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1.
Arch Dermatol Res ; 316(7): 478, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023568

ABSTRACT

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.


Subject(s)
Janus Kinase 3 , Protein Kinase Inhibitors , Vitiligo , Humans , Vitiligo/drug therapy , Vitiligo/diagnosis , Vitiligo/immunology , Male , Female , Adult , Janus Kinase 3/antagonists & inhibitors , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Treatment Outcome , Chemokine CXCL9/blood , Chemokine CCL5/blood , Young Adult , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , B7-H1 Antigen/blood , Melanocytes/drug effects , Double-Blind Method , Skin Pigmentation/drug effects , Administration, Oral , Interferon-gamma
2.
Medicina (Kaunas) ; 60(7)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39064606

ABSTRACT

The Koebner phenomenon (KP), also known as the isomorphic response, describes the process by which new lesions that are clinically and histologically identical to a patient's existing skin disease develop following trauma. Many skin diseases exhibit this characteristic, with variations that include possible, questionable, and pseudo-Koebner reactions, with the latter category occurring due to infectious agents seeding at a trauma site. Laser application, a type of controlled skin injury used for improving cutaneous lesions and skin rejuvenation, is also considered a form of trauma. This raises the question of whether controlled thermal injury can be regarded as a type of mechanical trauma capable of producing Koebner-related reactions. We conducted a literature review of cases or studies to identify laser-induced dermatoses that correspond to Koebner-related or pathergy reaction categories. As a whole, we identified nine case reports on true KPs, two cases on possible KPs, seventeen cases on laser-induced questionable KPs comprising cases of vasculitis, eczema or Meyerson reactions, and eruptive squamous atypia cases (ESA) as well as two pseudo-Koebner cases involving wart occurrences at laser application sites. Laser-induced Koebner reactions highlight several aspects of the KP. Firstly, the type of mechanical damage influences disease promotion, as different lasers are associated with different KPs. For example, hair removal lasers are linked with true and questionable KPs such as vasculitis while resurfacing lasers were found to be more connected with ESA occurrence. Secondly, the laser target is significant, with vascular laser application for port-wine stains tending to result in eczematous reactions, while hair follicle destruction can frequently lead to true KPs. Thirdly, the number of sessions matters; true KPs and eruptive squamous atypia questionable KPs typically appear after one to two sessions, whereas eczematous reactions require more sessions (at least four). Additionally, skin phototype is crucial, with darker phototypes showing a higher KP frequency as laser treatment for hypertrichosis relies on melanin absorption in the hair bulge or bulb for follicle destruction, as chromophore competes with the abundant melanin in the epidermis. Further research with larger-scale studies into trauma-specific Koebner reactions is vital for refining treatment protocols, minimizing post-laser adverse effects, and improving dermatological care outcomes.


Subject(s)
Lasers , Humans , Lasers/adverse effects , Skin Diseases/etiology , Laser Therapy/methods , Laser Therapy/adverse effects , Skin/radiation effects , Skin/injuries , Skin/pathology , Female
3.
BMC Genom Data ; 25(1): 72, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060965

