The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Alain Taïeb - One of the best experts on this subject based on the ideXlab platform.
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Vitiligo in Childhood
Vitiligo, 2020Co-Authors: Juliette Mazereeuw-hautier, Alain TaïebAbstract:Childhood Vitiligo differs from adult onset Vitiligo in several features, including more segmental forms, higher prevalence of halo nevi, and more common family history for autoimmune diseases. The major differential diagnoses are the post-inflammatory hypomelanoses for non- segmental Vitiligo (NSV) and nevus depigmentosus for segmental Vitiligo (SV). Thyroid anomalies are detected in NSV only, and actually The course of childhood Vitiligo is not well-known, since there is a lack of long-term follow-up studies.
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Vitiligo/nonsegmental Vitiligo Including Acrofacial and Universalis
Vitiligo, 2019Co-Authors: Thierry Passeron, Jean-paul Ortonne, Prasad Kumarasinghe, Alain TaïebAbstract:Based on the VGICC classification, Vitiligo/NSV, a consensus umbrella term for all forms of generalized Vitiligo, is meant to describe different clinical subtypes of Vitiligo that are all clearly distinct from SV including acrofacial, generalized, mucosal (multifocal), and universal. According to the VETF definition, generalized Vitiligo is characterized by asymptomatic well-circumscribed milky-white macules involving both sides of the body with usually a symmetrical pattern. In acrofacial Vitiligo (AFV), the involved sites are by definition limited to the face, head, hands, and feet with typically depigmentation of the distal fingers and facial orifices. Vitiligo universalisis a rapidly progressive form of the disease, which needs a more in-depth investigation especially for associated autoimmunity.
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Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy
Clinical Reviews in Allergy & Immunology, 2018Co-Authors: Katia Boniface, Julien Seneschal, Mauro Picardo, Alain TaïebAbstract: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.
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Vitiligo like lesions occurring in patients receiving anti programmed cell death 1 therapies are clinically and biologically distinct from Vitiligo
Journal of The American Academy of Dermatology, 2017Co-Authors: Maiana Larsabal, Alain Taïeb, S Prey, A Marti, Clement Jacquemin, Jerome Rambert, Denis Thiolat, L Dousset, C Dutriaux, Katia BonifaceAbstract:Background The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including Vitiligo-like lesions. Objective We sought to characterize clinically and biologically Vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with Vitiligo. Methods Eight patients receiving anti-PD-1 therapies with features of Vitiligo-like lesions seen in our department were recruited. Clinical features and photographs were analyzed. For some patients, skin and blood samples were obtained. Results were compared with the Vitiligo group. Results All patients developed lesions localized on photoexposed areas with a specific depigmentation pattern consisting of multiple flecked lesions without Koebner phenomenon. In contrast to Vitiligo, patients receiving anti-PD-1 therapies who developed Vitiligo-like lesions did not report any personal or family histories of Vitiligo, thyroiditis, or other autoimmune disorders. Analysis of blood and skin samples revealed increased C-X-C motif ligand 10 levels in serum of patients developing Vitiligo-like lesions, associated with skin infiltration of CD8 T-cells expressing C-X-C motif receptor 3 and producing elevated levels of interferon-γ and tumor necrosis factor-alfa. Limitations This cross-sectional study concerned a single center. Conclusions Clinical and biological patterns of Vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies differ from Vitiligo, suggesting a different mechanism.
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Inflammasome activation and Vitiligo/nonsegmental Vitiligo progression.
