Vitiligo: An Update on Pathophysiology and Treatment Options

Reinhart Speeckaert; Nanja van Geel


Am J Clin Dermatol. 2017;18(6):733-744. 

In This Article

Future Perspectives

Currently, firm guidelines for the management of vitiligo are difficult because of the heterogeneity in vitiligo trials. Important efforts have been undertaken for increased standardization. Using e-Delphi procedures, repigmentation, side effects, and maintenance of pigmentation have been identified as the core outcome domains.[90] New outcome measure instruments such as the Vitiligo Extent Score have also been developed to measure the extent of vitiligo.[91] This progress could help to improve the comparability of future vitiligo trials and drawing of accurate conclusions for the daily management of patients with vitiligo.

Biomarkers are being investigated that may help to identify patients with active disease and follow vitiligo activity during treatment. In this way, the response of therapy may be monitored more efficiently. Further research is necessary to confirm if these biomarkers could be used to follow individual patients over time to evolve towards a more personalized treatment approach.

Based on recent research, several new treatment targets have been identified. The identification of a central role of the IFN-γ-STAT1-CXCL10 pathway offers opportunities for targeted drug development.[92] Two case reports using Janus kinase inhibitors (tofacitinib citrate and ruxolitinib) were published, demonstrating signs of repigmentation.[93,94] Topical Janus kinase inhibitors are currently in the pipeline with clinical trials underway in pharmaceutical companies. Recently, the topical Janus kinase 1/2 inhibitor ruxolitinib showed significant repigmentation in facial vitiligo.[95] Consistent elevation of cytokines (especially IL-17, but also IL-2, IL-22, IL-23, and IL-33) has been documented in patients with active vitiligo and these cytokines can also be considered as treatment targets.[36–39]

To date, vitiligo can be considered as a chronic progressive disorder that is only partially reversible in most patients. In light of our expanding knowledge of the pathogenesis, stopping progression can be considered as an immunological issue while stimulation of repigmentation involves the differentiation and migration of melanocytes. Both outcomes are therefore likely to require a different treatment approach. Currently, most trials are focusing on repigmentation, which is contradictory as the majority of treatments are anti-inflammatory and do not necessarily induce repigmentation. Owing to its complex pathogenesis, vitiligo may benefit most from combination treatments. Indeed, to date, the best results have been obtained by combination treatments that work on both aspects.[85,96] Other molecules also need to be explored. The use of topical prostaglandins is promising. A recent trial found that topical prostaglandin F2α analogs were at least as effective as tacrolimus to induce repigmentation in combination with NB-UVB.[97]

Other methods to initiate melanocyte differentiation and proliferation need to be explored. The afamelanotide trial combining NB-UVB with an alpha-melanocyte-stimulating hormone analog showed more repigmentation compared with monotherapy with NB-UVB.[98] The best results were obtained in dark-skinned patients. The tanning-inducing capacity of afamelanotide increases the contrast between lesional and healthy skin, which may however exert negative effects on the quality of life.[99]

A better investigation into the working mechanisms of NB-UVB may lead to synergistic combination treatments. Wnt/β catenin regulates melanocyte stem cell differentiation and Kit signaling induces migration of differentiated melanoblasts in UVB-irradiated skin.[50] As the Wnt pathway can induce melanocyte differentiation and migration but is deregulated in vitiligo skin, the development of Wnt agonists could be a new treatment for repigmentation.[49]