Vitiligo Group Research Articles

Analysis of vitamin D metabolism, thyroid and autoimmune markers in the vitiligo pathways and their possible interaction with sleep.

Vitiligo is an autoimmune skin disease that can be influenced by stress, including that resulting from sleep deprivation and sleep disturbances. Sleep is essential in the regulation of several hormonal, metabolic and autoimmune pathways that may have important roles in vitiligo. This study aimed to investigate the potential interplay between hormonal, metabolic, and autoimmune markers in vitiligo patients, and the possible influence of sleep quality in these vitiligo pathways. A cohort of 30 vitiligo patients and 26 healthy controls were assessed for various laboratory markers, including thyroid-stimulating hormone (TSH), parathyroid hormone (PTH), serum calcium, 1.25(OH)2D, 25(OH)D, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and antinuclear antibodies (ANA). The study evaluated sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Positive anti-TPO were found in the vitiligo group, but did not in the control group. Vitamin D 25(OH)D mean levels were clinically insufficient in both groups (< 30mg/dL). Reactive ANA was analyzed with 2 variables related to vitiligo: phototherapy and skin activity. No statistical correlation was found in the chi-square test on this relationship. Descriptive findings have shown that the positivity to anti-TPO and anti-TG, associated or not with reactive ANA, was higher in vitiligo group. Great part (85.7%) of vitiligo group were "poor sleepers" (PSQI > 5), which has increased (88.2%) when considering only individuals with signs of vitiligo activity. Autoimmune hypothyroidism and positive anti-TPO are expected in vitiligo, although this marker is not usually measured in the first laboratory screening to this disease. Adequate vitamin D levels may be a key adjuvant in skin pigmentation, and be related to sleep quality and immune regulation, as this vitamin can be related to better sleep and immunomodulation in autoimmune diseases. Evaluating ANA before phototherapy can be controversial, but it should be considered in cases with a poor response to this treatment, or when there is a higher risk of other autoimmune diseases. Poor sleep predominated in the vitiligo group, based on PSQI scores that reported worse subjective sleep in these patients. Worse sleep predominated in individuals with signs of skin activity and reactive autoimmune markers. Screening these components could be important in the management of vitiligo, as maintaining body homeostasis can help to improve the disease course. Sleep should be considered as a potential modulator of several multidirectional vitiligo pathways.

Insights into the gut microbiome of vitiligo patients from India

BackgroundVitiligo is an autoimmune disease characterized by loss of pigmentation in the skin. It affects 0.4 to 2% of the global population, but the factors that trigger autoimmunity remain elusive. Previous work on several immune-mediated dermatological disorders has illuminated the substantial roles of the gut microbiome in disease pathogenesis. Here, we examined the gut microbiome composition in a cohort of vitiligo patients and healthy controls from India, including patients with a family history of the disease.ResultsOur results show significant alterations in the gut microbiome of vitiligo patients compared to healthy controls, affecting taxonomic and functional profiles as well as community structure. We observed a reduction in the abundance of several bacterial taxa commonly associated with a healthy gut microbiome and noted a decrease in the abundance of SCFA (Short Chain Fatty Acids) producing taxa in the vitiligo group. Observation of a higher abundance of genes linked to bacteria-mediated degradation of intestinal mucus suggested a potential compromise of the gut mucus barrier in vitiligo. Functional analysis also revealed a higher abundance of fatty acid and lipid metabolism-related genes in the vitiligo group. Combined analysis with data from a French cohort of vitiligo also led to the identification of common genera differentiating healthy and gut microbiome across populations.ConclusionOur observations, together with available data, strengthen the role of gut microbiome dysbiosis in symptom exacerbation and possibly pathogenesis in vitiligo. The reported microbiome changes also showed similarities with other autoimmune disorders, suggesting common gut microbiome-mediated mechanisms in autoimmune diseases. Further investigation can lead to the exploration of dietary interventions and probiotics for the management of these conditions.

