Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else?

Abstract

The pathobiology of vitiligo has been hotly disputed for as long as one remembers, and has been a magnet for endless speculation. Evidently, the different schools of thought--ranging, e.g. from the concept that vitiligo essentially is a free-radical disorder to that of vitiligo being a primary autoimmune disease--imply very different consequences for the best therapeutic strategies that one should adopt. As a more effective therapy for this common, often disfiguring pigmentary disorder is direly needed, we must strive harder to settle the pathogenesis debate definitively--on the basis of sound experimental evidence, rather than by a war of dogmatic theories. Recognizing, however, that it is theories which tend to guide our experimental designs and choice of study parameters, the various pathogenesis theories on the market deserve to be critically, yet unemotionally re-evaluated. This Controversies feature invites you to do so, and to ask yourself: is there something important or worthwhile exploring in other pathogenesis scenarios than those already favoured by you that may help you improve your own study design, next time you have a fresh look at vitiligo? Vitiligo provides a superb model for the study of many fundamental problems in skin biology and pathology. Therefore, even if it later turns out that, as far as your own vitiligo pathogenesis concept is concerned, you have barked-up the wrong tree most of the time, chances are that you shall anyway have generated priceless new insights into skin function along the way.

Stimulated human melanocytes express and release interleukin-8, which is inhibited by luteolin: relevance to early vitiligo

“…IL-8 is a powerful chemokine that has been reported to induce oxidative stress, leading indirectly to both keratinocyte and melanocyte apoptosis in vitiligo. 1 Apoptotic cells could in turn release high amounts of pro-inflammatory IL-1 and TNF, further enhancing skin inflammation. We previously showed that both preformed and newly synthesized TNF can be released from mast cells, 7 the numbers of which seem to be increased in the centre of vitiligo lesions.…”

“…It affects 1–3% of the general population, 1 and its exact pathogenesis remains obscure. However, recent evidence suggests that oxidative stress, auto-immunity and melanocyte apoptosis are involved.…”

“…However, recent evidence suggests that oxidative stress, auto-immunity and melanocyte apoptosis are involved. 1 …”

Vitiligo - Part 1

“…Among those, the autoimmune hypothesis is currently the most accepted by experts. 69,70 Besides this theory, others have been intensively studied, such as epidermal adhesion defect, biochemical and neural hypotheses. This article will discuss the adhesion defect, autoimmune and biochemical theories.…”

Dysfunction of Autophagy: A Possible Mechanism Involved in the Pathogenesis of Vitiligo by Breaking the Redox Balance of Melanocytes

“…Although vitiligo does not affect individual survival of patients, the change of the appearance may cause physical handicaps which seriously interfere with the lives of patients [3, 4]. In the past decades, a number of mechanisms such as oxidative stress, autoimmune, autocytotoxicity [5, 6], melanocytorrhagy [7], neural, and genetic factors [7] have been proposed for the pathogenesis of vitiligo. Oxidative stress hypothesis indicated imbalanced redox state of the vitiliginous skin.…”