Segmental vitiligo (SV) is a distinct clinical subtype of vitiligo characterized by unilateral, sharply demarcated depigmentation, rapid progression and early stabilization, and frequent leukotrichia. Compared with non-segmental vitiligo (NSV), SV is generally less strongly associated with systemic autoimmunity, suggesting potential differences in pathogenic mechanisms, although overlap phenotypes and mixed presentations have been reported. Accumulating clinical, epidemiological, and mechanistic evidence supports the concept that SV arises from somatic mosaicism, in which post-zygotic genetic or epigenetic alterations occur during embryogenesis and give rise to a clonally distinct melanocyte population distributed along developmental territories. Embryologic studies indicate that melanoblast migration from the neural crest, coupled with high proliferative activity during early development, creates a permissive context for mosaic mutation accumulation. The resulting melanocyte clones align with Blaschko's lines or other embryonic patterning units, accounting for the segmental distribution of SV. Beyond melanocytes, segment-restricted abnormalities in neural and vascular structures have also been reported, raising the possibility of broader neurocutaneous mosaicism, although whether these changes are primary or secondary to localized immune injury remains unresolved. Recognizing SV as a mosaic disorder has important clinical implications, particularly for early intervention, recurrence risk assessment, and the prominent role of autologous surgical therapies. Future advances will depend on multi-omics approaches to identify causal mosaic mutations, refined disease models, and long-term registries to translate developmental insights into precision management strategies.

Vitiligo is an autoimmune disorder primarily categorized into non-segmental (NSV) and segmental (SV) subtypes. Interleukin-21 (IL-21) is a pleiotropic cytokine implicated in immune dysregulation. To investigate the association of serum IL-21 levels and two genetic variants (rs2055979 and rs4833837) with susceptibility to NSV and SV in an Iranian cohort. The study included 264 vitiligo patients (225 NSV, 39 SV) and up to 390 healthy controls. Serum IL-21 was measured by ELISA. Genotyping for rs2055979 was performed by RFLP-PCR, and for rs4833837 by ASO-PCR. Serum IL-21 levels were significantly elevated in both NSV (median 71.50 pg/mL) and SV (median 65.35 pg/mL) patients compared to controls (median 18.70 pg/mL; p < 0.0001). For rs2055979, the GT genotype was associated with increased risk of NSV (unadjusted OR = 2.99, 95% CI = 1.86-4.80, p < 0.0001; age- and sex-adjusted OR = 1.809, 95% CI = 1.061-3.085, p = 0.029) and SV (unadjusted OR = 4.29, 95% CI = 1.45-12.7, p = 0.005; adjusted OR = 3.486, 95% CI = 1.006-12.077, p = 0.049). The unadjusted G allele was a risk factor for NSV (OR = 1.52, 95% CI = 1.19-1.94, p = 0.0009) but not for SV (p = 0.09). The GG genotype also conferred elevated unadjusted risk for NSV (OR = 2.51, 95% CI = 1.44-4.37, p = 0.0009). In contrast, rs4833837 showed no significant association with either vitiligo subtype. The IL-21 rs2055979 polymorphism is associated with vitiligo susceptibility, with the GT genotype representing a risk factor for both NSV and SV after adjustment for age and sex. The marked elevation of serum IL-21 in both NSV and SV further supports a pathogenic role for IL-21, suggesting the IL-21/IL-21R axis as a potential therapeutic target.

