The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte destruction. The goal of treatment is to not only halt disease progression but also promote repigmentation through melanocyte regeneration, proliferation, and migration. Treatment strategies that address all aspects of disease pathogenesis and repigmentation are likely to have greatest efficacy, a strategy that may require combination therapies. Current treatments generally involve nontargeted suppression of autoimmunity, whereas emerging treatments are likely to use a more targeted approach based on in-depth understanding of disease pathogenesis, which may provide higher efficacy with a good safety profile

No abstract

Background Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. Objective To investigate potential markers of disease activity directly in the skin of vitiligo subjects and healthy subjects. Methods Patient skin was sampled via a modified suction blister technique allowing for minimally invasive, objective assessment of cytokines and T cell infiltrates in interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. Results In screening and validation, CD8+ T cell number and CXCL9 protein concentration were significantly elevated in active lesional compared to non-lesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by ROC analysis. Suction blistering also allowed for phenotyping of the T cell infiltrate, which overwhelmingly expresses CXCR3. Limitations A small number of patients were enrolled for the study, including a single patient to define the treatment response. Conclusion Measuring CXCL9 directly in the skin may be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no FDA-approved treatments, and current treatments are time-consuming, expensive, and have low efficacy. We sought to identify new treatments for vitiligo, and first considered repurposed medications because of the availability of safety data and expedited regulatory approval. We previously reported that the IFN-γ-induced chemokine CXCL10 is expressed in lesional skin from vitiligo patients, and that it is critical for the progression and maintenance of depigmentation in our mouse model of vitiligo. We hypothesized that targeting IFN-γ signaling might be an effective new treatment strategy. STAT1 activation is required for IFN-γ signaling and recent studies revealed that simvastatin, an FDA-approved cholesterol-lowering medication, inhibited STAT1 activation in vitro. Therefore, we hypothesized that simvastatin may be an effective treatment for vitiligo. We found that simvastatin both prevented and reversed depigmentation in our mouse model of vitiligo, and reduced the number of infiltrating autoreactive CD8+ T cells in the skin. Treatment of melanocyte-specific, CD8+ T cells in vitro decreased proliferation and IFN-γ production, suggesting additional effects of simvastatin directly on T cells. Based on these data, simvastatin may be a safe, targeted treatment option for patients with vitiligo.