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Dermatology (Basel, Switzerland) 2020Vitiligo, a common depigmenting skin disorder, has an estimated prevalence of 0.5-2% of the population worldwide. The disease is characterized by the selective loss of... (Review)
Review
Vitiligo, a common depigmenting skin disorder, has an estimated prevalence of 0.5-2% of the population worldwide. The disease is characterized by the selective loss of melanocytes which results in typical nonscaly, chalky-white macules. In recent years, considerable progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Vitiligo is often dismissed as a cosmetic problem, although its effects can be psychologically devastating, often with a considerable burden on daily life. In 2011, an international consensus classified segmental vitiligo separately from all other forms of vitiligo, and the term vitiligo was defined to designate all forms of nonsegmental vitiligo. This review summarizes the current knowledge on vitiligo and attempts to give an overview of the future in vitiligo treatment.
Topics: Humans; Oxidative Stress; Quality of Life; Vitiligo
PubMed: 32155629
DOI: 10.1159/000506103 -
Annual Review of Immunology Apr 2020Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent... (Review)
Review
Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8 T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop. Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit. Here, we discuss basic, translational, and clinical research studies that provide insight into the pathogenesis of vitiligo, and how this insight has been utilized to create new targeted treatment strategies.
Topics: Animals; Autoimmunity; Biomarkers; Cytokines; Disease Management; Disease Susceptibility; Humans; Immunologic Memory; Vitiligo
PubMed: 32017656
DOI: 10.1146/annurev-immunol-100919-023531 -
Frontiers in Immunology 2022Vitiligo, whose treatment remains a serious concern and challenge, is an autoimmune skin disease characterized by patches of depigmentation. The increasing application... (Review)
Review
Vitiligo, whose treatment remains a serious concern and challenge, is an autoimmune skin disease characterized by patches of depigmentation. The increasing application of molecular-targeted therapy in skin diseases, such as psoriasis and systemic lupus erythematosus, has dramatically improved their condition. Besides, there is a favorable effect of repigmentation in the treatment of the above diseases combined with vitiligo, implying that molecular-targeted therapy may also have utility in vitiligo treatment. Recently, the role of cytokine and signaling pathways in vitiligo pathogenesis are increasingly recognized. Thus, investigations are underway targeting the molecules described above. In this paper, we present a synopsis of current practices in vitiligo treatment and introduce the improvement in identifying new molecular targets and applying molecular-targeted therapies, including those under development in vitiligo treatment, providing valuable insight into establishing further precision medicine for vitiligo patients.
Topics: Autoimmune Diseases; Cytokines; Humans; Psoriasis; Vitiligo
PubMed: 36119071
DOI: 10.3389/fimmu.2022.986918 -
Frontiers in Immunology 2021Vitiligo is a multifactorial reversible skin disorder characterized by distinct white patches that result from melanocyte destruction. Activated CXCR3 CD8 T cells... (Review)
Review
Vitiligo is a multifactorial reversible skin disorder characterized by distinct white patches that result from melanocyte destruction. Activated CXCR3 CD8 T cells promote melanocyte detachment and apoptosis through interferon-gamma (IFN-γ secretion and chemokines secreted by keratinocytes through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-1 signaling pathway results in further recruitment of CXCR3 CD8 T cells and the formation of a positive-feedback loop. JAK inhibitors target the JAK/STAT pathway and are now approved to treat many immune-related diseases. In the treatment of vitiligo, JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, are effective, supporting the implication of the IFN-γ-chemokine signaling axis in the pathogenesis of vitiligo. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.
Topics: Biomarkers; Cytokines; Disease Management; Disease Susceptibility; Humans; Interferon-gamma; Janus Kinase Inhibitors; Janus Kinases; Molecular Targeted Therapy; STAT1 Transcription Factor; Signal Transduction; Treatment Outcome; Vitiligo
PubMed: 34868078
DOI: 10.3389/fimmu.2021.790125 -
The Journal of Dermatology Mar 2021Vitiligo is the most common depigmenting disorder affecting 0.1%-2% of the population worldwide. The characteristic white patches result from the selective loss of... (Review)
Review
Vitiligo is the most common depigmenting disorder affecting 0.1%-2% of the population worldwide. The characteristic white patches result from the selective loss of melanocytes. Sustained recent efforts have resulted in a detailed understanding of the genetic architecture of vitiligo. About 80% of vitiligo risk is attributable to genetic factors; and the rest (20%) is attributable to the environment. Over the past decade, substantial progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Melanocytes from patients with vitiligo are more susceptible to oxidative stress which begets the release of exosomes and inflammatory cytokines that will lead to activation of the innate immune response and subsequently to adaptive immune response through activation of autoreactive cytotoxic CD8+ T cells. These produce interferon-γ (IFN-γ) which promotes disease progression through IFN-γ-induced chemokine secretion from surrounding keratinocytes to further recruit T cells to the skin through a positive feedback loop. CD8 tissue-resident memory T cells are in turn responsible for long-term maintenance and potential relapse of vitiligo in human patients through cytokine-mediated recruitment of T cells from the circulation. This review summarizes the current knowledge on vitiligo and attempt to give an overview of the future in vitiligo treatment.