Zinc, copper, and selenium levels in vitiligo: a systematic review and meta-analysis

Vitiligo is a dermatological disease characterized by loss of melanocytes, causing non-scaly white macules on the skin. Zinc, copper, and selenium are important micronutrients that play a role in the normal functioning of the body and have been found to potentially aid in vitiligo treatment, although the relationship between their serum levels and vitiligo is not yet fully understood. This is a systematic review aimed at assessing the levels of serum zinc, copper, and selenium and their association with vitiligo. This review was performed following the Preferred Reporting Items of the systematic Review and Meta-Analysis (PRISMA) checklist and Cochrane guidelines. A comprehensive literature search was conducted on PubMed, Google Scholar and 41 studies published between 1970 and 2022 including 3353 vitiligo cases and 10,638 controls were included in the meta-analysis conducted from August 2022 till September 2023. The quality of the studies was assessed using the National Heart Lung and Blood Institute Study Quality Assessment tool, and the risk of bias was represented using the RobVis tool. The statistical analysis was performed using Review Manager (RevMan) Version 5.4. This meta-analysis indicate a significant decline in serum zinc levels (Z = 4.97; P < 0.0001; SMD = − 0.86; 95% CI − 1.19 to − 0.52) in vitiligo group with high statistical heterogeneity (Tau2 = 0.74; Chi2 = 513.95, d.f. = 26 [P < 0.00001]; I2 = 95%). Similarly for serum copper levels there was decline (Z = 2.43; P < 0.0001; SMD = − 0.50; 95% confidence interval [CI] − 0.91 to − 0.10) in vitiligo group and high statistical heterogeneity (Tau2 = 0.92; Chi2 = 475.10, d.f. = 22 [P < 0.00001]; I2 = 95%). On the other hand, there was a increase of serum selenium levels in the vitiligo group (Z = 0.56; P < 0.0001; SMD = 0.23; 95% confidence interval [CI], 0.58 to 1.04) and the results reveals high statistical heterogeneity among studies (Tau2 = 1.93; Chi2 = 406.44, d.f. = 11 [P < 0.00001]; I2 = 97%) in vitiligo patients compared to healthy controls. Publication bias was not found for the studies analysed. This study analyses the association of serum micronutrient levels and vitiligo among patients and controls from published research along with sub-group analysis specific to Asian populations using a meta-analysis. Low serum levels of Zinc and copper and high selenium levels are associated with Vitiligo.

Immunohistochemical Expression of CXCL 10 in Vitiligo.

Vitiligo is a skin disorder characterized by the loss of melanocytes from the epidermis. Cysteine x cysteine motif chemokine ligand 10 (CXCL10) is linked to the Th1 pattern and has been suggested as one of the most relevant chemokine axes that promote T-cell migration in different autoimmune and inflammatory processes. The aim of this study was to assess the immunohistochemical (IHC) expression of CXCL 10 in skin lesions of patients with vitiligo to explore its possible role in the pathogenesis of the disease. In this prospective, case-control study, we examined biopsies from the lesional skin of 20 patients with vitiligo for IHC expression of CXCL 10: 10 patients presented with stable nonsegmental vitiligo (group A), 10 patients presented with active nonsegmental vitiligo (group B), and 10 apparently healthy volunteers were examined as controls (group C). Nine patients in group A had mild IHC expression of CXCL 10 (+1) and 1 patient had moderate expression (+2). In group B, 8 patients had strong expression of CXCL 10 (+3), and the remaining patients had moderate expression (+2). However, there was no expression of CXCL 10 in all skin specimens in the control group. CXCL10 IHC expression was increased in vitiligo lesions indicating a possible role in the pathogenesis of disease. The expression was significantly increased in active vitiligo compared with stable vitiligo.

Differential expression of serum CXCL9 and CXCL10 levels in vitiligo patients and their correlation with disease severity and stability: A cross-sectional study.

