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Based on existing research, we propose that vitiligo has a multi\u2010factorial etiology, characterized by multiple steps, but always involving an increase of external or internal phenol\/catechol concentration, serving as a preferred surrogate substrate of tyrosinase, competing with its physiological substrate tyrosine. The conversion of these substrates into reactive quinones is reinforced by a disturbed redox balance (increasing hydrogen peroxide). Such reactive quinones can be covalently bound to the catalytic centre of tyrosinase (haptenation). This could give rise to a new antigen, carried by Langerhans cells to the regional lymph node, stimulating the proliferation of cytotoxic T cells. However, the activation of such cytotoxic cells is only a first step in skin melanocyte killing, which also depends on a shift in the balance between immune defence and tolerance, e.g. resulting from a decrease in properly functioning T\u2010regulatory cells. With this new model, based on a synthesis of several of the existing theories, in mind, the external and internal factors involved in the etiopathogenesis of vitiligo are reviewed, against the background of reported clinical data, experimental studies and existing and potential new therapies. A similar complex mechanism may also lead to some other autoimmune diseases.<\/jats:p>","DOI":"10.1111\/j.1600-0749.2007.00399.x","type":"journal-article","created":{"date-parts":[[2007,8,7]],"date-time":"2007-08-07T05:31:25Z","timestamp":1186464685000},"page":"345-359","source":"Crossref","is-referenced-by-count":124,"title":["Vitiligo puzzle: the pieces fall in place"],"prefix":"10.1111","volume":"20","author":[{"given":"Wiete","family":"Westerhof","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"D\u2019Ischia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,8,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711700209"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.6.661"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.94"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700001"},{"key":"e_1_2_11_6_1","first-page":"669","article-title":"Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan\u2010A\/melanoma antigen recognized by T cells\u20101","volume":"9","author":"Ayyoub M.","year":"2003","journal-title":"Clin. 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