Katia Boniface

Pre‐ vs. post‐pubertal onset of vitiligo: multivariate analysis indicates atopic diathesis association in pre‐pubertal onset vitiligo

Background  Limited epidemiological data exist that compare clinical features of pre‐ and post‐pubertal nonsegmental vitiligo.

Development and validation of the K‐VSCOR for scoring Koebner's phenomenon in vitiligo/non‐segmental vitiligo

The relation of vitiligo/non‐segmental vitiligo (NSV) to Koebners phenomenon is variably appreciated. Our objective was to develop and validate a simple clinical score for Koebners phenomenon (KP) in patients with vitiligo/NSV. The study population was composed of 351 individuals in the development sample and 285 patients in the validation sample. Seven variables were independently associated with the presence of KP: disease duration of more than 3 yr, forehead + scalp areas, eyelids, wrists, genital + belt areas, knees and tibial crests. The score computed by the weighted sum of the rounded coefficients of these seven variables ranged from 0 to 56 (mean 38.39 ± 22.93). The probability of having KP was computed as follows: exp (−2.37 + 0.1*score)/exp [1 + (−2.37 + 0.1*score)]. When applying the score to each patient in the validation and the development sample, the score maintained adequate discrimination and calibration (AUC‐ROC = 0.78), arguing that KP can be adequately predicted using our score. Further studies should evaluate KP assessed by the K‐VSCOR in clinical practice with the aim to determine its association with clinical profile, course and treatment response of vitiligo.

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3

Vitiligo is a chronic autoimmune depigmenting skin disorder that results from a loss of melanocytes. Multiple combinatorial factors have been involved in disease development, with a prominent role of the immune system, in particular T cells. After repigmentation, vitiligo frequently recurs in the same area, suggesting that vitiligo could involve the presence of resident memory T cells (TRM). We sought to perform a thorough characterization of the phenotype and function of skin memory T cells in vitiligo. We show that stable and active vitiligo perilesional skin is enriched with a population of CD8 TRM expressing both CD69 and CD103 compared with psoriasis and control unaffected skin. CD8 TRM expressing CD103 are mainly localized in the epidermis. Expression of CXCR3 is observed on most CD8 TRM in vitiligo, including the population of melanocyte-specific CD8 T cells. CD8 TRM displayed increased production of IFN-γ and tumor necrosis factor-α with moderate cytotoxic activity. Our study highlights the presence of functional CD8 TRM in both stable and active vitiligo, reinforcing the concept of vitiligo as an immune memory skin disease. The CD8 TRM that remain in stable disease could play a role during disease flares, emphasizing the interest in targeting this cell subset in vitiligo.

Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy

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.

Comment: the mystery of melanocyte demise in vitiligo

Katia Boniface, Hamid R. Rezvani, Julien Seneschal and Alain Ta€ıeb INSERM U 1035, University of Bordeaux, Bordeaux, France; Department of Dermatology and Pediatric Dermatology, National Reference Centre for Rare Skin Disorders, Bordeaux University Hospitals, Bordeaux, France Correspondence: AlainTa€ıeb, INSERM U 1035, University of Bordeaux; National Reference Centre for Rare Skin Disorders, Department of Dermatology and Pediatric Dermatology, Bordeaux University Hospitals, Bordeaux, France, Tel.: +33(0)5 56 79 47 05, Fax: +33(0)5 56 79 49 75, e-mail: alain.taieb@chu-bordeaux.fr

In vitro models of vitiligo

Abstract Understanding the mechanisms leading to melanocyte loss in vitiligo is a mandatory step to improve the overall management of vitiligo patients. In vitro strategies to study vitiligo range from the analysis of the whole skin to different skin cell subsets, individually, using different techniques that will be described in this review: primary cell cultures (melanocytes, keratinocytes, or fibroblasts), three-dimensional skin models to reproduce the in vivo network, and isolation of blood or skin mononuclear cells to identify inflammatory cells that are involved in disease development. Cell culture models are useful to investigate the differences between healthy and vitiligo cells and to test potential treatment options in a cell-focusing approach. Beyond the study of vitiligo pathomechanisms or therapies using unmodified patients cells, in vitro approaches can be also adapted to generate melanocyte-specific silencing or overexpression of putative target genes or, in a further step, to design animal models using melanocyte-specific expression of modified genes.

Elevated total serum IgE in vitiligo might be protective for other autoimmune diseases

Vitiligo is a chronic inflammatory skin depigmenting disorder that is often associated with other autoimmune disease such as thyroiditis.1 Moreover, there is growing evidence that vitiligo is also associated with atopy, a genetic tendency to develop allergic hypersensitivity reactions, with production of immunoglobulin E (IgE). Indeed, the largest study conducted in the US population found a higher prevalence of atopic diseases in vitiligo.2 A Chinese study of 6516 patients with vitiligo found a higher prevalence of asthma in familial probands.3 This article is protected by copyright. All rights reserved.

Vitiligo therapy: restoring immune privilege?

The therapeutic hypothesis proposed by Speeckaert and van Geel in this issue (1) is based on the dramatic effects of the new drugs targeting immune privilege checkpoints (PD1/PDL, CTLA4) in current advanced melanoma therapy as major inductors of vitiligo changes in the skin. Such striking clinical manifestations cannot be classified as mere side effects without considering possible consequences for spontaneously occurring vitiligo.”