Cigarette smoking is an independent risk factor for developing vitiligo on the hands.

BACKGROUND: Vitiligo presents with varying clinical features based on the type and location. Treatment tends to be more effective on the face, neck, trunk, and mid-extremities, while the lips and distal extremities may be more resistant. Vitiligo in frequently exposed areas such as the face, arms, legs, and hands is typically associated with a lower Dermatology Life Quality Index. OBJECTIVES: We aimed to identify the characteristics and potential causes of vitiligo in challenging-to-treat regions, with particular focus on the hands. METHODS: We analyzed the clinical data of 337 patients with generalized vitiligo who visited our hospital between 2016 and 2022. For this study, we focused on patients with non-segmental vitiligo (NSV) specifically on their hands. Of the 337 patients, 248 had NSV and 89 had segmental vitiligo; 119 (47%) of those with NSV had vitiligo on their hands. Logistic regression models were applied to identify factors the factors linked to hand vitiligo, such as age, sex, duration of the condition, and smoking and alcohol history. RESULTS AND CONCLUSIONS: We developed a model to predict the risk of hand vitiligo using several factors. Among the factors analyzed, only smoking history was significantly associated with an increased risk (odds ratio: 3.13). In addition, we used clinical photography to evaluate color-graded frequency heat maps comprising 528 pixels. Vitiligo in nonsmokers widely distributed over the hand, predominantly the fingertips and joints, whereas vitiligo in smokers tended to be distributed mostly at the fingertips.

Frequency of skin cancer among psoriasis, vitiligo, and mycosis fungoides patients treated with narrowband ultraviolet B phototherapy.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is a popular and relatively contemporary treatment option. However, only a few studies to date have explored the potential risk of skin cancer following NB-UVB treatment. OBJECTIVE: This study aimed to investigate the potential long-term risk of skin cancer in patients treated with NB-UVB. METHODS: This cohort study included patients with psoriasis, vitiligo, and mycosis fungoides treated with NB-UVB at two university hospitals in Israel in 2000-2005. Patients were followed up for skin cancer for at least 10 years. Data were extracted from the hospital and community medical records. RESULTS: A total of 767 patients were included in this study: 509 with psoriasis, 122 with vitiligo, and 136 with mycosis fungoides. The mean follow-up duration was 13 years. Among these patients, 4.43% developed skin cancer during the follow-up (3.93% had psoriasis, 2.46% had vitiligo, and 8.09% had mycosis fungoides). Old age and fair skin type were the only significant independent risk factors for skin cancer. There was no significant difference in the mean number of NB-UVB treatments among patients who developed skin cancer and those who did not (99.09 vs. 94.79, respectively). CONCLUSION: No association was observed between the number of NB-UVB treatments and carcinogenesis in any study group. Age is a significant risk factor, and older patients treated with NB-UVB should be followed up carefully.

The causal relationship between vitiligo and autoimmune thyroid diseases: A bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: Vitiligo is an acquired autoimmune depigmented disorder characterized by the presence of white and well-defined patches on the skin, mucous membrane, or both. It is associated with a significant disease burden and has a profoundly impacts patients' quality of life. Autoimmune thyroid diseases (AITDs) result from an autoimmune system dysregulation, leading to an erroneous immune attack on the thyroid gland. Previous observational and epidemiological studies have suggested the association between vitiligo and AITDs. However, the bidirectional cause-effect relationship between vitiligo and AITDs has not been formally assessed. METHOD: Two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore potential causal relationships between genetically increased risk of vitiligo and AITDs, using summary statistics from genome-wide association studies in European populations. Causal effects were primarily estimated using the inverse variance weighted method, and additional quality control was performed using the MR-Egger, weighted median, simple mode, and weight mode methods. Sensitivity analysis was conducted to assess the robustness of the results. RESULTS: The forward MR analysis showed a positive causal relationship between vitiligo and autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves' disease (GD). The odds ratio (OR) were 1.17 (95% CI, 1.01-1.35; p = 0.04), 1.12 (95% CI, 1.03-1.22; p = 0.01), and 1.13 (95% CI, 1.06-1.20; p < 0.01), respectively. In the reverse MR analysis, a positive causal relationship was found between AIT and vitiligo, with an OR of 1.10 (95% CI, 1.01-1.35; p = 0.04). However, no causal relationship was observed between AIH (p = 0.10) or GD (p = 0.61) and vitiligo. Sensitivity analysis revealed no evidence of horizontal pleiotropy or heterogeneity. CONCLUSIONS: The genetic-level investigation provides evidence of a genetic causal association between susceptibility to vitiligo and an increased risk of AITDs. Additionally, the results demonstrate a genetic causal association between susceptibility to AIT and an increased risk of vitiligo, while not indicating a similar association with susceptibility to AIH or GD.

