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International audience; Tyrosinase-related protein 1 (TYRP1) is one of three tyrosinase-like glycoenzymes in human melanocytes that are key to the production of melanin, the compound responsible for the pigmentation of skin, eye, and hair. Difficulties with producing these enzymes in pure form have hampered the understanding of their activity and the effect of mutations that cause albinism and pigmentation disorders. Herein we show that the typical tyrosinase-like subdomain of TYRP1 contains two zinc ions in the active site instead of copper ions as found in tyrosinases, which explains why TYRP1 does not exhibit tyrosinase redox activity. In addition, the structures reveal for the first time that the Cys-rich subdomain, which is unique to vertebrate melanogenic proteins, has an epidermal growth factor-like fold and is tightly associated with the tyrosinase subdomain. Our structures suggest that most albinism-related mutations of TYRP1 affect its stability or activity

Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, as well as melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. By breeding ROSAmT/mG and Tyr::CreERT2 mice, we generated animals in which melanocytic lineage cells are identified through expression of green fluorescent protein. We also used defined conditions to systematically investigate the proliferation and migration responses of primary melanocytes on various extracellular matrix (ECM) substrates. Under our culture conditions, mouse melanocytes exhibit doubling times in the range of 10 days, and retain exponential proliferative capacity for 50-60 days. In culture, these melanocytes showed distinct responses to different ECM substrates. Specifically, laminin-332 promoted cell spreading, formation of dendrites, random motility and directional migration. In contrast, low or intermediate concentrations of collagen I promoted adhesion and acquisition of a bipolar morphology, and interfered with melanocyte forward movements. Our systematic evaluation of primary melanocyte responses emphasizes the importance of clearly defining culture conditions for these cells. This, in turn, is essential for the interpretation of melanocyte responses to extracellular cues and to understand the molecular basis of disorders involving the melanocytic cell lineage.

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earth's surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm2) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage.

SummaryBackground Skin whitening products, used for ages by Asian people for cultural and esthetic purposes, are very popular nowadays in Western countries as well, where the need to inhibit skin spots after sun exposure has become not only a cosmetic but also a health-related issue. Thus, the development of effective and safe depigmenting agents derived from natural products gets continuous attention by cosmetic brands and consumers. Objectives The aim of this study was to determine the effects of two preparations, obtained from the hairy root cultures of the species Brassica rapa, on melanogenesis and the expression of the extracellular matrix proteins involved in a correct pigment distribution. Methods The two preparations, obtained by water-ethanol extraction and by digestion of cell-wall glycoproteins of the root cells, were chemically characterized and tested on skin cell cultures and on human skin explants to investigate on their dermatological activities. Results Both the extracts were able to decrease melanin synthesis pathway in melanocytes and modulate the expression of genes involved in melanin distribution. One of the extracts was also effective in inducing the expression of laminin-5 and collagen IV, involved into the maintenance of tissue integrity. The two extracts, when tested together on human skin explants, demonstrated a good synergic hypopigmenting activity. Conclusions Taken together, the results indicate that the extracts from B. rapa root cultures can be employed as cosmetic active ingredients in skin whitening products and as potential therapeutic agents for treating pigmentation disorders.

Cronkhite-Canada syndrome is an acquired inflammatory polyposis syndrome in which alopecia, onychomadesis and hyperpigmentation occur concurrently with gastrointestinal symptoms. The pathophysiology of alopecia in Cronkhite-Canada syndrome has not been definitively elucidated. We present evidence for alopecia areata incognita as a possible mechanism of hair loss.

Background: Vitiligo is an acquired and commonly found pigmentation disorder characterized by milky-white patches on the skin, hair, and mucosa due to melanocyte damage. The cause of vitiligo is still unclear. A study proves that cell-mediated immunity plays a role in the pathogenesis of vitiligo. Melan-A is a melanoma-related antigen that is recognized by autologous cytotoxic T cells and one of the critical markers for detecting melanocytes. Objective: To evaluate the expression of Melan-A in depigmented lesions of vitiligo patients. Methods: A descriptive study aimed to describe the expression of Melan-A in the depigmented skin of vitiligo patients at the Dermatovenerology Outpatient Clinic Cosmetic Division of Academic General Hospital Dr. Soetomo Surabaya. Eleven study subjects were selected through a sequence of selection. Results: Melan-A expression in the depigmented skin of vitiligo patients was lower than the average. This result was found in 6 (54.55%) out of 11 patients. Conclusion: Melan-A expressions on depigmented skins of vitiligo patients are generally below the average value; therefore, adequate intervention is needed to increase the Melan-A expression.

