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Dermatologic Clinics Apr 2017The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte... (Review)
Review
The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte destruction. The goal of treatment is to not only halt disease progression but also promote repigmentation through melanocyte regeneration, proliferation, and migration. Treatment strategies that address all aspects of disease pathogenesis and repigmentation are likely to have greatest efficacy, a strategy that may require combination therapies. Current treatments generally involve nontargeted suppression of autoimmunity, whereas emerging treatments are likely to use a more targeted approach based on in-depth understanding of disease pathogenesis, which may provide higher efficacy with a good safety profile.
Topics: Adaptive Immunity; Antioxidants; Autoimmunity; Humans; Immunity, Innate; Immunosuppressive Agents; Melanocytes; Oxidative Stress; Phototherapy; Regeneration; Self Tolerance; T-Lymphocytes, Cytotoxic; Vitiligo
PubMed: 28317534
DOI: 10.1016/j.det.2016.11.014 -
The Journal of Allergy and Clinical... Jan 2024Vitiligo is an autoimmune depigmenting disorder with no effective and safe treatments. Its pathogenesis is not fully elucidated. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vitiligo is an autoimmune depigmenting disorder with no effective and safe treatments. Its pathogenesis is not fully elucidated.
OBJECTIVE
This substudy of a randomized, double-blind, placebo-controlled phase 2b trial (NCT03715829) evaluated effects of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on skin and blood biomarkers in participants with nonsegmental vitiligo (NSV).
METHODS
Sixty-five adults with NSV participated in the substudy and received daily treatment for 24 weeks with placebo (n = 14) or ritlecitinib with or without a 4-week loading dose: 200 (loading dose)/50 mg (n = 13), 100/50 mg (n = 12), 50 mg (n = 11), 30 mg (n = 8), or 10 mg (n = 6). Skin (lesional and nonlesional) biopsy samples were obtained at baseline and at 4 and 24 weeks. Changes from baseline to weeks 4 and 24 in skin and blood molecular and cellular biomarkers were evaluated by RNA sequencing, quantitative real-time PCR, proteomic analysis, and flow cytometry.
RESULTS
Ritlecitinib-treated groups showed downregulation of immune biomarkers and upregulation of melanocyte-related markers at weeks 4 and 24 compared to baseline and/or placebo. Significant reductions were seen in CD3/CD8 T-cell infiltrates, with significant increases in melanocyte markers (tyrosinase; Melan-A) in NSV lesions in the 50 mg ritlecitinib groups (both P < .05). There was significant, dose-dependent downregulation in T-cell activation, NK, cytotoxic, and regulatory markers in lesional skin (IL-2, IL2-RA, IL-15, CCR7, CD5, CRTAM, NCR1, XCL1, KIR3DL1, FASLG, KLRD; P < .05). T1 and T2 markers were also downregulated in lesional skin and blood in a dose-dependent manner (P < .05). Changes in immune biomarkers correlated with clinical response.
CONCLUSIONS
Ritlecitinib significantly downregulated proinflammatory biomarkers and increased melanocyte products in skin and blood of participants with NSV, suggesting its potential in treatment. Ritlecitinib-mediated changes positively correlated with clinical response.
Topics: Adult; Humans; Vitiligo; Proteomics; Melanocytes; Skin; Biomarkers; Janus Kinase 3
PubMed: 37777018
DOI: 10.1016/j.jaci.2023.09.021 -
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 -
Skin Therapy Letter May 2023As systemic administration of Janus kinase-inhibitors is associated with safety concerns, local alternatives, such as topical ruxolitinib, have been developed. This... (Review)
Review
As systemic administration of Janus kinase-inhibitors is associated with safety concerns, local alternatives, such as topical ruxolitinib, have been developed. This review summarizes utilization of topical ruxolitinib in dermatology. A literature search was performed of studies reporting topical use of ruxolitinib in dermatologic conditions. Twenty-four articles were included, representing 2618 patients. Results show improvement with topical ruxolitinib formulations in atopic dermatitis, vitiligo, psoriasis, and lichen planus. Results are conflicting in alopecia areata. Minimal bioavailability and low rates of mild-to-moderate treatment-related adverse events support a favorable safety profile and higher tolerability of topical ruxolitinib compared to oral Janus kinase-inhibitors.