British Journal of Dermatology, 2014Co-Authors: J. Marie, Alain Taïeb, Mauro Picardo, Daniela Kovacs, Carlo Cota, Khaled Ezzedine, C. Pain, Thomas Jouary, B. Vergier, Muriel Cario-andréAbstract:Summary Background Polymorphisms of NLR (nucleotide-binding domain and leucine rich repeat containing) family, pyrin domain containing protein 1 (NLRP1) have been found in patients with Vitiligo/nonsegmental Vitiligo (NSV), and increased NLRP1 expression has been detected in the leading edge of lesional skin biopsies. Objectives To evaluate the presence and intensity of NLRP1 immunostaining in lesional and perilesional skin of patients with Vitiligo/NSV and to search for possible correlations between NLRP1 and interleukin (IL)-1β expression, lymphocytic infiltrates and disease activity. Methods Of 14 consecutive Vitiligo/NSV patients, eight had active disease [Vitiligo European Task Force (VETF) spreading score +1 to +5], one patient had stable disease and five patients had regressive disease (VETF spreading score −1 to −3). We performed immunostaining for NLRP1, B and T lymphocytes, IL-1β and kallikrein 7 on lesional and perilesional Vitiligo skin. Results NLRP1 and IL-1β immunostaining in perilesional Vitiligo/NSV skin was significantly associated with progressive disease (P = 0·009 and 0·04, respectively) and performed better than the simple detection of lymphocytic infiltrates. Conclusions Our findings suggest that markers of the NLRP1 inflammasome could be a useful test for assessing disease activity in addition to the detection of inflammatory infiltrates in the progressing margins of Vitiligo/NSV lesions.
K Ezzedine - One of the best experts on this subject based on the ideXlab platform.
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revised classification nomenclature of Vitiligo and related issues the Vitiligo global issues consensus conference
Pigment Cell & Melanoma Research, 2012Co-Authors: K Ezzedine, Tamio Suzuki, Ichiro Katayama, Iltefat Hamzavi, Tag S Anbar, Silva C De Castro, Davinder Parsad, N Van Geel, I Le C Poole, Naoki OisoAbstract:During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for Vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune Vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental Vitiligo be classified separately from all other forms of Vitiligo and that the term ‘Vitiligo’ be used as an umbrella term for all non-segmental forms of Vitiligo, including ‘mixed Vitiligo’ in which segmental and non-segmental Vitiligo are combined and which is considered a subgroup of Vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for Vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune Vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of Vitiligo likely involves autoimmune or inflammatory mechanisms.
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halo naevi and leukotrichia are strong predictors of the passage to mixed Vitiligo in a subgroup of segmental Vitiligo
British Journal of Dermatology, 2012Co-Authors: K Ezzedine, Abou Diallo, C Leautelabreze, J Seneschal, S Prey, F Ballanger, Khalid M Alghamdi, Muriel Carioandre, T Jouary, Yvon GauthierAbstract:Summary Background Until now, segmental Vitiligo has been considered as a stable entity and mixed Vitiligo, the association of segmental and nonsegmental Vitiligo, has been reported rarely. Objectives The aim of this study was to search for factors associated with the generalization of Vitiligo in patients with segmental Vitiligo. Patients and methods This was a prospective observational study conducted in the Vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental Vitiligo after exclusion of other forms of Vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Results One hundred and twenty-seven patients were recruited: 101 had segmental Vitiligo and 26 had segmental Vitiligo that evolved into mixed Vitiligo; 56 were male and 71 were female. Most patients had onset of segmental Vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients’ disease from segmental Vitiligo to mixed Vitiligo: initial percentage of body surface involvement of the segment > 1% [odds ratio (OR) 15·14, P = 0·002], the presence of halo naevi (OR 24·82, P = 0·0001) and leukotrichia (OR 25·73, P = 0·0009). Conclusions Halo naevi association and leukotrichia at first consultation in segmental Vitiligo are risk factors for the progression of segmental Vitiligo to mixed Vitiligo. In addition, this progression of segmental Vitiligo to mixed Vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.
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segmental Vitiligo associated with generalized Vitiligo mixed Vitiligo a retrospective case series of 19 patients
Journal of The American Academy of Dermatology, 2011Co-Authors: K Ezzedine, C Leautelabreze, T Jouary, Yvon Gauthier, Sonia Marquez, Serge Bouchtnei, Alain TaïebAbstract:Background Mixed Vitiligo (MV), the association of segmental Vitiligo (SV) and nonsegmental Vitiligo, has been rarely reported. Objective The aim of this study was to delineate the clinical spectrum of MV through a case series of patients with typical SV associated with patchy bilateral Vitiligo. Methods This was a cross-sectional evaluation in the setting of a prospective observational study conducted in the Vitiligo clinic of the department of dermatology in Bordeaux, France. Results Nineteen patients with MV were identified. Four were male and 15 were female. Most patients had an onset of SV before the age of 18 years (18 of 19). In all patients, SV preceded nonsegmental Vitiligo with a delay ranging from 6 months to more than 24 months. Limitations This study was cross-sectional and based on a single-center experience. Conclusion MV is not yet part of a conventional classification. However, this entity may have been neglected until now and should be included in the classification of Vitiligo in addition to SV and nonsegmental Vitiligo. Moreover, MV may be essential to the understanding of the pathogenesis of Vitiligo as a primary skin disorder.
