An acquired pigmenting disorder, vitiligo, occurs worldwide with a prevalence of 0.5-2% and in India with 0.25%-4%. Stress-related pathways are involved may contribute to autoimmune melanocyte loss and HSP 70 (a stress-response molecular chaperone with immune- modulatory effects) may be a key link between stress and disease activity. In this case-control study, 40 vitiligo patients and 40 age and sex-matched controls underwent skin biopsies (lesional and non-lesional skin in patients; normal skin in controls) and HSP 70 mRNA expression was quantified using real-time PCR; patients were also grouped as highly active, moderately active or inactive based on clinical activity. Lesional vitiligo skin showed significantly higher HSP 70 expression than non-lesional skin and control skin (both P < 0.001), with higher mean levels in active compared with inactive vitiligo, while no association was found with age, sex or disease duration-supporting a role of HSP 70-related stress mechanisms in vitiligo pathogenesis and activity.

Disfiguring skin diseases refer to skin diseases that significantly affect one's appearance. The development of disfiguring skin diseases is multifactorial, such as genetic, immune, and endocrine factors. However, recent research suggests that emotional distress (such as anxiety, depression, and sleep disorders) has been implicated as a key contributing factor to the onset and progression of disfiguring skin diseases, including acne, rosacea, and vitiligo; in turn, the psychosocial burden imposed by these conditions exacerbates emotional disturbances, thereby creating a self-perpetuating vicious cycle. Therefore, understanding the relationship between emotional distress and disfiguring skin diseases is essential. In recent years, the proposed concept of the "brain-skin axis" has framed the nervous, endocrine, and immune systems as an intricate regulatory network, highlighting the multilayered connections between the brain and the skin. Within the mechanistic framework of the brain-skin axis, emotional distress may alter neural and endocrine signaling, potentially disrupt normal skin homeostasis, exacerbate inflammatory responses and immune dysregulation, and impair skin barrier function; based on experimental and observational evidence, these changes may elevate susceptibility to disfiguring skin diseases. In this review, we examined the complex relationship between emotional distress and three disfiguring skin diseases (acne, rosacea, and vitiligo) from the perspective of the brain-skin axis. We also discussed the potential value of various psychosomatic interventions, including psychotherapy, pharmacotherapy and integrated therapy in improving both dermatological symptoms and psychiatric comorbidities. Understanding the interactions and mechanisms linking emotional distress and disfiguring skin diseases through the lens of the brain-skin axis can provide new insights into the diagnosis and treatment of these skin conditions.

Traditionally, vitiligo is known as a cutaneous autoimmune disease characterized by progressive melanocyte loss. However, this paradigm alone does not fully explain disease chronicity, relapse, or the limited therapeutic responses. Evidence supports a broader conceptual framework in which vitiligo is sustained by defective immune control of dysregulated responses, coupled with impaired regeneration, resulting in persistent inflammation and failure to restore cutaneous homeostasis. Here, we reinterpret vitiligo immunopathogenesis as a disorder of failed restoration of immunological homeostasis, extending beyond classical immune activation to include defects in regulatory mechanisms that normally constrain autoreactive responses. Rather than focusing exclusively on broad immunosuppression, emerging strategies increasingly aim to restore local immune regulation, constrain pathogenic immune memory, and preserve or reconstitute melanocyte regenerative niches. Advances in cutaneous immunology and biotechnology have expanded the therapeutic landscape to include targeted cytokine and kinase inhibition, immune checkpoint modulation, pro-melanogenic and regenerative approaches, cell- and vesicle-based therapies, nucleic acid-based interventions, and advanced skin delivery systems. Accumulating knowledge supports combined and sequential treatment paradigms integrating immune modulation, induction of repigmentation, and long-term maintenance. Nevertheless, translation into routine clinical practice remains limited by cutaneous pharmacokinetic barriers, regulatory and manufacturing constraints, and the lack of long-term safety and efficacy data. Within this evolving landscape, precision medicine offers a framework for patient stratification, therapeutic timing, and rational treatment design. Importantly, many of these approaches remain in early or preclinical stages, highlighting the need for robust translational validation. On the other hand, delivery platforms based on nanotechnology emerge as potential tools capable of bridging diverse therapeutic modalities by enhancing stability, targeting, and cutaneous bioavailability. Finally, this review positions vitiligo as a disease of failed immune resolution and impaired tissue regeneration, highlighting precision immunoengineering and technological innovation as promising pathways toward more targeted, personalized, and durable disease-modifying therapies.

