Demodex mites are commonly found on human skin, but excessive proliferation can contribute to inflammatory eruptions. Pityriasis folliculorum is a Demodex‑associated condition characterized by follicular roughness and fine scale. Although it most often affects the cheeks, its presentation can vary and may resemble other papulopustular disorders. We describe a patient who developed a perioral papulopustular eruption with prominent follicular roughness. The condition persisted despite treatment with topical metronidazole, topical tretinoin, and topical antifungal therapy. Given the lack of response to topical therapies, a potassium hydroxide (KOH) skin scraping was performed and demonstrated numerous Demodex mites, with rapid resolution following the initiation of topical ivermectin. This case highlights the importance of considering Demodex‑related disease in the evaluation of perioral papulopustular eruptions when standard therapies are ineffective. Early recognition can help guide appropriate management and prevent prolonged symptoms.

Melasma is a chronic acquired hyperpigmentation disorder that commonly affects sun-exposed areas of the face and may significantly impact quality of life. Treatment can be challenging because of frequent recurrence and variable responses to conventional therapies. This case report describes the management of refractory facial melasma in a 64-year-old patient with a history of prolonged ultraviolet exposure and persistent facial hyperpigmentation. The patient previously underwent multiple treatment modalities, including chemical peels, mechanical peels, and laser-based therapies, without achieving satisfactory clinical improvement. Due to the limited response to these conventional approaches, treatment with the NewMelan Depigmentation System, a topical depigmenting formulation containing arbutin 1.5%, kojic acid 1%, and azelaic acid 1.5%, was initiated. The treatment protocol consisted of topical application three times daily during the first week, twice daily during the second week, and once daily during the subsequent two weeks, followed by maintenance therapy and continued photoprotection. Progressive reduction in facial hyperpigmentation was observed throughout the treatment period. After one month of therapy, the pigmentation became markedly less noticeable, resulting in substantial cosmetic improvement and high patient satisfaction. Continued maintenance treatment and daily sun protection contributed to preservation of the clinical outcome. This case highlights the potential role of the NewMelan Depigmentation System as a therapeutic option for patients with refractory facial melasma who have not responded adequately to conventional treatment modalities. Further clinical studies are warranted to evaluate long-term outcomes, safety, and efficacy in larger patient populations.

UV radiation (UVR) drives high mutational burdens, yet precursor melanocytes accumulate these mutations without triggering immune clearance. Here, we investigated whether melanocyte-intrinsic transcriptional program(s) underlie immune tolerance to mutations resulting from UVR exposure. In primary human melanocytes, expression of PD-L1 (CD274) was dependent on microphthalmia-associated transcription factor (MITF), a crucial regulator of melanocyte development and an intermediate in the UV-tanning pathway. MITF directly activated PD-L1 transcription by binding a conserved upstream enhancer containing functional E-box elements. MITF determined both baseline melanocytic PD-L1 expression in healthy skin and its induction following UVR, independent of interferon signaling. Melanocyte-restricted Pd-l1 deletion in mice triggered CD8[+] T cell infiltration and depigmentation after long-term UVB exposure, recapitulating features of human vitiligo. PD-L1-deficient human induced pluripotent stem cell (iPSC)-derived melanocytes underwent increased apoptosis and were more susceptible than PD-L1-intact melanocytes to gp100-specific CD8[+] T cell killing. Thus, a melanocyte-intrinsic MITF-PD-L1 tolerance program protects melanocytes from autoimmune destruction, potentially facilitating early immune evasion during melanoma development and conversely underlying the responsiveness of melanoma to PD-1/PD-L1 blockade.

