Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study

Background Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors ( PPI s) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. Objective We investigated the effect of PPI s on melanogenesis in vivo and in vitro . Methods We examined the effect of PPI s on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase ( TYR ) activity. TYR and tyrosinase‐related protein‐1 ( TRP ‐1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. Results In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPI s decreased both melanin content and TYR activity. Western blotting showed that PPI s decreased TYR and TRP ‐1 protein levels. In the zebrafish test, PPI s inhibited body pigmentation in a dose‐dependent manner. Conclusion These results suggest that the functional inhibition of melanization by PPI s may induce or aggravate vitiligo lesions in genetically predisposed patients.