The inhibition of VDAC1 oligomerization promotes pigmentation through the CaMK-CRTCs/CREB-MITF pathway.

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.

Skin dark spot mapping and evaluation of brightening product efficacy using Line-field Confocal Optical Coherence Tomography (LC-OCT).

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.

How many is too many? A review of the significant numbers in pediatric skin lesions and their recommended evaluation.

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.

Oral melanoacanthoma: Clinicopathological and immunohistochemical features of a case series and a scoping review.

BACKGROUND: This study presents a case series and scoping review of oral melanoacanthoma to examine its clinical, histopathological, and immunohistochemical characteristics. METHODS: Nine cases of oral melanoacanthoma were included in the case series. Clinical data were collected from biopsy charts. Hematoxylin-eosin and immunohistochemistry for TRP2, CD3, and CD20 were done. For the scoping review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. RESULTS: Case series: The mean age was 46.8 years (female-to-male ratio 2:1). Lesion's mean size was 11.0 mm (±9.3). Lesions were mainly macular (77.8%) with brown or black coloration (88.9%) and often affected multiple sites (44.4%). The evolution time ranged from 15 days to 96 months. Lesions commonly showed epithelial acanthosis (66.7%), spongiosis (55.6%), exocytosis (77.8%), melanin incontinence (88.9%), and inflammatory infiltrate in the lamina propria (77.8%), from which all showed lymphocytes. TRP2-positive melanocytes were identified in the basal and spinous layer of all cases, and in the superficial layer of three cases. CD3-positive cells predominate over the CD20-positive. Scoping review: 85 cases of oral melanoacanthoma were retrieved from 55 studies. Patients were primarily female (female-to-male ratio 2.2:1), black-skinned (64.1%), with a mean age of 36.13 (± 17.24). Lesions were flat (81.9%), often brown (62.4%). Buccal mucosa was the preferred site (32.9%), followed by multiple sites (28.2%). CONCLUSION: Oral melanoacanthoma mainly affects women across a wide age range, with lesions commonly appearing as brown/black macules, particularly on the buccal mucosa. TRP2-positive melanocytes and T-lymphocytes were consistently found and could participate in oral melanoacanthoma pathogenesis.

Automatic identification of benign pigmented skin lesions from clinical images using deep convolutional neural network.

OBJECTIVE: We aimed to develop a computer-aided detection (CAD) system for accurate identification of benign pigmented skin lesions (PSLs) from images captured using a digital camera or a smart phone. METHODS: We collected a total of 12,836 clinical images which had been classified and location-labeled for training and validating. Four models were developed and validated; you only look once, v4 (YOLOv4), you only look once, v5 (YOLOv5), single shot multibox detector (SSD) and faster region-based convolutional neural networks (Faster R-CNN). The performance of the models was compared with three trained dermatologists, respectively. The accuracy of the best model was further tested and validated using smartphone-captured images. RESULTS: The accuracies of YOLOv4, YOLOv5, SSD and Faster R-CNN were 0.891, 0.929, 0.852 and 0.874, respectively. The precision, sensitivity and specificity of YOLOv5 (the best model) were 0.956, 0.962 and 0.952, respectively. The accuracy of YOLOv5 model for images captured using a smart-phone was 0.905. The CAD based YOLOv5 system can potentially be used in clinical identification of PSLs. CONCLUSION: We developed and validated a CAD system for automatic identification of benign PSLs using digital images. This approach may be used by non-dermatologists to easily diagnose by taking a photo of skin lesion and guide on management of PSLs.

A case of palmar hypopigmentation induced by capecitabine in a gastrointestinal cancer patient.

INTRODUCTION: Capecitabine is an antimetabolite antineoplastic agent widely used in the treatment gastrointestinal cancers. The common frequently reported cutaneous adverse drug reaction associated with capecitabin are a palmar-plantar erythrodysesthesia syndrome, rash and hyperpigmentation. This case reports a capecitabine-induced palmar hypopigmentation. CASE REPORT: We report the case of a 74-years old patient with jejunum adenocarcinoma treated by capecitabine. The patient developed a pseudo-vitiligo after 2 cycles capecitabine and without history of cutaneous disorders. The skin lesions were characterized with skin hypopigmentation on both hands.Management and outcome: The hypopigmentation slowly recovered after capecitabine discontinuation. CONCLUSION: This is the first described case of pseudo-vitiligo induced by capecitabine. This impressive but non-severe adverse effect should be known by oncologists and oncology pharmacists to reassure the patients in particular about the possible recovery after discontinuation of capecitabine.

Comparison of fractional erbium:YAG laser-assisted tranexamic acid delivery alone and in combination with oral tranexamic acid in melasma.

