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Science Translational Medicine Sep 2021Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results...
Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8 T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in coordinating autoimmunity during disease progression. We confirmed that type 1 cytokine signaling occupied a central role in disease, but we also found that this pathway was used by regulatory T cells (T) to restrain disease progression in nonlesional skin. We determined that CCL5-CCR5 signaling served as a chemokine circuit between effector CD8 T cells and T, and mechanistic studies in a mouse model of vitiligo revealed that CCR5 expression on T was required to suppress disease in vivo but not in vitro. CCR5 was not required for T recruitment to skin but appeared to facilitate T function by properly positioning these cells within the skin. Our data provide critical insights into the pathogenesis of vitiligo and uncover potential opportunities for therapeutic interventions.
Topics: Humans; RNA, Small Cytoplasmic; Receptors, CCR5; Single-Cell Analysis; T-Lymphocytes, Regulatory; Vitiligo
PubMed: 34516831
DOI: 10.1126/scitranslmed.abd8995 -
International Journal of Molecular... Jun 2023Vitiligo is an acquired chronic depigmenting disorder of skin. It is mostly asymptomatic and characterized by amelanotic macules and patches that affects 0.5% to 2% of... (Review)
Review
Vitiligo is an acquired chronic depigmenting disorder of skin. It is mostly asymptomatic and characterized by amelanotic macules and patches that affects 0.5% to 2% of the world's population. The etiology of vitiligo has not been clearly elucidated and multiple theories have been proposed regarding the causes of the disorder. Among the most prevalent theories, the genetic predisposition, oxidative stress theory, promotion of cellular stress and pathologic influence of lymphocytes T have been highlighted. As a result of increases in in-depth knowledge concerning the pathogenetic processes in vitiligo, we review the most recent information concerning its etiopathogenesis and treatment methods including topical and oral Janus kinase inhibitors, prostaglandins and their analogues, namely afamelanotide, Wnt/β-catenin-signaling agonists and cell-based therapies. Topical ruxolitinib has been registered for vitiligo treatment, whereas other agents as oral ritlecitinib, afamelanotide and latanoprost have been studied in ongoing clinical trials. New highly effective therapeutic strategies may be developed thanks to molecular and genetic studies.
Topics: Humans; Vitiligo; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Skin; Prostaglandins
PubMed: 37298700
DOI: 10.3390/ijms24119749 -
Journal of the American Academy of... Feb 2023Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin.
OBJECTIVE
To evaluate the efficacy and safety of ritlecitinib, an oral JAK3 (Janus kinase)/TEC (tyrosine kinase expressed in hepatocelluar carcinoma) inhibitor, in patients with active nonsegmental vitiligo in a phase 2b trial (NCT03715829).
METHODS
Patients were randomized to once-daily oral ritlecitinib ± 4-week loading dose (200/50 mg, 100/50 mg, 30 mg, or 10 mg) or placebo for 24 weeks (dose-ranging period). Patients subsequently received ritlecitinib 200/50 mg daily in a 24-week extension period. The primary efficacy endpoint was percent change from baseline in Facial-Vitiligo Area Scoring Index at week 24.
RESULTS
A total of 364 patients were treated in the dose-ranging period. Significant differences from placebo in percent change from baseline in Facial-Vitiligo Area Scoring Index were observed for the ritlecitinib 50 mg groups with (-21.2 vs 2.1; P < .001) or without (-18.5 vs 2.1; P < .001) a loading dose and ritlecitinib 30 mg group (-14.6 vs 2.1; P = .01). Accelerated improvement was observed after treatment with ritlecitinib 200/50 mg in the extension period (n = 187). No dose-dependent trends in treatment-emergent or serious adverse events were observed across the 48-week treatment.
LIMITATIONS
Patients with stable vitiligo only were excluded.
CONCLUSIONS
Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo.
Topics: Humans; Vitiligo; Double-Blind Method; Skin; Janus Kinases; Protein Kinase Inhibitors; Chronic Disease; Treatment Outcome
PubMed: 36370907
DOI: 10.1016/j.jaad.2022.11.005 -
JAMA Dermatology Mar 2021Surgical interventions are a key part of the therapeutic arsenal, especially in refractory and stable vitiligo. Comparison of treatment outcomes between the different... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Surgical interventions are a key part of the therapeutic arsenal, especially in refractory and stable vitiligo. Comparison of treatment outcomes between the different surgical procedures and their respective adverse effects has not been adequately studied.
OBJECTIVE
To investigate the reported treatment response following different surgical modalities in patients with vitiligo.
DATA SOURCES
A comprehensive search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases from the date of database inception to April 18, 2020, was conducted. The key search terms used were vitiligo, surgery, autologous, transplantation, punch, suction blister, and graft.
STUDY SELECTION
Of 1365 studies initially identified, the full texts of 358 articles were assessed for eligibility. A total of 117 studies were identified in which punch grafting (n = 19), thin skin grafting (n = 10), suction blister grafting (n = 29), noncultured epidermal cell suspension (n = 45), follicular cell suspension (n = 9), and cultured epidermal cell suspension (n = 17) were used.
