Both poliosis (circumscribed depigmentation of the hair in any area of the body) and halo nevi (a melanocytic nevus which acquires a surrounding depigmented rim) are characterized by depigmentation driven by a T-cell-mediated loss of functional melanocytes within the epidermis and hair bulbs. Halo nevi and poliosis are a relatively frequent phenomenon occurring in 1% of the children and adolescents with an average age of onset of 15 years and has no gender predisposition. Both can be associated with vitiligo and are occasionally seen together as the same cytotoxic immune response (specifically CD8+ T cells) that destroys nevus melanocytes which can attack the same melanocyte-specific targets surrounding epidermal and follicular melanocytes. While poliosis is frequently seen on the scalp, halo nevi on the scalp have been scarcely reported in the literature. The timing of occurrence of the destruction of both epidermal and follicular melanocytes may be supported by a case of a 13-year-old Caucasian male with three halo nevi on the trunk which preceded the development of four scalp patches of poliosis. This may indicate that the halo nevi on the trunk induced a temporary systemic autoimmune reaction during the halo phenomenon, collaterally destroying melanocytes at distance on the scalp causing poliosis.

Vitiligo is an immune-mediated disease characterized by depigmentation of the skin. Although transcriptomic studies have advanced the mechanistic understanding of the disease, comprehensive proteomic characterization of vitiligo-affected skin is lacking. This study aimed to investigate proteomic alterations in non-segmental vitiligo. Punch biopsies (2 mm) were collected from lesional (n = 10), perilesional (n = 62), and non-lesional skin (n = 62) from patients with vitiligo and from demographically matched (age, sex, and anatomical site) healthy controls (n = 12). Proteomic profiling was performed using mass spectrometry, and the data were analyzed in pairwise comparisons. The proteomic analyses quantified a total of 4556 proteins, including 40 differentially expressed proteins (false discovery rate <0.05). The comparison between lesional and healthy skin revealed the highest number of differentially expressed proteins, which were predominantly associated with inflammatory and immune-related processes, including TNF-α signaling, complement pathways, and signal transducer and activator of transcription 6 signaling. The comparison between lesional and non-lesional skin showed differences in protein quantification related to melanocyte differentiation and keratinocyte stress responses. These proteins included protein O-fucosyltransferase 1, which is involved in melanocyte development via Notch-1 signaling, and keratin 6B, which is implicated in keratinocyte migration during wound repair. This study provides insights into vitiligo pathophysiology, identifying proteins that, to our knowledge, have not previously been associated with vitiligo.

The treatment for refractory non-segmental vitiligo (RNSV) remains unsatisfactory, particularly for acral vitiligo (AV) and phototherapy platform-stage vitiligo (PPV), despite the numerous treatment modalities available for vitiligo. The efficacy of a triple combination therapy comprising a 308-nm excimer lamp, a fractional CO2 laser, and a topical formulation was examined in this study. A better topical formulation and fractional CO2 laser settings were tested on 64 fresh human foreskin samples. At 15 mJ pulse energy and 10% coverage, the fractional CO2 laser and topical halometasone cream achieved a more widespread and consistent distribution with minimal side effects. The clinical trial included 98 individuals with 158 RNSV lesions. A total of 46 patients with 98 AV lesions and 52 with 60 PPV lesions were randomly assigned to T and C groups. T groups received fractional CO2 laser, plastic-wrapped halometasone cream, and 308-nm excimer lamp therapy. The C group received 308-nm excimer lamp, topical calcineurin inhibitor and halometasone cream (without fractional CO2 laser). A twice-weekly 308-nm excimer lamp therapy was used for three months. In the T group of PPV, 50% of lesions were successful at the conclusion of the research, while only 10% of lesions in the C group of PPV were successful (P ≤ 0.000). Success was attained by 8.16% of lesions in the T group of AV, while only 6.12% of lesions in the C group of AV were successful (P = 0.425). The PPV is definitively influenced by the tripartite combination therapy of a 308-nm excimer lamp, topical halometasone cream, and fractional CO2 laser. The treatment duration of PPV can be shortened and the phototherapy platform stage can be avoided. Conversely, the combination treatment did not yield satisfactory results for vitiligo in the acral region.