Real-World Experience of Vitiligo Patients: A Retrospective Chart Review.

BACKGROUND: Vitiligo is a common depigmenting skin disorder with an estimated prevalence of 0.5% to 2% worldwide. OBJECTIVE: We conducted a study to characterize the presentation of vitiligo in community dermatology clinic setting in Ontario, Canada. METHODS: A retrospective cross-sectional study was performed through an electronic chart review at a community dermatology clinic with 2 sites in Ontario, Canada. RESULTS: We found a male to female ratio of 1:1.3. The average age at the time of assessment was 40.8 years (ranging from 7 to 75 years). Sixteen percent of the patients were children (less than 18 years of age). Hands were the most common location for vitiligo (55.8%). CONCLUSIONS: Our findings are in keeping with previously described epidemiologic data. To our knowledge, this is the first Canadian study looking at the population in a community setting.

Demographic and clinical feature disparity between progress and non-progress patients with vitiligo after COVID-19 vaccination: A cross-sectional study.

There have been several case reports regarding newly developed vitiligo following the coronavirus disease 19 (COVID-19) vaccination. However, the relationship between COVID-19 vaccine and vitiligo progression remains unclear. To explore the relationship between COVID-19 vaccine and vitiligo progression and its potential influencing factors, A cross-sectional study was conducted on 90 patients with vitiligo who received inactivated COVID-19 vaccination. Detailed information covering demographic characteristics (age and sex), vitiligo clinical features (disease subtypes, duration, stage and comorbidities) and disease activity was collected through an electronic questionnaire. Ninety patients with vitiligo included 44.4% males, with an average age of 38.1 years (standard deviation, SD = 15.0). Patients were divided into progress group (29, 32.2%) and normal group (61, 67.8%) based on whether they experienced vitiligo progression after inactivated COVID-19 vaccination. 41.3% of patients in the progress group experienced vitiligo progression within 1 week after vaccination, and disease progression mainly occurred after the first dose inoculation (20, 69.0%). Logistic regression revealed that patients aged <45 years (odds ratio (OR) was 0.87, 95% confidence interval (CI): 0.34-2.22) and male patients (OR = 0.84, 95% CI: 0.34-2.05) had lower risk for vitiligo progression, while patients with segmental vitiligo (SV) subtype (OR = 1.68, 95% CI: 0.53-5.33), with <5 years disease duration (OR = 1.32, 95% CI: 0.51-3.47) had higher risk for vitiligo progression after COVID-19 vaccination, but without statistical significance. Over 30% patients experienced vitiligo progression after inactivated COVID-19 vaccination, and female patients, elder age, shorter disease duration and SV subtype are potential risk factors for vitiligo progression.

Vitiligo and Crohn's disease form an autoimmune cluster: insights from a population-based study.

BACKGROUND: While the coexistence of vitiligo and Crohn's disease (CD) has been reported in individual patients, the epidemiological association between these autoimmune conditions remains inconclusive. OBJECTIVE: To assess the bidirectional association between vitiligo and CD. METHODS: A population-based study was performed to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting CD. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by multivariable Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset CD was evaluated at 3.6 (95% CI, 2.7-4.9) cases per 10,000 person-years (PY) in patients with vitiligo and 2.4 (95% CI, 2.0-2.9) cases per 10,000 PY in controls. Patients with vitiligo experienced an elevated risk of CD (fully adjusted HR, 1.60; 95% CI, 1.10-2.34; p = 0.015). Congruently, a history of preexisting CD predicted elevated odds of having subsequent vitiligo (fully adjusted OR, 1.49; 95% CI, 1.15-1.93; p = 0.002). Compared to other patients with vitiligo, those with vitiligo and comorbid CD were older and had a higher prevalence of diabetes mellitus, hyperlipidemia, and hypertension but a comparable all-cause mortality rate. CONCLUSIONS: The current study depicts a robust bidirectional association between vitiligo and CD. This knowledge is of clinical implication for physicians managing patients with both conditions. The diagnostic threshold for CD should be lowered in vitiligo patients with compatible symptoms.

