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Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder characterized by widespread skin hyperpigmentation, café-au-lait spots, and hypopigmented circular macules, resulting from KITLG variants. KITLG, expressed by keratinocytes, binds to KIT on melanocytes, stimulating melanogenesis. Disturbances in the KITLG-KIT interaction result in diffuse hyperpigmentation in FPHH. However, the mechanisms behind hypopigmented macule formation remain unclear. This report presents a unique FPHH case in a patient with a novel KITLG mutation (Ser78Leu). Notably, the patient showed multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction analysis of the DNA from skin and blood tissues indicated a copy-neutral loss of heterozygosity at the KITLG locus, only in the hypopigmented macule. These findings suggest that the hypopigmented macules might result from revertant mosaicism. Conversely, café-au-lait spots do not follow the lines of Blaschko and can superimpose on the hypopigmented striae, indicating a distinct pathogenesis. This case contributes to the understanding of the genetic mechanisms in FPHH.

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Pediatric dermatologists are frequently consulted to evaluate children for cutaneous signs of systemic disorders. Numerical thresholds of significance have been described in the dermatologic literature for various skin findings where the likelihood of an associated extracutaneous abnormality or known genetic syndrome increases significantly. Knowledge of these numerical thresholds facilitates diagnosis and management, which improves clinical outcomes and avoids severe complications. This review highlights the clinical presentation, complications, evaluation, and numerical significance, when applicable, for the following skin findings: infantile hemangiomas, capillary malformations, café-au-lait macules, hypopigmented macules, juvenile xanthogranulomas, pilomatricomas, and angiofibromas.

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Background: Hyperpigmentation results in uneven skin tone, with darker skin types disproportionately affected. Objective: Assess efficacy and safety of a novel, hydroquinone (HQ)-free, multimodal pigment-correcting serum (Advanced Brightening Treatment [ABT]) versus 4% HQ in moderate to severe hyperpigmentation, including melasma. Methods: In this split-face study, ABT and 4% HQ were applied topically on randomly assigned facial sides twice daily for 12 weeks. Hyperpigmentation, skin tone evenness, modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life Questionnaire (MelasQoL), self-assessment questionnaires, and tolerability were assessed. Results: Subjects (n = 113; melasma subgroup, n = 44) were Asian (22%), Black/African American (27%), Hispanic (22%), and White/Caucasian (28%). ABT achieved comparable results to 4% HQ. ABT was well tolerated and resulted in improvement versus baseline at all visits in mean overall hyperpigmentation (-11.7% at week 12; P ≤ .001), skin tone evenness (-8.8%, P ≤ .005), and, in the melasma subgroup, mMASI (-50.6%; P ≤ .011) and MelasQoL scores (33.0 vs 46.6 for week 12 vs baseline, respectively; P ≤ .011), with similar results across racial subgroups. ABT was preferred over 4% HQ, with high satisfaction rate (≥89%). Limitations: Quality of life improvements per treatment were not evaluated separately. Conclusion: Efficacy and safety of ABT is comparable to 4% HQ in individuals with facial hyperpigmentation, including melasma, across multiple racial/ethnic backgrounds.

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The aim of this study is to explore the pharmacological properties of the essential oil derived from Ptychotis verticillata Duby (PVEO), a medicinal plant native to Morocco, focusing on its antidiabetic, anti-tyrosinase, and anti-inflammatory effects. Additionally, the study aims to characterize the phytochemical composition of PVEO and evaluate its potential as a natural therapeutic alternative for various health conditions. To achieve this, phytochemical analysis was conducted using gas chromatography-mass spectrometry (GC-MS). Furthermore, in vitro assessments were conducted to investigate PVEO's antidiabetic activity by inhibiting α-amylase, xanthine oxidase, and α-glucosidase. Tests were also undertaken to evaluate the anti-inflammatory effect of PVEO on RAW 264.7 cells stimulated by lipopolysaccharide (LPS), as well as its efficacy as an anti-tyrosinase agent and its lipoxygenase inhibition activity. The results of the phytochemical analysis revealed that PVEO is rich in terpene compounds, with percentages of 40.35 % γ-terpinene, 22.40 % carvacrol, and 19.77 % ß-cymene. Moreover, in vitro evaluations demonstrated that PVEO exhibits significant inhibitory activity against α-amylase, xanthine oxidase, and α-glucosidase, indicating promising antidiabetic, and anti-gout potential. Furthermore, PVEO showed significant anti-tyrosinase activity, with an IC50 of 27.39 ± 0.44 µg/mL, and remarkable lipoxygenase inhibition (87.33 ± 2.6 %), suggesting its candidacy for dermatoprotection. Additionally, PVEO displayed a dose-dependent capacity to attenuate the production of NO and PGE2, two inflammatory mediators implicated in various pathologies, without compromising cellular viability. The findings of this study provide a solid foundation for future research on natural therapies and the development of new drugs, highlighting the therapeutic potential of PVEO in the treatment of gout, diabetes, pigmentation disorders, and inflammation.