Tranexamic acid (TA) emerged as a promising agent for melasma. However, due to its hydrophilic structure, topical TA should be combined with a penetration-enhancing strategy to augment efficacy. To evaluate the efficacy of fractional erbium:YAG laser-assisted delivery (LAD) of topical TA 5% either with or without oral TA treatment in recalcitrant melasma patients. The authors retrospectively assessed the treatment outcomes of melasma patients treated by fractional erbium:YAG LAD of topical TA 5%. Patients receiving a standard protocol including four biweekly laser sessions were eligible. The study included two groups: group 1 patients received oral TA and LAD of topical TA 5%, and group 2 patients received only LAD of topical TA 5%. Two blinded dermatologists reported pre-treatment and post-treatment modified MASI (mMASI) scores. Mean mMASI scores in both group 1 (n = 15) and group 2 (n = 19) were significantly lower at the end of the treatment than baseline values (p = 0.001; p = 0.022, respectively). The decrease of mMASI scores were higher in group 1 (median = 2.1) (64.7%) than in group 2 (median = 1.2) (41.8%) (p = 0.027). Fractional erbium:YAG LAD of topical TA 5% is an efficient treatment regimen for melasma patients recalcitrant to conventional treatment approaches. The implementation of oral TA to this regimen improves the therapeutic outcomes.

Efficacy of a laser with a pulse duration of 300 ps in skin rejuvenation and treatment of pigmentation disorders in Asians: a series of four cases.

The photothermal effect of lasers is minimized and the photoacoustic effect is maximized as the pulse duration is shortened. Therefore, picosecond lasers with a short pulse and high peak power can be used to effectively treat various pigment disorders by reducing tissue damage. The first picosecond lasers were used for tattoo removal; they are also widely used for pigment treatment because of their reduced side effects compared with nanosecond lasers. Recently, picosecond lasers have been shown to be effective in the treatment of various skin conditions such as acne scars and large pores. There are many studies on picosecond lasers; however, there are no studies on a laser with a pulse duration of 300 ps. This report describes the use of a 300 ps Nd:YAG laser for treating pigment disorders and for skin rejuvenation in four Asians, with no side effects. Determining the clinical significance of the 300 ps pulse duration through comparative studies with various picosecond lasers is needed.

Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials.

Skin evolves essential appendages and indispensable types of cells that synergistically insulate the body from environmental insults. Residing in the specific regions in the skin such as epidermis, dermis and hair follicle, melanocytes perform an array of vital functions including defending the ultraviolet radiation and diversifying animal appearance. As one of the adult stem cells, melanocyte stem cells in the hair follicle bulge niche can proliferate, differentiate and keep quiescence to control and coordinate tissue homeostasis, repair and regeneration. In synchrony with hair follicle stem cells, melanocyte stem cells in the hair follicles undergo cyclic activation, degeneration and resting phases, to pigment the hairs and to preserve the stem cells. Disorder of melanocytes results in severe skin problems such as canities, vitiligo and even melanoma. Here, we compare and summarize recent discoveries about melanocyte in the skin, particularly in the hair follicle. A better understanding of the physiological and pathological regulation of melanocyte and melanocyte stem cell behaviours will help to guide the clinical applications in regenerative medicine.

Terra firma-forme dermatosis: Differential diagnosis and response to salicylic acid therapy.

Terra firma-forme dermatosis (TFFD), first described by Duncan in 1987, is a relatively common but probably underdiagnosed condition, characterized by a reticular hyperpigmented dirtlike eruption resistant to washing with common soap but typically removed with rubbing with 70% isopropyl alcohol. We present a case of TFFD in an 8-year-old boy with rapid response to 5% salicylic acid in petrolatum ointment.

Congenital Hypopigmentary Disorders with Multiorgan Impairment: A Case Report and an Overview on Gray Hair Syndromes.

The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak⁻Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.

Natural options for management of melasma, a review.

A blemish free, even-toned skin is universally associated with healthy skin. This reasoning makes people desire to have a flawless skin. Melanin is a naturally occurring pigment in humans. This pigment is responsible for skin, hair, and eye color, therefore determines our race and phenotypic appearance. On darker skin types, it is common that melanin production processes malfunctions. These malfunctions often lead to overproduction and secretion of melanin. As a result, unwanted pigmentary problems such melasma occur. Due to unknown etiology and its recurrence in nature, melasma is challenging to treat. The current available melasma treatment options often produce undesired side effects and suboptimum results. First-line topical treatments usually involve hydroquinone or topical steroids. Apart from the irritant reactions, this treatment mode is not suitable for all skin types. Skin care specialists are in search of an effective long-term cosmetics and cosmeceuticals to address hypermelanosis problems. Understanding of naturally occurring depigmenting agents provides an opportunity for more effective ways to manage melasma in all skin types. This review considers the benefits of naturally occurring ingredients which could help address skin pigmentation problems and broaden the choice for skin-lightening treatments.