Prevalence of Vitiligo among Children and Adolescents in the United States.

BACKGROUND: Vitiligo is an autoimmune disorder that causes patchy loss of skin pigmentation. Up to 2.16% of pediatric patients may have vitiligo. This study estimated vitiligo point prevalence in children and adolescents (ages: 4-11 and 12-17 years) in the United States (US). METHODS: An online, population-based survey of a nationally representative sample of individuals based on 2017 US Census Bureau estimates for age, race, Hispanic origin, income, and geographic region was conducted from December 2019 to March 2020. Parent/legal guardian proxies responded on behalf of their children or adolescents to vitiligo screening questions. Proxy-reported vitiligo status was adjudicated by expert dermatologists who reviewed photographs of vitiligo lesions uploaded by proxies using a teledermatology application. Estimated point prevalence (including diagnosed and undiagnosed vitiligo and its subtypes) was calculated for proxy-reported and clinician-adjudicated vitiligo. RESULTS: There were 9,118 eligible proxy responses (5,209 children, mean age 7.7 years; 3,909 adolescents, mean age 14.4 years). The proxy-reported vitiligo prevalence (95% confidence interval) for children and adolescents was 1.52% (1.11-1.93) and 2.16% (1.66-2.65), respectively. The clinician-adjudicated prevalence (sensitivity analysis bounds) was 0.84% (0.83-1.23) and 1.19% (1.18-1.74), respectively. Approximately 69% of children and 65% of adolescents had nonsegmental vitiligo (clinician adjudicated) and up to 50% may be undiagnosed. CONCLUSION: Based on the clinician-adjudicated prevalence estimates, there were more than 591,000 cases of vitiligo in children and adolescents in the US in 2020. More than two-thirds had nonsegmental vitiligo and nearly half may be undiagnosed. Future studies should confirm these findings.

Incidence of skin malignancies in patients with vitiligo or psoriasis who received narrowband ultraviolet B phototherapy (308 nm/311 nm): A retrospective review of 3730 patients.

BACKGROUND: Previous studies regarding the risk of skin malignancy with NBUVB have been performed in Caucasian patients, but few studies have been conducted in Asians. AIM: The aim of the study was to determine the risk of skin cancer in Asian patients with psoriasis and vitiligo receiving NBUVB phototherapy. METHODS: We performed a 9-year retrospective study including all patients with psoriasis and vitiligo receiving NBUVB (either 311 nm wavelength through cabin phototherapy or 308 nm through excimer lamp phototherapy) at the National Skin Centre. We matched the identification numbers of patients to the National Registry of Diseases Office database and collected data on all skin cancers diagnosed. RESULTS: A total of 3730 patients were included. During the course of the study, 12 cases of skin cancer were diagnosed, of which 10 were basal cell carcinomas, and 2 were squamous cell carcinomas. No cases of melanoma were detected in the study. The age-standardized incidence of skin cancer in psoriasis and vitiligo patients who received phototherapy was 47.5 and 26.5, respectively, which is higher than the incidence of skin cancers in the general population. Risk of skin malignancy was positively correlated with the cumulative (p = .008) and maximum dose of phototherapy (p = .011) as well as previous systemic treatments (p = .006). LIMITATIONS: Limitations include a relatively short follow-up period as well as the lack of quantification of solar exposure. CONCLUSIONS: NBUVB phototherapy in Asian skin increases the risk of skin malignancy. The risk of skin malignancy is higher with psoriasis patients, greater cumulative and maximal dose of phototherapy as well as the use of systemic therapy. Despite the increased risk, the absolute number of skin malignancies remains low, especially for vitiligo patients, with no cases of melanoma diagnosed-a reassuring finding that phototherapy remains a safe alternative in the treatment of psoriasis and vitiligo.

Prevalence and incidence of vitiligo and associated comorbidities: a nationwide population-based study in Korea.