Background Vitiligo is an acquired disorder of pigmentation with an elusive pathogenesis, though various theories have been proposed. The presence of peri-lesional autoreactive CD8+ T cell infiltrate suggests the involvement of abnormal immune responses and autoimmunity in vitiligo. Recent studies have identified the IFN-γ-CXCL9/CXCL-10 axis as a key component of the autoimmune response that perpetuates disease activity in vitiligo. Objectives The primary objective was to estimate serum CXCL9 and CXCL10 levels in vitiligo patients compared to age- and sex-matched controls. Additionally, the study aimed to find correlations between CXCL9 and CXCL10 levels and disease severity and stability. Secondary objectives included comparing levels in segmental/nonsegmental vitiligo and stable/progressive vitiligo and assessing the impact of age and gender. Methods A hospital-based cross-sectional study included 60 vitiligo patients and 30 age- and sex-matched controls. Serum levels of CXCL9 and CXCL10 were assessed using Enzyme-linked immunosorbent assay (ELISA). Cases were clinically evaluated for the type of vitiligo (segmental or non-segmental), disease severity (VASI score), and disease stability (VIDA score). Statistical analysis included t-tests, chi-square tests, and correlation coefficients. P value less than 0.5 was taken as significant. Results Serum CXCL9 and CXCL10, both, were significantly raised in vitiligo patients as compared to controls (p-value = 0.001* & 0.001* respectively) and correlated positively with both VASI score (p-value = 0.001* & 0.001* respectively) and with VIDA score (p-value = 0.032* & 0.001* respectively). Serum CXCL10 showed significant elevation in progressive vitiligo, and CXCL9 exhibited a non-significant trend. No significant difference was observed between segmental and non-segmental vitiligo. Both chemokines positively correlated with disease severity and stability, while age and gender did not significantly impact chemokine levels. Conclusion The expression of chemokines CXCL9 and CXCL10 is markedly increased and correlated positively with disease severity & instability, underscoring their mechanistic role in vitiligo pathogenesis. The values were also higher in the progressive group than in the stable group, inferring their conceivable potential as serum biomarkers. Both serum CXCL9 and CXCL10 were significantly elevated in vitiligo patients compared to controls and they can be used as potential serum biomarkers for assessing the disease activity. Limitations Small sample size of control population. The voluntary sampling technique led to an unequal number of patients in progressive and stable vitiligo groups, as well as in segmental and non-segmental groups. The current study did not include blister fluid analysis and the effect of therapy on the chemokine levels. Conclusion The expression of chemokines CXCL9 and CXCL10 is markedly increased and correlates positively with disease severity and instability, underscoring their mechanistic role in vitiligo pathogenesis. The values were also higher in the progressive group than in the stable group, inferring their conceivable potential as serum biomarkers. *represents statistically significant results.

Comparative Analysis of P-selectin Levels in Psoriasis, Vitiligo, and Nonskin Disease in a Tertiary Care Hospital: A Case-Control Study.

The role and function of P-selectin levels in various inflammatory and immune-mediated diseases have been established. Whether they have an association with inflammatory skin diseases such as vitiligo and psoriasis needs to be established. The objective of this study was to assess P-selectin levels in psoriasis and vitiligo and to compare them with matched controls without skin disease. The study included a total of 90 subjects with age- and sex-matched - 30 each in psoriasis, vitiligo and 30 controls without skin disease. Psoriasis and vitiligo severity was assessed using the Psoriasis Area and Severity Index and the Vitiligo Area Scoring Index scores. P-selectin levels were assessed and compared among the groups. P-selectin levels were also compared with the severity of psoriasis and vitiligo. Chi-square and analysis of variance tests were used to compare the data. The mean age of subjects was 36.28 ± 11.80 years. Majority of the subjects were males (65.6%). The three groups were matched for age, sex, and other demographics. The mean P-selectin levels were 610.43 ± 134.19, 292.52 ± 60.99, and 158.97 ± 34.76 ng/ml, respectively, in the psoriasis, vitiligo, and control groups, respectively (P < 0.001). No significant association of P-selectin levels was observed with psoriasis severity; however, with increasing vitiligo severity, there was a significant increase in P-selectin levels (P < 0.001). Patients with skin diseases have raised P-selectin levels. Within skin diseases, inflammatory diseases such as psoriasis have higher P-selectin levels as compared to autoimmune diseases such as vitiligo. A significant association of P-selectin levels was observed with vitiligo severity but not with psoriasis severity.