Vitiligo assessment traditionally focuses on lesion extent, depigmentation burden, and disease activity using clinical examination, Wood's lamp evaluation, and scoring systems, such as the Vitiligo Area Scoring Index (VASI) and Vitiligo Disease Activity (VIDA) score. Although lesion border morphology is routinely recognized during clinical evaluation and may contribute to assessments of disease stability, objective quantitative characterization of pigmentary transition morphology remains largely unexplored. We present an exploratory image-analysis approach based on grayscale intensity profiling of Wood's lamp images obtained from a 68-year-old woman with vitiligo affecting both hands. Images were converted to 8-bit grayscale using Fiji/ImageJ, and linear intensity profiles were generated across representative lesional borders, healthy skin, and intralesional depigmented areas. To objectively quantify pigmentary transition morphology, we propose an exploratory Border Sharpness Index (BSI) integrating grayscale intensity variation and transition distance. Border-crossing profiles demonstrated reproducible directional intensity transitions that differed from both healthy skin and intralesional control tracings. Healthy skin exhibited minimal physiologic fluctuation, whereas intralesional tracings showed local oscillatory variation without organized directional transition patterns. These findings suggest that grayscale intensity profiling can objectively characterize the spatial architecture of the pigmentary transition zone using standard digital images and freely available image-analysis software. The proposed BSI represents one possible quantitative descriptor of pigmentary transition morphology, integrating morphometric and colorimetric information. While exploratory and nonvalidated, this proof-of-concept methodology introduces a previously underexplored quantitative dimension of vitiligo assessment focused on the spatial architecture of the pigmentary transition zone rather than lesion extent or disease activity alone. Further studies are needed to evaluate reproducibility, clinical correlation, and potential applications in the assessment of lesion stability and therapeutic response.

Pigmentation abnormalities, ranging from hypo- to hyperpigmentation, can serve as biomarkers of developmental disruption in fish exposed to environmental contaminants. However, the mechanistic pathways underlying these alterations remain poorly understood. Studies have shown that pattern formation in fish development requires specific pigment cell interactions. Motivated by experimental observations of pigmentation alterations following contaminant exposure, we investigate how pollutants influence pigment cell self-organization using a continuum reaction-diffusion-advection framework. The model incorporates non-local Morse-type kernels to describe short- and long-range interactions among melanophores and xanthophores. Our results show that perturbations to the strengths of adhesion or repulsion can drive transitions between stripes, spots and mixed patterns, reproducing phenotypes characteristic of fish pigmentation mutants. In particular, homotypic interactions are sensitive to contamination, leading to pronounced changes in melanophore density and resulting pigmentation patterns. Time-dependent simulations indicate that pigment changes from early short-term contaminant exposure may be recoverable, whereas prolonged exposure can lead to sustained pigment loss. In a growing fish, contaminant-induced changes in cell-cell interactions directly influence stripe formation rate, stripe number and pigmentation levels. Overall, our study provides insight into the mechanistic link between experimentally observed pigmentation alterations and the changes in spatial patterns of adult fish.

Clinically refractory melasma remains difficult to treat because it is driven by a multidimensional pathological microenvironment that includes melanocyte hyperactivity, aberrant vascular growth, oxidative stress and chronic inflammation. Single-pathway therapies therefore often produce incomplete or transient responses. To remodel this microenvironment more broadly, we developed a bioinspired, stimulus-responsive co-delivery microneedle platform (TXA/Exo@HAMA-PBA MNs). Inspired by the backward-curved barbs on the tick hypostome, the microneedles were engineered with outward-facing barbs to improve anchoring within skin tissue. Chemically, adipose-derived stem cell exosomes (ADSC-Exos) acted as bioactive crosslinking nodes. They were coupled to the HAMA-PBA matrix through ROS-sensitive dynamic boronate ester bonds, while tranexamic acid (TXA) was physically co-encapsulated. After insertion into ROS-rich melasma-like lesions, oxidative cleavage of carbon-boron bonds accelerated matrix degradation and promoted on-demand release of both payloads. Mechanistically, this platform produced an asymmetric but coordinated blockade of the pathological microenvironment: ADSC-Exos mainly scavenged local ROS, including ·OH, whereas TXA preferentially disrupted abnormal capillary networks. Together, they suppressed melanogenesis through the MITF/TYRP1 cascade and shifted macrophages from a pro-inflammatory M1 phenotype towards a tissue-reparative M2 phenotype. In a UV/progesterone-induced mouse model of melasma validated by bulk RNA sequencing, the system produced multidimensional microenvironmental regulation and visible depigmentation. This bioinspired, spatiotemporally responsive co-delivery microneedle platform integrates complementary and synergistic therapeutic actions and offers a translational strategy for complex, multifactorial hyperpigmentary disorders.