African ancestry is associated with facial melasma in women: a cross-sectional study.

BACKGROUND: Melasma is a chronic acquired focal hypermelanosis affecting photoexposed areas, especially for women during fertile age. Several factors contribute to its development: sun exposure, sex steroids, medicines, and family history. Melanic pigmentation pathway discloses several SNPs in different populations. Here, we evaluated the association between genetic ancestry and facial melasma. METHODS: A cross-sectional study involving women with melasma and an age-matched control group from outpatients at FMB-Unesp, Botucatu-SP, Brazil was performed. DNA was extracted from oral mucosa swabs and ancestry determined by studying 61 INDELs. The genetic ancestry components were adjusted by other known risk factors by multiple logistic regression. RESULTS: We evaluated 119 women with facial melasma and 119 controls. Mean age was 39 ± 9 years. Mean age at beginning of disease was 27 ± 8 years. Pregnancy (40%), sun exposure (37%), and hormonal oral contraception (22%) were the most frequently reported melasma triggers. All subjects presented admixed ancestry, African and European genetic contributions were significantly different between cases and controls (respectively 10% vs 6%; 77% vs 82%; p < 0.05). African ancestry (OR = 1.04; 95% CI 1.01 to 1.07), first generation family history (OR = 3.04; 95% CI 1.56 to 5.94), low education level (OR = 4.04; 95% CI 1.56 to 5.94), and use of antidepressants by individuals with affected family members (OR = 6.15; 95% CI 1.13 to 33.37) were associated with melasma, independently of other known risk factors. CONCLUSIONS: Facial melasma was independently associated with African ancestry in a highly admixed population.

The State of Ethnic Dermatology in Canada.

Approximately 30% of Canadians will be members of a visible minority by 2031. When dermatology became an independent medical discipline in the late 18th and early 19th centuries, most residents of Canada and the United States were of Northern European descent. Morphology and descriptions of dermatoses are based on patients with light skin. Skin of colour dermatology refers to a unique field in dermatology dedicated to the diagnosis and management of disorders that are more prevalent in patients with moderately to richly pigmented skin. Important differences in the presentation of common dermatoses such as seborrheic dermatitis and acne exist in patients with darker skin types. The effect of traditional treatments for common and uncommon dermatoses is also an important consideration in managing patients with skin of colour. Such treatments may result in adverse effects such as postinflammatory hyperpigmentation or keloid scarring at a higher rate. Most respondents from a 2013 UK study of dermatology residents and consultants agreed that individuals with 'ethnic skin' had specific and unique dermatological problems. The Royal College of Physician and Surgeons of Canada's Objectives of Training in Dermatology states that residents must demonstrate the requisite knowledge, skills, and attitudes for effective patient-centred care and service to a diverse population. Future steps include creating a national society of dermatologists interested in clinical and academic aspects of ethnic dermatology. As well, presentations on skin of colour dermatology could be encouraged at major Canadian dermatology meetings.

Low 25-hydroxyvitamin D levels are associated with vitiligo: a systematic review and meta-analysis.

BACKGROUND: Vitamin D deficiency is associated with a number of autoimmune diseases. We completed a meta-analysis of observational studies to establish whether there was a relationship between hypovitaminosis D and the autoimmune skin disease vitiligo. METHODS: Comprehensive search was applied in the MEDLINE and EMBASE databases from their inception to December 2015. Inclusion criteria were observational studies that assessed 25-hydroxyvitamin D (25(OH)D) levels in adults with vitiligo. The main outcome was the mean difference in serum 25(OH)D level between patients with vitiligo and controls. RESULTS: Our search strategy identified 383 articles; seventeen studies met the criteria for full-length review and seven studies, containing the data of 1200 patients, were included in a random-effects model meta-analysis. The pooled mean difference in serum 25-hydroxyvitamin D concentration between patients with vitiligo and controls was -7.45 ng/ml (95% confidence interval, -12.99 to -1.91, P-value = 0.01). The between-study heterogeneity (I(2) ) was 96%, P = value<0.001. CONCLUSIONS: This meta-analysis identifies a significant relationship between low 25-hydroxyvitamin D levels and vitiligo, but does not prove causation. Our findings emphasize the importance of measuring 25-hydroxyvitamin D levels in patients with vitiligo. Further studies will be needed to establish whether vitamin D supplementation in this population improves the outcome of vitiligo.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS.

Efficacy of castor oil cream in treating infraorbital hyperpigmentation: An exploratory single-arm clinical trial.

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.