Oxidative stress is identified as a potential factor in vitiligo pathogenesis. We aimed here to evaluate whether USP11 regulates the oxidative stress of melanocytes in vitiligo. Human melanocyte PIG1 cells were induced with 1 mM H2O2 and pre-infected with lentiviruses for genetic intervention. The dorsal skin of C57BL/6J mice was applied with 5% H2O2, and genetic intervention was elicited through adenoviruses. USP11, SIRT3, and TRIM28 were reduced in melanocytes (Melan-A positive) from vitiligo mouse skin tissues and in the H2O2-induced PIG1 cells. TRIM28 transcriptionally activated USP11 to promote deubiquitination of SIRT3. H2O2 decreased viability and melanin and tyrosinase contents and increased apoptosis and oxidative stress in PIG1 cells. H2O2 induced severe depigmentation of the dorsal skin in mice, reduced melanin deposition in hair follicles, loss of melanocytes, and increased oxidative stress. Overexpression of either USP11 or TRIM28 inhibited H2O2-induced melanocyte damage and vitiligo, while combined knockdown of SIRT3 or USP11 reversed the effects of USP11 or TRIM28 overexpression. These findings suggest that TRIM28 exerts its effect by reducing oxidative stress in melanocytes through USP11-mediated SIRT3 deubiquitination. This observation provides a mechanistic insight that could inform future therapeutic exploration in vitiligo. Graphical abstract text. The diagram. TRIM28 inhibits oxidative stress damage in melanocytes and alleviates vitiligo by transcriptionally upregulating USP11 and promoting deubiquitination modification of SIRT3.

Vitiligo is a chronic depigmenting disorder characterized by oxidative stress-driven melanocyte loss and T cell-mediated immune activation. While melanocytes and keratinocytes have been extensively studied, the contribution of dermal fibroblasts to the oxidative and immune microenvironment remains unclear. Here, we identify the mitochondrial translocator protein (TSPO) as a key regulator of redox, inflammatory, and adhesion signaling in dermal fibroblasts. TSPO expression was markedly upregulated in both H2O2-treated fibroblasts and skin biopsies from vitiligo patients, suggesting a compensatory response to oxidative injury. TSPO deficiency aggravated mitochondrial dysfunction, lipid peroxidation, and apoptosis, while its overexpression restored mitochondrial potential, ATP production, and calcium homeostasis. Mechanistically, TSPO activated the p62/Keap1/Nrf2/HO-1 pathway to enhance antioxidant defense and concurrently suppressed NF-κB, NLRP3, and STAT1 signaling, reducing the expression of pro-inflammatory mediators and adhesion regulators. Pharmacological activation of TSPO with the high-affinity ligand Ro5-4864 restored mitochondrial function, reinforced antioxidant capacity, and alleviated depigmentation in an H2O2-induced vitiligo mouse model, while also diminishing CD8[+] T cell infiltration and enhancing HO-1 expression. Our findings establish TSPO as a mitochondrial safeguard in dermal fibroblasts, integrating redox control and inflammatory restraint, and highlight TSPO ligands as promising therapeutics for vitiligo.

Psoriasis frequently coexists with other immune-mediated conditions such as arthritis, alopecia areata, vitiligo, and hidradenitis suppurativa, many of which remain challenging to manage. To date, there have been rarely reported cases of treating psoriasis combined with lichen planus. We report a case of coexisting psoriasis and lichen planus in a female patient. Despite initial efficacy with acitretin and topical mometasone, the patient self-discontinued treatment over safety concerns, prompting a relapse. Upadacitinib was subsequently initiated and yielded marked improvement within 3 months. By discussing the disease interplay and treatment rationale, this report seeks to inform clinical decision-making.

