Racial and Ethnic Diversity in Vitiligo Clinical Trials: A Retrospective Cross-Sectional Study Assessing Demographic Reporting of Participants.

BACKGROUND: While the prevalence of vitiligo is similar across racial and ethnic groups, the effects of vitiligo vary by demographic group, culture, and skin color, with darker-skinned individuals facing greater stigma due to increased visibility of the disease.1,2 The recruitment of diverse participants that are representative of the United States (US) population is crucial to ensuring the generalizability of findings and understanding the impacts of vitiligo across diverse patient groups.   Objectives: This study aimed to determine demographic reporting trends in US vitiligo clinical trials and to determine whether participants are representative of the US population. METHODS: A search for US vitiligo clinical trials was conducted on clinicaltrials.gov. Trials conducted between 2006 to September 5, 2023, were included if they intended to treat vitiligo, were conducted in the US, and were completed or terminated.  Results: Of the 15 trials meeting inclusion criteria, only 60% (n=9) reported participant race/ethnicity. These 9 studies included 1,510 participants, of which only 25.43% (n=384) were non-White and 20.40% were Hispanic. There was disproportionately low representation of racial minorities, particularly Black, Native American, and Native Hawaiian groups.   Limitations: Limitations of our study include small sample size, variations in demographic reporting between trials, and undercounting of minority groups by the US Census.  Conclusions: Racial and ethnic minority groups remain underrepresented in US vitiligo clinical trials. Given that the impact of vitiligo can vary by the affected individual’s demographic group and skin color, investigators must be intentional about including a more diverse and representative population in vitiligo clinical trials.  J Drugs Dermatol. 2024;23(7):e164-e166. doi:10.36849/JDD.8117e.

Lack of association of IL-10 (rs1800896) and IL-13 (rs1800925) with non-segmental vitiligo susceptibility in South Indian population.

BACKGROUND: Vitiligo is an autoimmune depigmentation disorder caused by multiple etiologies. Genetic polymorphisms in cytokine genes influence their expression and augment disease development. Analyzing the influence of genetic polymorphisms will help in better understanding of the complex etiopathogenesis of vitiligo. AIM: To study the influence of interleukin IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms on vitiligo risk in South Indian population. METHODS: Two hundred and sixty-four vitiligo patients and 264 controls were recruited in this study. Genotyping was done by quantitative PCR and plasma cytokine levels were measured by ELISA. RESULTS: Allele frequencies of IL-10 (rs1800896) and IL-13 (rs1800925) SNPs were observed to be equal in the groups. Mutant allele G of IL-10 (rs1800896) enhanced the familial inheritance of vitiligo (P < 0.0001, OR-25.1, 95% CI-7.64-82.7) and influenced the development of vulgaris type of vitiligo (P = 0.034, OR-1.83, 95% CI-1.07-3.13). Ancestral allele A of IL-10 (rs1800896) conferred protection against development of acrofacial vitiligo (P = 0.04, OR-0.56, 95% CI-0.33-0.95). Circulatory IL-10 levels in vitiligo patients were higher than controls (P < 0.0001). Individuals with genotype GG of IL-10 (rs1800896) had the highest circulatory levels of IL-10 (P < 0.0001). Among the genotypes of IL-13 (rs1800925) variant, none influenced the phenotype of nonsegmental vitiligo such as gender, family history, age of onset and types of vitiligo (P > 0.05). In addition, no difference was noted in the circulatory levels of IL-13 between patients and controls (P = 0.48). Within patients, CC genotype of IL-13 (rs1800925) was observed to enhance the circulatory IL-13 levels (P < 0.0001). LIMITATION: Replication group analysis in a larger multicentric cohort in future would validate further understanding of vitiligo susceptibility in South Indian ethnics. CONCLUSION: IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms did not confer risk to develop vitiligo in South Indian population.

Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC reference panel.

