Vitiligo is a skin disease characterized by the loss of skin melanocytes, featuring the dual pathology of melanocyte damage due to oxidative stress and immune-mediated inflammation, which ultimately classifies it as an autoimmune condition. Sappanone A (SA), isolated from Caesalpinia sappan L., exhibits notable anti-oxidative stress and anti-inflammatory activity in various diseases. However, its potential effects and mechanisms in vitiligo remain uninvestigated. This study was designed to investigate the effects of SA on melanocytes and keratinocytes under oxidative stress and to evaluate its therapeutic potential in the monobenzone-induced vitiligo model. In vitro, SA protected PIG1 cells from H2O2-induced cytotoxicity and suppressed HMGB1 expression, nuclear export, and extracellular release. Furthermore, SA reduced HMGB1-induced overexpression of inflammatory cytokines in HaCaT cells, including CXCL8, CXCL9, CXCL10, CXCL11, and TNF-α. In vivo, SA administration alleviated monobenzone-induced depigmentation and CD8[+] T-cell infiltration in C57BL/6 mice. Transcriptomic analysis, protein-protein interaction network construction, and molecular docking revealed that Wnt5a may be a potential target of SA, and SA significantly reversed monobenzone-induced Wnt5a expression and activation of noncanonical Wnt signaling. Overall, SA effectively attenuated the HMGB1-mediated inflammatory response in keratinocytes. Furthermore, it exerted repigmentation effects in monobenzone-induced vitiligo mice via inhibiting the Wnt5a-mediated noncanonical Wnt signaling pathway. These results suggest that SA is a promising therapeutic candidate for vitiligo.

To address the challenges of instability and low bioavailability that limit the application of (-)-epigallocatechin gallate (EGCG) as a whitening agent, we engineered a cucumber-derived exosome-like nanovesicle (CEV) as a synergistic nanocarrier. A hybrid isolation method combining polyethylene glycol precipitation with electrophoretic dialysis (PED) was established to obtain high-purity CEVs. The resulting EGCG-loaded CEVs (EGCG@CEVs) achieved 95.43% encapsulation efficiency with enhanced stability and a sustained release profile. Metabolomics and network pharmacology identified the STAT3/MAPK signaling axis as the primary target, a mechanism subsequently validated in B16F10 melanocytes and zebrafish models. Compared with free EGCG, EGCG@CEVs significantly decreased tyrosinase activity and melanin production. With the stable EGCG@CEV system, the ERK-STAT3-MITF pathway can be regulated, potentially functioning as a plant-based cosmetic system.

Albinism is characterized by a reduced or absent production of melanin in the skin, hair and eyes to a variable extent. Various inheritance patterns and genes can lead to a typical clinical phenotype. A distinction is made between three manifestations, oculocutaneous, ocular and syndromic forms of albinism. In an ophthalmological context, albinism is usually manifested in early childhood through nystagmus and visual impairment. Typical findings include iris transillumination, foveal hypoplasia and retinal hypopigmentation, each varying in severity. Children with albinism also present with strabismus, refractive errors and amblyopia. An atypical chiasmal decussation of ganglion cell axons can be demonstrated using visually evoked potentials. Advanced imaging techniques, such as optical coherence tomography and magnetic resonance imaging, provide important insights into the anatomy of the visual pathway in albinism and shed light on the plasticity of the human visual system.

Several clinical entities are associated with ACTB pathogenic variants. Most notably, constitutional missense gain-of-function variants are linked to Baraitser-Winter cerebrofrontofacial syndrome, and recurrent somatic gain-of-function Arg147 variants are reported in Becker's nevus or in smooth muscle hamartomas. We describe three individuals with mosaic hypopigmentation following Blaschko's lines, associated or not with neurodevelopmental features, with postzygotic ACTB variants identified with deep next-generation sequencing on skin biopsy from an affected area. We identified the same missense p.(Arg335His) variant in individuals #1 and #3, already reported in a constitutional state in a fetus. Individual #2 carried an unreported in-frame insertion-deletion (p.(Ser348_Leu349insPheHisLeuProProSerIle)). Thus, we describe a previously unreported phenotype related to postzygotic ACTB variants with hypopigmentation associated or not with neurodevelopmental features, distinct from Becker presentations, bridging constitutional neurodevelopmental and somatic cutaneous phenotypes.

