Vitiligo is an acquired depigmenting disorder characterized by destruction of epidermal melanocytes and skin depigmentation. Although treatments have developed substantially, there is still a considerable proportion of vitiligo patients fail to achieve satisfactory repigmentation or experience disease recurrence after treatment withdrawal. Vitiligo treatment failure involves heterogeneous clinical states, including persistent disease activity, treatment resistance, site-related limitations, and disease recurrence. Importantly, refractory and recurrent vitiligo are heterogeneous and partially overlapping clinical issues rather than a single biological damage requiring a uniform management strategy. Oxidative stress serves as a critical factor in the pathogenesis of vitiligo, linking melanocyte injury, release of danger-associated molecular patterns (DAMPs), innate immune activation, and IFN-γ driven adaptive immune amplification, associated with active and refractory disease. Interleukin (IL)-15-dependent tissue-resident memory T (TRM) cells provide a mechanism for local immune reactivation and recurrence. However, the role of oxidative stress in treatment resistance and recurrence remains incompletely defined. Importantly, available studies of antioxidant therapy are heterogeneous, with no evidence demonstrates that antioxidant therapy eliminates TRM cells or prevents recurrence. In this review, we propose a hypothesis-generating clinical framework that distinguishes refractory and recurrent vitiligo based on disease activity, IFN-γ signaling, anatomical sites, phototherapy responses and recurrence risk. Currently, antioxidant therapy should be considered as an investigational adjunctive therapy. The review investigates the relationship between oxidative stress and antioxidant therapy in refractory and recurrent vitiligo, and evaluates the role of antioxidant therapy in the management of vitiligo. In the future, it will be essential to conduct prospective biomarker based stratified clinical trials to define the targeted vitiligo patients for antioxidant combination therapies, as well as to continuously develop novel antioxidant-based anti-inflammatory therapeutic approaches for refractory and recurrent vitiligo.

Transient Receptor Potential Melastatin 2 (TRPM2), a Ca[2+]-permeable cation channel, regulates innate and adaptive immunity and has recently been implicated in vitiligo, an autoimmune pigmentary disorder. However, whether TRPM2 exerts cell-autonomous immunoregulatory functions and how such signaling intersects with pigmentation remain unknown. Here, we reveal an unexpected role for TRPM2 as an intrinsic suppressor of pigmentation through type-I interferon (IFN) signaling in melanocytes. Pharmacological inhibition, genetic silencing, and gain-of-function approaches demonstrate that TRPM2 negatively regulates melanogenesis in vitro. Notably, TRPM2-deficient zebrafish and TRPM2[-]/[-] mice exhibit enhanced pigmentation in vivo, establishing physiological relevance. Transcriptomic profiling uncovers autonomous activation of the type-I-IFN pathway upon TRPM2 loss, leading to induction of IFN-stimulated gene 15 (ISG15). Mechanistically, ISG15 attenuates global ubiquitination and stabilizes microphthalmia-associated transcription factor (MITF), the master regulator of melanogenesis, thereby promoting pigmentation. Collectively, our findings define a previously unrecognized TRPM2-type-I-IFN-ISG15-MITF signaling axis that functionally integrates cell-autonomous immune surveillance pathways with pigmentary control. Further, it provides a conceptual framework linking type-I-IFN signaling to pigmentation homeostasis and pigmentary disorders.

Myelin oligodendrocyte glycoprotein antibody-associated disease is a demyelinating disorder affecting the central nervous system. Autoimmune regulator mutations disrupt central tolerance and cause immunodeficiency and autoimmune manifestations. We report the case of a 49-year-old Asian male with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease and a heterozygous dominant-negative autoimmune regulator mutation (c.901G > A, p.Val301Met), alongside vitiligo, cryptococcal disease and nasopharyngeal carcinoma. This case raises a potential link between negative selection failure and myelin oligodendrocyte glycoprotein antibody-associated disease and suggests that autoreactive T cells may be primary pathogenetic drivers, implying that restoring immune tolerance could inform future therapeutic approaches.

Hypopigmented disorders in childhood encompass a broad spectrum of presentations, including depigmentation, hypopigmentation, and pseudo-hypopigmentation arising from non-melanin mechanisms. In clinical practice, the primary challenge often lies in distinguishing these conditions from vitiligo, the most common acquired depigmentation disorder. Although vitiligo is categorized into nonsegmental and segmental subtypes, many children initially present with an undetermined or focal form before the clinical subtype is clearly established. A systematic diagnostic approach begins with Wood's lamp examination and ultraviolet photography to distinguish complete depigmentation from partial hypopigmentation, followed by assessment of onset, extent, distribution, and associated extracutaneous manifestations. Accurate diagnosis enables early therapeutic intervention for vitiligo, averts unnecessary anxiety regarding self-limiting conditions, and prompts appropriate systemic evaluation. This review provides a comprehensive, evidence-based clinical framework for the differential diagnosis of pediatric hypopigmented disorders, highlighting key diagnostic clues to facilitate accurate diagnosis and optimal management.