ABSTRACT

BACKGROUND: Vitiligo is an auto-immune progressive depigmentation disorder of the skin due to loss of melanocytes. Genetic risk is one of the important factors for development of vitiligo. Preponderance of vitiligo in certain ethnicities is known which can be analysed by understanding the distribution of allele frequencies across normal populations. Earlier GWAS identified 108 risk alleles for vitiligo in Europeans and East Asians. In this study, 64 of these risk alleles were used for analysing their enrichment and depletion across populations (1000 Genomes Project and IndiGen) with reference to 1000 Genomes dataset. Genetic risk scores were calculated and Fisher's exact test was performed to understand statistical significance of their variation in each population with respect to 1000 Genomes dataset as reference. In addition to SNPs reported in GWAS, significant variation in allele frequencies of 1079 vitiligo-related genes were also analysed. Two-tailed Chi-square test and Bonferroni's multiple adjustment values along with fixation index (≥ 0.5) and minimum allele frequency (≥ 0.05) were calculated and used to prioritise the variants based on pairwise comparison across populations. RESULTS: Risk alleles rs1043101 and rs10768122 belong to 3 prime UTR of glutamate receptor gene SLC1A2 are found to be highly enriched in the South Asian population when compared with the 'global normal' population. Intron variant rs4766578 (ATXN2) was found to be deleted in SAS, EAS and AFR and enriched in EUR and AMR1. This risk allele is found to be under positive selection in SAS, AMR1 and EUR. From the ancillary vitiligo gene list, nonsynonymous variant rs16891982 was found to be enriched in the European and the Admixed American populations and depleted in all others. rs2279238 and rs11039155 belonging to the LXR-α gene involved in regulation of metalloproteinase 2 and 9 (melanocyte precursors) were found to be associated with vitiligo in the North Indian population (in earlier study). CONCLUSION: The differential enrichment/depletion profile of the risk alleles provides insight into the underlying inter-population variations. This would provide clues towards prioritisation of SNPs associated with vitiligo thereby elucidating its preponderance in different ethnic groups.


Subject(s)
Gene Frequency , Polymorphism, Single Nucleotide , Vitiligo , Vitiligo/genetics , Vitiligo/epidemiology , Humans , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Genomics , Alleles , Genetic Variation/genetics , Genetics, Population
4.
Ecancermedicalscience ; 18: 1716, 2024.
Article in English | MEDLINE | ID: mdl-39021544

ABSTRACT

Vitiligo is a disease characterised by the autoimmune destruction of melanocytes, manifesting as depigmentation of the skin. We present the case of a female patient with a history of breast cancer who developed vitiligo in the area of the treatment field 12 months after the end of radiotherapy. It has been reported in the literature that vitiligo can occur in patients with a history of vitiligo after radiotherapy, attributable to the Koebner phenomenon, where some treatments can induce new vitiligo lesions in the patient.

5.
Skin Res Technol ; 30(7): e13868, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39031921

ABSTRACT

BACKGROUND: Both psoriasis and vitiligo are autoimmune skin diseases. Previous observational studies have indicated a relationship between the two conditions, and simultaneous onset of both diseases poses increased health risks to patients. However, limited research has explored the causal relationship between psoriasis and vitiligo. OBJECTIVES: To investigate whether a causal association exists between psoriasis and vitiligo. METHODS: A case of Chinese patients diagnosed with psoriasis and vitiligo has been reported. Transcriptome sequencing was performed on normal, psoriasis, vitiligo, and co-morbid skin tissues of the patients, and single-cell transcriptome sequencing was conducted on the co-morbid skin tissues. A comprehensive Mendelian randomization analysis of Genome-wide association studies (GWAS) was performed on a cohort of 261 018 European individuals with psoriasis from the IEU Open GWAS Project and vitiligo from the National Institutes of Health (NIH) Database of Genotypes and Phenotypes. RESULTS: Case report and transcriptome results showed that skin tissue with vitiligo combined with psoriasis exhibited both vitiligo and psoriasis. Single-cell transcriptome sequencing results showed that in comparison to normal skin and psoriatic skin, the proportions of CD8+ T cells, natural killer cells, naive T cells, T helper cells 17, regulatory T cells, conventional type 1 dendritic cells, Conventional type 2 dendritic cells, and plasmacytoid dendritic cells were all increased in skin tissue with vitiligo combined with psoriasis. Mendelian randomization analysis included 4510 patients with psoriasis and 4680 patients with vitiligo. The results showed no causal relationship between vitiligo and psoriasis in the forward direction (p = 0.192; odds ratio [OR], 1.059; 95% confidence interval [CI], 0.971-1.155) or in the reverse direction (p = 0.459; OR, 0.927; 95% CI, 0.757-1.134). CONCLUSIONS: This study suggests that the association between psoriasis and vitiligo may be closely related to immunity, however, Mendelian randomization studies do not support a causal relationship. These findings hold significant implications for clinicians aiming to enhance their understanding and treatment approaches for psoriasis and vitiligo.


