Future horizons in vitiligo research: focusing on the recommendations of the Cochrane systematic review 'Interventions for vitiligo' 2010.
The British journal of dermatology
The 'Implications for research' section of the Cochrane systematic review, 'Interventions for vitiligo', published in 2010, highlighted three main issues that impact the standard of vitiligo research: (i) lack of consensus on the classification and definition of vitiligo; (ii) lack of consensus on the methods of assessment and outcome measures for vitiligo; and (iii) heterogeneity of interventions compared. This article provides an update of the progress made to resolve these issues since the publication of the Cochrane systematic review in 2010, 'Interventions for vitiligo'.
Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy.
Boniface Katia,Seneschal Julien,Picardo Mauro,Taïeb Alain
Clinical reviews in allergy & immunology
Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants. A series of hypopigmented disorders may masquerade as vitiligo, and some of them need to be ruled out by specific procedures including a skin biopsy. Multiple mechanisms are involved in melanocyte disappearance, namely genetic predisposition, environmental triggers, metabolic abnormalities, impaired renewal, and altered inflammatory and immune responses. The auto-immune/inflammatory theory is the leading hypothesis because (1) vitiligo is often associated with autoimmune diseases; (2) most vitiligo susceptibility loci identified through genome-wide association studies encode immunomodulatory proteins; and (3) prominent immune cell infiltrates are found in the perilesional margin of actively depigmenting skin. However, other studies support melanocyte intrinsic abnormalities with poor adaptation of melanocytes to stressors leading to melanocyte instability in the basal layer, and release of danger signals important for the activation of the immune system. Recent progress in the understanding of immune pathomechanisms opens interesting perspectives for innovative treatment strategies. The proof of concept in humans of targeting of the IFNγ /Th1 pathway is much awaited. The interplay between oxidative stress and altered immune responses suggests that additional strategies aiming at limiting type I interferon activation pathway as background stabilizing therapies could be an interesting approach in vitiligo. This review covers classification and clinical aspects, pathophysiology with emphasis on immunopathogenesis, and promising therapeutic approaches.