Oxidative stress, particularly H2O2 accumulation, is a key pathogenic factor in vitiligo, yet therapies that directly protect melanocytes remain limited. Adipose-derived stem cell-derived exosomes (ADSC-Exos) are cell-free vesicles with reported antioxidant effects, but whether they act through the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is unknown. This study aimed to investigate the protective effects of ADSC-Exos on hydrogen peroxide (H2O2)-induced oxidative damage in human melanocytes and to elucidate the underlying molecular mechanisms, focusing on the Keap1-Nrf2 signaling pathway. ADSCs and their exosomes were isolated and characterized using flow cytometry, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. An oxidative stress model was established by treating PIG1 human melanocytes with H2O2. The therapeutic effects of ADSC-Exos were assessed by measuring cell viability, migration, intracellular ROS levels, DNA damage, and antioxidant enzyme activities. The involvement of the Keap1-Nrf2 pathway was examined by western blot and immunofluorescence. H2O2 treatment significantly induced oxidative stress in PIG1 cells, evidenced by reduced cell viability and migration, increased ROS accumulation, and elevated DNA damage. Treatment with ADSC-Exos markedly restored cellular functions. Mechanistically, ADSC-Exos downregulated the expression of Keap1, facilitated the nuclear translocation of Nrf2, and upregulated the expression of downstream antioxidant enzymes, including heme oxygenase 1 (HO-1) and glutathione peroxidase 4 (GPX4). The findings demonstrate that ADSC-Exos effectively ameliorate H2O2-induced oxidative damage in melanocytes. The cytoprotection is mediated through the activation of the Keap1-Nrf2-ARE signaling pathway. These findings support further investigation of ADSC-Exos as a potential therapeutic strategy for vitiligo.

Ferroptosis is a regulated form of cell death driven by iron-dependent phospholipid peroxidation, but its immunological identity is not fixed. This context dependence complicates therapeutic development: ferroptosis may eliminate malignant cells but can also amplify inflammation or impair protective immune responses. Moreover, sublethal ferroptosis-associated stress can alter cellular function without causing cell death. The skin provides an informative model for investigating these divergent effects because epidermal differentiation and cutaneous compartmentalization create spatial heterogeneity in iron handling, lipid composition, and redox status. This review integrates the core molecular machinery of ferroptosis with the spatial biology and immunology of the skin. We examine ferroptotic death and sublethal stress across skin-resident and immune-cell populations, focusing on their distinct immunological consequences. Evidence from melanoma, psoriasis, vitiligo, systemic and cutaneous lupus erythematosus, ultraviolet-induced skin injury, and atopic dermatitis is evaluated with particular attention to the distinction between molecular associations, mechanistic evidence, and causal contributions to disease. Finally, we assess emerging skin-directed delivery platforms, including nanoparticles, microneedles, and extracellular vesicles, and critically compare their delivery characteristics, potential for cell-type-selective modulation, and translational readiness. Key translational challenges include in vivo stability, off-target effects, long-term safety, and manufacturing scalability. Progress toward clinical translation will require spatially resolved, cell-type-specific functional validation and more selective therapeutic strategies.

Psoriasis is an inflammatory skin disorder characterized by epithelial hyperplasia and infiltration of inflammatory cells. Several immunological therapies have been developed for its treatment, including IL-17 inhibitors such as secukinumab, ixekizumab and bimekizumab. The safety profile of IL-17 inhibitors includes infectious diseases, gastrointestinal disorders, headaches, and cutaneous conditions such as eczema. Here, we report the first case of vitiligo, a depigmenting skin disorder characterized by the selective loss of melanocytes, occurring during treatment with bimekizumab. This case involved a 42-year-old man who achieved complete skin clearance of psoriasis plaques under bimekizumab therapy. After 11 months of treatment, he developed vitiligo patches on his face. These lesions resolved following discontinuation of bimekizumab, minipulse therapy and ruxolitinib cream application. Vitiligo occurrence has been previously observed with other IL-17 inhibitors, including secukinumab and ixekizumab (11 other cases). Although IL-17 is believed to play a role in the pathophysiology of vitiligo, its exact mechanism remains unclear. Paradoxal vitiligo may represent a class effect of IL-17 inhibitors, particularly in patients with psoriasis. This potential adverse effect should be considered, especially in patients with a personal or family history of vitiligo or other depigmentation disorders. Interestingly, stability or even repigmentation has been observed in patients who continued anti-IL-17 therapy, regardless of whether they received symptomatic treatment. Given the efficacy of anti-IL17 inhibitors in psoriasis, the risk-benefit balance should be carefully discussed in this context.