DATA EXTRACTION AND SYNTHESIS
Three reviewers independently extracted data on study design, patients, intervention characteristics, and outcomes. Random effects meta-analyses using generic inverse-variance weighting were performed.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the rates of greater than 90%, 75%, and 50% repigmentation response. These rates were calculated by dividing the number of participants in an individual study who showed the corresponding repigmentation by the total number of participants who completed the study. The secondary outcomes were the factors associated with treatment response to the surgical intervention.
RESULTS
Among the 117 unique studies and 8776 unique patients included in the analysis, rate of repigmentation of greater than 90% for surgical interventions was 52.69% (95% CI, 46.87%-58.50%) and 45.76% (95% CI, 30.67%-60.85%) for punch grafting, 72.08% (95% CI, 54.26%-89.89%) for thin skin grafting, 61.68% (95% CI, 47.44%-75.92%) for suction blister grafting, 47.51% (95% CI, 37.00%-58.03%) for noncultured epidermal cell suspension, 36.24% (95% CI, 18.92%-53.57%) for noncultured follicular cell suspension, and 56.82% (95% CI, 48.93%-64.71%) for cultured epidermal cell suspension. The rate of repigmentation of greater than 50% after any surgical intervention was 81.01% (95% CI, 78.18%-83.84%). In meta-regression analyses, the treatment response was associated with patient age (estimated slope, -1.1418), subtype of vitiligo (estimated slope, 0.3047), and anatomical sites (estimated slope, -0.4050).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that surgical intervention can be an effective option for refractory stable vitiligo. An appropriate procedure should be recommended based on patient age, site and size of the lesion, and costs.
Topics: Age Factors; Blister; Epidermal Cells; Humans; Skin Transplantation; Treatment Outcome; Vitiligo
PubMed: 33595599
DOI: 10.1001/jamadermatol.2020.5756 -
American Journal of Clinical Dermatology Nov 2021Patients with vitiligo experience reduced quality of life.
BACKGROUND
Patients with vitiligo experience reduced quality of life.
OBJECTIVE
To comprehensively describe the available evidence for psychosocial burden in vitiligo.
METHODS
A systematic review of observational studies and clinical trials identified using PubMed, EMBASE, Scopus, and the Cochrane databases was performed through 1 March, 2021, to assess psychosocial comorbidities in vitiligo. Two independent reviewers performed an assessment of articles and extracted data for qualitative synthesis.
RESULTS
Included studies (N = 168) were published between 1979 and 1 March, 2021; 72.6% were published since 2010. Disorders including or related to depression (41 studies, 0.1-62.3%) and anxiety (20 studies, 1.9-67.9%) were the most commonly reported. The most prevalent psychosocial comorbidities were feelings of stigmatization (eight studies, 17.3-100%), adjustment disorders (12 studies, 4-93.9%), sleep disturbance (seven studies, 4.6-89.0%), relationship difficulties including sexual dysfunction (ten studies, 2.0-81.8%), and avoidance or restriction behavior (12.5-76%). The prevalence of most psychosocial comorbidities was significantly higher vs healthy individuals. Factors associated with a significantly higher burden included female sex, visible or genital lesions, age < 30 years (particularly adolescents), and greater body surface area involvement, among others. The most commonly reported patient coping strategy was lesion concealment.
LIMITATIONS
Available studies were heterogeneous and often had limited details; additionally, publication bias is possible.
CONCLUSIONS
The results of this systematic review show that vitiligo greatly affects psychosocial well-being. The extent of psychosocial comorbidities supports the use of multidisciplinary treatment strategies and education to address the vitiligo-associated burden of disease.
PROTOCOL REGISTRATION
PROSPERO (CRD42020162223).
Topics: Adaptation, Psychological; Adjustment Disorders; Age Factors; Body Surface Area; Clinical Trials as Topic; Comorbidity; Female; Humans; Male; Observational Studies as Topic; Personality Disorders; Prevalence; Quality of Life; Risk Factors; Severity of Illness Index; Social Stigma; Vitiligo
PubMed: 34554406
DOI: 10.1007/s40257-021-00631-6 -
Ugeskrift For Laeger Jan 2023Vitiligo is an autoimmune disease of the skin characterized by melanocyte loss resulting in white patches, but there is also a well-known association of vitiligo-like...
Vitiligo is an autoimmune disease of the skin characterized by melanocyte loss resulting in white patches, but there is also a well-known association of vitiligo-like depigmentation and melanoma. This is a case report of a 67-year-old male with late onset of vitiligo, with a history of melanoma, who was referred to a plastic surgery department 3,5 years after the onset of vitiligo and was now diagnosed with disseminated malignant melanoma. The aim of this study is to raise awareness that onset of vitiligo, especially in patients with higher age and previously melanoma history, could represent undiagnosed primary or recurrent melanoma.