The natural coat color is an important trait of vertebrate animals. For example, the coat color can help avoid harm to human beings caused by chemical dyeing, and it has economic significance for domestic animals. The bone morphogenetic protein 4 (BMP4) and its antagonist Noggin can regulate pigmentation and the generation of coat color in mice; thus, they may also regulate the coat color of Kazakh sheep. To gain mechanistic insight into this possibility, we determined the relative expression levels of BMP4 and Noggin in the skin of white and brown Kazakh sheep by quantitative real-time polymerase chain reaction (qPCR) and western blotting analysis. The localization of BMP4 and Noggin were detected by immunohistochemistry (IHC). The results of qPCR and western blot analysis demonstrated that the relative expression levels of BMP4 and Noggin in the skin of brown Kazakh sheep were significantly higher than those in white Kazakh sheep. Our IHC results showed that the BMP4 protein was expressed in the epidermis and root sheath of the Kazakh sheep skin. The Noggin protein was expressed in the epidermis, root sheath, hair shaft, and dermal papilla of the Kazakh sheep skin. These results provide a theoretical basis for additional studies regarding the association and mechanism of BMP4 and Noggin in coat-color formation in Kazakh sheep. These results may provide new methods for developing treatment strategies for pigmentation disorders and diseases.

Skin rejuvenation is a treatment that targets age-related pigmentation disorders and telangiectasia or improves wrinkles and skin texture [1]. It can be classified by treatment methods; ablative rejuvenation (AR) by CO2 laser and erbium-doped yttrium aluminium garnet (Er:YAG) laser or nonablative rejuvenation (NAR), which induces a selective thermal reaction to the dermis and subcutaneous fat while sparing the epidermis. It can also be classified by treatment targets; type I rejuvenation targets pigmentation and vascular disorders while type II rejuvenation focuses on improving wrinkles and skin texture. For example, AR and NAR are both treatment modalities for type II rejuvenation (Table 9.1). Generally, NAR refers to rejuvenation treatment that uses nonablative methods to improve wrinkles and skin texture (type II rejuvenation).

This chapter provides an overview of the epidemiology, pathophysiology, course, measurement, and potential therapies for pigmentation disorders in scars. Pigmentation problems are a common consequence of deep partial- and full-thickness burns, other skin trauma or disease, and surgical procedures. Both hypopigmentation and hyperpigmentation can cause esthetic and psychological issues, which may influence quality of life. The role of melanocytes and the maturation of pigmentation problems are discussed. To determine the severity of pigmentation problems and for therapeutic evaluation, different subjective and objective methods have been validated. Simple and easy-to-use measurement instruments are available based on spectrophotometric techniques. Also scar assessment scales with subscales for color and pigmentation are convenient and validated methods for quantitative evaluation of skin pigment disorders. Treatment options are discussed and include camouflage therapy, topical treatments, chemical peels, laser therapy, dermatography, dermabrasion, microneedling, skin grafting, cell therapy, and excision. It is advised to first try the conservative options and to dose and monitor the treatment to prevent overshoot and complications.

Introduction Xanthelasma palpebrarum (XP) is a common xanthomatous lesion of the eyelid and periorbital skin. Several methods of treatment have been reported in the literature, each having its own indications and risks. We present a new treatment method for removing XP using a plasma exeresis device (Plexr®, GMV, Italy). Methods Fifteen patients with a total of 27 treated XPs were assessed and clinically identified by the treating dermatologist. Patients were photographed and assessed by a dermatologist prior to and immediately after treatment. A patient survey was conducted 12 months after the procedure, which assessed the outcome of the procedure (redness, pigmentation disorders, and scars). Results After just a single treatment session using a plasma sublimation, all 27 XPs showed complete clearance. There were no reports of scars, pigmentary alteration, or recurrence of lesions up to 12 months. Conclusions We present plasma sublimation as a new method for the treatment of XP. During the procedure, the method allows to control the depth of tissue destruction and the presence of xanthoma tissue, and to minimize pain and trauma, making it particularly ideal for treating areas around the eye.