BACKGROUND: The prevalence of vitiligo shows regional variance. Recently, an association between vitiligo and extracutaneous conditions including other autoimmune, metabolic and dermatological disorders has been suggested. Despite its increasing incidence, the epidemiological trends and comorbidities in people with vitiligo have rarely been quantified in Asia. AIM: To determine the prevalence and incidence of vitiligo and the disorders associated with vitiligo using the National Health Insurance Service database. METHODS: We included all patients with vitiligo, classified by the International Classification of Disease, 10th revision (ICD-10) code of L80, with ≥ 3 documented visits from 2003 to 2019. The incidence and prevalence of vitiligo were estimated for the study period. Age-, sex-, insurance type- and income level-matched controls (ratio 1 : 5) were selected to compare comorbidities. The odds ratios between comorbidities and vitiligo were calculated through conditional logistic regression. RESULTS: The incidence and annual prevalence of vitiligo in Korea increased from 2003 to 2019, with incidence peaking in summer. Age-specific incidence showed a bimodal distribution, with the steepest increase in the group aged < 20 years. Many comorbidities, including alopecia areata, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, Crohn disease, ulcerative colitis, Sjögren syndrome, diabetes mellitus, dyslipidaemia, chronic hepatitis, anxiety disorder and mood disorder showed higher odds ratios in patients with vitiligo than controls. CONCLUSION: The incidence and prevalence of vitiligo are increasing, particularly among younger patients in Korea. In addition, various comorbidities are associated with vitiligo, therefore, if patients with vitiligo present with extracutaneous symptoms, physicians should consider the possibility of other comorbid diseases.

Vitiligo patient population and disease burden in France: VIOLIN study results from the CONSTANCES cohort.

BACKGROUND: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation. OBJECTIVES: This study assessed the prevalence, disease burden and treatment of vitiligo in France. METHODS: VIOLIN was a cross-sectional study nested in the national CONSTANCES cohort, which consists of randomly selected adults aged 18-69 years in France. In VIOLIN, longitudinal data were collected prospectively from 158,898 participants during 2012-2018 and linked to the National Health Data System (SNDS), a healthcare utilization database. Patients with physician-diagnosed vitiligo were matched (1:3) with control participants based on age, sex, geographic region, year of inclusion and skin phototype. Patients completed a questionnaire in 2022 to collect disease characteristics, disease burden and quality-of-life (QoL) data. RESULTS: Vitiligo prevalence was 0.71% (681/95,597) in 2018. The mean age in the vitiligo population was 51.2 years; 51.4% were women. Most patients (63%) were diagnosed before age 30 years, mainly by dermatologists (83.5%). Most patients (81.1%) had visible lesions (i.e. on face, hands). Vitiligo was limited to <10% of the body surface area (BSA) in 85.8% of patients. Comorbidities including thyroid disease (18.0% vs. 9.0%), psoriasis (13.7% vs. 9.7%), atopic dermatitis (12.4% vs. 10.3%), depression (18.2% vs. 14.6%) and alopecia areata (4.3% vs. 2.4%) were significantly more common in patients with vitiligo versus matched controls (n = 2043). QoL was significantly impaired in patients with >5% BSA involvement or visible lesions, particularly with ≥10% facial involvement. Vitiligo-specific instruments (i.e. Vitiligo Impact Patient scale and Vitiligo-specific QoL instrument) were more sensitive to QoL differences among subgroups versus general skin instruments, and generic instruments were least sensitive. Most patients (83.8%) did not receive any prescribed treatment. CONCLUSIONS: Patients with vitiligo in France have a high disease burden, particularly those with visible lesions or higher BSA involvement. Most patients are not receiving treatment, highlighting the need for new effective treatments and patient/physician education.

Shining a Light on Vitiligo and Associated Comorbidities: What Is the Evidence?

CITATION: Desai S, McCormick E, Sodha P, et al. Shining a light on the vitiligo and associated comorbidities: What is the evidence? J Drugs Dermatol. 2023;22(4):428-430. doi:10.36849/JDD.NVRN0423.

A cross-sectional study of pediatric dermatoses in a specialized pigment and skin-of-color center in Australia.