Topics: Male; Humans; Aged; Vitiligo; Melanoma; Skin Neoplasms; Skin; Melanoma, Cutaneous Malignant
PubMed: 36636935
DOI: No ID Found -
Indian Journal of Dermatology,... 2016Targeted phototherapy is a new form of phototherapy which has many advantages and disadvantages over conventional phototherapy. This article reviews the different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Targeted phototherapy is a new form of phototherapy which has many advantages and disadvantages over conventional phototherapy. This article reviews the different technologies and outlines recommendations based on current evidence.
METHODS
A literature search was performed on targeted phototherapy to collect data. Relevant literature published till March 2014 was obtained from PubMed, EMBASE, and the Cochrane Library. Keywords like "targeted phototherapy", "excimer laser", "excimer lamp", "Nonchromatic ultraviolet light", "vitiligo", and "psoriasis", were used for literature search. All systematic reviews, meta-analysis, national guidelines, randomized controlled trials (RCT), prospective open label studies and retrospective case series in English were reviewed.
RESULTS
Three hundred and forty studies were evaluated, 24 of which fulfilled the criteria for inclusion in the guidelines.
CONCLUSIONS AND RECOMMENDATIONS
All forms of targeted phototherapy are useful in vitiligo. Good responses were seen in localized involvement, resistant lesions and in children in whom their use is more accepted and convenient (Level of evidence 2+, Grade of recommendation B). Similarly it is useful in psoriasis, either alone or in combination with drugs, even in resistant forms such as palmoplantar psoriasis. In view of expense and practical application, their use is limited to resistant lesions and localized disease. (Level of evidence 2+, Grade of recommendation B). But in other conditions there is no convincing evidence for its use. (Level of evidence 3+, Grade of recommendation C).
Topics: Female; Humans; Low-Level Light Therapy; Male; Phototherapy; Practice Guidelines as Topic; Prognosis; Prospective Studies; Psoriasis; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 26728802
DOI: 10.4103/0378-6323.172902 -
Skin Therapy Letter May 2019Vitiligo is an acquired, autoimmune disease characterized by depigmented macules and patches on the skin, which occur secondary to melanocyte destruction. Available... (Review)
Review
Vitiligo is an acquired, autoimmune disease characterized by depigmented macules and patches on the skin, which occur secondary to melanocyte destruction. Available therapeutic options are broadly divided into medical, surgical and phototherapy, though treatment of vitiligo can be challenging. Early diagnosis and management can maximize treatment efficacy. The purpose of this discussion is to review updates in the management of vitiligo, including existing and emerging therapies.
Topics: Humans; Vitiligo
PubMed: 31095346
DOI: No ID Found -
International Journal of Molecular... Nov 2019Cutaneous melanoma represents the most aggressive form of skin cancer, whereas vitiligo is an autoimmune disorder that leads to progressive destruction of skin... (Review)
Review
Cutaneous melanoma represents the most aggressive form of skin cancer, whereas vitiligo is an autoimmune disorder that leads to progressive destruction of skin melanocytes. However, vitiligo has been associated with cutaneous melanoma since the 1970s. Most of the antigens recognized by the immune system are expressed by both melanoma cells and normal melanocytes, explaining why the autoimmune response against melanocytes that led to vitiligo could be also present in melanoma patients. Leukoderma has been also observed as a side effect of melanoma immunotherapy and has always been associated with a favorable prognosis. In this review, we discuss several characteristics of the immune system responses shared by melanoma and vitiligo patients, as well as the significance of occurrence of leukoderma during immunotherapy, with special attention to check-point inhibitors.
Topics: Autoimmune Diseases; Humans; Immunotherapy; Melanoma; Prognosis; Vitiligo
PubMed: 31731645
DOI: 10.3390/ijms20225731 -
Frontiers in Immunology 2020The autoimmune basis of segmental vitiligo (SV) has only recently been recognized. Systemic autoimmune diseases are less frequently associated compared to non-segmental... (Review)
Review
The autoimmune basis of segmental vitiligo (SV) has only recently been recognized. Systemic autoimmune diseases are less frequently associated compared to non-segmental vitiligo (NSV), but localized skin disorders - in particular linear morphea - have been repeatedly observed in patients with SV. The inflammatory response is documented on a clinical level with cases displaying erythematous borders or a hypochromic stage, on a histopathological level with predominantly CD8 lymphocytes migrating toward the basal layer and by flow cytometry demonstrating the antimelanocyte specificity of these cytotoxic T cells. The increased risk for halo naevi and NSV in these patients further underline the immune-mediated mechanisms of SV. Nonetheless, the localized and unique distribution pattern points to somatic mosaicism. This places SV in a category of similar diseases such as lichen striatus, blaschkitis, linear lupus erythematosus, and linear scleroderma where an immune reaction against genetically mutated skin cells is believed to be the underlying cause. All these disorders are characterized by a young age of onset, a temporary disease activity with spontaneous resolution, limited response to treatment, and often long-term sequelae. Although challenging, genetic research proving this genetic mosaicism could offer crucial insights into the pathogenesis of both segmental and non-segmental vitiligo.
Topics: Animals; Autoimmunity; Humans; Mosaicism; Vitiligo
PubMed: 33193342
DOI: 10.3389/fimmu.2020.568447