Acquired brachial cutaneous dyschromatosis (ABCD) is an acquired disorder of pigmentary change that presents as chronic, asymptomatic, geographic-shaped, gray-brown patches, consisting of mixed hyper and hypopigmented macules on the dorsal aspect of the forearms. We report a case of a 40-year-old male who presented with asymptomatic, multiple brown-colored macules on the outer aspects of both arms. He had no history of hypertension and had never taken angiotensin converting enzyme inhibitors. He also denied chronic sun exposure history. Histologic examination demonstrated epidermal atrophy, increased basal layer pigmentation, and several telangiectatic vessels in the upper dermis. Solar elastosis was not remarkable. The patient's clinical and histopathologic features were consistent with a diagnosis of ABCD. Poikiloderma of Civatte, melasma, acquired bilateral telangiectatic macules and other pigmentary disorders should be considered in the differential diagnosis of ABCD. Herein, we report a case of ABCD in a middle-aged male without hypertension and medication.

Our laboratory has developed a scaffold-free cell-based method of tissue engineering to produce bilayered tissue-engineered skin substitutes (TESs) from epidermal and dermal cells. However, TES pigmentation is absent or heterogeneous after grafting, due to a suboptimal number of melanocytes in culture. Our objectives were to produce TESs with a sufficient quantity of melanocytes from different pigmentation phototypes (light and dark) to achieve a homogeneous color and to evaluate whether the resulting pigmentation was photoprotective against ultraviolet radiation (UVR)-induced DNA damage in the dermis and the epidermis. TESs were cultured using different concentrations of melanocytes (100, 200, and 1,500 melanocytes/mm2 ), and pigmentation was evaluated in vitro and after grafting onto an athymic mouse excisional model. Dermal and epidermal DNA damage was next studied, exposing pigmented TESs to 13 and 32.5 J/cm2 UVR in vitro. We observed that melanocyte cell density increased with culture time until reaching a plateau corresponding to the cell distribution of native skin. Pigmentation of melanocyte-containing TESs was similar to donor skin, with visible melanin transfer from melanocytes to keratinocytes. The amount of melanin in TESs was inversely correlated to the UVR-induced formation of cyclobutane pyrimidine dimer in dermal fibroblasts and keratinocytes. Our results indicate that the pigmentation conferred by the addition of melanocytes in TESs protects against UVR-induced DNA damage. Therefore, autologous pigmented TESs could ensure photoprotection after grafting.

Melanogenesis is a critical self-defense mechanism against ultraviolet radiation (UVR)-induced skin damage and carcinogenesis; however, dysregulation of melanin production and distribution causes skin-disfiguring pigmentary disorders. Melanogenesis is initiated by UVR-induced cAMP generation and ensuing activation of transcription factor CREB, which induces expression of the master melanogenic regulator MITF. Recent studies have demonstrated that recruitment of CRTCs to the CREB transcription complex is also required for UVR-stimulated melanogenesis. Therefore, modulation of cAMP-CRTC/CREB-MITF signaling may be a useful therapeutic strategy for UVR-associated skin pigmentary disorders. Methods: We identified the small-molecule Ro31-8220 from CREB/CRTC activity screening and examined its melanogenic activity in cultured mouse and human melanocytes as well as in human skin. Molecular mechanisms were deciphered by immunoblotting, RT-PCR, promoter assays, tyrosinase activity assays, immunofluorescent examination of CRTC3 subcellular localization, and shRNA-based knockdown. Results: Ro31-8220 suppressed basal and cAMP-stimulated melanin production in melanocytes and human melanocyte co-culture as well as UVR-stimulated melanin accumulation in human skin through downregulation of MITF and tyrosinase expression. Mechanistically, down regulation of MITF expression by Ro31-8220 was due to inhibition of transcriptional activity of CREB, which was resulted from phosphorylation-dependent blockade of nuclear translocation of CRTC3 via JNK activation. The selective JNK activator anisomycin also inhibited melanin production through phosphoinhibition of CRTC3, while JNK inhibition enhanced melanogenesis by stimulating CRTC3 dephosphorylation and nuclear migration. Conclusions: Melanogenesis can be enhanced or suppressed via pharmacological modulation of a previously unidentified JNK-CRTC/CREB-MITF signaling axis. As Ro31-8220 potently inhibits UVR-stimulated melanin accumulation in human skin, suggesting that small-molecule JNK-CRTC signaling modulators may provide therapeutic benefit for pigmentation disorders.