There is a paucity of literature on pediatric skin conditions in skin of color, of which old epidemiological data are likely to become outdated as the ethnic diversity in developed countries such as Australia continues to grow. We analyzed the prevalence of presenting conditions of pediatric patients with skin of color attending an urban dermatology clinic in Melbourne, Australia over an 18-month period. The major presenting issues were vitiligo, atopic dermatitis, and acne vulgaris, the majority of which did not significantly differ by ethnicity; however, there was a statistically significantly higher proportion of Chinese and Indian patients presenting with atopic dermatitis. Given the varying presentations of these conditions in skin of color, our findings highlight the importance of increasing education for dermatologists and health personnel in pigmentary disorders and the need for further focused studies comparing the prevalence of skin disease across ethnicities.

Alopecia areata and occurrence of vitiligo and hypothyroidism in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited disorder of immunity which leads to increased risk for mucocutaneous candidiasis and multiorgan autoimmune disease. While alopecia areata (AA) has been described in some patients with APECED, the extent and timing of AA is not well established and extent and timing of concomitant vitiligo and hypothyroidism has not been described. We evaluated an APECED cohort followed at the National Institutes of Health for the timing of development of associated diseases. We found AA occurred earlier in those with APECED than in the general population, was rarely the first sign of APECED, and the timing of AA onset did correlate with the timing of onset of vitiligo or hypothyroidism which also occurred at high rates and early age.

Vitiligo and systemic sclerosis: Are they associated?- Lessons from a population-based study.

BACKGROUND: The epidemiological relationship of vitiligo with systemic sclerosis (SSc) remains to be precisely evaluated. OBJECTIVE: To investigate the bidirectional association between vitiligo and SSc. METHODS: A population-based study was carried out to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting SSc. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by the Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset SSc was calculated at 2.4 (95% CI, 1.6-3.4) and 0.4 (95% CI, 0.3-0.6) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had an increased risk of SSc (fully adjusted HR, 5.37; 95% CI, 3.03-9.54; p < 0.001). Correspondingly, a history of SSc predicted elevated odds of developing vitiligo (fully adjusted OR, 2.09; 95% CI, 1.23-3.55; p = 0.006). Relative to other patients with vitiligo, those with vitiligo and comorbid SSc were older and had a higher prevalence of ischaemic heart disease, hyperlipidaemia, and hypertension. CONCLUSIONS: A robust bidirectional association exists between vitiligo and SSc. This knowledge is valuable for physicians managing patients with both conditions. Patients with vitiligo and comorbid SSc might be monitored for cardiovascular and metabolic comorbidities.

Association between acetaminophen use and vitiligo in US women and men.

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.

Evaluation of CAT Variants A-89T, C389T, and C419T in Patients with Vitiligo in the Saudi Population.

Background and Objectives: Vitiligo is a chronic autoimmune and depigmentation disorder in humans that manifests as whitening lesions. Reactive oxygen species (ROS) are involved in cell damage. Catalase (CAT) is a well-known oxidative stress regulator and is primarily responsible for the catalytic decomposition of hydrogen peroxide into water and oxygen. Based on previous case-control and meta-analysis studies, we assessed the prevalence of three single-nucleotide polymorphisms (SNPs) of the CAT genes A-89T (rs7943316), C389T (rs769217) and C419T (rs11032709) in participants with vitiligo and healthy controls in the Saudi population. Materials and Methods: We recruited 152 participants with vitiligo and 159 healthy controls for A-89T, C389T, and C419T SNP genotyping studies using PCR and RFLP analysis. Additionally, we performed linkage disequilibrium and haplotype analyses between vitiligo cases and controls. Results: The rs7943316 and rs11032709 SNPs of the CAT genes showed a positive association with vitiligo for both heterozygous genotypes and dominant genetic models (TT + AT vs. AA in A-89T and TT + CT vs. CC in C389T), in the CAT gene. Linkage disequilibrium analysis revealed a moderate linkage between rs7943316 and rs11032709 SNPs in vitiligo cases and controls. Haplotype frequency estimation revealed a significant association (p = 0.003) among the three SNP alleles. Conclusions: The rs7943316 and rs11032709 SNPs of the CAT genes were strongly associated with susceptibility to vitiligo.