Subject(s)
Genome-Wide Association Study , Psoriasis , Vitiligo , Humans , Vitiligo/genetics , Vitiligo/epidemiology , Psoriasis/genetics , Psoriasis/complications , Psoriasis/epidemiology , Male , Mendelian Randomization Analysis , Female , Adult , Middle Aged , Transcriptome
6.
Diagn Pathol ; 19(1): 92, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961434

ABSTRACT

AIMS: Vitiligo is a chronic dermatological condition characterized by the progressive loss of melanocytes, for which traditional therapy has shown limited efficacy. This study aimed to establish a vitiligo model with easy operability, high repeatability, and stable depigmentation to provide a foundation for studying the pathogenesis and developing novel therapies for vitiligo. METHODS: (1) Establishing vitiligo model: Firstly, deliver B16F10 cells to the back skin of C57BL/6 J via intradermal injection (day 0), and the CD4 depletion antibody was injected intraperitoneally on day 4 and 10. Secondly, the melanoma was surgically removed on day 12. Thirdly, CD8 antibody was administered intraperitoneally every fourth day till day 30. (2) Identification of vitiligo model: H&E staining, immunohistochemistry, and immunofluorescence were used to detect the melanocytes. The melanin was detected by transmission electron microscopy (TEM), Lillie ferrous sulfate staining and L-DOPA staining. RESULTS: (1) The back skin and hair began to appear white on day 30. Melanin loss reached peak on day 60; (2) Hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence results showed melanocytes were reduced. L-DOPA staining, Lillie ferrous sulfate staining and TEM results showed that melanin decreased in the epidermis. CONCLUSION: We successfully establishment a vitiligo mouse model which can be more capable to simulate the pathogenesis of human vitiligo and provide an important basis for the study of pathogenesis and therapy of vitiligo.


Subject(s)
Disease Models, Animal , Melanocytes , Mice, Inbred C57BL , Vitiligo , Animals , Vitiligo/pathology , Vitiligo/metabolism , Vitiligo/therapy , Melanocytes/pathology , Melanocytes/metabolism , Mice , Melanins/metabolism
7.
Skin Res Technol ; 30(7): e13846, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38967217

ABSTRACT

BACKGROUND: Although observational studies have suggested a correlation between vitiligo and rheumatic diseases, conclusive evidence supporting a causal relationship is still lacking. Therefore, this study aims to explore the potential causal relationship between vitiligo and rheumatic diseases. METHODS: Using genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis. In our analysis, the random-effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave-one-out" analyses. RESULTS: The genetically predicted vitiligo was associated with an increased risk of rheumatoid arthritis (RA) (OR, 1.47; 95% confidence interval [CI], 1.29-1.68; p < 0.001), and systemic lupus erythematosus (SLE) (OR, 1.22; 95% CI, 1.06-1.39; p = 0.005). The causal associations were supported by sensitivity analyses. In Sjögren's syndrome and ankylosing spondylitis, no causal relationship with vitiligo was found in the study. CONCLUSION: Our MR results support the causal effect that vitiligo leads to a higher risk of RA and SLE. Individuals with vitiligo should be vigilant for the potential development of RA and SLE. Managing and addressing this potential requires regular monitoring.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Rheumatic Diseases , Vitiligo , Vitiligo/genetics , Humans , Genetic Predisposition to Disease/genetics , Rheumatic Diseases/genetics , Rheumatic Diseases/complications , Polymorphism, Single Nucleotide/genetics , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/complications , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/complications
8.
Sci Rep ; 14(1): 16580, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020008

ABSTRACT

Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases.


