The initial clinical evaluation of a vitiligo patient is a step frequently neglected. Some new variants have been described only recently such as mixed and follicular vitiligo, and the frontiers of the disease challenge an unambiguous delineation of the disease (e.g. vitiligoid depigmentation after cancer immunotherapies, hypochromic vitiligo...). Major progresses have been made to understand heritability, but more epidemiological data are needed to address in particular environmental factors, natural history, and comorbidities to confirm on a large scale a protection against cancer. At this time point, available clinical data do not support a significant involvement of non-skin melanocytes in vitiligo/NSV.
Major initial determinants are probably situated directly in the skin and activated in a subset of patients by largely unknown stressors. Vitiligo/NSV can be considered as a marker of an auto-inflammatory/autoimmune diathesis, and microinflammation is central to its pathophysiology. The skewing of the immune system towards vitiligo seems of benefit to fight skin cancer and possibly internal cancer. If inflammation and autoimmunity are pivotal in all subset of vitiligo, other factors are involved predisposing to premature melanocyte ageing.
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