Prevalence of depression and anxiety among adults with vitiligo in a Malaysian tertiary hospital.

INTRODUCTION: Vitiligo is a chronic disorder resulting in skin depigmentation with reported global prevalence of 1-2%. This disease is often accompanied by psychosocial distress owing to the cosmetic disfigurement associated with it. The primary objective of this study was to determine the prevalence of depression and anxiety among adults with vitiligo in a local tertiary hospital. In addition, this study also evaluated the association of depression and anxiety with patients' characteristics. MATERIALS AND METHODS: This cross-sectional study was conducted among vitiligo patients aged 18 years and older in Hospital Klang, Selangor between October 2021 and June 2022. Assessment instruments used were Vitiligo Area Scoring Index (VASI) and Hospital Anxiety and Depression Scale (HADS). Demographic data and clinical characteristics of vitiligo patients were recorded. RESULTS: Of the 100 participants, 12 (12%) and 21 (21%) had depression and anxiety, respectively. The mean depression score (HADS-depression component) was 3.4 (SD 3.4) and mean anxiety score (HADS-anxiety component) was 4.7 (SD 3.9). There were significantly higher number of patients with abnormal HADS-D score in the age group of 35-51 years (p=0.029), single status (p=0.001), with employment (p=0.014) and disease duration <2 years (p=0.004). Patients in the divorced/widowed group had a significant association with anxiety (p=0.011). CONCLUSION: The prevalence of depression was 12% while anxiety was 21% in our cohort. Vitiligo has a significant psychosocial impact, thus clinicians should actively evaluate the mental health of these patients with the use of screening tools such as HADS and provide appropriate referrals and management.

Occurrence of inflammatory bowel disease in patients with chronic inflammatory skin diseases: a cohort study: Classification: Epidemiology.

BACKGROUND: Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) in a range of data sources with mixed conclusions. OBJECTIVES: We compared the incidence of IBD - ulcerative colitis (UC) and Crohn disease (CD) - in patients with a CISD vs. similar persons without a CISD. METHODS: In this cohort study using nationwide, longitudinal, commercial insurance claims data from the USA, we identified adults and children who were seen by a dermatologist between 2004 and 2020, and diagnosed with either psoriasis, atopic dermatitis, alopecia areata, vitiligo or hidradenitis suppurativa. Comparator patients were identified through risk-set sampling; they were eligible if they were seen by a dermatologist at least twice and not diagnosed with a CISD. Patient follow-up lasted until either IBD diagnosis, death, disenrolment or end of data stream, whichever came first. IBD events, UC or CD, were identified via validated algorithms: hospitalization or diagnosis with endoscopic confirmation. Incidence rates were computed before and after adjustment via propensity-score decile stratification to account for IBD risk factors. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated to compare the incidence of IBD in CISD vs. non-CISD. RESULTS: We identified patients with atopic dermatitis (n = 123 614), psoriasis (n = 83 049), alopecia areata (n = 18 135), vitiligo (n = 9003) or hidradenitis suppurativa (n = 6806), and comparator patients without a CISD (n = 2 376 120). During a median follow-up time of 718 days, and after applying propensity-score adjustment for IBD risk factors, we observed increased risk of both UC (HRUC 2·30, 95% CI 1·61-3·28) and CD (HRCD 2·70, 1·69-4·32) in patients with hidradenitis suppurativa, an increased risk of CD (HRCD 1·23, 1·03-1·46) but not UC (HRUC 1·01, 0·89-1·14) in psoriasis, and no increased risk of IBD in atopic dermatitis (HRUC 1·02, 0·92-1·12; HRCD 1·08, 0·94-1·23), alopecia areata (HRUC 1·18, 0·89-1·56; HRCD 1·26, 0·86-1·86) or vitiligo (HRUC 1·14, 0·77-1·68; HRCD 1·45, 0·87-2·41). CONCLUSIONS: IBD was increased in patients with hidradenitis suppurativa. CD alone was increased in patients with psoriasis. Neither UC nor CD was increased in patients with atopic dermatitis, alopecia areata or vitiligo. What is already known about this topic? Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) utilizing a range of data sources, with mixed conclusions. What does this study add? This large-scale, claims-based cohort study expands current knowledge by providing background rates for IBD across multiple CISDs using consistent methods and within a single, nationally representative patient population. We observed a relative increased risk of IBD in patients with hidradenitis suppurativa, but the overall incidence rate difference of IBD was generally low. Crohn disease alone was significantly increased in patients with psoriasis, and neither ulcerative colitis nor Crohn disease was increased in patients with atopic dermatitis, vitiligo or alopecia areata.