Subject(s)
Antigens, Differentiation, T-Lymphocyte , Killer Cells, Natural , Nevus, Halo , Vitiligo , Humans , Vitiligo/metabolism , Vitiligo/pathology , Antigens, Differentiation, T-Lymphocyte/metabolism , Male , Nevus, Halo/metabolism , Nevus, Halo/pathology , Female , Adult , Killer Cells, Natural/metabolism , Killer Cells, Natural/immunology , Middle Aged , Skin/metabolism , Skin/pathology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , Melanocytes/metabolism , Melanocytes/pathology , Young Adult , CD56 Antigen/metabolism , Case-Control Studies
9.
Clin Immunol ; 265: 110300, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38950722

ABSTRACT

A comprehensive analysis of spatial transcriptomics was carried out to better understand the progress of halo nevus. We found that halo nevus was characterized by overactive immune responses, triggered by chemokines and dendritic cells (DCs), T cells, and macrophages. Consequently, we observed abnormal cell death, such as apoptosis and disulfidptosis in halo nevus, some were closely related to immunity. Interestingly, we identified aberrant metabolites such as uridine diphosphate glucose (UDP-G) within the halo nevus. UDP-G, accompanied by the infiltration of DCs and T cells, exhibited correlations with certain forms of cell death. Subsequent experiments confirmed that UDP-G was increased in vitiligo serum and could activate DCs. We also confirmed that oxidative response is an inducer of UDP-G. In summary, the immune response in halo nevus, including DC activation, was accompanied by abnormal cell death and metabolites. Especially, melanocyte-derived UDP-G may play a crucial role in DC activation.


Subject(s)
Dendritic Cells , Melanocytes , Nevus, Halo , Humans , Dendritic Cells/immunology , Dendritic Cells/metabolism , Melanocytes/metabolism , Melanocytes/immunology , Nevus, Halo/metabolism , Nevus, Halo/immunology , Uridine Diphosphate Glucose/metabolism , Vitiligo/immunology , Vitiligo/metabolism , Male , Female , Adult , Apoptosis , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Young Adult , Adolescent
10.
J Am Acad Dermatol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977219
11.
Eur J Dermatol ; 34(3): 251-259, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-39015958

ABSTRACT

The European prevalence of vitiligo diagnosis is 0.2%-0.8%, with country-specific and methodological differences. Although vitiligo profoundly impacts quality of life, limited studies have evaluated disease burden and treatment patterns. This real-world study describes the prevalence, incidence, characteristics, and treatment patterns of vitiligo among patients in Spain during 2015-2021. This retrospective observational study using the IQVIA Electronic Medical Records database in Spain included patients with vitiligo (International Classification of Diseases, Ninth Revision codes 709.01/374.53). Incident and prevalent cohorts comprised registered patients with vitiligo diagnoses during and before 2015-2021, respectively. Patient characteristics and treatment data were extracted. Vitiligo incidence was 0.016 (95% CI: 0.014-0.018) per 100 person-years, and prevalence was 0.19% (95% CI: 0.18%-0.19%) in 2021. Females were more affected than males (0.16% vs 0.13%, respectively). Among 1,400 incident patients, mean (SD) age was 40.7 (19.7) years; most were female (53.9%). The most common comorbidities after vitiligo diagnosis were eczema (20.8%), hypercholesterolaemia/hypertriglyceridaemia (17.9%), anxiety (10.9%), thyroid disorders (9.1%), and diabetes (6.4%). In 2021, 78.6% of prevalent patients did not receive vitiligo-related treatments. The most prescribed vitiligo-related treatments were topical calcineurin inhibitors (13.9%) and topical corticosteroids (13.0%); 11.9% had a record of psychiatric medications. This study confirms the association between vitiligo and comorbidities (e.g., eczema, thyroid disorders) and high disease burden. The prevalence in Spain in 2021 (0.19%) was within the lower band of European estimates based on surveys/medical screenings. Most patients are not receiving vitiligo-related treatment and could benefit from new, effective treatments.