In non-pigmented skin tumors the diagnosis is mainly based on the evaluation of the vascular morphology and vessels´ distribution dermoscopically [1-4]. However, up to date, no study formally correlated the prevailing vascular morphology with the thickness of melanoma according to Breslow and amount of pigmentation.

O dedo azul não-isquémico espontâneo consiste no aparecimento súbito de uma coloração violácea digital isolada, sem outros sintomas associados e de resolução rápida e espontânea. É um fenómeno raro e benigno e constitui um diagnóstico de exclusão, sendo importante realizar o diagnóstico diferencial com outras etiologias mais frequentes, nomeadamente eventos trombóticos, isquémicos ou patologia autoimune. Descreve-se o caso de uma mulher de 83 anos, que recorreu à consulta de uma unidade de saúde por início súbito de cor violácea e edema do terceiro dedo da mão direita, indolor e sem envolvimento da extremidade distal. A avaliação analítica para trombofilias e autoimunidade revelou-se negativa, assim como a investigação imagiológica de isquemia ou trauma. Ao fim de sete dias a doente foi reavaliada, havendo resolução completa do quadro. Este caso assume importância devido à sua semelhança com patologias de prognóstico potencialmente mais grave.

Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while expression of CDK4.R24C and RAC1.P29S had no detectable effect. Time-lapse tracking of melanocytes in co-culture revealed dynamic interaction phenotypes and hyper-motile cell states that indicated that, in addition to the known role in activating mitogenic signalling, MEK-pathway-activating mutations may also allow melanocytes to escape keratinocyte control and increase their invasive potential. Expanding this combinatorial platform will identify other therapeutic target mutations and melanocyte genetic variants, as well as increase understanding of skin cell interactions.

Non-tumorous facial pigmentation, though not fatal, adversely affects one's quality of life and may indicate concurrence of systemic diseases. Automatic diagnosis method such as voting-based probabilistic discriminant analysis (V-PLDA) has been explored, but the accuracy of classification is not satisfactory due to the limited number of data for training. This paper proposes to use the pre-trained deep learning network of Inception-ResNet-v2 so that information from similar datasets can be utilized. Furthermore, data augmentation using synthetic minority over-sampling technique (SMOTE) is also applied to make full use of available training data. A clinical dataset of five most common types of non-tumorous facial pigmentation disorders in Asia, namely freckles, lentigines, melasma, Hori's nevus, and nevus of Ota, is used for training and testing. The classification accuracy has shown significant improvement (> 7%) compared to the state-of-the-art method.

Skin depigmentation diseases, such as vitiligo, are pigmentation disorders that often destroy melanocytes. However, their pathological mechanisms remain unclear, and therefore, promising treatments or prevention has been lacking. Here, we demonstrate that a zebrafish insertional mutant showing a significant reduction of nicastrin transcript possesses melanosome maturation defect, Tyrosinase-dependent mitochondrial swelling, and melanophore cell death. The depigmentation phenotypes are proven to be a result of γ-secretase inactivation. Furthermore, live imaging demonstrates that macrophages are recruited to and can phagocytose melanophore debris. Thus, we characterize a potential zebrafish depigmentation disease model, a nicastrinhi1384 mutant, which can be used for further treatment or drug development of diseases related to skin depigmentation and/or inflammation.

AIM The aim of the present study was to retrospectively investigate the dermatological diseases seen in geriatric patients, and their distribution according to age, sex and season, making a significant contribution to the few previous prevalence studies. METHODS Data from 7092 geriatric patients examined at our dermatology clinic from 1 January to 31 December 2017 were retrospectively analyzed. The data were analyzed according to age, sex and seasons. RESULTS The seven most frequently occurring diseases were eczematous dermatitis, fungal infections, pruritus, precancerous and malignant neoplasm, xerosis cutis, benign neoplasms, and papulosquamous diseases, respectively. In the youngest group, the most frequent disease was eczematous dermatitis, whereas in the older group it was precancerous and malignant neoplasms. The most common disease for both men and women was eczematous dermatitis. Eczematous dermatitis, pruritus, xerosis cutis, rash and general drug eruptions, and papulosquamous diseases were most frequent in the winter, but less in the summer (P

Immunotherapy with checkpoint inhibitors significantly improves the outcome for stage III and IV melanoma. Cutaneous adverse events during treatment are often reported. We herein aim to review the principal pigmentation changes induced by immune check-point inhibitors: the appearance of vitiligo, the Sutton phenomenon, melanosis and hair and nail toxicities.