Iltefat Hamzavi - One of the best experts on this subject based on the ideXlab platform.
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standardizing serial photography for assessing and monitoring Vitiligo a core set of international recommendations for essential clinical and technical specifications
Journal of The American Academy of Dermatology, 2019Co-Authors: Nanja Van Geel, Iltefat Hamzavi, Amit G Pandya, John E. Harris, Indermeet Kohli, Albert Wolkerstorfer, Steven Thng Tien Guan, Marwa Abdallah, Samia Esmat, J SeneschalAbstract:Background Clinical photography is an important component of the initial assessment and follow-up of patients with Vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time. Objective The aim is to develop an international consensus for a core set of recommendations for standardized Vitiligo clinical photography. Methods Based an international meeting of Vitiligo experts, a standard operating procedure was developed for Vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 Vitiligo experts until agreement was reached. Results The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described. Conclusions This consensus-based protocol for Vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.
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Phototherapy for Vitiligo
Dermatologic Clinics, 2019Co-Authors: Raheel Zubair, Iltefat HamzaviAbstract:: Vitiligo is a common disorder with a severe impact on quality of life. The authors review recent advances in phototherapy for Vitiligo focusing on narrowband ultraviolet B including mechanisms, treatment recommendations, and combination therapies. Phototherapy is the first-line treatment of choice for Vitiligo with narrowband UVB preferred for widespread Vitiligo and excimer used for localized lesions. However, unfamiliarity with prescribing phototherapy may be limiting clinicians from using it to its full potential. This article provides clinicians with the critical information needed to safely and effectively provide phototherapy for their patients with Vitiligo.
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International Initiative for Outcomes (INFO) for Vitiligo: workshops with patients with Vitiligo on repigmentation.
British Journal of Dermatology, 2018Co-Authors: Viktoria Eleftheriadou, Iltefat Hamzavi, Nada Elbuluk, Amit G Pandya, Richard H Huggins, Pearl E. Grimes, John E. Harris, B. Bhatia, Andrea Tovar-garzaAbstract:BACKGROUND: There is no cure or firm clinical recommendations for the treatment of Vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for Vitiligo. OBJECTIVES: To define successful repigmentation from the patients' point of view and to propose how and when repigmentation should be evaluated in clinical trials in Vitiligo. METHODS: We conducted three workshops with patients with Vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California. RESULTS: Seventy-three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of 'successful repigmentation' was 80-100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used. CONCLUSIONS: This was the largest patients' outcomes workshop. We followed the guidance from the CSG-COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0-25%, 26-50%, 51-79%, 80-100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre-existing organisational support and the availability of funding.
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revised classification nomenclature of Vitiligo and related issues the Vitiligo global issues consensus conference
Pigment Cell & Melanoma Research, 2012Co-Authors: K Ezzedine, Tamio Suzuki, Ichiro Katayama, Iltefat Hamzavi, Tag S Anbar, Silva C De Castro, Davinder Parsad, N Van Geel, I Le C Poole, Naoki OisoAbstract:During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for Vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune Vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental Vitiligo be classified separately from all other forms of Vitiligo and that the term ‘Vitiligo’ be used as an umbrella term for all non-segmental forms of Vitiligo, including ‘mixed Vitiligo’ in which segmental and non-segmental Vitiligo are combined and which is considered a subgroup of Vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for Vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune Vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of Vitiligo likely involves autoimmune or inflammatory mechanisms.