Vitiligo is an immune-related disease with patchy depigmentation of skin and hair caused by selective destruction of melanocytes. In recent decades, many studies have shown the association between vitiligo and HLA genes; however, the results of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation method with a newly built large-scale Han-MHC reference panel. Three new four-digit HLA alleles (HLA-DQB1 ∗ 02:02, HLA-DQA1 ∗ 02:01 and HLA-DPB1 ∗ 17:01) were identified to be associated with the risk of vitiligo, and four previously reported alleles were confirmed. Further conditional analysis revealed that two important variants, HLA-DQß1 amino acid position 135 (OR = 1.79, P = 1.87 × 10-11) and HLA-B amino acid positions 45-46 (OR = 1.44, P = 5.61 × 10-11), conferred most of the MHC associations. Three-dimension ribbon models showed that the former is located within the ß2 domain of the HLA-DQß1 molecule, and the latter lies in the α1 domain of the HLA-B molecule, while both are involved in specific antigen presenting process. Finally, we summarized all significant signals in the MHC region to clarify their complex relationships, and 8.60% of phenotypic variance could be explained based on all reported variants in Han Chinese so far. Our findings highlight the complex genetic architecture of the MHC region for vitiligo in Han Chinese population and expand our understanding of the roles of HLA coding variants in the etiology of vitiligo.

Serum 25-hydroxyvitamin D status in chinese children with vitiligo: a case-control study.

BACKGROUND: Vitamin D can play a vital role in autoimmune diseases. Epidemiologic evidence demonstrates vitamin D deficiency excited in adult patients with vitiligo. OBJECTIVES: To investigate 25-hydroxyvitamin D (25(OH)D) levels in children with vitiligo and explore possible relevant factors. METHODS: A total of 114 patients and 100 controls were included in our case-control study. We analyzed the required data collected by the questionnaire and examination to reveal the correlation with 25(OH)D levels. RESULTS: The mean serum 25(OH)D levels in patients and controls were 43.62 ± 19.23 and 67.87 ± 19.45 nmol/L, respectively. The rate of deficient in patients and controls are 14.9% and 2%, respectively. There was significant difference between the 2 groups. Significant differences also existed on different ages comparing serum vitamin D levels of patients with controls ( P < .001). Age was an independent factor affecting 25(OH)D level ( P = .032). Two (1.8%) and 4 (3.5%) of children with vitiligo have comorbid autoimmune diseases and family history, respectively. There was no correlation between sex, duration of disease, type of vitiligo, skin lesion location, stage, family history, and comorbid autoimmune diseases with 25(OH)D levels. CONCLUSION: Serum vitamin D level was associated with onset vitiligo children. More sunshine and vitamin D fortified foods are necessary among children with age. The rates of children vitiligo with family history has decreased in China.

Ethnic skin: Kids are not just little people.

There are numerous skin conditions that occur commonly in children with ethnic skin, including vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae, pseudofolliculitis barbae, and keloids. Though these conditions occur in both children and adults, children may have different patterns of clinical presentation and response to therapy. In caring for such patients, important treatment considerations include side effects of systemic medications and tolerability of invasive procedures. Quality of life is an important measure and should not be compromised by either the skin disease or its treatment.

Quality of life in patients with vitiligo: an analysis of the dermatology life quality index outcome over the past two decades.

Vitiligo is one of the most important skin disorders that does not cause much physical impairment, but due to its disfiguring appearance, patients have disturbances in mental health and quality of life (QoL). The dermatology life quality index (DLQI), as one of the most specific QoL instruments, is now used widely for patients with vitiligo. The main objective of this review is to collect and present detailed information about issues and disturbances related to the QoL of patients with vitiligo by reviewing the DLQI studies worldwide in the past 20 years. The impact of vitiligo assessed by the DLQI varies according to the clinical and demographic characteristics of patients. In the majority of our reviewed studies, women showed more QoL impairment than men did, as did young patients compared to elderly ones, married women with vitiligo than singles, and patients with involvement on exposed sites than those on unexposed sites. Dark-skinned people showed more life quality effects than white people did. Dermatologists should pay particular attention to such patients who experience insufficient QoL, as they require more effort to cure their disease.