Today, innovative restorative materials and techniques allow for minimally invasive prosthetic procedures, which are paramount to the preservation of hard and soft dental tissues. An integrated approach combining dental and esthetic medical therapies could be useful to improve the quality of life of patients, improving function, esthetics, and self-confidence. Oral esthetics depends on several variables, including tooth visibility and proportions as well as healthy gingival tissues. Proper integration between teeth and periodontal tissues plays an important role in esthetic success, which is mainly represented by an appealing smile. The present case report was aimed at describing the multidisciplinary treatment of a woman who was unsatisfied with the shape of her central incisors and the dark gingival pigmentation displayed by a high smile line. The patient was treated with minimally invasive combined periodontal, prosthetic, and esthetic medical techniques. The described multidisciplinary approach based on surgical gingival depigmentation, adhesive ceramic veneers, and selective botulinum toxin injection was effective in solving the undesired high smile line and achieving patient satisfaction.

Buccal mucosa color is explained by hemoglobin in the vessels and melanin in the epithelium. Abnormal presence of melanin pigments (hypermelaninosis, hypermelanocytosis), hematic pigments (hemoglobin, hemosiderin, iron) but also some exogenous circonstancies explain pigmented lesions (figure 1). These lesions could be localized (single lesions), multifocal (multiple lesions) or diffused. In case of a localized pigmentation with melanic appearance, melanoma must be systematically eliminated with a biopsy. In the case of a more diffused lesion, systemic disease must be evoked. A drug etiology is also possible. A blood pigment excess could be a vascular malformation (flat lesions) or a tumoral process (nodular or swollen lesions). In both cases, Kaposi's disease should be systematically eliminated. Pigmentations near dental restorations (amalgams, prosthetic crowns) could be explained by an exogenous factor but a biopsy should be performed in case of a doubt with melanoma.

First described in 1978, Griscelli syndrome (GS) is a rare autosomal recessive disorder featuring pigmentary dilution of hair and skin.1 GS is caused by mutations in any of three genes encoding a tripartite protein complex essential for melanosome transport.2 GS1 (MIM214450) presents as hypomelanosis with primary neurological defects and is caused by mutations in MYO5A,3 and which also may be the same entity as Elejalde syndrome (MIM256710).4 This article is protected by copyright. All rights reserved.

To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR. The melanocyte-specific gene transcripts TYR, DCT, TYRP1 and PMEL were significantly upregulated in our NBUVB-treated melanocyte samples as compared with the keratinocyte samples, while keratinocyte-specific genes (KRT5 and KRT14) were expressed significantly higher in the keratinocyte samples as compared with the melanocyte samples. Furthermore, in both NBUVB-treated vitiligo skin and normal skin, when bulge melanocytes were compared with epidermal melanocytes, we found significantly lower expression of melanocyte-specific genes and significantly higher expression of three melanocytic stem cell genes (SOX9, WIF1 and SFRP1), while ALCAM and ALDH1A1 transcripts did not show significant variation. We found significantly higher expression of melanocyte-specific genes in the epidermis of NBUVB-treated vitiligo, as compared to the normal skin. When comparing bulge melanocyte samples from untreated vitiligo, NBUVB-treated vitiligo and normal skin, we did not find significant differences in the expression of melanocyte-specific genes or melanocytic stem cell genes. These techniques offer valuable opportunities to study melanocytes and their precursors in vitiligo and other pigmentation disorders.