Serum Granulysin as a Possible Key Marker of Vitiligo Activity and Severity

Abstract Background: Vitiligo is an immune-mediated, chronic skin condition that affects both the innate and adaptive immune systems. Antimicrobial peptide overexpression is one of its defining characteristics. Granulysin (GNLY), an antimicrobial peptide, may play a role in the pathogenesis of various autoimmune diseases. Objectives: To estimate the serum GNLY levels in vitiligo patients and to correlate those levels with the severity and activity of the disease. Materials and Methods: This case-control study included 60 non-segmental vitiligo patients (Group A) and a control group of 60 people who were matched for age and sex, appeared to be in good health, and were not suffering from vitiligo (Group B). The serum granulysin levels of all subjects were measured using an enzyme-linked immunosorbent assay. Results: When compared to the control group, vitiligo patients had significantly higher serum GNLY levels (P = 0.001). When compared to patients with stable disease, those with active vitiligo had significantly higher serum GNLY levels (P = 0.008). Additionally, there was a positive correlation between the serum GNLY levels and the vitiligo area severity index and vitiligo disease activity scores (P = 0.004 and &lt;0.001, respectively). Limitations: Study population was relatively small. Evaluation of serum granulysin before and after treatment could have been more beneficial. Conclusions: Blood granulysin levels could contribute to the pathogenesis of vitiligo. A higher serum granulysin level may also be a trustworthy predictor of the severity and progression of a disease.

Association of Vitiligo with ABO/Rh System and its Influence on Thyroid Stimulating Hormone and Vitamin D

This study was conducted to determine if there is a relationship between vitiligo and ABO blood groups, the Rhesus (Rh) factor, thyroid stimulating hormone (TSH) and vitamin D. For vitiligo analysis, two hundred subjects participated in this study, 100 vitiligo patients and 100 control cases (without vitiligo). ABO blood grouping and Rh typing were tested by a slide method. TSH testing involved 80 vitiligo patients and 80 controls (without vitiligo) and the hormone was analyzed by separating the serum in a centrifuge for two minutes and the results were obtained by Beckman fully automatic analyzer. For vitamin D, 50 vitiligo patients and 50 healthy people (without vitiligo) were included. The data on vitamin D were obtained from private laboratory services. Statistical analysis was performed using IBM SPSS version 26. P&lt;0.05 was considered significant. Most patients with vitiligo had a significantly lower level of serum vitamin D compared with controls (p-value &lt; 0.05), while no statistically significant difference in TSH serum levels between vitiligo cases and controls, was found (p-value &gt; 0.05). Furthermore, despite showing that subjects with blood group O are more susceptible to vitiligo as compared to other groups, there was no significant association of vitiligo with ABO blood groups (p-value &gt; 0.05). Similarly, the incidence of Rh positive and Rh negative was not statistically different between the two groups (p-value &gt; 0.05). This study showed that vitiligo patients are often vitamin D deficient. This study highlights the need to evaluate vitamin D status in vitiligo patients to improve the level of skin pigment loss. It remains unknown whether vitamin D deficiency causes vitiligo. However, a collection of larger sample sizes of different ethnicities should be required to achieve a precise conclusion.

A determination of the quality of life of patients with vitiligo using the dermatological life quality index

Background/aims: Vitiligo is a severe skin disease that significantly affects individuals’ quality of life due to striking color changes in external appearance, and one that causes the majority of patients to feel stigmatized. This study was conducted to determine the effects of vitiligo on patients’ psychological and social lives and to elucidate how they perceive the disease. Methods: The research was conducted as an epidemiological study. The Dermatological Life Quality Index (DLQI) was applied to patients with vitiligo presenting to our clinic and to a control group. Results: Fifty patients with vitiligo and 50 healthy individuals were enrolled. The vitiligo group consisted of 26 (52%) women and 24 (48%) men, and the healthy control group of 24 (48%) women and 26 (52%) men. The patients’ mean age was 37.2 ± 13.1 years, and that of the healthy controls 34.7 ± 9.2 years. (p=0.2). No significant age or sex differences were observed between the patient and control groups (p=0.2 and p&amp;lt;0.05, respectively). The mean duration of the disease was 83.9 ± 72.9 months. The most common vitiligo subtype was focal vitiligo, at 52%. The vitiligo and control groups’ mean DLQI scores were 5.5 ± 5.0 and 1.4 ± 1.3, respectively, the difference being statistically significant (p&amp;lt;0.05) Conclusion: The findings of this study show that the quality of life of the patients with vitiligo was significantly impaired compared to the control group.

An Evaluation of the Hematological Markers of Systemic Inflammation and Oxidative Stress in Vitiligo: A Case-Control Study.