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Revised classification/nomenclature of Vitiligo and related issues: the Vitiligo Global Issues Consensus Conference
Pigment Cell & Melanoma Research, 2012Co-Authors: Khaled Ezzedine, Tamio Suzuki, Ichiro Katayama, Iltefat Hamzavi, Tag S Anbar, C. Silva De CastroAbstract:During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for Vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune Vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental Vitiligo be classified separately from all other forms of Vitiligo and that the term ‘Vitiligo’ be used as an umbrella term for all non-segmental forms of Vitiligo, including ‘mixed Vitiligo’ in which segmental and non-segmental Vitiligo are combined and which is considered a subgroup of Vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for Vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune Vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of Vitiligo likely involves autoimmune or inflammatory mechanisms.
Naoki Oiso - One of the best experts on this subject based on the ideXlab platform.
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revised classification nomenclature of Vitiligo and related issues the Vitiligo global issues consensus conference
Pigment Cell & Melanoma Research, 2012Co-Authors: K Ezzedine, Tamio Suzuki, Ichiro Katayama, Iltefat Hamzavi, Tag S Anbar, Silva C De Castro, Davinder Parsad, N Van Geel, I Le C Poole, Naoki OisoAbstract:During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for Vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune Vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental Vitiligo be classified separately from all other forms of Vitiligo and that the term ‘Vitiligo’ be used as an umbrella term for all non-segmental forms of Vitiligo, including ‘mixed Vitiligo’ in which segmental and non-segmental Vitiligo are combined and which is considered a subgroup of Vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for Vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune Vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of Vitiligo likely involves autoimmune or inflammatory mechanisms.
Richard A. Spritz - One of the best experts on this subject based on the ideXlab platform.
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The genetic architecture of Vitiligo.
Pigment Cell & Melanoma Research, 2019Co-Authors: Genevieve H. L. Roberts, Stephanie A. Santorico, Richard A. SpritzAbstract:: Vitiligo is an autoimmune disease in which destruction of skin melanocytes results in patches of white skin and hair. Genome-wide linkage studies and genome-wide association studies in European ancestry cases identified over 50 Vitiligo susceptibility loci, defining a model of melanocyte-directed autoimmunity. Vitiligo heritability is exceedingly high, ~2/3 coming from common and ~1/3 from rare genomic variants; ~20% of Vitiligo risk is environmental. Vitiligo genetic risk is polygenic, with greater additive risk in multiplex Vitiligo families than simplex cases. Vitiligo age-of-onset is bimodal, also involving a major genetic component; a MHC enhancer haplotype confers extreme risk for Vitiligo (OR 8.1) and early disease onset, increasing expression of HLA-DQB1 mRNA and HLA-DQ protein and thus perhaps facilitating presentation of triggering antigens. Vitiligo triggering also involves a major environmental component; dramatic delay in Vitiligo age-of-onset, especially from 1973 to 2004, suggests that exposure or response to a key Vitiligo environmental trigger diminished during this period. Together, these findings provide deep understanding of Vitiligo pathogenesis and genetic architecture, suggesting that Vitiligo represents a tractable model for investigating complex disease genetic architecture and predictive aspects of personalized medicine.
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family clustering of autoimmune Vitiligo results principally from polygenic inheritance of common risk alleles
American Journal of Human Genetics, 2019Co-Authors: Genevieve H. L. Roberts, Stephanie A. Santorico, Richard A. Spritz, Subrata Paul, Daniel YorgovAbstract:Vitiligo is an autoimmune disease that results in patches of depigmented skin and hair. Previous genome-wide association studies (GWASs) of Vitiligo have identified 50 susceptibility loci. Variants at the associated loci are generally common and have individually small effects on risk. Most Vitiligo cases are "simplex," where there is no family history of Vitiligo, though occasional family clustering of Vitiligo occurs, and some "multiplex" families report numerous close affected relatives. Here, we investigate whether simplex and multiplex Vitiligo comprise different disease subtypes with different underlying genetic etiologies. We developed and compared the performance of several different Vitiligo polygenic risk scores derived from GWAS data. By using the best-performing risk score, we find increased polygenic burden of risk alleles identified by GWAS in multiplex Vitiligo cases relative to simplex cases. We additionally find evidence of polygenic transmission of common, low-effect-size risk alleles within multiplex-Vitiligo-affected families. Our findings strongly suggest that family clustering of Vitiligo involves a high burden of the same common, low-effect-size variants that are relevant in simplex cases. We furthermore find that a variant within the major histocompatibility complex (MHC) class II region contributes disproportionately more to risk in multiplex Vitiligo cases than in simplex cases, supporting a special role for adaptive immune triggering in the etiology of multiplex cases. We suggest that genetic risk scores can be a useful tool in analyzing the genetic architecture of clinical disease subtypes and identifying subjects with unusual etiologies for further investigation.