Altered Levels of Negative Costimulatory Molecule V-Set Domain-Containing T-Cell Activation Inhibitor-1 (VTCN1) and Metalloprotease Nardilysin (NRD1) are Associated with Generalized Active Vitiligo.

BACKGROUND: Vitiligo is characterized by depigmented macules on the skin caused due to autoimmune destruction of melanocytes. V-set domain-containing T-cell activation inhibitor-1 (VTCN1) is a negative costimulatory molecule that plays a vital role in suppressing autoimmunity and tuning immune response. Nardilysin (NRD1), a metalloproteinase, cleaves membrane-tethered VTCN1 resulting in the shedding of soluble-VTCN1 (sVTCN1). However, the role of VTCN1 and NRD1 in vitiligo pathogenesis is unexplored. OBJECTIVES AND METHODS: This study was aimed to (i) Investigate the association of VTCN1 intronic polymorphisms (rs10923223 T/C and rs12046117 C/T) with vitiligo susceptibility in Gujarat population by using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) (ii) Estimate VTCN1 & NRD1 transcript levels from peripheral blood mononuclear cells (PBMCs) and skin samples of vitiligo patients by real-time PCR, (iii) Estimate sVTCN1 and NRD1 protein levels from plasma by ELISA and (iv) Estimate VTCN1 protein levels in the skin samples of vitiligo patients by immunofluorescence. RESULTS: The analysis revealed increased VTCN1 and NRD1 transcript levels in the skin (p = .039, p = .021 respectively), increased sVTCN1 and NRD1 levels (p = .026, p = .015 respectively) in the plasma, and decreased VTCN1 protein levels (p = .0002) in the skin of vitiligo patients as compared to healthy controls. The genetic analysis revealed no significant association of VTCN1 intronic polymorphisms rs10923223 T/C and rs12046117 C/T with vitiligo susceptibility in Gujarat population (p = .359, p = .937, respectively). CONCLUSIONS: The present study revealed altered VTCN1 and NRD1 expressions in the blood and skin of vitiligo patients, suggesting their potential role in the development and progression of Vitiligo.

Ocular Abnormalities in Patients with Vitiligo: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitiligo is a skin depigmentation disorder that results from the autoimmune destruction of cutaneous melanocytes. Several ocular abnormalities, including uveitis, dry eye, glaucoma, and retinal diseases, have been reported in patients with vitiligo. The aim of our study was to investigate the association of ocular abnormalities with vitiligo. METHODS: This meta-analysis was registered in PROSPERO (CRD42021224167) and adhered to MOOSE checklist and PRISMA guidance for all processes. PubMed, Embase, Web of Science, and Cochrane databases were searched for studies examining the association between ocular abnormalities and vitiligo from inception to December 10, 2020. Studies recruiting patients with Sjogren's syndrome or Vogt-Koyanagi-Harada syndrome were excluded. The primary outcomes were the Schirmer test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) of vitiligo patients compared to the controls. The risk of bias of the selected studies was assessed using the Newcastle-Ottawa Scale (NOS) of case-control studies. RESULTS: This meta-analysis of 16 case-control studies showed that patients with vitiligo had significantly lower Schirmer test values (mean difference [MD], -1.65; 95% CI, -2.81 to -0.49), shorter TBUTs (MD, -4.66; 95% CI, -7.05 to -2.26), higher ocular surface disease indices (MD, 18.02; 95% CI, 5.7-30.35), and thinner subfoveal choroidal thicknesses (MD, -53.10; 95% CI, -69.84 to -36.36). No significant differences were found in the prevalence of glaucoma and the level of intraocular pressure. CONCLUSIONS: Our study supports an association between dry eye and thinner subfoveal choroidal thickness in patients with vitiligo. Dermatologists should be aware of these possible comorbidities and refer vitiligo patients with ocular symptoms to ophthalmologists for further management.