IntroductionAdipose tissue has been shown to contain adipose-derived stem cells (ADSCs), which constitute a very convenient source of stem cells because it can be obtained easily in large quantities. Vitiligo is a pigmentation disorder caused by loss of skin melanocytes and can be treated by graftin

Our skin is the first line of defense from external environment. It covers whole body and protects the tissues and organs from various external assaults. Skin also keeps a stable internal environment for body’s metabolism, like regulating temperature and saving necessary water. Furthermore the nerve of skin gives us tactile sensation, which makes us to better adapt to our living environment. When skin diseases occur, the partial functionality of skin cannot be accomplished. One of fatal diseases is skin cancer. With skin cancer progression, the color of skin will change on different stage. Paper proposes an algorithm to detect and quantize this kind of visual change. The program tries to assist people to diagnosis skin cancer, even self-exam. The proposed algorithm mainly contains three parts. Initially paper segments the skin area from images. Then two main components of skin color are retrieved by ICA. Finally paper estimates if there is pigmentation disorder through comparing the ratio of two main components, and a novel comparing model, projective coordinates is used in this process.

Changes in the human pigmentary system can lead to imbalances in the distribution of melanin in the skin resulting in artefacts known as pigmented lesions. Our work takes as departing point biological data regarding human skin, the pigmentary system and the melanocytes life cycle and presents a reaction-diffusion model for the simulation of the shape features of human-pigmented lesions. The simulation of such disorders has many applications in dermatology, for instance, to assist dermatologists in diagnosis and training related to pigmentation disorders. Our study focuses, however, on applications related to computer graphics. Thus, we also present a method to seamless blend the results of our simulation model in images of healthy human skin. In this context, our model contributes to the generation of more realistic skin textures and therefore more realistic human models. In order to assess the quality of our results, we measured and compared the characteristics of the shape of real and synthesized pigmented lesions. We show that synthesized and real lesions have no statistically significant differences in their shape features. Visually, our results also compare favourably with images of real lesions, being virtually indistinguishable from real images.

Background Terra firma-forme dermatosis was first described in 1987. It is characterized by the appearance in children or adolescents of dirt-like patches despite normal cleansing. The lesions are removed when the skin is rubbed with a 70°C alcohol swab. This largely unknown condition is of uncertain origin but could be due to a keratinisation disorder. Patients and methods Herein we report the case of a 17-year-old male patient who, after seeking the opinions of a number of doctors, consulted in dermatology for multiple pigmented patches on the trunk and limbs that had appeared one year earlier. These lesions had persisted despite appropriate cleansing. He had no history of endocrine disorders and no familial history of pigmentation disorders. A skin biopsy revealed compact orthokeratotic hyperkeratosis resembling a second layer of stratum corneum on top of a normal layer. Very small granules were seen within this layer and PAS staining revealed spores. These skin lesions disappeared when rubbed with an alcohol swab, resulting in a diagnosis of terra firma-forme dermatosis. Discussion Where a diagnosis of terra firma-forme dermatosis is suspected, confirmation is easy to obtain using an alcohol swab. Nevertheless, the disease is not familiar to dermatologists. The most common differential diagnoses are acanthosis nigricans, reticulate and confluent papillomatosis, and Dowling-Degos disease. Their histopathological appearances are very different and skin biopsy can be useful for diagnosis. These entities belong to a group of disorders involving abnormal keratinisation and pigmentation. Anatomoclinical correlation is essential for optimal management. The appearance of the stratum corneum may play an important role in the diagnosis of terra firma-forme dermatosis.

Dermatologic disease often presents in the primary care setting. Therefore, it is important for the primary care provider to be familiar with the presentation, diagnosis, and treatment of common skin conditions. This article provides an overview of acne, rosacea, melasma, vitiligo, alopecia, nonmelanoma, and melanoma skin cancer, dermatitis, and lichen sclerosus.

Laugier-Hunziker syndrome is a rare benign idiopathic condition characterized by acquired macular pigmentation of lips and buccal mucosa, often accompanied with melanonychia. The main concern with this condition is to rule out other differential diagnosis with systemic repercussions and similar hyperpigmentation patterns, such as Peutz-Jeghers syndrome, adrenal insufficiency and melanoma. We report a 58-year-old female with a 20-year history of Sjogren’s syndrome, presenting with melanonychia and hyperpigmentation in the buccal mucosa. She had no relevant medication history and is a non-smoker. The patient denied any other symptoms. The histopathology confirmed the diagnosis of Laugier-Hunziker syndrome.