Facial wrinkles are a major concern in aesthetic dermatology, particularly in patients with darker phototypes, in whom laser treatments require careful parameter selection to minimize pigmentary adverse events. This retrospective study evaluated the effectiveness and tolerability of a nanosecond Q-switched 1064 nm Nd laser for the management of facial photoaging in Asian patients. Fifty Asian patients with Fitzpatrick skin types III-IV and facial wrinkles underwent three monthly treatment sessions with a Q-switched 1064 nm Nd: YAG laser. Clinical outcomes were assessed using the Fitzpatrick Wrinkle and Elastosis Scale, standardized pre- and post-treatment photographs, pain Visual Analogue Scale, and adverse event monitoring. Mean Fitzpatrick Wrinkle and Elastosis Scale score significantly decreased from 4.54 ± 1.55 at baseline to 3.42 ± 0.97 at three-month follow-up after the last treatment, corresponding to a mean absolute reduction of 1.12 ± 0.75 points. Forty-one patients showed an improvement of at least one FWS point, while thirteen patients improved by two or more points. Nine patients remained stable, and no clinical worsening was observed. Treatment was well tolerated, with a mean pain score of 2.0 ± 0.78. Mild transient erythema occurred in four patients, while no cases of blistering, scarring, burns, hypopigmentation, or post-inflammatory hyperpigmentation were recorded. Nanosecond Q-switched 1064 nm Nd laser treatment may represent a well-tolerated option for mild-to-moderate facial photoaging in Asian skin. However, the retrospective design, lack of a control group, and absence of instrumental objective measurements should be considered when interpreting these findings.

Vitiligo is a depigmentation disorder whose treatment remains a serious challenge. While it is generally accepted that topicals and phototherapy are helpful for generalized symmetric disease, randomized controlled trials (RCTs) provide the best evidence for treatment. Our objective was to identify and summarize RCTs for vitiligo from 2013 to 2023. A systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO) was performed per PRISMA guidelines. We searched CENTRAL, ClinicalTrials.gov, Embase, PubMed, and Web of Science for RCTs using keywords such as 'vitiligo' and/or 'treatment' or 'intervention.' A total of 652 studies underwent full-text review, and 151 studies met the inclusion criteria. We focused our study on RCTs using the vitiligo area scoring index (VASI) as the primary outcome measure, leading to 36 studies. We further narrowed our focus to studies that could be aggregated into the intervention categories: phototherapy and systemic combination therapy (n=10), topical and topical combination therapy (n=15), and systemic monotherapy (n=5). Treated versus control subjects showed statistically improved VASI after the following interventions were added to phototherapy: oral psoralen, oral minipulsed prednisone, implanted afamelanotide, topical ethyl vanillate, topical bimatoprost, and oral vitamins A and E. Effective topical therapies were ruxolitinib, calcipotriol and betamethasone, tacrolimus and mometasone, and microdermabrasion and tacrolimus. None of the systemic monotherapies was superior to their corresponding comparator.

Vitiligo is a common acquired depigmentation disorder affecting approximately 0.5-2% of the global population, characterized by the selective destruction of melanocytes leading to white patches on the skin. The pathogenesis of vitiligo involves complex interactions between genetic susceptibility, autoimmune responses, oxidative stress, and melanocyte dysfunction. Recent studies have demonstrated that ferroptosis, a novel iron-dependent form of programmed cell death, may play a critical role in melanocyte loss in vitiligo. Ferroptosis is characterized by iron accumulation, lipid peroxidation, glutathione (GSH) depletion, and decreased glutathione peroxidase 4 (GPX4) activity. This form of cell death differs fundamentally from apoptosis, necrosis, and autophagy in its morphological, biochemical, and genetic characteristics. Understanding the role of ferroptosis in vitiligo pathogenesis opens new avenues for therapeutic intervention and may explain why melanocytes in vitiligo patients are particularly vulnerable to oxidative damage. Multiple experimental and clinical studies have now confirmed the upregulation of ferroptosis biomarkers including transferrin receptor 1 (TFR1), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in vitiligo lesions, alongside downregulation of GPX4 and the cystine/glutamate antiporter System Xc-. Emerging evidence further implicates epigenetic regulators such as SIRT7 and RNA-binding proteins such as SLC3A2 in modulating melanocyte ferroptosis susceptibility. This comprehensive review systematically summarizes current knowledge on ferroptosis mechanisms in vitiligo, including the System Xc-/GPX4 axis, iron metabolism dysregulation, lipid peroxidation pathways, and their interactions with autoimmune responses. We also explore emerging therapeutic strategies targeting ferroptosis-related pathways, including iron chelation, GPX4 enhancement, lipid peroxidation inhibitors, NRF2 activators, and natural compounds such as baicalein. By integrating basic research findings with clinical observations, this review provides novel insights into vitiligo pathogenesis and establishes a theoretical foundation for developing innovative treatment strategies based on ferroptosis regulation. Crucially, by contrasting the ferroptosis-hypersensitive profile of vitiligo melanocytes with the ferroptosis-resistant molecular landscape of melanoma cells, this review proposes a novel framework for melanocyte-lineage-selective ferroptosis modulation as a therapeutic strategy.

