The convergence theory for vitiligo: A reappraisal

Abstract

Vitiligo is characterized by progressive loss of skin pigmentation. The search for aetiologic factors has led to the biochemical, the neurologic and the autoimmune theory. The convergence theory was then proposed several years ago to incorporate existing theories of vitiligo development into a single overview of vitiligo aetiology. The viewpoint that vitiligo is not caused only by predisposing mutations, or only by melanocytes responding to chemical/radiation exposure, or only by hyperreactive T cells, but rather results from a combination of aetiologic factors that impact melanocyte viability, has certainly stood the test of time. New findings have since informed the description of progressive depigmentation. Understanding the relative importance of such aetiologic factors combined with a careful selection of the most targetable pathways will continue to drive the next phase in vitiligo research: the development of effective therapeutics. In that arena, it is likewise important to acknowledge that pathways affected in some patients may not be altered in others. Taken together, the convergence theory continues to provide a comprehensive viewpoint of vitiligo aetiology. The theory serves to intertwine aetiologic pathways and will help to define pathways amenable to disease intervention in individual patients.

Keywords: autoimmune; depigmentation; melanocyte; vitiligo aetiology.

FIGURE 1

A, Vitiligo aetiology explored between 1990 and 2015. When the convergence theory was first proposed, it united emerging concepts surrounding vitiligo etiopathology. A PubMed search was performed using the terms “vitiligo” plus either “immune,” “genetic,” “oxidative stress” or “neuronal” and the year of publication. When separated into these four mainline theories to explain vitiligo development, the number of publications addressing each between 1990 and 2015 indicates shifts in vitiligo research over time, with the attention shifting towards genetic and immune factors by the mid-nineties and more recently, renewed attention for oxidative stress. B, Increase in vitiligo publications over time. A PubMed search was performed using the year of publication, with or without the term “vitiligo.” The proportion of publications relating to vitiligo has increased 3-fold over the 25-year period of analysis

FIGURE 2

Publications related to vitiligo treatment. A PubMed search was performed with the year of publication combined with ‘vitiligo’ plus the terms shown in the legend, with the exception of the black line. Here, the year of publication was combined with the search terms ‘vitiligo treatment’ and the total number was divided by five, as represented in the graph. Not represented in the graph are recent developments including JAK inhibitors and Tregs.