Topics: Humans; Dermatology; Psoriasis; Janus Kinase Inhibitors; Vitiligo; Janus Kinases
PubMed: 37339609
DOI: No ID Found -
Frontiers in Immunology 2021Vitiligo is an acquired multifactorial disease that affects melanocytes and results in skin depigmentation. In this review, we examine the role of cells stress and... (Review)
Review
Vitiligo is an acquired multifactorial disease that affects melanocytes and results in skin depigmentation. In this review, we examine the role of cells stress and self-reactive T cells responses. Given the canonical and non-canonical functions of NKG2D, such as authenticating stressed target and enhance TCR signaling, we examine how melanocyte stress leads to the expression of ligands that are recognized by the activating receptor NKG2D, and how its signaling results in the turning of T cells against self (melanocyte suicide by proxy). We also discuss how this initiation phase is followed by T cell perpetuation, as NKG2D signaling results in self-sustained long-lasting T cells, with improved cytolytic properties.
Topics: Animals; Autoimmunity; CD8-Positive T-Lymphocytes; Cellular Microenvironment; Cytotoxicity, Immunologic; Humans; Melanocytes; NK Cell Lectin-Like Receptor Subfamily K; Oxidative Stress; Signal Transduction; Skin; Skin Pigmentation; Vitiligo
PubMed: 33717132
DOI: 10.3389/fimmu.2021.624131 -
Actas Dermo-sifiliograficas Mar 2024
Topics: Humans; Vitiligo; Hypopigmentation
PubMed: 38184103
DOI: 10.1016/j.ad.2024.01.001 -
Autoimmunity Reviews Apr 2016IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have... (Review)
Review
IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments.
Topics: Animals; Autoimmune Diseases; Humans; Interleukin-17; Melanocytes; Th17 Cells; Ultraviolet Therapy; Vitiligo
PubMed: 26804758
DOI: 10.1016/j.autrev.2016.01.004 -
International Journal of Molecular... Apr 2024Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment... (Review)
Review
Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.
Topics: Alopecia Areata; Humans; Vitiligo; Animals; Immune Privilege; Cytokines
PubMed: 38673994
DOI: 10.3390/ijms25084409 -
Indian Journal of Dermatology,... 2014
Topics: Dermoscopy; Humans; Vitiligo
PubMed: 25382503
DOI: 10.4103/0378-6323.144141 -
Molecular Diagnosis & Therapy Nov 2023Vitiligo is a chronic skin disorder characterised by the loss of melanocytes and subsequent skin depigmentation. Although many theories have been proposed in the... (Review)
Review
Vitiligo is a chronic skin disorder characterised by the loss of melanocytes and subsequent skin depigmentation. Although many theories have been proposed in the literature, none alone explains the pathogenesis of vitiligo. Oxidative stress has been identified as a potential factor in the pathogenesis of vitiligo. A growing body of evidence suggests that antioxidant therapies may offer a promising approach to managing this condition. This review summarises the potential mechanisms of oxidative stress and the types of melanocyte death in vitiligo. We also provide a brief overview of the most commonly studied antioxidants. Melanocytes in vitiligo are thought to be damaged by an accumulation of reactive oxygen species to destroy the structural and functional integrity of their DNA, lipids, and proteins. Various causes, including exogenous and endogenous stress factors, an imbalance between prooxidants and antioxidants, disruption of antioxidant pathways, and gene polymorphisms, lead to the overproduction of reactive oxygen species. Although necroptosis, pyroptosis, ferroptosis, and oxeiptosis are newer types of cell death that may contribute to the pathophysiology of vitiligo, apoptosis remains the most studied cell death mechanism in vitiligo. According to studies, vitamin E helps to treat lipid peroxidation of the skin caused by psoralen ultra-violet A treatment. In addition, Polypodium leucotomos increased the efficacy of psoralen ultra-violet A or narrow-band ultraviolet B therapy. Our review provides valuable insights into the potential role of oxidative stress in pathogenesis and antioxidant-based supporting therapies in treating vitiligo, offering a promising avenue for further research and the development of effective treatment strategies.
Topics: Humans; Antioxidants; Vitiligo; Reactive Oxygen Species; Oxidative Stress; Furocoumarins
PubMed: 37737953
DOI: 10.1007/s40291-023-00672-z