Pediatric Patients with Vitiligo in Eastern China: Abnormalities in 145 Cases Based on Thyroid Function Tests and Immunological Findings.

BACKGROUND: The aim of this study was to evaluate abnormalities in thyroid function according to tests and the humoral immune systems of patients from Eastern China with pediatric vitiligo. MATERIAL AND METHODS: A total of 145 pediatric patients with vitiligo were investigated in this study, along with 59 children without autoimmune diseases as controls. Laboratory tests of thyroid function were conducted, and these tests examined free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab), antinuclear antibodies (ANAs), immunoglobulins (IgA, IgM, and IgG), and complements (C3 and C4). RESULTS: A total of 63 patients (43.4%), including 39 boys (44.3%) and 24 girls (42.1%), displayed abnormalities in thyroid function according to the tests. This finding indicated that patients with vitiligo differed significantly from those in the control group (P<0.001), particularly in terms of FT3 and TSH abnormalities (P<0.05). However, these groups did not deviate significantly with respect to FT4, Tg-Ab, and TPO-Ab abnormalities (P>0.05). Thirteen patients (8.9%) and 1 (1.7%) control were positive for ANA. All 12 specific antibodies were detected in 8 patients. Anti-SSA/Ro-60 and anti-SSA/Ro-52 were the most prevalent antibodies, followed by anti-dsDNA and then by anti-SmD1 and CENB-P. The serum levels of IgA and IgG decreased more significantly in the vitiligo group than in the control group (P<0.001). However, no significant difference was observed in terms of IgM levels (P>0.05). C4 serum levels also decreased more significantly in the vitiligo group than in the control group (P=0.035). CONCLUSIONS: Results suggest that the incidence of abnormalities in the thyroid functions of children and adolescents is significantly higher in those with vitiligo than that in those in the control group. In addition, immunological dysfunction is common in the vitiligo group.

A functional single-nucleotide polymorphism in the ERCC1 gene alters the efficacy of narrowband ultraviolet B therapy in patients with active vitiligo in a Chinese population.

BACKGROUND: T lymphocytes have been shown to cause the destruction of melanocytes in vitiligo pathogenesis. Narrowband ultraviolet B (NB-UVB), as an effective therapeutic strategy in vitiligo, can lead to the formation of DNA photoproducts such as cyclobutane pyrimidine dimers (CPDs) in perilesional lymphocytes and thus induce skin immunosuppression. The repair of DNA photoproducts is performed mainly through the nucleotide excision repair (NER) pathway. We hypothesized that single-nucleotide polymorphisms (SNPs) in NER genes might influence the repair capacity of CPDs and thus contribute to variations in phototherapy efficiency. OBJECTIVES: To detect genetic polymorphisms in NER genes and their relationship with the efficacy of NB-UVB therapy in patients with active vitiligo. METHODS: We investigated the association of NER SNPs (XPA A23G, XPC Ci11A, XPC C2919A and ERCC1 C118T) with phototherapy efficacy in 86 patients with vitiligo who received NB-UVB treatment. Furthermore, we examined the impact of ERCC1 C118T on the apoptosis of T lymphocytes and CPD accumulation after NB-UVB irradiation. RESULTS: We found that patients with vitiligo with the ERCC1 codon 118 CC genotype showed better efficacy after NB-UVB irradiation than those with the ERCC1 118 TT and CT genotypes, whereas no such association was documented among the genotypes of XPA A23G, XPC Ci11A or XPC C2919A. Additionally, the apoptosis rates and CPD levels of lymphocytes after NB-UVB irradiation in patients with the ERCC1 118 CC genotype were significantly higher than those in patients with the ERCC1 118 TT and CT genotypes. CONCLUSIONS: The ERCC1 118 CC genotype confers better efficacy of NB-UVB therapy in patients with active vitiligo.

Phototherapy for the treatment of vitiligo in Asian children.