Subject(s)
Electronic Health Records , Vitiligo , Humans , Vitiligo/epidemiology , Vitiligo/therapy , Male , Female , Spain/epidemiology , Retrospective Studies , Adult , Middle Aged , Prevalence , Incidence , Young Adult , Databases, Factual , Comorbidity , Adolescent , Aged , Thyroid Diseases/epidemiology , Child
12.
Article in English | MEDLINE | ID: mdl-39030934

ABSTRACT

Non-cultured epidermal suspension (NCES) is one of the most widely used surgical therapy for stable vitiligo patients in which recipient size preparation plays an important role in the outcome of NCES. The primary objective is to evaluate and compare the efficacy and safety of conventional suspension delivery after manual dermabrasion (CSMD) versus tattooing pen-assisted suspension delivery (TPSD) in NCES. Paired vitiligo units (VU) in 36 patients, matched with respect to size and location were divided into two groups. The VU in Group 1 underwent suspension delivery by CSMD while the VU in Group 2 underwent same by TPSD. All the VU were followed up at regular intervals until 24 weeks. At the end of 24 weeks, 31 VU (86.1%) in Group 1 achieved >75% repigmentation which was significantly higher (p = .02, chi-square test) as compared to 22 VU (61.1%) in Group 2. The color matching in both the groups VU was also comparable (p = .84, chi-square test). The patient global assessment (PGA) was significantly higher in Group 1 VU as compared to Group 2. Treatment response in terms of repigmentation and PGA was significantly better in VU treated with CSMD as compared to TPSD. Recipient site complications were seen more commonly in Group 1 VU as compared to Group 2. Perilesional halo at the recipient site was seen in none of the VU in Group 2 which was significantly lower than 6 VU in Group 1 than (p = .02, chi-square test). Better results may be possible with technical improvisations in tattooing pen needle diameter and depth of penetration.

13.
J Pathol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989633

ABSTRACT

The basement membrane zone is the interface between the epidermis and dermis, and it is disrupted in several skin conditions. Here, we report the results of a comprehensive investigation into the structural and molecular factors of the basement membrane zone in vitiligo, a dermatological disorder characterised by depigmented patches on the skin. Using electron microscopy and immunofluorescence staining, we confirmed abnormal basement membrane zone morphology and disrupted basement membrane zone architecture in human vitiliginous skin. Furthermore, we identified elevated expression of matrix metalloproteinase 2 (MMP2) in human dermal fibroblasts as a key factor responsible for basement membrane zone matrix degradation. In our in vitro and ex vivo models, overexpression of MMP2 in fibroblasts led to basement membrane zone disruption and melanocyte disappearance. Importantly, we reveal that the loss of melanocytes in vitiligo is primarily linked to their weakened adhesion to the basement membrane, mediated by binding between integrin ß1 and laminin and discoidin domain receptor 1 and collagen IV. Finally, inhibition of matrix metalloproteinase 2 expression reversed depigmentation in a mouse model of vitiligo. In conclusion, our research shows the importance of basement membrane zone integrity in melanocyte residence and offers new avenues for therapeutic interventions to address this challenging skin condition. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

14.
Cureus ; 16(6): e62293, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39006687

ABSTRACT

Cyclin-dependent kinase (CDK) 4 and 6 inhibitors, such as palbociclib, have emerged as essential in managing hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. While effective, these inhibitors can cause rare dermatologic side effects, including vitiligo-like depigmentation. We report a rare case of a 52-year-old female with HR+, HER2- metastatic breast cancer who developed vitiligo-like depigmentation following palbociclib treatment. The patient presented with asymptomatic depigmented lesions on the lower limbs and abdomen, appearing seven months after starting palbociclib. Examination and investigations confirmed the diagnosis after excluding other potential causes. Despite treatment with topical steroids and calcineurin inhibitors, there was no significant improvement, highlighting the need for more research into effective management strategies for drug-induced vitiligo. This case emphasizes the importance of recognizing rare dermatologic side effects of CDK4/6 inhibitors like palbociclib. Ongoing vigilance, reporting, and research are necessary to improve understanding and management of these side effects, ultimately enhancing patient care in oncology.