Segmental vitiligo (SV) is a distinct subtype of vitiligo characterized by an early onset, unilateral distribution, and rapid stabilization. Although traditionally considered neurogenic in origin, recent evidence suggests an immune-mediated pathomechanism. However, the molecular mechanisms underlying SV remain poorly characterized, and therapeutic options are limited. Topical calcineurin inhibitors (TCI) are widely used in immune-mediated dermatoses, but clinical data supporting their use in SV are scarce. We conducted a retrospective observational study of paediatric patients with SV treated with TCI, recording demographics, disease duration and 3-month clinical response. In parallel, selected public transcriptomic datasets were re-analysed to examine enrichment of TCR/Ca2 + -calcineurin/NFAT-related pathways as supportive mechanistic context. Five of eight patients (62.5%) achieved significant repigmentation (VNS ≥ 4) after 12 weeks, with shorter disease duration correlating with better outcomes (p = 0.0002451). Early intervention determined good clinical response even in cases with leukotrichia, and no adverse effects were observed. Transcriptomic re-analysis provided supportive, descriptive signals consistent with activation of T-cell signalling and Ca2 + -calcineurin/NFAT pathways in SV blood, while proxy datasets from non-segmental vitiligo skin did not show similar enrichment. Overall, in this small retrospective paediatric case series, early use of topical calcineurin inhibitors was associated with favourable clinical outcomes in SV and demonstrated a good safety profile. Larger, prospective studies are warranted to confirm these preliminary findings and refine therapeutic strategies.

Introduction and Purpose: Vitiligo is a chronic, acquired autoimmune disorder characterized by the selective destruction of melanocytes, leading to the appearance of well-defined depigmented patches affecting the skin and mucous membranes. It is estimated to affect approximately 0.5 – 2% of the global population. Even though it was once regarded as mainly a cosmetic condition, now it is increasingly being recognized as a systemic disease with substantial psychological consequences. This review aims to summarize current knowledge regarding its genetic background, key immunological pathways and the emerging therapeutic approaches, constantly reshaping patient outcomes. Description of The State of Knowledge: Recent research has highlighted the complex nature of vitiligo pathogenesis, involving oxidative stress, genetic predisposition and immune-mediated mechanisms. In particular, the IFN-γ-chemokine axis, including CXCL9 and CXCL10, appears to play a central role in melanocyte loss. Clinically, Segmental Vitiligo usually follows a unilateral, dermatomal pattern and is often linked to somatic mosaicism, whereas Non-segmental Vitiligo remains as the most common form and typically presents with symmetrical distribution. Diagnostic precision has also advanced, through the introduction of non-invasive imaging techniques, including reflectance confocal microscopy and molecular biomarkers. From a therapeutic perspective, treatment strategies have moved beyond traditional phototherapy and topical agents to targeted interventions, most notably Janus Kinase inhibitors with ruxolitinib, representing one of the most promising options. Surgical procedures may also be considered in carefully selected patients with stable disease. Conclusions: Despite remaining a challenging dermatological condition, the progress made in understanding the immunological and molecular mechanisms underlying vitiligo, has opened new possibilities for more targeted and effective treatment. The modern approach increasingly combines precise diagnostic evaluation with individualized therapeutic strategies. Effective management now requires a holistic approach that balances both medical and psychological aspects faced by patients.

Shining Light on Treatments: A Systematic Review of Existing Therapies for Pediatric Segmental Vitiligo

A 34-year-old schoolteacher noticed small white patches spreading across her hands three weeks before her wedding—a scenario repeated thousands of times each year in Scandinavian dermatology clinics, yet one for which clinicians still lack reliable predictive tools. This research investigated the genetic underpinnings and treatment responses in a Danish cohort of 243 vitiligo patients enrolled between March 2020 and December 2021 at two academic medical centers. Whole-exome sequencing was performed to identify risk variants across established susceptibility loci, and treatment outcomes were compared across five therapeutic modalities. The HLA-A locus showed the highest variant frequency in generalized vitiligo at 52.6%, followed by TYR at 41.2%. Combination therapy involving narrowband ultraviolet B phototherapy with topical tacrolimus produced the highest mean repigmentation rates at 68.4%, surpassing monotherapy approaches. Autoimmune comorbidities were notably prevalent, with thyroid disease affecting 31.4% of participants compared to 9.2% in age-matched controls (OR 4.53, 95% CI: 2.87-7.14). Genetic profiling identified a novel FOXD3 variant enriched in segmental vitiligo at 35.1% versus 18.9% in generalized forms (p = 0.008). These findings point toward genotype-informed treatment selection as a promising direction for personalized vitiligo management.