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BACKGROUND: Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB-HQ) in comparison to the isolated use of 4% hydroquinone (HQ). METHODS: A double-blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB-HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. RESULTS: There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB-HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1-21.3%) and 43.1% (32.2-54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9-27.5%) and 44.8% (33.2-52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB. CONCLUSION: The sequential CLOB-HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma.

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BACKGROUND: Facial dark spots remain a significant challenge for the cosmetic industry, in terms of providing effective treatment. Using Line-field Confocal Optical Coherence Tomography (LC-OCT), we investigated the internal structural features of photo-aging spot areas and evaluated the efficacy of a skin-brightening cosmetic product. MATERIALS AND METHODS: Twenty-six Asian female volunteers, aged between 29 and 65 years, applied a cosmetic product on their entire face twice a day for 2 months. LC-OCT was used to evaluate the dermal-epidermal junction (DEJ) undulation and the volume density of melanin in the epidermis at D0 and D56. Skin brightening and redness were also assessed by photography (SkinCam). RESULTS: Using LC-OCT technology, various microscopic dark spot morphologies, spanning from minimally deformed DEJ to complex DEJ patterns, were identified. Dark spots characterized by slight deformities in the DEJ were predominantly observed in the youngest age group, while older volunteers displayed a wavier pattern. Furthermore, a total of 44 spots were monitored to evaluate the brightening product efficacy. A statistically significant reduction in melanin volumetric density of 7.3% in the spots and 12.3% in their surrounding area was observed after 56 days of product application. In line with these results, an analysis of color parameters using SkinCam reveals a significant increase in brightening and decrease in redness in both pigmented spots and the surrounding skin following application. CONCLUSIONS: LC-OCT proves to be a valuable tool for in-depth dark spots characterization and assessment of skin brightening products, enabling various applications in the field of dermatological sciences.

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Linear and whorled nevoid hypermelanosis is a rare skin pigmentation disorder, characterized by linear streaks and whorls of hyperpigmented macules along Blaschko's lines. Lesions are commonly restricted to the trunk, neck, and extremities, sparing the face, palms, soles, and mucosae. Associated with this, certain cardiovascular, musculoskeletal, neurological, and developmental anomalies have been reported in the literature. Herein, we present a rare case of linear and whorled nevoid hypermelanosis involving the face, with musculoskeletal, genital, aural, and ocular abnormalities.

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BACKGROUND: Facial hyperpigmentation can negatively affect an individual's emotional and psychosocial well-being. AIMS: Assess safety and tolerability of a combination of microdermabrasion (DG) procedures using a novel brightening pro-infusion serum (EC-DG) with a targeted at-home treatment regimen in subjects with mild to severe facial hyperpigmentation, including melasma, post-inflammatory hyperpigmentation, and dark spots. PATIENTS/METHODS: This 12-week, open-label study enrolled 18 subjects (Fitzpatrick skin types I-IV) who underwent 6 in-office DG procedures with EC-DG (one procedure administered biweekly), along with daily topical application of a brightening treatment serum and dark spot cream. End points included change from baseline across multiple skin quality attributes and the Melasma Area and Severity Index (MASI), self-assessment questionnaires, and tolerability assessments. RESULTS: The combination treatment was well tolerated and resulted in significant (p ≤ 0.05) improvements from baseline in radiance, tactile roughness, and moisturization/hydration immediately after the first treatment, in MASI score at day 3, and in overall hyperpigmentation at week 4. Most (94.1%) subjects were satisfied with treatment. CONCLUSIONS: DG procedures using EC-DG combined with a targeted at-home skincare regimen are effective and tolerable for treating facial hyperpigmentation across a broad range of skin types.

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INTRODUCTION: Infraorbital hyperpigmentation represents one of the most prevalent conditions in cosmetic dermatology. To treat this condition, many patients prefer natural remedies. This study explored the efficacy of topical castor oil cream in treating patients with infraorbital hyperpigmentation. METHODS: We conducted an exploratory single-arm clinical trial at the Shahid Faghihi Dermatology Clinic and Molecular Dermatology Research Center of Shiraz University of Medical Sciences, Shiraz, Iran, during 2021-2022. Using the convenience sampling method, we enrolled 25 patients with infraorbital hyperpigmentation. We instructed the patients to apply topical castor oil cream twice daily for 2 months. The darkness, melanin, and erythema levels were evaluated by VisioFace® 1000 D and SkinColorCatch® devices. We used a visual analog scale to assess skin laxity, wrinkles, and patient satisfaction. Data analysis was done with Stata version 14.2. RESULTS: The data of 22 patients with a mean age of 40.92 ± 7.33 years were analyzed. The VisioFace® scores decreased significantly by the end of the study [right eyes: mean difference (MD): -5.63 (95% CI: -7.12 to -4.15), p < 0.001; left eyes: MD: -5.91 (95% CI: -7.46 to -4.36), p < 0.001]. Moreover, castor oil cream significantly reduced the melanin level, wrinkles, and skin laxity in the infraorbital region (p < 0.05). CONCLUSIONS: Castor oil cream seems to be an effective alternative for treating infraorbital hyperpigmentation. Randomized clinical trials are needed to confirm our findings.