Background: Zebrafish (Danio rerio) embryos are transparent in early stages of embryonic development; however, pigment formation at later stages hinders internal organ visualization during imaging. Chemicals such as 1-phenyl-2-thiourea (PTU) and kojic acid, used to block pigmentation, pose significant toxicity risks to human health. Therefore, effective and risk-free depigmentation agents are needed. This study investigates the efficacy of Alchemilla vulgaris (Lady's mantle) as a safe, natural alternative for zebrafish embryo depigmentation. Methods: A. vulgaris was extracted using four solvents of varying polarities and evaluated for depigmentation efficacy and toxicity. Gas chromatography-mass spectrometry (GC-MS) was used to identify major constituents of the extract. Results: Ethyl acetate extract was more effective at removing pigments than all other extracts, and exhibited the lowest toxicity compared to PTU and kojic acid. Ethyl acetate extract of A. vulgaris remained effective even when administered 48 h post fertilization (post-pigmentation), making it suitable for long-term experiments requiring optical clarity. GC-MS revealed that this extract was rich in linoleic acid, various fatty acid esters, and phenolics, which likely contributed to its depigmentation activity. Conclusions: Based on these findings, we propose that ethyl acetate extract of A. vulgaris is a safer, natural alternative to PTU and kojic acid for depigmenting zebrafish embryos, particularly in long-term imaging experiments. The extract exhibits high efficacy at low concentrations, accompanied by a favorable toxicity profile, demonstrating potential as a depigmentation agent during early zebrafish development. However, further studies are needed to elucidate its mechanism of action.

Objectives: Oculocutaneous albinism (OCA), a group of inherited disorders characterized by deficient melanin synthesis, leads to hypopigmentation of the skin, hair, and eyes. OCA type 2 (OCA2) is caused by mutations in OCA2. This study aimed to characterize the comprehensive clinical and genetic spectrum of OCA2, and to identify the key ocular determinants of visual acuity. Methods: We enrolled 90 probands clinically diagnosed with albinism. Whole-exome sequencing and comprehensive ophthalmic examinations were performed. Results: OCA2 was confirmed in 29 probands (32.2%). Visual impairment was distributed as mild/no impairment (30.8%), moderate (53.8%), and severe/blindness (15.4%). All patients exhibited nystagmus and photophobia. Ocular phenotype grading showed distinct distributions: iris translucency (n = 25) was 68% grade 3, 20% grade 2, 8% grade 1, and 4% grade 4; fundus hypopigmentation (n = 26) was 42.3% grade 1, 30.8% grade 2, and 26.9% grade 3; and foveal hypoplasia (n = 20) was 70% grade 4, 25% grade 3, and 5% grade 1. We identified 33 OCA2 variants (26 compound heterozygous and 3 homozygous), with missense variants accounting for 62.1% of alleles. Five variants were identified to be novel. The severity of foveal hypoplasia demonstrated a strong, statistically significant negative correlation with visual acuity (r = -0.71, p < 0.001). Conclusions: OCA2 accounts for 32.2% of albinism cases, with moderate visual impairment being the most common (53.8%). Graded phenotyping demonstrated moderate-to-severe iris translucency (88%), mild fundus hypopigmentation (42.3%), and severe (grade 4) foveal hypoplasia (70%). The severity of foveal hypoplasia emerged as an important determinant of visual acuity.

Immune checkpoint inhibitors (ICIs) have substantially improved outcomes in advanced melanoma but are frequently linked to immune-related adverse events (irAEs). Vitiligo is a common cutaneous irAE and has been consistently associated with improved patient outcome, including prolonged progression-free and overall survival. It also represents significant visual stigma, particularly when the face is involved. Traditional treatment comprises topical steroids, calcineurin inhibitors, laser, and phototherapy which often have insufficient effects. Since 2023, the first approved drug for non-segmental vitiligo (NSV) with facial involvement, the topical Janus kinase inhibitor ruxolitinib, has been available. However, experience with its use in ICI-induced vitiligo remains limited. In this exploratory analysis, three patients who developed facial vitiligo following ICI therapy applied 1.5% ruxolitinib cream to affected facial areas twice daily. After six (two patients), and twelve months (one patient), extensive repigmentation was observed, quantified at 95.7%, 78.9%, and 99.1% using a novel semi-automatic tool. Quality-of-life questionnaires showed mean reductions of 57.6% (Vitiligo DLQI) and 68.2% (Vitiligo-specific Quality of Life) in disease burden. Treatment was associated with substantial repigmentation without observed side effects. Further evaluation in larger, prospective cohorts is warranted to better define treatment effects, clinical applicability, and long-term safety.

Hypopigmented lesions in pediatric patients can present a diagnostic challenge, particularly when clinical and histopathologic findings do not clearly support a single diagnosis, and this may be further complicated in individuals with skin of color, where distinguishing hypopigmented from depigmented lesions can be more difficult. A 12-year-old Hispanic female presented with long-standing, progressive hypopigmented patches involving the face, neck, and torso. Vitiligo was initially suspected based on clinical appearance; however, Wood's lamp and histologic findings argued against a definitive diagnosis. The biopsies favored post-inflammatory hypopigmentation, although the clinical history was not entirely supportive. Progressive macular hypomelanosis was considered a diagnosis of exclusion based on the overall clinical context. The patient and family pursued counseling during the course of evaluation, after which she developed greater self-confidence, embraced her skin findings, and declined further treatment. This case highlights the importance of clinicopathologic correlation and diagnostic restraint when evaluating benign hypopigmented lesions in pediatric patients. Premature labeling of non-vitiliginous conditions as vitiligo may have significant psychosocial implications, particularly in younger patients, and may contribute to increased distress for both patients and their families.