Segmental vitiligo: A distinct entity with unique pathogenesis and clinical implications.

Abstract Vitiligo ( Baraṣ ) is a pigmentary disorder of the skin marked by circumscribed depigmented patches due to selective melanocyte loss, affecting 0.5%–2% of the population. The condition manifests as asymptomatic milky-white lesions that may be focal, segmental, or generalized. Conventional treatments, including corticosteroids, calcineurin inhibitors, phototherapy, and psoralen (PUVA), are often effective; however, they can induce adverse effects and may be refractory, particularly in cases of childhood or segmental vitiligo (SV). Herein we report a case of vitiligo which was treated with Unani drugs. A 10-year-old female presented with a 4-month history of depigmented patches on the right forehead, right angle of the mouth, jawline, and neck. Previous allopathic treatments provided no relief. She was prescribed topical application of Waj ( Acorus calamus Linn.) mixed with water and applied once daily in the morning to lesions. After 1 month of topical Waj application, approximately 40%–50% repigmentation was achieved. A notable improvement was observed primarily along the peripheral margins of the patches. Previously, depigmented areas had exhibited scattered islands of pigments that were slightly lighter than the surrounding normal skin. Smaller patches on the neck and the angle of the mouth showed near-complete repigmentation, whereas larger facial patches demonstrated partial repigmentation. No adverse events were reported. This case suggests that Unani therapy may serve as a safe, effective, and culturally acceptable alternative for SV. Further controlled studies are warranted to validate the efficacy of this treatment.

Chemically induced vitiligo is a disorder that can occur in genetically susceptible individuals after repeated exposure to a substance.Hydroquinone, a drug commonly found in skin depigmenting formulations, can induce or exacerbate vitiligo.We report a case of a patient who developed segmental vitiligo following the use of a topical depigmenting agent containing hydroquinone.We report the first case in the literature of hydroquinone-induced segmental vitiligo, during melasma treatment, in a genetically susceptible patient.This case highlights the importance of medical precaution when prescribing skin depigmenting agents to patients with a possible genetic predisposition to vitiligo.

Vitiligo is an acquired autoimmune depigmenting disorder that affects approximately 0.36% of the global population and presents in three forms based on lesion distribution: non-segmental, segmental and mixed vitiligo. Beyond its visible impact on the skin, vitiligo deeply affects mental well-being and quality of life. The pathogenesis of non-segmental vitiligo is influenced by genetic polymorphisms that are linked to immune response and melanogenesis pathways, whereas environmental factors contribute to disease onset. Diagnosis is generally clinical, with laboratory tests or biopsies rarely required. Melanocyte loss involves mechanisms, such as cellular stress, innate immune activation and adaptive immune responses, that specifically target melanocytes, with a central role for tissue-resident memory T cells. This cascade ultimately leads to the depletion of epidermal melanocytes and impairs melanocyte stem cell regeneration. Clinical management emphasizes shared decision-making with three primary objectives: halting depigmentation, initiating repigmentation and sustaining pigment restoration. Signs of active disease help clinicians toidentify patients in need of intervention. Treatments approved in the past 2 years offer potential for reversing disease progression, and emerging therapies targeting key pathways to modulate immune activation and stimulate melanocyte regeneration and differentiation are being tested in clinical trials.