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The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane, which plays critical roles in many physiological processes. Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis, dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions, which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation. Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants, highlighting their potential as a therapeutic strategy for skin pigmentation disorders.

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Objective:To investigate the clinical efficacy of subcutaneous asymmetric tension reduction combined with dermal buried angular mattress suture in surgical treatment of benign pigmented facial lesions in infants and preschoolers.Methods:Totally, 100 infants and preschoolers with pigmented facial lesions were enrolled from the Department of Dermatology, Hanzhong Central Hospital and the Second Affiliated Hospital of Xi′an Jiaotong University from January 2018 to January 2019, and their clinical data were analyzed retrospectively. Among these patients, there were 59 males and 41 females, and their age ranged from 3 months to 5 years, with an average age of 15 months. All patients underwent outpatient surgery under local anesthesia, and sedative drugs were used before operation. The skin lesions were excised once or in stages according to their areas, and incisions were closed by using a subcutaneous asymmetric suture-based tension reduction technique, followed by dermal buried angular mattress sutures. After surgery, medical silicone gels and tension reduction devices were used for 6 months to 1 year, and postoperative follow-up was performed.Results:All patients were followed up for more than 1 year after surgery. Four patients showed suture rejection reaction within two months after surgery, and the incisions completely healed after the suture knots were discharged; cat′s ear-shaped scars were formed at the upper and lower ends of the incisions in 3 cases when the sutures were removed 1 week after surgery, no treatment was given, and the cat′s ear-shaped scars gradually became flat after 1 year of follow-up; fat liquefaction occurred in 1 case 4 days after surgery, re-suturing of the incision was done 1 week after the removal of internal sutures and drainage, and the incision healed well; 1 case developed infection 3 days after surgery, and then received the removal of internal sutures, drainage, and anti-infection treatment, re-suturing was performed after complete regression of the incision swelling, and the incisions healed well; scar hyperplasia occurred in 4 cases 3 to 6 months after surgery, and the scars became flat after the local injection of triamcinolone acetonide. In the remaining children, fine white linear scars were formed after the healing of incisions, the depressions and ridges at both ends of the incisions became flat, and there was no obvious pulling sensation in facial organs or formation of cat′s ear-shaped scars.Conclusions:Subcutaneous asymmetric tension reduction combined with dermal buried angular mattress suture can effectively reduce tension twice during delicate facial surgery in infants and preschoolers, and help to avoid incision widening and scar hyperplasia. The follow-up showed favorable long-term efficacy and aesthetic effect.

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Skin pigmentation abnormalities, ranging from aesthetic concerns to severe hyperpigmentation disease, have profound implications for individuals' psychological and economic wellbeing. The intricate etiology of hyperpigmentation and our evolving comprehension of its underlying mechanisms underscore the need for robust animal models. Zebrafish, renowned for their transparent embryos and genetic parallels to humans, have been spotlighted as a pivotal model for skin pigmentation studies. This review offers a concise overview of zebrafish skin attributes, highlighting the shared melanin production pathways with humans. We systematically dissect the diverse strategies to craft zebrafish models of abnormal skin pigmentation, spanning physical, chemical, and genetic interventions, while critically appraising the merits and constraints of each approach. Additionally, we elucidate the metrics employed to gauge the efficacy of these models. Concluding, we cast a visionary gaze on prospective breakthroughs in the domain, aiming to steer forthcoming efforts in refined zebrafish models for skin pigmentation research.

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Background and Aims: Melasma is a common skin condition. Microneedling acts as a dermal delivery system that facilitates the penetration of lightening agents such as vitamin C and tranexamic acid (TXA) into the deeper layers of the skin. Therefore, this study aimed to compare the effectiveness of microneedling with TXA with microneedling and vitamin C in treating melasma. Methods: In patients with melasma, microneedling was performed at 2-3 mm depth. During that, TXA and vitamin C were poured on the skin of each side of the face, and then each ampoule was soaked for 15 min. This method was performed three times in 2-week intervals, and the results were compared by measuring the Melasma Area and Severity Index (MASI) score before, during, and 2 months after the completion of the treatment. Results: The average MASI score in the baseline in the TXA group was 4.61, and in the vitamin C group was 4.58. The average MASI score in the patients treated with TXA in the last treatment session was 2.40, and the group treated with vitamin C was 2.44. The study results showed that the treatment was effective in both groups based on MASI score. Although there was a difference between the responses of the two groups, it was not significant. Conclusion: Microneedling with vitamin C and TXA is a safe and effective treatment option without side effects for treating melasma.