Introduction Melanocyte dysfunction in vitiligo is considered to be due to genetics, inflammation, and autoimmunity. Research has shown that oxidative stress plays a significant role in triggering these conditions. Currently, there are several markers indicating hematological inflammation and oxidative stress. This study aimed to investigate the status of inflammation and oxidative stress markers in vitiligo. Methods This study included patients with vitiligo and age-gender-matched healthy controls.C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-high-density lipoprotein ratio (MHR) and extent of vitiligo were calculated and compared. Results The study included 138 participants (69 vitiligo and 69 controls). The mean was 41.46 years with a female predominance (55.1%). The patient group demonstrated higher levels of platelets, neutrophils, CRP, NLR, MLR, PLR, and HDL and lower levels of lymphocytes and HDL compared to the control group (p>0,05).The only significantly different value between the groups was MHR (p=0.03). The generalized vitiligo group demonstrated higher levels of platelets, neutrophils, monocytes, CRP, NLR, PLR, and MLR, and lower levels of lymphocytes and HDL compared to the localized group. The only significantly different values between the groups were MHR and MLR (p=0.02, p=0.03). Conclusion This study found that MHR and CRP values were higher in vitiligo patients. Additionally, MHR and MLR values were higher in patients with generalized vitiligo. These results suggest that MHR is a reliable indicator marker for systemic inflammation and oxidative stress in vitiligo.

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

BackgroundThe pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined.ResultsSingle-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4.ConclusionWe identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

Circulating Podocalyxin, Tumstatin/Col-IVα3 and Chitinase 1: New Culprits in Vitiligo Occurrence.

The roles of anti-adhesive podocalyxin (PODXL), anti-angiogenetic tumstatin/ Col-IVα3 and neuro-inflammation and innate immunity modulator Chitinase 1 (CHIT-1) in the etiology of vitiligo have not been studied yet. This study was planned to detect changes in serum PODXL, tumstatin/Col-IVα3 and CHIT1 levels in vitiligo patients. This case-controlled study was performed on a total of 50 patients, 25 with vitiligo and 25 healthy controls. Participants in the vitiligo and control groups were matched in pairs for age and sex. At least 8-10 hours of overnight fasting, venous blood samples were taken from the participants in both groups and serum levels of podocalyxin, tumstatin/Col-IVα3 and CHIT 1 levels were measured by sandwich enzyme immunoassay. In the classification made according to the vitiligo European Task Force evaluation criteria, 18 of 25 vitiligo patients were in the slowly progressive phase and 7 patients were in the active progressive phase. Serum podocalyxin levels increased significantly in the vitiligo group compared to the controls (7.03±2.09 ng/ml vs. 4.99±1.20 ng/ml, p<0.02). However, serum tumstatin levels in vitiligo patients showed a significantly lower course compared to controls (4.88±1.76 ng/ml vs. 6.05±2.19 ng/nl, p<0.03). Serum CHIT-1 levels of vitiligo patients (42.4±7.22 ng/ml) were found to be significantly higher than the serum levels of the control group (34.5±5.33 ng/ml) (p<0.01). High podocalyxin and CHIT1versus low tumstatin levels are new biomarkers that support the role of anti-adhesive, anti-angiogenic and neuroinflammatory pathways in the formation of vitiligo.

The impact on the quality of life and sleep complaints in a vitiligo sample and the influence of inflammatory cytokines in the interaction between vitiligo and sleep

IntroductionVitiligo is an autoimmune dermatosis that affects quality of life, which englobes sleep quality. Sleep regulates the immune system, including inflammatory cytokines, and other pathways, which may influence vitiligo pathogenesis. ObjectivesTo analyze levels of immune serum components (cytokines) in a vitiligo group, and assess whether there was any association with sleep. MethodsThis study comprised 30 vitiligo patients and 26 control individuals. Quality of life and sleep questionnaires were completed [Dermatology Life Quality Index (DLQI), Short-Form Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)]. Seven cytokines have been measured: IFN-γ, interleukin (IL)-4, IL-6, IL-10, IL-17A, IL-12 p40 and TNF-α. ResultsThe mean age of the vitiligo group was 47.7 years-old, with prevalence of females (66.7 %). Mucosal (70 %), acral (60 %) and focal subtype (53.3 %) predominated. Signs of vitiligo activity were identified in 63.3 % of the disease sample. Total PSQI scores and scores for domain 4 (sleep efficiency) were statistically worse in vitiligo group. The SF-36 and ISI total scores were worse in the vitiligo group, although not statistically significant compared with controls. Four SF-36 domains were statistically worse in vitiligo sample, and the DLQI mean score was mild to moderate (5.57). Cytokine levels were not different between groups, or when associated with PSQI. Higher ISI scores (more severe insomnia) were related to increased IL-17A. Higher IL-4, IL-6 and IL-10 levels were associated with previous phototherapy. ConclusionsPoor sleep and impaired aspects of quality of life predominated in the vitiligo sample. Insomnia was related to IL-17A increase in vitiligo. Increased levels of IL-4, IL-6 and IL-10 were related to previous ultraviolet B narrow band (UVB-NB) phototherapy, suggesting an interaction of this treatment on immune system. Sleep disruption and the course of vitiligo may have common pathways in respect of circadian cytokines, which may represent an important subject in vitiligo management.