Vitiligo is an acquired autoimmune disease characterized by depigmented macules resulting from melanocyte loss. It is a complex multifactorial disorder in which genetic predisposition is combined with environmental factors; however, its detailed etiology remains unclear. Although Janus kinase (JAK) inhibitors have recently emerged as a therapeutic option, the range of available molecularly targeted drugs is limited compared to those for atopic dermatitis or psoriasis, necessitating an urgent elucidation of its pathogenesis. The pathogenesis of vitiligo is centrally mediated by cytotoxic CD8+ T cells (CTLs) specific for melanocyte antigens and their production of interferon-gamma (IFN-γ). In recent years, however, the involvement of other immune cells, such as resident memory T cells and regulatory T cells, innate immune cells, and non-immune cells including keratinocytes and fibroblasts has also garnered attention. Furthermore, pathogenic alterations are also present in clinically normal-appearing non-lesional skin, indicating that this tissue is "primed" for disease development. This finding supports a paradigm shift toward viewing vitiligo as a systemic disease rather than a localized skin disorder. Herein, this review summarizes the current knowledge on the factors leading to the onset and progression of non-segmental vitiligo, while also briefly addressing segmental vitiligo.

Abstract Background VItiligo, the most common depigmented disorder, is an acquired disease characterized by progressive loss of melanocytes. Vitiligo occurs worldwide with an estimated prevalence of 0.5-1% in most populations. Objective To compare the effect of topical MTX 1% gel with microneedling versus microneedling alone in stable non segmental vitiligo. Patients and Methods This prospective self-controlled clinical trial included 30 patients diagnosed with stable non segmental vitiligo. Patients were randomly selected from outpatient clinic at Dermatology, Venereology and Andrology department, Ain shams university hospitals over 10 months from January 2023 to October 2023. Results Our results revealed statistically significant better response 2weeks after last session and at follow-up visit compared to before treatment with Physician’s Global Assessment. However, no significant difference was detected with VESTA score. Statistically significant higher patients’ satisfaction was noticed with microneedling and MTX compared to microneedling alone. Concerning the side effects, the most common side effects reported in microneedling and MTX treated lesions were peri- lesional hyperpigmentation followed by erythema then mild pain and exfoliation, while in microneedling treated lesions there were erythema followed by mild pain. Conclusion Our findings, topical MTX after microneedling is safe and tolerable method of treatment of stable non-segmental vitiligo. It can induce repigmentation in vitiligo lesion. However, it is better to be used as an adjuvant therapy with other modalities of treatment to improve the results.

Vitiligo is an acquired pigmentation disorder. Childhood vitiligo can differ from adult-onset vitiligo in several aspects. We aimed to evaluate demographics, clinical features of vitiligo in children, and laboratory results. A retrospective, cross-sectional study was conducted on &amp;lt; 18-year-old pediatric patients with vitiligo. Demographics, clinical features, and laboratory test results performed at the time of diagnosis were retrieved from medical records. Vitiligo was classified as non-segmental (NSV), segmental (SV), and unclassified vitiligo. A total of 179 patients were included. The female/male ratio was 1.2/1. The most common form was NSV (87.7%), followed by SV (7.3%). Among NSV, generalized vitiligo was the most common subtype (42.5%), followed by localized (32.4%) and acrofacial (8.9%) vitiligo. Vitiligo began ≤ 12 years of age in 156 (88.6%) patients. NSV and SV were not significantly different in sex, age of disease onset, disease duration, halo nevi, or Koebner phenomenon. Leukotrichia was more common in SV (84.6%) than NSV (7.6%) (P &amp;lt; 0.001). Face (67.6%) was the most frequently involved body site. Neutrophil percentage, mean platelet volume (MPV), MPV/platelet ratio, MPV/lymphocyte ratio, neutrophil/lymphocyte ratio (NLR), derived NLR, and systemic inflammatory response index were significantly lower in patients with early-onset (≤ 12 years) vitiligo (P &amp;lt; 0.05), possibly indicating the differences in inflammatory response between young children and adolescents. It was noteworthy that eosinophil counts, eosinophil/monocyte ratio, and eosinophil/neutrophil ratio were significantly lower in female patients (P &amp;lt; 0.05), which might reflect the effect of sex hormones on eosinophils. Further studies are warranted to extend our results.