15.
Skin Res Technol ; 30(7): e13787, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38992866

ABSTRACT

BACKGROUD: Previous observational studies have shown that vitiligo usually co-manifests with a variety of dysglycemic diseases, such as Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). Mendelian randomization (MR) analysis was performed to further evaluate the causal association between fasting plasma glucose, glycosylated hemoglobin (HbA1c), T1DM, T2DM and vitiligo. MATERIALS AND METHODS: We used aggregated genome-wide association data from the Integrative Epidemiology Unit (IEU) online database of European adults vitiligo; HbA1c data were from IEU. Fasting blood glucose data were obtained from the European Bioinformatics Institute (EBI). T1DM and T2DM data were from FinnGen. We used bidirectional two-sample and multivariate MR analyses to test whether dysglycemic measures (fasting blood glucose, HbA1c), diabetes-related measures (T1DM, T2DM) are causatively associated with vitiligo. Inverse variance weighting (IVW) method was used as the main test method, MR-Egger, Weighted mode and Weighted median were used as supplementary methods. RESULTS: We found no statistically significant evidence to support a causal association between dysglycemic traits and vitiligo, but in the correlation analysis of diabetic traits, our data supported a positive causal association between T1DM and vitiligo (p = 0.018). In the follow-up multivariate MR analysis, our results still supported this conclusion (p = 0.016), and suggested that HbA1c was not a mediator of T1DM affecting the pathogenesis of vitiligo. No reverse causality was found in any of the reverse MR Analyses of dysglycemic traits and diabetic traits. CONCLUSIONS: Our findings support that T1DM is a risk factor for the development of vitiligo, and this conclusion may explain why the co-presentation of T1DM and vitiligo is often seen in observational studies. Clinical use of measures related to T1DM may be a new idea for the prevention or treatment of vitiligo.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Genome-Wide Association Study , Glycated Hemoglobin , Mendelian Randomization Analysis , Vitiligo , Vitiligo/genetics , Vitiligo/blood , Vitiligo/epidemiology , Humans , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , Glycated Hemoglobin/metabolism , Risk Factors , Adult , Male , Female
16.
J Dermatol Sci ; 115(1): 33-41, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38955622

ABSTRACT

BACKGROUND: Tryptophan metabolism dysregulation has been observed in vitiligo. However, drawing a mechanistic linkage between this metabolic disturbance and vitiligo pathogenesis remains challenging. OBJECTIVE: Aim to reveal the characterization of tryptophan metabolism in vitiligo and investigate the role of tryptophan metabolites in vitiligo pathophysiology. METHODS: LC-MS/MS, dual-luciferase reporter assay, ELISA, qRT-PCR, small interfering RNA, western blotting, and immunohistochemistry were employed. RESULTS: Kynurenine pathway activation and KYAT enzyme-associated deviation to kynurenic acid (KYNA) in the plasma of stable non-segmental vitiligo were determined. Using a public microarray dataset, we next validated the activation of kynurenine pathway was related with inflammatory-related genes expression in skin of vitiligo patients. Furthermore, we found that KYNA induced CXCL10 upregulation in keratinocytes via AhR activation. Moreover, the total activity of AhR agonist was increased while the AhR concentration per se was decreased in the plasma of vitiligo patients. Finally, higher KYAT, CXCL10, CYP1A1 and lower AhR expression in vitiligo lesional skin were observed by immunohistochemistry staining. CONCLUSION: This study depicts the metabolic and genetic characterizations of tryptophan metabolism in vitiligo and proposes that KYNA, a tryptophan-derived AhR ligand, can enhance CXCL10 expression in keratinocytes.


