The enigma and challenges of vitiligo pathophysiology and treatment

Abdel‐Malek, Zalfa; Jordan, Christian S.; Ho, Tina; Upadhyay, Parth Rajendrakumar; Fleischer, Alan B.; Hamzavi, Iltefat

doi:10.1111/pcmr.12878

Cited by 64 publications

(66 citation statements)

References 115 publications

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“…Vitiligo is considered to be an autoimmune disease because cytokines such as (IFN)-γ, IL-1, IL-6, IL-8, and IL-10 are overexpressed in lesions, and activated CD8 + T lymphocytes, TH17, and other immune cells are significantly aggregated in the lesion area (16)(17)(18)(19). However, some researchers have suggested that autoimmunity may be secondary to high oxidative stress in vitiligo skin, leading to inherent defects of melanocytes and changes in its microenvironment (4). At present, the unified view is that the inherent defect of melanocytes is an early event in vitiligo, and the gradual disappearance of epidermal melanocytes leads to skin depigmentation of vitiligo lesions.…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of vitiligo manifests as oxidative stress, infiltration of inflammatory mediators, melanocyte loss, and autoimmune responses (3). It is caused due to the complex interaction among environmental and genetic factors that eventually leads to melanocyte dysfunction (4). However, the inherent defect in melanocytes is an early event in vitiligo; the gradual disappearance of melanocytes may involve multiple processes, including immune system attack, cell degeneration, and exfoliation among others (1).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

Chen

et al. 2021

Front. Immunol.

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Vitiligo is an pigmentation disorder caused by a variety of pathogenic factors; its main pathophysiological conditions include oxidative stress, immune activation, and genetic background. Additionally, DNA methylation is often associated with the pathogenesis of vitiligo; however, the underlying mechanism remains unknown. In the present study, we used the Human Methylation 850K BeadChip platform to detect DNA methylation changes in the vitiligo melanocytes. We then integrated the results with the transcriptome data of vitiligo melanocytes and lesions to analyse the correlation between differentially methylated levels and differentially expressed genes. The results showed that there was a significant negative correlation between methylation levels and differentially expressed genes. Subsequently, we enriched GO and KEGG based on methylated differentially expressed genes (MDEGs) using R package ClusterProfiler, and the results were closely related to the pathogenesis of vitiligo. In addition, we also constructed a PPI network of MDEGs and excavated three important functional epigenetic modules, involving a total of 12 (BCL2L1, CDK1, ECT2, HELLS, HSP90AA1, KIF23, MC1R, MLANA, PBK, PTGS2, SOX10, and TYRP1) genes. These genes affect melanocyte melanogenesis, cellular oxidative stress and other important biological processes. Our comprehensive analysis results support the significant contribution of the status of DNA methylation modification to vitiligo, which will help us to better understand the molecular mechanism of vitiligo and explore new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

Chen

et al. 2021

Front. Immunol.

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“…1 It is the most common depigmenting skin disorder which affects approximately 0.5-1% of the population across the world. 2 Vitiligo has a serious negative influence on patients' self-esteem and confidence; it often occurs at exposed sites such as the face, 1 which seriously affects patients' quality of life.…”

Section: Introductionmentioning

confidence: 99%

“…Melanin metabolic abnormalities play a crucial role in the development of vitiligo. 2,3 Abnormal melanin loss leads to vitiligo associated pathological processes. 4 Therefore, therapies that promote melanogenesis and melanocyte proliferation have been considered as the most promising treatment methods for vitiligo.…”

Section: Introductionmentioning

confidence: 99%

<p>308-nm Excimer Laser Plus Platelet-Rich Plasma for Treatment of Stable Vitiligo: A Prospective, Randomized Case–Control Study</p>

Deng¹,

Li²,

Yang³

2020

CCID

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Purpose: 308-nm excimer laser has a confirmed treatment effect on vitiligo. Platelet-rich plasma (PRP) is an autologous preparation which contains a variety of growth factors. The effect of 308-nm excimer laser combined with PRP on vitiligo has been rarely reported. This study investigated the effect of PRP combined with 308-nm excimer laser on stable vitiligo. Patients and Methods: A total of 60 patients with localized stable vitiligo who received treatment at Beijing Friendship Hospital and Xi'an Vitiligo Specialist Hospital between May 2019 and January 2020 were consecutively enrolled. They were equally randomized into three groups according to different treatment methods: intradermal PRP injection (group I), 308-nm excimer laser alone (group II), and 308-nm excimer laser plus PRP injection (group III). All treatments lasted for 3 months. At 3 months after treatment, clinical assessments were performed in terms of the visual analogue scale (VAS) score, repigmentation response and side effects. Results: The VAS scores showed significant differences among the three groups (P<0.001), with the highest score in group III, followed by group II and then group I. Repigmentation responses also showed significant differences among the groups (P<0.001), and the best effect was observed in group III. No side effects were reported in any of the groups. Conclusion: The effect of PRP combined with 308-nm excimer laser on stable vitiligo is significantly better than that of PRP and 308-nm excimer laser alone. It is safe and satisfactorily tolerant.

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“…Vitiligo is a pigmentary disorder that results in depigmented patches due to melanocyte loss (Abdel‐Malek et al., 2020). There are two forms of vitiligo: segmental and non‐segmental vitiligo.…”

Section: The Upr/isr In Disease Pathologymentioning

confidence: 99%

The unfolded protein and integrated stress response in melanoma and vitiligo

Manga

Choudhury

2020

Pigment Cell Melanoma Res

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Epidermal melanocytes are constantly exposed to environmental stressors such as ultraviolet light (UV) and chemotoxins. Several evolutionarily conversed survival mechanisms are deployed to ensure melanocyte recovery after damage including the unfolded protein response (UPR) and integrated stress response (ISR). The UPR/ISR promote restoration of homeostasis, by modulating transcription and translation as well as activating nuclear factor erythroid 2‐related factor 2 (NRF2)‐mediated antioxidant activity. If repair fails, the UPR/ISR either stimulate cell death, or adaptation that can lead to survival of damaged cells and promote disease. For example, the UPR/ISR may support melanomagenesis by allowing UV‐damaged, mutated cells to survive and adapt to a hostile tumor microenvironment that subjects cells to hypoxia, nutrient deprivation, and sub‐optimal pH. The UPR and ISR can also promote transcriptional changes that support tumor growth and/or metastasis. Furthermore, these pathways may also underlie acquisition of chemoresistance and modulation of protein expression that alters the efficacy of immunotherapies. UPR activation has also been implicated in the pathogenesis of vitiligo and may promote increased expression of chemokines such as interleukin 6 and interleukin 8 that trigger an autoimmune response against melanocytes. We herein review the potential roles of the UPR/ISR in the etiology of melanoma and vitiligo.

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The enigma and challenges of vitiligo pathophysiology and treatment

Cited by 64 publications

References 115 publications

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

<p>308-nm Excimer Laser Plus Platelet-Rich Plasma for Treatment of Stable Vitiligo: A Prospective, Randomized Case–Control Study</p>

The unfolded protein and integrated stress response in melanoma and vitiligo

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