiligo. OBJECTIVE: We sought to determine if confetti-like depigmentation is a marker of rapidly progressing vitiligo. METHODS: Review of patient records and images of patients from a vitiligo registry resulted in 7 patients with 12 images that fit inclusion criteria and were evaluated for percent depigmentation by 3 independent reviewers. The Vitiligo Disease Activity Score and the Koebner Phenomenon in Vitiligo Score in an additional cohort of patients with confetti-like lesions were compared with patients who had vitiligo without confetti-like lesions. RESULTS: The mean percentage of depigmentation at baseline was 19.2%, which increased to 43.9% in images obtained at a mean of 16 weeks of follow-up. Vitiligo Disease Activity Score and Koebner Phenomenon in Vitiligo Score were significantly higher in the patients with confetti-like lesions compared with those without confetti-like lesions. A skin biopsy specimen of a confetti-like lesion in 1 patient revealed an inflammatory infiltrate in the papillary dermis with CD8(+) T cells localized to the dermoepidermal junction. LIMITATIONS: Small, single-center retrospective review and lack of full-body photographs are limitations. CONCLUSIONS: A confetti-like pattern of depigmentation may be a negative prognostic indicator for patients with rapidly progressing vitiligo. Further, prospective studies to evaluate this physical finding should be performed.