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the genetics of generalized Vitiligo and associated autoimmune diseases
Pigment Cell Research, 2007Co-Authors: Richard A. SpritzAbstract:Summary Vitiligo is an acquired disorder in which patches of depigmented skin and often overlying hair, and mucous membranes, are the result of progressive autoimmune loss of melanocytes from the involved areas. Considered the most common pigmentary disorder, Vitiligo involves complex interaction of environmental and genetic factors that ultimately contribute to melanocyte destruction, resulting in the characteristic depigmented lesions. In the past few years, studies of the genetic epidemiology of Vitiligo have led to the recognition that generalized Vitiligo is part of a broader autoimmune disease diathesis. Attempts to identify genes involved in susceptibility to generalized Vitiligo have involved gene expression studies, genetic association studies of candidate genes, and genome-wide linkage analyses to discover new genes. These studies have begun to yield results that shed light on the mechanisms of Vitiligo pathogenesis. It is anticipated that the discovery of biological pathways of Vitiligo pathogenesis will provide novel targets for future approaches to the treatment and prevention of Vitiligo and its associated autoimmune diseases.
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the genetics of generalized Vitiligo and associated autoimmune diseases
Journal of Dermatological Science, 2006Co-Authors: Richard A. SpritzAbstract:Generalized Vitiligo is an acquired disorder in which patches of depigmented skin, overlying hair, and oral mucosa result from progressive autoimmune loss of melanocytes from the involved areas. Although Vitiligo is perhaps the most common pigmentary disorder, insufficiently clear clinical definition of the disorder and lack of a good laboratory animal model have inhibited progress in understanding its pathobiology, its environmental triggers, and in developing specific and effective therapeutic approaches. Vitiligo results from a complex interaction of environmental, genetic, and immunologic factors, which ultimately contribute to melanocyte destruction, resulting in the characteristic depigmented lesions. In the past few years, studies of the genetic epidemiology of generalized Vitiligo have led to the recognition that Vitiligo is part of a broader, genetically-determined, autoimmune/autoinflammatory diathesis. Attempts to identify genes involved in Vitiligo susceptibility have involved both allelic association studies of candidate genes and genome-wide linkage analyses to discover new genes, and these studies have begun to shed light on the mechanisms of Vitiligo pathogenesis. It is anticipated that the discovery of biological pathways of Vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of Vitiligo and its associated autoimmune diseases.
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early disease onset and increased risk of other autoimmune diseases in familial generalized Vitiligo
Pigment Cell Research, 2005Co-Authors: Greggory S Laberge, Christina M Mailloux, Katherine Gowan, Paulene J Holland, Dorothy C Bennett, Pamela R Fain, Richard A. SpritzAbstract:Generalized Vitiligo is an autoimmune disorder in which acquired white patches of skin and overlying hair result from autoimmune loss of melanocytes from involved areas. Although usually sporadic, family clustering of Vitiligo may occur, in a non-Mendelian pattern typical of multifactorial, polygenic inheritance. Sporadic Vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus; these same disorders occur at increased frequency in patients' first-degree relatives. Here, we studied 133 'multiplex' generalized Vitiligo families, with multiple affected family members. The age of onset of Vitiligo is earlier in these 'multiplex' families than in patients with sporadic Vitiligo. Affected members of the multiplex Vitiligo families have elevated frequencies of autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anemia, and Addison's disease. Probands' unaffected siblings have elevated frequencies of most of these same autoimmune diseases, particularly if the proband had non-Vitiligo autoimmune disease. Familial generalized Vitiligo is thus characterized by earlier disease onset and a broader repertoire of associated autoimmune diseases than sporadic Vitiligo. This mostly likely reflects a greater inherited genetic component of autoimmune susceptibility in these families. These findings have important implications for autoimmune disease surveillance in families in which multiple members are affected with Vitiligo.
