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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 -
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 -
Frontiers in Immunology 2022Vitiligo is a common depigmenting skin disorder characterized by the selective loss of melanocytes. Autoimmunity, genetic, environmental, and biochemical etiology have... (Review)
Review
Vitiligo is a common depigmenting skin disorder characterized by the selective loss of melanocytes. Autoimmunity, genetic, environmental, and biochemical etiology have been proposed in vitiligo pathogenesis. However, the exact molecular mechanisms of vitiligo development and progression are unclear, particularly for immunometabolism. Sporadic studies have suggested mitochondrial dysfunction, enhanced oxidative stress, and specific defects in other metabolic pathways can promote dysregulation of innate and adaptive immune responses in vitiligo. These abnormalities appear to be driven by genetic and epigenetic factors modulated by stochastic events. In addition, glucose and lipid abnormalities in metabolism have been associated with vitiligo. Specific skin cell populations are also involved in the critical role of dysregulation of metabolic pathways, including melanocytes, keratinocytes, and tissue-resident memory T cells in vitiligo pathogenesis. Novel therapeutic treatments are also raised based on the abnormalities of immunometabolism. This review summarizes the current knowledge on immunometabolism reprogramming in the pathogenesis of vitiligo and novel treatment options.
Topics: Humans; Vitiligo; Melanocytes; Oxidative Stress; Skin; Autoimmunity
PubMed: 36439174
DOI: 10.3389/fimmu.2022.1055958 -
Anais Brasileiros de Dermatologia 2022Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte... (Review)
Review
Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte adhesion to the epithelium, and immunity (innate and adaptive), which culminate in aggression against melanocytes. In vitiligo, melanocytes are more sensitive to oxidative damage, leading to the increased expression of proinflammatory proteins such as HSP70. The lower expression of epithelial adhesion molecules, such as DDR1 and E-cadherin, facilitates damage to melanocytes and exposure of antigens that favor autoimmunity. Activation of the type 1-IFN pathway perpetuates the direct action of CD8+ cells against melanocytes, facilitated by regulatory T-cell dysfunction. The identification of several genes involved in these processes sets the stage for disease development and maintenance. However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis.
Topics: Autoimmunity; Humans; Melanocytes; Oxidative Stress; Vitiligo
PubMed: 35643735
DOI: 10.1016/j.abd.2021.09.008 -
Medicinal Research Reviews Mar 2021Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation.... (Review)
Review
Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation. Genome-wide associated studies have identified single-nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background. Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, a minority of melanocyte demise, and melanocyte-specific antigens exposure. Of note, the self-responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo. The aberrantly heightened innate immunity, type-1-skewed T helper, and incompetent regulatory T cells tip the balance toward autoreaction and CD8 cytotoxic T lymphocytes finally execute the killing of melanocytes, possibly alarmed by resident memory T cells. In addition to the well-established apoptosis and necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, and necroptosis that are probably employed in melanocyte destruction. This review focuses on the various mechanisms of melanocytic death in vitiligo pathogenesis to demonstrate a panorama of that. We hope to provide new insights into vitiligo pathogenesis and treatment strategies by the review.
Topics: Apoptosis; CD8-Positive T-Lymphocytes; Humans; Melanocytes; Oxidative Stress; Vitiligo
PubMed: 33200838
DOI: 10.1002/med.21754 -
Anais Brasileiros de Dermatologia 2021Of all the therapeutic options available in Dermatology, few of them have the history, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1...
Of all the therapeutic options available in Dermatology, few of them have the history, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1 are currently the most common types of phototherapy used. Although psoriasis is the most frequent indication, it is used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma, and cutaneous sclerosis, among others. Before indicating phototherapy, a complete patient assessment should be performed. Possible contraindications should be actively searched for and it is essential to assess whether the patient can come to the treatment center at least twice a week. One of the main method limitations is the difficulty that patients have to attend the sessions. This therapy usually occurs in association with other treatments: topical or systemic medications. Maintaining the regular monitoring of the patient is essential to identify and treat possible adverse effects. Phototherapy is recognized for its benefits and should be considered whenever possible.
Topics: Humans; Phototherapy; Psoriasis; Skin Neoplasms; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 33849754
DOI: 10.1016/j.abd.2021.03.001 -
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 -
International Journal of Molecular... Mar 2023Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded,... (Review)
Review
Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.
Topics: Humans; Vitiligo; Hypopigmentation; Melanocytes; Skin; Oxidative Stress
PubMed: 36902341
DOI: 10.3390/ijms24054910 -
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