Subject(s)
Chemokine CXCL10 , Keratinocytes , Kynurenic Acid , Receptors, Aryl Hydrocarbon , Skin , Tryptophan , Up-Regulation , Vitiligo , Humans , Vitiligo/metabolism , Vitiligo/genetics , Vitiligo/blood , Chemokine CXCL10/metabolism , Chemokine CXCL10/genetics , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/genetics , Tryptophan/metabolism , Tryptophan/blood , Kynurenic Acid/blood , Kynurenic Acid/metabolism , Male , Keratinocytes/metabolism , Skin/metabolism , Skin/pathology , Adult , Female , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Kynurenine/metabolism , Kynurenine/blood , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Middle Aged , Case-Control Studies , Signal Transduction , Young Adult
17.
J Ethnopharmacol ; 334: 118595, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038503

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Qinglongyi-Buguzhi herbal pair (QB) is one of commonly used herbal combinations for treating vitiligo in traditional Chinese medicine, consisting of the exocarp of the immature fruit of Juglans regia L. or Juglans mandshurica Maxim., and dried, mature fruit of Psoralea corylifolia L. However, the active components and potential mechanisms of QB in the treatment of vitiligo are still unclear. AIM OF THE STUDY: The purpose of this study is to clarify the effects and mechanisms of QB on vitiligo treatment through integration of network pharmacology and empirical examinations. MATERIALS AND METHODS: The active components and targets of QB as well as the targets linked to vitiligo were obtained from network databases. Visualization networks were constructed with Cytoscape 3.9.1. GO and KEGG enrichment analysis were conducted to investigate the possible mechanism. Molecular docking was employed to evaluate the binding affinities between the primary active ingredients of QB and essential targets of the PI3K/Akt/Nrf2 pathway. In vivo and in vitro experiments were carried out to confirm the results of network pharmacology. RESULTS: We evaluated 44 active compounds and 602 genes from QB, and 107 of these genes linked to vitiligo. GO analysis suggested QB might lessen vitiligo by regulating oxidative stress. KEGG pathway analysis indicated the PI3K/Akt pathway may be crucial for treating vitiligo. Molecular docking results demonstrated the key active ingredients of QB had good binding activity with the major targets in the PI3K/Akt/Nrf2 pathway. In vivo, QB significantly ameliorated vitiligo model mouse's skin pathologies by reducing ROS, elevating CAT and SOD levels. Western blot showed that QB increased the phosphorylation of PI3K and Akt and the expressions of Nrf2 and HO-1 in the skin. In vitro, QB reversed H2O2-induced oxidative injury of melanocytes, enhanced cell survival rate, reduced ROS level, upregulated SOD and CAT activities, and raised the content of melanin. Moreover, QB upregulated the expression levels of Akt, Nrf2, HO-1 mRNA, Akt phosphorylation, HO-1, and nuclear Nrf2 proteins, and also encouraged the nuclear translocation of Nrf2. However, LY294002 treatment significantly reversed the regulatory effect of QB on oxidative damage of melanocytes. CONCLUSIONS: This study revealed that the therapeutic effect of QB on vitiligo was achieved through multiple components, targets and pathways. Experimental investigation demonstrated that QB could improve vitiligo via reducing oxidative stress, which was probably accomplished by activating the PI3K/Akt/Nrf2 signaling pathway.

18.
Indian Dermatol Online J ; 15(4): 612-615, 2024.
Article in English | MEDLINE | ID: mdl-39050072

ABSTRACT

Background: In vitiligo, there is a significant decrease in melanocytes and melanin. The decrease in melanin causes oxidative stress, with a chance of causing metabolic syndrome. Hence, there is a need to look for metabolic syndrome in vitiligo. Aim and Objectives: To estimate the prevalence of metabolic syndrome in vitiligo patients and to evaluate the relationship between the severity and progression of vitiligo and metabolic syndrome. Materials and Methods: A hospital-based cross-sectional study was conducted on 178 vitiligo cases and 178 controls who were age- and sex-matched. The type of vitiligo, stability by vitiligo disease activity score (VIDA), and severity by vitiligo area severity index (VASI) were noted. The waist circumference, blood pressure, fasting lipid profile, and fasting blood sugar were measured for cases and controls. Metabolic syndrome was diagnosed based on Harmonization Asian criteria. Results: The mean age in cases was 34.38 years, and in controls, it was 35.67 years. The majority were females in both cases (52.2%) and controls (55.6%). Most have a VIDA score of 2+ (41.6%). The mean VASI score was 2.54. The percentage of metabolic syndrome was higher in cases (36%) compared to controls (24.2%) (P = 0.015). The mean age was lower in vitiligo cases with metabolic syndrome (38.83 years) compared to controls with metabolic syndrome (43.14 years). Metabolic syndrome was more frequent in the vitiligo vulgaris type (48.9%) than in acral and segmental vitiligo. Metabolic syndrome was more common in patients with high VIDA (45%) and VASI (52.3%) scores compared to patients with low VIDA (25%) and VASI (27.3%) scores. Limitation: It is a hospital-based study, so controls were not from the general population. Conclusion: The prevalence of metabolic syndrome was higher in vitiligo patients compared to controls, and it was higher in patients with active and severe disease. Screening and close monitoring of vitiligo patients help in the early diagnosis of metabolic syndrome and reduce the risk of cardiovascular disease.