The correlation analysis between alterations of serum vitamin D, IL-33 levels, and clinical improvement after narrow-band UVB treatment in vitiligo patients: A case-control study.

The etiology of vitiligo has not been completely elucidated. Recently, 25-hydroxyvitamin D (25(OH)D) and IL-33 levels were found to be associated with the development of the vitiligo. The aim was to assess relationship between 25(OH)D, IL-33 levels, and clinical improvement after narrow-band UVB treatment in vitiligo. Patients with vitiligo who underwent at least 48 sessions of narrow-band UVB treatment were included in this study. Age, gender, smoking status, family history of vitiligo, type of vitiligo, body surface area affected by vitiligo, and vitiligo activity were recorded. 25(OH)D and IL-33 were measured and compared at baseline, second month, and fourth month. Twenty patients with vitiligo and 20 healthy controls were included in this study. The mean baseline 25(OH)D level of vitiligo group was statistically significantly lower than the control group's (p < .05). The mean baseline IL-33 level was higher in vitiligo group with no statistically significantly difference (p > .05). The increase in 25(OH)D level and the decrease in vitiligo-affected body surface area were found to be statistically significant during treatment (p < .05). The mean IL-33 levels were found to be lower at the second and fourth month compared to baseline. However, there were no statistical significance (p > .05). Low levels of 25(OH)D are thought to play a role in the etiopathogenesis of vitiligo. 25(OH)D increase due to phototherapy may have a role in repigmentation independently from the direct effect of narrow-band UVB.

Reversal and prevention of deregulated autophagy in cutaneous autoimmune disorders—a pilot study on vitiligo with nutrigenomics based approach of “Maximum Nutrition and Minimum Medication”

Abstract Nutritional status of patients, specially prolonged starvations is an important sub-component of the environmental factors, speculated to have indirect impact on the initiation, propagation, resolution, and exacerbation stages of autoimmunity. The study was based on the hypothesis of conscious, selective, and self-destruction, that is, deregulated autophagy of skin and hair in low dietary protein scenario triggered with prolonged starvations. It was aimed to reverse the self-destruction/deregulated autophagy by providing early morning, low carb-high protein nutrition, and correcting underlying micronutrient deficiency and studying its effect on reducing auto-immunity and eventually reducing disease burden and recurrence. Methods: In this retrospective study, patients were divided into two categories based on disease activity and nutrition. Group A: “novice group” of vitiligo patients who presented at an early stage of their disease were managed with basic standard of therapeutics. Group B: “stabilized group” of vitiligo who were given surgical treatment and followed up for 3 years for any recurrences. Personalized diet plan aimed at reversing high carb-low protein diet and avoiding prolonged overnight starvation adhering to early morning breakfast respecting the circadian rhythm and balanced with additional plant based protein was advised. All detectable underlying micronutrient deficiencies were corrected. Results: Thirty patients were enrolled in the study, 20 in group A and 10 in group B. We observed visible signs of improvement in group A, with early vitiligo (90%) with topical therapy and nutritional intervention as early as 3 weeks. Following surgical procedure in group B, 50% patients had near complete pigmentation at the end of 3 months and 30% within next 3 months. At the end of 6 months, all patients had significant improvement in VASI and VIDA score, however two patients in each group had recurrence at end of 1 year who deviated from nutritional protocol and were found to be deficient in protein intake and micronutrients deficiency was detected on blood investigation. The improvement in VASI scores with conventional treatment and nutritional intervention was found to be statistically significant at 6 months and 1-year interval in group A with paired t test (P = 0.013). Similarly, improvement in VASI was statistically very significant at 6 months and 1-year duration in surgically treated vitiligo group B (P = 0.001). These patients were put on immunosuppressive therapies in first group after correction of deficiencies and managed with supportive and conventional therapy in second group in subsequent 3 years follow up. Conclusion: Nutritious diet aimed at correction of underlying protein and micronutrient deficiency with special emphasis on circadian rhythm may arrest the natural progression of disease at an early stages of the disease and prime the body for oral immunosuppressive drugs. This approach may prevent the recurrence in patients already stabilized with standard care of therapeutics and surgery in future.