Topics: Humans; Interferon-gamma; Keratinocytes; Melanocytes; Skin; Vitiligo
PubMed: 33404102
DOI: 10.1111/1346-8138.15743 -
Frontiers in Immunology 2021Vitiligo is a disease of the skin characterized by the appearance of white spots. Significant progress has been made in understanding vitiligo pathogenesis over the past... (Review)
Review
Vitiligo is a disease of the skin characterized by the appearance of white spots. Significant progress has been made in understanding vitiligo pathogenesis over the past 30 years, but only through perseverance, collaboration, and open-minded discussion. Early hypotheses considered roles for innervation, microvascular anomalies, oxidative stress, defects in melanocyte adhesion, autoimmunity, somatic mosaicism, and genetics. Because theories about pathogenesis drive experimental design, focus, and even therapeutic approach, it is important to consider their impact on our current understanding about vitiligo. Animal models allow researchers to perform mechanistic studies, and the development of improved patient sample collection methods provides a platform for translational studies in vitiligo that can also be applied to understand other autoimmune diseases that are more difficult to study in human samples. Here we discuss the history of vitiligo translational research, recent advances, and their implications for new treatment approaches.
Topics: Animals; Autoimmunity; Dermatologic Agents; Disease Models, Animal; Genetic Testing; Humans; Melanocytes; Oxidative Stress; Phenotype; Skin; Skin Pigmentation; Translational Research, Biomedical; Vitiligo
PubMed: 33737930
DOI: 10.3389/fimmu.2021.624517 -
The Journal of Investigative Dermatology Feb 2021Vitiligo is a complex disease in which autoimmune destruction of epidermal melanocytes results in patches of depigmented white skin. Vitiligo has an estimated prevalence... (Review)
Review
Vitiligo is a complex disease in which autoimmune destruction of epidermal melanocytes results in patches of depigmented white skin. Vitiligo has an estimated prevalence of about 0.2-2% in different populations and approximately 0.4% in the European-derived white (EUR) population. The fraction of disease risk attributable to genetic variation, termed heritability, is high, with estimates from family studies in EUR of 0.75-0.83 and from SNP based studies estimated at 0.78. About 70% of genetic risk comes from common genetic variants and about 30% from rare genetic variants. Through candidate gene, genomewide linkage, and genomewide association studies, over 50 vitiligo susceptibility loci have been discovered. These have been combined into a vitiligo polygenic risk score, which has allowed various aspects of vitiligo genetic architecture in the EUR population to be better understood. Vitiligo has thus proved to be a particularly tractable model for investigation of complex disease genetic architecture. Here, we summarize progress to date including dissection of heritability, discovery of vitiligo susceptibility loci through candidate gene, genomewide linkage, and genomewide association studies, relationships to other autoimmune diseases, polygenic architecture of vitiligo risk, vitiligo triggering, and disease onset, and provide suggestions for future directions.
Topics: Age of Onset; Autoimmune Diseases; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Vitiligo
PubMed: 32778407
DOI: 10.1016/j.jid.2020.06.004 -
JAMA Dermatology Sep 2021
Topics: Humans; Hypopigmentation; Vitiligo
PubMed: 34287629
DOI: 10.1001/jamadermatol.2021.1688 -
Expert Opinion on Emerging Drugs Mar 2020: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to... (Review)
Review
: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments.: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localized vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy.: The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB.
Topics: Administration, Oral; Administration, Topical; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Cytokines; Dermatologic Agents; Humans; Janus Kinase Inhibitors; MAP Kinase Signaling System; Randomized Controlled Trials as Topic; Vitiligo
PubMed: 31958256
DOI: 10.1080/14728214.2020.1712358 -
PloS One 2020Vitiligo is an acquired depigmenting skin disease which is often accompanied by mental distress. There are numerous studies dedicated to local and global prevalence of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitiligo is an acquired depigmenting skin disease which is often accompanied by mental distress. There are numerous studies dedicated to local and global prevalence of depression in patients with vitiligo but anxiety has not been recognized as a major mental problem within named population. We aimed to evaluate the prevalence of anxiety among patients with vitiligo from different countries and to compare it with patients suffering from eczema, psoriasis, and acne.
METHODS
In November 2019, we conducted a systematic search for observational studies that examined the prevalence of anxiety in vitiligo patients. Fifteen studies comprising 1176 patients with vitiligo were included to our systematic review.
RESULTS
The general prevalence of anxiety among vitiligo patients was equal to 35.8%. Statistically significant difference in anxiety rates was found among female and male patients (47.32% vs 42.4%) (P = 0.03), but the clinical relevance of this issue remains arguable. In addition, the pooled odds ratio among vitiligo and non-vitiligo patients did not indicate a statistical significance among patients coming from different continents.
CONCLUSIONS
The pooled prevalence of anxiety among vitiligo patients worldwide was comparable to other severe skin disorders. This finding accentuates the necessity of anxiety awareness in management of patients with skin diseases.
Topics: Adult; Anxiety; Female; Humans; Male; Prevalence; Vitiligo
PubMed: 33170870
DOI: 10.1371/journal.pone.0241445