Facial vitiligo affects a substantial proportion of patients with vitiligo and is associated with significant psychosocial burden due to its visibility. Facial vitiligo is primarily classified into nonsegmental and segmental subtypes, each with distinct distribution patterns and prognostic features. Nonsegmental vitiligo is further divided into 3 morphological patterns-centrofacial, panfacial, and hairline-each with unique clinical characteristics and treatment responses. The pathogenesis is multifactorial, involving genetic susceptibility, oxidative stress, and autoimmune destruction of melanocytes. Diagnosis is primarily clinical, supported by Wood lamp examination, dermoscopy, and advanced imaging techniques. First-line treatment includes topical calcineurin inhibitors and ruxolitinib, often combined with phototherapy to maximize repigmentation. The 308-nm excimer laser offers targeted delivery of ultraviolet (UV) radiation, minimizing photodamage to uninvolved skin. For progressive disease, systemic corticosteroids are commonly used for stabilization, with methotrexate, cyclosporine, or azathioprine as alternatives. Surgical interventions, particularly micropunch grafting, are effective options for stable, treatment-refractory cases. Emerging therapies, including oral Janus kinase inhibitors and biologics targeting tissue-resident memory T cells, are under investigation with encouraging preliminary results. Lifestyle modifications, including avoidance of mechanical friction, UV protection, and antioxidant-rich dietary patterns, may serve as supportive adjuncts to medical therapy. Recognizing the clinical heterogeneity of facial vitiligo, this review highlights the necessity of individualized treatment strategies based on clinical phenotypes to optimize therapeutic outcomes and improve quality of life.

Chronic skin diseases such as psoriasis, vitiligo, eczema, and acne can have substantial psychosocial effects beyond physical symptoms. Visible dermatological conditions often lead to stigmatization, which may negatively influence social interactions, emotional well-being, and quality of life. However, limited research has examined perceived stigmatization among patients with chronic skin diseases in the Eastern Province of Saudi Arabia. This study aimed to quantify and compare perceived stigmatization among patients with chronic skin diseases and identify demographic and clinical factors associated with stigma severity. A cross-sectional study was conducted among 446 patients with chronic skin diseases. Data were collected using a structured questionnaire, including sociodemographic characteristics, clinical information, and the 6-Item Stigmatization Scale. Descriptive statistics were used to summarize participant characteristics. Independent t-tests, one-way analysis of variance (ANOVA), and multivariable linear regression analysis were performed to examine associations between stigma scores and demographic and clinical variables. A total of 446 participants were included, with females comprising 264 (59.2%) and most aged 18-40 years (291, 65.2%). Vitiligo (114, 25.6%) and psoriasis (102, 22.9%) were the most common conditions. Many participants reported stigma-related experiences, including feeling unattractive sometimes or very often (326, 73.0%). Stigma scores were significantly higher among males than females (8.12±3.93 vs. 7.03±4.73, p=0.011) and varied by monthly income (p<0.001). Stigma also differed across disease types (p<0.001), with the highest scores among vitiligo patients (8.74±3.98). In regression analysis, gender (B=1.039, p=0.016), age at disease onset (B=0.052, p=0.002), disease duration (B=-1.268, p=0.003), and family history (B=1.825, p<0.001) were significant predictors of stigma. To conclude, stigmatization is a common psychosocial burden among patients with chronic skin diseases. Addressing stigma through patient support, public education, and integrated psychological care may help improve the well-being of affected individuals.

Vitiligo is an acquired depigmentation disorder characterized by the loss of epidermal melanocytes and can markedly impair patients' quality of life. Because of its dual effects on immunosuppression and repigmentation, UVB phototherapy has become a first-line treatment for vitiligo. It is particularly valuable in inducing repigmentation of skin lesions. Since epidermal melanocytes are markedly reduced or even absent in vitiligo lesions, migration of melanocyte stem cells (McSCs) from the hair follicle bulge to the interfollicular epidermis is considered a critical step in UVB-induced repigmentation, as it enables the replenishment of epidermal melanocytes. Therefore, this review summarizes the molecular mechanisms by which UVB induces McSC migration. Current evidence suggests that UVB primarily regulates McSC migration, proliferation, and differentiation indirectly by remodeling the McSC niche. In this process, keratinocytes, inflammatory cells, and other niche-associated cells release multiple paracrine mediators, including SCF, EDN1, bFGF, PGE2, and WNT. These factors coordinately regulate the physiological activities of McSCs. In addition, we propose that changes in the expression of melanocyte surface receptors may be an important limiting factor governing the migratory response of McSCs. This review also discusses the molecular markers of McSCs and the physiological changes that accompany their migration. Based on current evidence, we further hypothesize that some melanocytes migrating to the epidermis may retain the ability to dedifferentiate and return to the hair follicle. This process may represent an important mechanism by which UVB-induced McSC migration does not deplete the McSC reservoir.