Vitiligo is a chronic autoimmune depigmentation skin disorder characterized by the acquired loss of melanocytes, with a complex multifactorial pathophysiology. Among the potential predisposing factors, some drugs, including monoclonal antibodies, have been associated to disease onset.

Vitiligo and melasma frequently coexist, creating a treatment dilemma, since agents effective for one condition can destabilize the other, and no consensus currently exists on safe management. We conducted a scoping literature review (through June 2023) on treatment of patients with concomitant vitiligo and melasma, followed by a two-round international e-Delphi survey (22 experts from 14 countries; consensus defined as ≥ 70% agreement) and a final online consensus meeting. Only one study supported the safe use of oral tranexamic acid for melasma in vitiligo patients. Expert consensus favored prioritizing vitiligo treatment, particularly when active, while incorporating patient's preferences. Targeted phototherapy is suitable for localized facial lesions of vitiligo, and non-facial vitiligo can be treated alongside melasma after covering the face. Topical calcineurin inhibitors, ruxolitinib, tretinoin, corticosteroids, and oral tranexamic acid can be used. Lasers and chemical peels were recommended only with caution by experienced pigment specialists. Until there is enough scientific evidence, hydroquinone would be replaced by other safer cosmetic lightening agents (e.g., niacinamide, ascorbic acid, thiamidol, melasyl), which show comparable efficacy with less theoretical risk. This first international consensus offers practical, patient-centered guidance for managing coexisting vitiligo and melasma, emphasizing individualized, disease-activity-based treatment sequencing. Trial Registration: PROSPERO reference number: RD42023395586 Significance. Depigmenting agents used for melasma inhibit melanogenesis, a mechanism that can further compromise the already-stressed melanocyte populations characteristic of vitiligo. This consensus gives clinicians an expert-informed pathway through a common but understudied comorbidity. It also identifies a clear research gap: controlled, mechanistic comparisons of hydroquinone against newer tyrosinase inhibitors specifically in vitiligo-prone skin are still lacking.

Despite growing interest in exosome-based regenerative therapies, conventional mesenchymal stem cell (MSC) and somatic cell derived exosomes face persistent translational barriers, including donor heterogeneity, ethical constraints, limited scalability, and batch-to-batch variability. It remains unclear how far induced pluripotent stem cell (iPSC) derived exosomes can address these limitations, and how their advantages and remaining translational barriers compare with those of established MSC exosome platforms. This review synthesizes current evidence on the biology, therapeutic applications, and bioengineering of exosomes across cellular sources, with a focus on critically comparing MSC- and iPSC-derived exosomes rather than cataloguing individual sources in isolation. iPSC-derived exosomes are, on the evidence reviewed here, the more promising long-term platform; their unlimited, genetically homogeneous, and engineerable source material addresses the donor heterogeneity, ethical, and scalability limits that constrain MSC exosomes at their root, rather than merely working around them. This advantage remains largely theoretical in practice, however, since iPSC exosome production, GMP manufacturing, and clinical validation currently lag behind the more established MSC exosome pipeline. Closing that gap, rather than the underlying biological case for iPSCs, is therefore the critical bottleneck this review identifies. The first registered human trials of iPSC derived exosomes have now appeared, in stable vitiligo, atopic dermatitis, and Moyamoya disease, but these small, early phase, and dermatology or topical delivery led, underscoring that closing translational gaps, GMP compliant and AI assisted manufacturing, standardized potency and safety assays, exosome specific rather than cell inherited genomic risk assessment, and clearr regulatory pathways will determine whether either platform, or a combination of both, moves from this narrow clinical foothold to routine use.