Vitiligo is a common acquired progressive depigmenting condition that can have devastating psychological effects in dark-skinned patients. We performed a retrospective review of patients younger than 16 years of age with a clinical diagnosis of vitiligo treated using phototherapy at the National Skin Center, Singapore, over a 5-year period. Seventy-one Asian patients ages 5 to 15 years when they underwent phototherapy were identified. There was a higher proportion of Indian patients in our cohort than in the population. The duration of disease ranged from 2 months to 12 years. More than half of the patients had generalized vitiligo and more than one-third had segmental vitiligo. Patients with generalized vitiligo had a better response than those with segmental vitiligo. Reported response rates were highest for narrowband ultraviolet B (UVB) phototherapy, followed by targeted phototherapy combining ultraviolet A1 (UVA1) and UVB; 308-nm excimer lamp phototherapy and paint psoralen-UVA photochemotherapy had marginally lower reported response rates. The duration of treatment ranged from 3 to 40 months and the total number of treatments ranged from 20 to 209 sessions. Reported side effects were mild and included itching, scaling, erythema, pain, sunburn, blistering, and phototoxicity. We consider phototherapy to be a safe and efficacious modality for the treatment of vitiligo in Asian children.

Regional variation of and association of US birthplace with vitiligo extent.

IMPORTANCE Little is known about population-based risk factors and regional differences for vitiligo.OBJECTIVE To determine the impact of place of birth and residence on vitiligo extent.DESIGN, SETTING, AND PARTICIPANTS A prospective questionnaire-based study using an online questionnaire with 2786 adults (72.2%of whom resided in the United States) with a history of physician-diagnosed vitiligo.EXPOSURES Regions of birth and residence.MAIN OUTCOMES AND MEASURES Body surface area (BSA) of vitiligo lesions.RESULTS Patients with vitiligo who were born outside the United States had lower odds of vitiligo-affected BSA greater than 25%, even after controlling for race/ethnicity, sex, and current age (logistic regression; adjusted odds ratio [aOR], 0.57 [95%CI, 0.46-0.60]).Birthplace in all continents was associated with lower odds of affected BSA greater than 25%than was birthplace in North America. Adults born outside the United States had less affected BSA whether they resided inside (aOR, 0.58 [96%CI, 0.41-0.81]) or outside the United States(aOR, 0.60 [95%CI, 0.48-0.76]). Birthplace and residence at latitudes closer to the equator were associated with lower rates of affected BSA greater than 25%(P .002). The prevalence of affected BSA greater than 25%varied greatly by state of residence (range,27.3%in Maryland to 100% in North Dakota, South Dakota, and Wyoming) (global Moran index = 0.37; P < .001; G statistic = 0.62; P < .001). Spatial regression models that controlled for the regional variation were constructed and confirmed that birthplace outside the United States was associated with lower odds of affected BSA greater than 25%(aOR, 0.61 [95%CI,0.45-0.83]) but not race/ethnicity.CONCLUSIONS AND RELEVANCE There was significant statewide and intercontinental variation for rates of extensive vitiligo. These results suggest that previously unrecognized regional environmental risk factors, especially early in life, play an important role in vitiligo. Additional studies are needed to confirm these early findings and identify such risk factors.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01401374

A retrospective study of 231 Japanese vitiligo patients with special reference to phototherapy.

Although the outcomes of various treatment modalities for vitiligo have been studied extensively, the influence of the participant's characteristics on treatment response has not been thoroughly investigated. Therefore, we retrospectively investigated treatment effects and their association with clinical characteristics in Japanese patients with vitiligo. The charts of patients with vitiligo treated in our institution were reviewed. Clinical response was evaluated as a marked response rate, defined as repigmentation in >75% of the initial lesional area. 162 patients were treated with phototherapy, while 69 were treated with topical mono-therapy. The patients treated with phototherapy and those treated with both phototherapy and topical treatment demonstrated significantly higher clinical response rates compared to patients treated solely with topical mono-therapy (marked response rate: 19.1% vs. 5.8%, P<0.05; and 23.5% vs. 5.8%, P<0.01, respectively). Among the phototherapy-treated patients, younger subjects (≤15 years old) were more responsive to phototherapy compared to older patients (37.0% vs. 15.6%; P=0.015). The disease subtypes did not affect treatment response. In conclusion, phototherapy appears to have a therapeutic effect superior to topical mono-therapy on both focal and generalized vitiligo, especially in younger patients. Thus, any type of psychosocially devastating lesions in a pediatric patient may be a good target for phototherapy.