Evaluation of atrial conduction properties and atrial arrhythmia propensity in vitiligo patients

Aims: Vitiligo is a skin condition characterized by melanocyte loss. It is thought to have a robust association with various systemic and metabolic disorders, such as insulin resistance, atherosclerotic cardiovascular disease, and metabolic syndrome. Atrial fibrillation (AF) is a prevalent disorder in clinical practice and appears to be predictable by atrial electromechanical delay (EMD). This study aimed to detect atrial conduction time through tissue Doppler echocardiography, a non-invasive method used for patients with vitiligo. Methods: We conducted this study with 32 patients diagnosed with generalized vitiligo and 38 age- and sex-matched controls. We evaluated all participants' blood samples, including neutrophil/lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), and other laboratory parameters. Then, we calculated atrial EMD, intra-atrial EMD, and left atrial EMD. Results: We found neutrophil count, NLR levels, and hs-CRP levels to be significantly higher in the vitiligo group (6 ± 1.4 vs. 4.5 ± 2.3, p = 0.001; 3.5 ± 1.4 vs. 2.5 ± 1.9, p = 0.024; 6.2 ± 1.9 mg/dl vs. 4.1 ± 1.3 mg/dl, p &lt; 0.001, respectively). In addition, inter-atrial and intra-atrial EMD were significantly higher in the vitiligo group compared to the control group (36.3 ± 8.5 vs. 24.2 ± 10.8, p &lt; 0.001; 18.1 ± 8.3 vs. 10.9 ± 5.8, p &lt; 0.001, respectively). Finally, left atrial EMD was higher in the vitiligo group, but we could not reach statistical significance (15.3 ± 6.9 vs. 13.2 ± 7.2, p = 0.33). Conclusion: We concluded that intra-atrial EMD and inter-atrial EMD were significantly prolonged in the vitiligo patients. Our results suggest that vitiligo patients are at risk for atrial fibrillation.

Choroidal vascularity index and choroidal thickness assessment in vitiligo

ABSTRACT Clinical relevance Vitiligo is a skin disease characterised by depigmentation and loss of melanocytes. Melanocyte loss may not be limited to the skin in vitiligo, and various abnormalities may occur in the choroid, which is dense in melanocytes. Background To evaluate structural changes in the choroid by measuring choroidal thickness and vascularity index using optical coherence tomography in patients with vitiligo and comparing them to healthy subjects. Methods This study included 168 participants: 84 with vitiligo (30 females, 54 males) and 84 controls (36 females, 48 males). Choroidal thickness and vascularity index were measured using the enhanced depth imaging mode in spectral-domain optical coherence tomography. The choroidal thickness was measured at the following five points; subfoveal (SF), 500 μm (NCT1) and 1000 μm (NCT2) nasal to the fovea; and 500 μm (TCT1) and 1000 μm (TCT2) temporal to the fovea. The choroidal vascularity index was calculated using the ImageJ software. Results SF (p < 0.001), NCT1 (p < 0.001), NCT2 (p = 0.021), TCT1 (p = 0.001), and TCT2 (p < 0.006) choroidal thicknesses were significantly smaller in the vitiligo group than in the control group. Total choroidal (p < 0.001) and stromal (p < 0.001) areas were significantly smaller in the vitiligo group than in the control group. Choroidal vascularity indices were significantly higher in the vitiligo group than in the control group (p < 0.001). However, luminal areas did not differ significantly between groups (p = 0.935). Conclusion Patients with vitiligo should be regularly monitored for choroidal alterations and, if necessary, referred to an ophthalmologist.

Serum Inflammatory and Oxidative Stress Markers in Patients with Vitiligo.