This case report describes a 75-year-old woman presenting with diffuse facial melasma, lentigines, and associated dyschromia. The NewMelan multimodal depigmentation protocol, developed by Dr. Eduardo Krulig, was utilized in the management of this patient, who was treated under his supervision. Clinical examination demonstrated bilateral facial hyperpigmentation with uneven skin tone and photoaging-related pigmentary changes consistent with mixed melasma and lentiginous pigmentation. A physician-supervised depigmentation regimen was initiated. During the first week, the depigmenting product was applied three times daily, followed by twice daily applications during the second week. After 15 days, the protocol continued with once daily application as part of the maintenance regimen. Marked clinical improvement in facial hyperpigmentation and skin tone uniformity was observed within approximately two weeks of treatment initiation. Serial clinical photography demonstrated substantial reduction in pigmentation intensity, near-complete resolution of the most prominent melasma lesions, and improvement in overall facial appearance. Post-treatment, the patient was instructed to continue daily maintenance therapy. This case demonstrates short-term clinical improvement following treatment with the NewMelan multimodal depigmentation protocol. Further studies with larger patient populations and longer follow-up periods are necessary to evaluate long-term outcomes, recurrence rates, and broader clinical applicability.

Background Malignant melanoma (MM) arises from melanocytes, and vitiligo is an autoimmune condition targeting these cells. Although an association between MM and vitiligo has been proposed, underlying mechanisms remain unclear. Because several melanoma treatments modulate immune responses, this study evaluated the relationship between MM and vitiligo across commonly used systemic therapies. Methods In September 2025, using the TriNetX network, patients with MM receiving programmed cell death protein 1 (PD-1) inhibitors, interferon alpha-2b (IFN-α2b), B-Raf serine/threonine kinases (BRAF)/ mitogen-activated protein kinase kinases (MEK) inhibitors, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors were identified and 1:1 propensity score-matched to patients without MM receiving the same therapy. Demographics and vitiligo incidence were analyzed using risk ratios (RRs) and 95% confidence intervals (CIs) via Wald's method. Counts <10 were suppressed per platform guidelines. Results Baseline demographics were well balanced between MM and matched non-MM patients. MM was significantly associated with higher vitiligo risk among those treated with PD-1 inhibitors (RR: 24.84; 95% CI: 16.92-36.45), IFN-α2b (RR: 3.10; 95% CI: 1.53-6.30), and CTLA-4 inhibitors (RR: 32.04; 95% CI: 18.05-56.88). In the BRAF/MEK cohort, vitiligo occurred only in patients with MM, preventing RR calculation. Conclusions Across multiple therapeutic classes, MM consistently conferred a greater risk of developing vitiligo compared with matched non-MM patients. The strong associations observed with immune-modulating agents support vitiligo as a potential marker of antitumor immune activation rather than a coincidental adverse event. Even rare cases in BRAF/MEK-treated patients suggest that targeted therapy may also influence melanocyte-directed immunity. Further prospective studies are needed to characterize the clinical and immunologic significance of treatment-associated vitiligo.