Lentigines, café-au-lait macules (CALMs), and vitiligo are pigmentary disorders that seldom occur together in a single individual. Their co-occurrence may indicate underlying genetic syndromes requiring differential diagnosis. We report an 18-year-old male who developed CALMs at age 11, agminated lentigines at age 13, and vitiligo on the right chest six months thereafter. Comprehensive examinations excluded Peutz-Jeghers syndrome, Leopard syndrome, Carney complex, and Neurofibromatosis type 1. Eight-year follow-up-the longest reported for this combination-demonstrated a benign natural history: Stable vitiligo throughout and lentigines reaching a plateau by early adulthood. Negative autoimmune screening suggests localized immune dysregulation, supporting the Immunocompromised Cutaneous District hypothesis. A staged therapeutic approach prioritizing vitiligo stabilization is recommended.

As cellular energy metabolic hubs, mitochondria undergo dynamic fusion-fission cycles and autophagy that enable rapid adaptation to cellular energy demands and stress conditions. In addition to their role in energy metabolism, mitochondria are integral to cellular homeostasis and regulate cell cycle progression, differentiation, and apoptosis pathways. In recent years, the importance of mitochondrial function in skin health and disease has garnered increasing attention. Mitochondrial dysfunction has been implicated in a spectrum of skin disorders, including skin aging, psoriasis, vitiligo, keloids, scleroderma, and skin cancer. The pathogenesis of these conditions is closely linked to mitochondrial deoxyribonucleic acid (mtDNA) damage, excessive reactive oxygen species (ROS) production, and alterations in mitochondrial metabolic pathways. In terms of therapeutic strategies, this review summarizes a range of mitochondrion-targeted interventions. These treatments include the activation of the PGC-1α pathway to increase mitochondrial adenosine triphosphate synthesis, the use of antioxidants to mitigate mitochondrial ROS production, and the application of bioactive compounds and drugs to protect mitochondria or promote mtDNA repair. These approaches not only contribute to improved skin health but also provide novel insights for the treatment of skin diseases. Additionally, mitochondrial transplantation technology has shown considerable promise in skin regeneration and wound healing and is emerging as a new frontier for skin tissue repair.

Vitiligo is a chronic depigmenting disorder that imposes a substantial psychological, social, and economic burden, extending beyond its physical manifestations. This narrative review synthesizes and critically evaluates current evidence on the determinants of quality of life impairment among individuals with vitiligo. A review of the published literature was conducted, focusing on studies evaluating health-related quality of life, psychosocial outcomes, stigma, psychiatric comorbidities, and validated quality of life assessment instruments in patients with vitiligo. Evidence from systematic reviews, cohort studies, cross-sectional analyses, and instrument validation studies was examined to identify the clinical, demographic, and sociocultural factors associated with disease burden. Across studies, vitiligo was consistently associated with significant impairment in psychological and social domains of quality of life. Disease visibility, particularly involvement of the face or genital regions; greater body surface area involvement; active disease progression; and longer disease duration emerged as key clinical factors associated with worse outcomes. Several demographic and sociocultural characteristics, including female sex, younger age, darker skin phototype, unmarried status, and residence in highly stigmatizing cultural environments, were also associated with greater quality of life impairment. Depression and anxiety were more frequently reported in individuals with vitiligo than in the general population, with pediatric and adolescent patients demonstrating particularly high vulnerability. Although dermatology-specific instruments such as the Dermatology Life Quality Index are commonly used in research and clinical practice, vitiligo-specific tools may more accurately capture stigma, social participation limitations, and disease-specific psychosocial impact. Overall, the available evidence indicates that vitiligo imposes a profound psychosocial burden that often exceeds the objective clinical severity of depigmentation. Quality of life impairment appears to be driven primarily by lesion visibility, sociocultural context, and psychological comorbidity rather than symptom severity alone. These findings underscore the importance of incorporating validated quality of life assessment tools into routine clinical care, screening for psychiatric comorbidities, and adopting culturally sensitive and patient-centered approaches to vitiligo management.