Vitiligo is a common chronic hypomelanotic skin disorder. An intricate pool of markers associated with a complex combination of biological and environmental factors is thought to be implicated in etiology. This study aims to investigate the most important markers associated with vitiligo pathogenesis, including redox status, inflammation, and immune profile, in patients with vitiligo. The study included a total of 96 subjects: 30 patients with active non-segmental vitiligo, 30 patients with stable non-segmental vitiligo, and 36 controls. The vitiligo area severity index (VASI) and vitiligo disease activity score (VIDA) were determined. The following serum parameters were assessed: antioxidant status (TAS), superoxide dismutase activity (SOD), catalase activity (CAT), glutathione peroxidase activity (GPx), glutathione-S-transferase activity (GST), malondialdehyde (MDA), advanced oxidation protein products (AOPP), C reactive protein (CRP), interleukin-15 (IL-15), and chemokines (CXCL9, CXCL10). The VASI score was not significantly different between active and stable vitiligo patients, as it was approximately 0.1. TAS, CAT, GPx, and GST were significantly lower in vitiligo patients compared to controls (p < 0.05). They were also significantly lower in active vitiligo when compared to stable vitiligo (p < 0.05). However, SOD levels were significantly higher in vitiligo patients than in controls and in the active vitiligo group than in the stable vitiligo group (p < 0.05). MDA and AOPP levels were significantly higher in patients with active and stable vitiligo compared to controls (p < 0.05). However, they did not significantly differ between active and stable vitiligo patients (p < 0.05). In both active and stable vitiligo, CRP and IL-15 were significantly higher than controls (p < 0.05). Whereas CRP was significantly higher in active (range = 2.0-7.2, mean = 4.46 ± 1.09) than in stable vitiligo (range = 1.6-6.7, mean = 3.75 ± 1.08) (p < 0.05). There was no significant difference in IL-15 levels between active and stable vitiligo. In both active and stable vitiligo, CXCL9 and CXCL10 were significantly higher than controls (p < 0.05), and they were significantly higher in active than stable vitiligo (p < 0.05). In vitiligo, oxidative damage induces an increase in pro-inflammatory IL-15, which in turn promotes IFN-γ-inducible chemokines such as CXCL9 and CXCL10. Further, there seems to be a link between the VASI score and IL-15 levels. These data imply that inhibiting IL-15 could be a promising method for developing a potentially targeted treatment that suppresses the early interplay between oxidant stress and IL-15 keratinocyte production, as well as between resident and recirculating memory T cells.

Histopathological differences between vitiligo and lichen sclerosus et atrophicus using quantitative immunohistochemical analysis.

Lichen sclerosus et atrophicus (LS) is rare skin condition characterized by the presence of whitish patches primarily affecting the genital and perianal areas, though it can occur other parts of the body. LS may result in skin depigmentation without textural changes and should be differentiated from vitiligo. However, the histopathological features of hypopigmentation during vitiligo and LS have rarely been compared and have not been precisely described using quantitative immunohistochemical analysis. This study, therefore, aimed to investigate and compare the pigmentary characteristics of LS and vitiligo lesions using histochemical and immunohistochemical staining. We included 31 and 46 patients diagnosed with LS and vitiligo, respectively, at Ajou University Hospital between March 2009 and March 2020 in this study. Their medical charts and skin biopsy specimens were retrospectively reviewed. Additionally, Fontana-Masson staining for melanin and immunohistochemical staining for Melan-A, NKI/beteb, tyrosinase, and microphthalmia-associated transcription factor was performed. The melanin content, as well as the number of melanocytes was, in general, significantly higher in the epidermis of patients in the LS group compared with that in the vitiligo group. However, 22.6% of LS tissues showed less melanin pigmentation, 25.8% of LS specimens exhibited a lower number of melanocytes, and 29.0% of LS specimens demonstrated less melanocyte activity when compared with the average of vitiligo specimens. As lower melanin pigmentation and the near absence number of melanocytes were also observed in several LS specimens, both the clinical and histological findings must be comprehensively reviewed to differentiate vitiligo from LS.

TMT-Based Quantitative Proteomic and Physiological Analyses on Serums of Chinese Patients with Active Vitiligo.

Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo. Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population. A total of 31 DEPs were identified (P < 0.05, fold change >1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as "extracellular exosome" and "immunoglobulin receptor binding", as well as KEGG pathways including "cysteine and methionine metabolism" and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group. Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.