Segmental vitiligo, segmental morphea, and lichen striatus are distinct dermatological conditions that may share pathogenic mechanisms involving genetic mosaicism and immune dysregulation. Their simultaneous occurrence is extremely rare and may offer insights into their shared etiology. A 24-year-old female presented with a 6-year history of progressive indurated and discolored skin lesions. Dermatological examination revealed dermatomal depigmented macules consistent with segmental vitiligo on the right trunk, a violaceous Blaschkoid macule compatible with lichen striatus on the right lateral trunk, and multiple sclerotic plaques on the left side, consistent with segmental morphea. Histopathological examination confirmed the diagnosis of all three entities: loss of melanocytes in vitiligo, dermal sclerosis in morphea, and epidermal spongiosis with lymphocytic infiltrates and melanophages in lichen striatus. To our knowledge, this is the first reported case presenting the concurrent manifestation of segmental vitiligo, segmental morphea, and lichen striatus in the same patient. The segmental and Blaschkoid distribution patterns support a common pathogenic basis likely rooted in genetic mosaicism triggered by an autoimmune mechanism. Recognition of this rare co-occurrence may help elucidate the shared immunopathological mechanisms underlying these conditions.

The progression of non-segmental vitiligo is highly unpredictable, exhibiting various phenotypes that can range from rapid progression to stability. Due to limited literature, we conducted a scoping review to identify factors influencing the outcomes of non-segmental vitiligo, focusing on disease progression, extent, and response to therapy. This review adhered to PRISMA-ScR guidelines and involved searching the PubMed and Google Scholar databases for studies published in English from January 1995 to December 2023. We included observational, retrospective, case-control, and cohort studies while excluding case reports, systematic reviews, meta-analyses, and studies on segmental vitiligo. Out of 922 records identified, 819 were screened, resulting in 792 exclusions based on titles or abstracts. Ultimately, 22 articles were selected for review after evaluating the full texts of 27 articles. Several factors were consistently linked to poorer prognoses in multiple studies: family history of vitiligo, mucosal involvement, Koebnerization, and the presence of adverse clinical markers. Age of onset yielded conflicting results regarding disease progression but showed general agreement concerning the extent of involvement. Specific lesions such as confetti-like lesions were also associated with progression in limited studies. Additionally, longer disease duration, leukotrichia, and mucosal involvement correlated with a greater body surface area affected by vitiligo, often resulting in poor repigmentation responses to medical treatments. Patients exhibiting poor prognostic markers-such as family history, mucosal lesions, or Koebnerization-should be advised to monitor for new lesions closely and consider early treatment initiation. Understanding the factors influencing the course of non-segmental vitiligo's course can guide clinicians in tailoring management strategies that reflect individual patient needs while considering the complexities associated with this condition. A prospective study with at least 1 year of follow-up is needed to comprehensively describe observed progression, along with well-defined predictors and outcome measures including temporal course patterns. Prospero Registration: CRD42023446544.

Background:Vitiligo is chronic autoimmune disease characterized by pale white patches developing on the skin caused by lack of melanin pigment which produced by melanocytes. Most common autoimmune disease association with vitiligo is autoimmune thyroid disease that characterized by presence of autoantibody (anti-thyroperoxidase, anti-thyroglobulin) in serum of vitiligo patients. Aim of study:Detection of serum anti-thyroperoxidase and anti-thyroglobulin antibodies in patients with non-segmental vitiligo.Subject and Methods:Serum level of Anti-thyroperoxidase and anti-thyroglobulin antibodies were assessed in 50 non segmental vitiligo patients in the dermatology Consultation Clinic of IMAM ALSADIQ Teaching Hospital / Babil Health Directorate compare with 30 apparently healthy control, their age and sex matched to the patients&rsquo; group, number of males in this study was 46 (57.5%) and female were 34 (42.5%)., using enzyme linked immunosorbent assay (ELISA) technique in the medical city\teaching laboratories\immunity unit. Results:Found significant association between positive anti &ndash;thyroperoxidase antibody and vitiligo patients p value 0.036, the rate of anti-TPO positive in males (80 %) more than females (20%) p value=0.058 and no significant association between positive anti &ndash; thyroglobulin antibody and vitiligo patients p value 0.0596. Both antibodies were elevated in same patient . Conclusion:Both antibodies could be used as screening test to autoimmune thyroid diseases in vitiligo patients.