19.
Front Med (Lausanne) ; 11: 1408409, 2024.
Article in English | MEDLINE | ID: mdl-39050532

ABSTRACT

Objective: To analyze the clinical efficacy of CO2 fractional laser combined with compound betamethasone in treating vitiligo and its impact on inflammatory factors. Methods: The clinical treatment effects, levels of inflammatory factors [interleukin-17 (IL-17), interferon-gamma (IFN-γ), interleukin-10 (IL-10)], prognosis regarding repigmentation and relapse, psychological health (satisfaction). Results: ① Clinical treatment effects: the total effective rate in Group A was 92.73%, Group B was 74.55%, and Group C was 67.27%, with Group A showing significantly higher effectiveness than Groups B and C (p < 0.05). ② Inflammatory factors: prior to treatment, there was no significant difference in IL-17, IFN-γ, and IL-10 levels among the three groups (p > 0.05); after 3 and 6 months of treatment, the levels of IL-17 and IFN-γ decreased significantly while IL-10 levels increased significantly across all three groups, with Group A showing a more pronounced change compared to Groups B and C (p < 0.05). ③ Prognosis regarding repigmentation and relapse: after 3 and 6 months of treatment, Group A exhibited significantly higher repigmentation rates compared to Groups B and C (p < 0.05); in terms of relapse, Group A had a relapse rate of 5.45%, Group B had 21.82%, and Group C had 23.64%, with Group A showing significantly lower relapse rates compared to Groups B and C (p < 0.05). ④ Quality of life and psychological health: at the end of the 6 month follow-up, the quality of life and psychological health of patients in Group A were significantly higher than those in Groups B and C (p < 0.05). ⑤ Occurrence of adverse reactions: the incidence of adverse reactions was 12.73% in Group A, 10.91% in Group B, and 9.09% in Group C, with no significant difference observed among the three groups (p > 0.05). Conclusion: The application of CO2 fractional laser combined with compound betamethasone in vitiligo patients demonstrates significant efficacy. Compared to sole treatment with CO2 fractional laser or compound betamethasone injections, this combined approach further improves the levels of inflammatory factors in vitiligo patients, reduces the risk of relapse, enhances skin repigmentation, improves quality of life, psychological well-being, without increasing the risk of related adverse reactions. This combined approach merits clinical promotion and application.

20.
Front Immunol ; 15: 1419660, 2024.
Article in English | MEDLINE | ID: mdl-39040109

ABSTRACT

Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that are secreted by most cells into the extracellular space. This review examines the formation and function of exosomal miRNAs in biological information transfer, explores the pathogenesis of vitiligo, and highlights the relationship between exosomal miRNAs and vitiligo. The aim is to deepen the understanding of how exosomal miRNAs influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, and melanogenesis disorders in the development of vitiligo. This enhanced understanding may contribute to the development of potential diagnostic and therapeutic options for vitiligo.


Subject(s)
Exosomes , Melanocytes , MicroRNAs , Vitiligo , Vitiligo/genetics , Vitiligo/metabolism , Humans , Exosomes/metabolism , Exosomes/genetics , MicroRNAs/genetics , Melanocytes/metabolism , Animals , Oxidative Stress , Keratinocytes/metabolism
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