Role of oxidative stress and autoimmunity in onset and progression of vitiligo.

Vitiligo is an acquired depigmentation disorder characterized by the loss of functional melanocytes from the epidermis. Two major theories of vitiligo pathogenesis include autoimmunity and oxidative stress-mediated toxicity in melanocytes. The present study aimed to evaluate both the hypotheses in vitiligo patients and to investigate their role in the disease onset and progression. Antimelanocyte antibody levels and lipid peroxidation (LPO) levels were evaluated in 427 patients and 440 controls; antithyroid peroxidase (TPO) antibody levels were estimated in 102 patients and 72 controls. Patients showed a significant increase in LPO and antimelanocyte antibody levels compared to controls. Antimelanocyte antibody and LPO levels were higher in active vitiligo compared to stable. Only 9.8% of patients showed the presence of anti-TPO antibodies in their circulation. Oxidative stress may be the initial triggering event to precipitate vitiligo in Gujarat population, which is exacerbated by contributing autoimmune factors together with oxidative stress.

Type 2A Koebner phenomenon in vitiligo is distinct from other subtypes: observations from an Indian cohort.

BACKGROUND: Koebner phenomenon (KP) in vitiligo has been redefined and classified recently. OBJECTIVES: To study the clinical characteristics of various grades of KP. METHODS: In this prospective cross-sectional study, 202 patients with vitiligo were studied between January 2011 and December 2012 for the presence of KP. Based on the new Vitiligo European Task Force guidelines, KP was classified as type 1-3 and grades Ι-IV. Disease characteristics were studied in the various groups and subgroups based on the presence of KP. RESULTS: Koebner phenomenon was seen in 130 of 202 patients. The mean age of patients showing KP was 23.9 ± 13.6 years, compared with 19.3 ± 12.4 years for patients not showing KP (P = 0.02). The mean body surface area involved in the KP-positive group was 4.6 ± 5.6%, vs. 1.5 ± 1.1% in the KP-negative group (P = 0.001). Fifty-five patients experiencing KP received low-dose dexamethasone oral minipulse therapy compared with nine of those who did not (P = 0.01). Of the 130 patients with KP, grade Ι KP was seen in 32, grade II KP in 116, grade III KP in 22 and grade IV KP in 16. There was a significant difference between type 1 and type 2A KP, and between type 2A and type 2B KP. In contrast, type 1 and type 2B KP were found not to be significantly different and had a good degree of correlation. CONCLUSIONS: Patients with KP have a significantly higher age at onset, more extensive cutaneous involvement and are more likely to receive systemic steroids for disease control. Type 2A disease was found to be distinct from the other subtypes.

Quantification and comparison of psychiatric distress in African patients with albinism and vitiligo: a 5-year prospective study.

BACKGROUND: Vitiligo and albinism are two disorders of pigmentation that make the affected African highly visible and strikingly different from their peers. Both pose considerable management challenges, attract significant stigma and profound impairment of quality of life. OBJECTIVE AND METHODS: To determine and compare psychiatric distress in vitiligo and albinism using the Hospital Anxiety and Depression Scale (HADS). Participants were 87 albinos and 102 vitiligo adult patients seen at an urban tertiary hospital in Nigeria between 2004 and 2009. RESULTS: Prevalence of psycho morbidity was 59% (60/102) in vitiligo compared with 26% (23/87) in the albinos. The mean anxiety score was estimated to be 2.55 points lower for albino patients (95% CI: 1.47 to 3.64), and the mean depression score 2.76 points lower (95% CI: 1.84 to 3.68), after adjustment for age, sex and marital status. However, significant differences were not observed when comparing the vitiligo patients with the subset of albino patients with skin cancer. Older patients had significantly higher anxiety and depression scores. Females had significantly higher anxiety scores (but not depression scores) compared to males. Genital involvement in vitiligo was significantly associated with anxiety but not depression. CONCLUSIONS: We found that the African with vitiligo suffers significantly higher psychiatric distress than the African albino on average. Clinical evaluation of these patients would be incomplete without assessment of their psycho morbidity. There is need for increased focus on cancer prevention strategies in the African albino.