Introduction: Vitiligo is characterised by a patchy loss of skin pigmentation, which most commonly occurs due to the immune system targeting melanocytes in the epidermis. A few studies have shown the effectiveness of Homoeopathy in halting the progression and replacing the hypo-pigmented patches with normal-pigmented skin. Case Summary: A 15-year-old boy came to the clinic complaining of white patches that appeared suddenly on various parts of his body within one week. Tuberculinum proved to be the constitutional medicine in this case. The photographic evidence taken at regular intervals and a follow-up of over nine months showed the potential of constitutional homoeopathic prescription for treating and managing difficult-looking segmental vitiligo. The Vitiligo Symptom Scale was used to show the regression in the vitiligo patches with the help of individualised homoeopathic medicine. Modified Naranjo Criteria for Homeopathy (MONARCH) was used to assess the correlation between the treatment and outcome.

Vitiligo is a complex acquired pigmentary disorder whose pathogenesis is closely linked to oxidative stress. Although bilirubin, a potent endogenous antioxidant, has been implicated in various dermatological conditions, its specific role in vitiligo remains poorly defined. This study aims to investigate the causal associations between bilirubin and vitiligo using Mendelian randomization (MR) analysis, complemented by bioinformatics validation to unravel the underlying molecular mechanisms. Genome-wide association study (GWAS) data pertaining to vitiligo and bilirubin were obtained, followed by the execution of a bidirectional MR analysis. Additionally, we performed a bioinformatics analysis using microarray datasets to identify differentially expressed genes (DEGs) in relation to bilirubin in patients with vitiligo. Pathway enrichment and gene interaction networks were constructed to explore the molecular mechanisms linking bilirubin to vitiligo pathogenesis. Forward MR analysis demonstrated a significant causal relationship between elevated levels of total bilirubin (P=0.038) and direct bilirubin (P=0.013) with reduced risk of vitiligo. In contrast, reverse MR analysis showed no significant causal effect of vitiligo on bilirubin (P>0.05). Bioinformatics analyses identified 136 DEGs in generalized vitiligo, 32 in segmental vitiligo, and 9 in non-segmental vitiligo. Enrichment analysis highlighted significant associations with oxidative stress-related pathways, including PI3K-Akt and JAK-STAT signaling, which are critical in melanocyte survival and immune regulation. This study provides robust evidence supporting a causal relationship between elevated bilirubin and a reduced risk of vitiligo, driven by its antioxidant properties. The identified DEGs and enriched pathways further elucidate the molecular mechanisms of bilirubin in the pathogenesis of vitiligo through oxidative stress, and may provide insights for future therapeutic strategies.

Varicella zoster virus-induced depigmentation in pre-existing segmental vitiligo: Wolf’s isotopic response

Vitiligo is the most common skin depigmentation disease, affecting 0.1%-2% of people in the world. 3.5%-20.5% of segmental patients account for the total number of vitiligo patients. It has been clinically observed that segmental vitiligo patients are more likely to generate white hair, which may be related to neuroendocrine factors. The color of human skin and hair is affected by the number and functional status of melanocytes. Vitiligo affects patients' physical and mental health due to the shame it causes from the white patches and hair. This article reviews the underlying mechanisms of segmental vitiligo with white hair based on skin and hair follicle melanocytes. The article attempts to propose possible targets for the treatment of this disease.