Association of NLRP1 genetic variants and mRNA overexpression with generalized vitiligo and disease activity in a Gujarat population.

BACKGROUND: It has been suggested that NLRP1 is involved in susceptibility to a wide range of autoimmune diseases including generalized vitiligo (GV). Genetic polymorphisms in the gene encoding NLRP1 (previously known as NALP1) have previously been shown to be associated with GV and there is speculation about their involvement in the regulation of NLRP1 expression. OBJECTIVES: To explore NLRP1 polymorphisms and investigate their association with NLRP1 mRNA expression and disease activity in patients with GV. METHODS: Polymerase chain reaction (PCR)-restriction fragment length polymorphism and TaqMan single nucleotide polymorphism (SNP) genotyping techniques were used to genotype NLRP1 A/G (rs2670660), T/C (rs6502867) and A/T (rs12150220) polymorphisms in 537 patients with GV and 645 controls in Gujarat. NLRP1 mRNA levels were measured in the whole blood of 122 patients with GV and 175 controls using real-time PCR. RESULTS: The NLRP1 rs2670660 and rs6502867 polymorphisms were found to be in significant association with GV, minor alleles of these SNPs being prevalent in active cases of GV. The rs12150220 polymorphism was found have a marginal association with GV. The frequency of susceptible haplotype 'GCT' was significantly higher in patients with GV and increased the risk of vitiligo twofold. A significant increase in NLRP1 mRNA expression was observed in patients with GV and patients with active GV. NLRP1 mRNA expression was increased in patients with GV with the susceptible GG (rs2670660) and CC (rs6502867) genotypes. Patients with the susceptible GG (rs2670660) and CC (rs6502867) genotypes had early age of onset of GV. Moreover, patients in the age at onset group of 1-20 years showed increased expression of NLRP1 mRNA compared with the older age groups. Female patients showed a significant increase in NLRP1 mRNA and early age at onset of GV compared with male patients. CONCLUSIONS: Our results suggest that NLRP1 rs2670660 and rs6502867 polymorphisms may be genetic risk factors for susceptibility to and progression of GV. The upregulation of NLRP1 mRNA in patients with susceptible genotypes advocates the crucial role of NLRP1 in GV.

Association of FOXP3 (rs3761548) promoter polymorphism with nondermatomal vitiligo: A study from India.

BACKGROUND: The rs3761548 polymorphism (-3279 C>A) of FOXP3 gene is associated with several autoimmune disorders. OBJECTIVE: We sought to determine whether rs3761548 polymorphism is associated with nondermatomal vitiligo in Indian subjects. METHODS: Genomic DNA was isolated from blood samples of 303 patients and 305 control subjects and genotyping was done by allele-specific primers. Data analysis was carried out for the entire cohort and separately for male and female participants as FOXP3 is an X-linked marker. Statistics were performed using software. RESULTS: The genotype frequencies differed significantly from patients to control subjects (P = .002). Further analysis demonstrated female participants with CC genotype were protected (CC vs CA+AA; odds ratio 0.38, 95% confidence interval 0.238-0.615) and those with CA genotype were at higher risk to develop vitiligo (CA vs CC+AA; odds ratio 2.634, 95% confidence interval 1.604-4.325). However, no such statistical difference was observed in male participants. LIMITATIONS: Our study is, to our knowledge, the first report from India with respect to vitiligo and rs3761548; however, we lack adequate literature assistance. CONCLUSIONS: The rs3761548 of FOXP3 gene in our population may be associated with susceptibility to vitiligo because of altered expression. CC genotype appears to be protective and CA genotype seems to impart nearly 3-fold risk to develop vitiligo in women and girls.