Background: Pigmented purpuric dermatosis (PPD) is known as a chronic recurrent eruption which usually presents with petechiae and pigmented macules on the lower extremities. Dermoscopy is a noninvasive diagnostic tool in identifying pigmented and vascular lesions, which can also be beneficial in the evaluation of PPD. Objective: We aimed to analyze the common dermoscopic characteristics of PPD, and correlate those findings with the histopathologic features. Additionally, dermoscopic and pathological findings in this study population were compared with other similar studies from the literature review. Methods: A retrospective analysis was performed using data of 60 patients who were diagnosed as PPD by skin biopsy and had dermoscopic examination. The pathologic analysis was performed by categorizing the pattern into lichenoid, perivascular, interface, and spongiotic subtype, and the dermoscopic assessment was performed by the three authors independently. Results: In dermoscopy, 96.7% of the patients showed red globules and dots, followed by brownish patch, coppery-red pigmentation, and annular comma-like vessels. The pathologic pattern analysis revealed statistically significant association of lichenoid pattern with coppery red pigmentation, perivascular pattern with annular/comma-like vessels, and spongiosis pattern with reticular pigmented network and linear vessels. The interrater similarity test showed total kappa value of 0.811 which referred to “very good”. Conclusion: In this study, the prevalence of dermoscopic features in Asian PPD patients was identified, which was similar with previous studies. The dermoscopic-pathologic correlation was found in four dermoscopic features. We suggest that dermoscopic examination is helpful in clinical diagnosis and pathological prediction of PPD. (Ann Dermatol 33(3) 214∼221, 2021)

Cutaneous vasculature systems play a role in regulating skin pigmentation. We analysed RNA sequencing data to identify novel antimelanogenic factors secreted from endothelial cells and found that one of the secreted factors, clusterin, is highly expressed by HDMECs. To investigate the paracrine effect of clusterin from HDMECs on the regulation of melanogenesis, HDMECs were infected with clusterin or sh-clusterin lentivirus and the HDMEC-derived conditioned media were used to treat normal human melanocytes. It was found that HDMEC-derived clusterin inhibits melanogenesis through MITF/tyrosinase downregulation. The findings here suggest that HDMECs secrete copious amounts of clusterin and that the clusterin is a factor contributing to the inhibitory effect of endothelial cells on melanogenesis via paracrine crosstalk between endothelial cells and melanocytes.

Vertebrate pigmentation is a process directed by various transcriptional regulators, that drive the specification of melanoblasts from neural crest cells, their proliferation and migration, and terminal differentiation into melanocytes, culminating in the generation of pigment and it's distribution to surrounding keratinocytes. The transcription factor MITF has been coined the “master regulator” of melanocyte development (reviewed in (Steingrimsson, Copeland and Jenkins, 2004)), as it drives both the specification and differentiation of melanocytes. It is associated with pigmentation disorders in human, and Mitf mutant mice have a varying degree of pigmentation defects. This article is protected by copyright. All rights reserved.

Melanogenesis is a complex process that can lead to pigmentation defects. Various chemical skin-lightening products have been developed to treat pigmentation disorders. However, these chemical products can cause harmful adverse effects. Therefore, the development of safer, natural bleaching ingredients is a trend for sustainability. It has been reported that unsaturated fatty acids exhibit significant antimelanogenic effects. Sapindus mukorossi seed oils contain abundant unsaturated fatty acids; however, these have not yet been investigated for beneficial effects on skin tone evenness. In this study, we tested the possibility of using S. mukorossi oil for the treatment of hyperpigmentation in an in vitro model. Free fatty acid compositions and β-sitosterol were determined by gas chromatography-mass spectrometry and high-pressure liquid chromatography, respectively. The effect of S. mukorossi oil on melanoma B16F10 cell viability was detected using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide assay. The inhibitive effects of fatty acids and β-sitosterol in S. mukorossi oil on α-melanocyte-stimulating hormone (MSH)-induced melanogenesis was evaluated by detecting melanin formation and tyrosinase activity. Our results showed that S. mukorossi oil produced no significant cytotoxicity in B16F10 cells at various concentrations compared with the control group. The enhancement of melanin formation induced by α-MSH was reduced by S. mukorossi oil. We also found that the primary fatty acid contributing to the antimelanogenesis effect was eicosenoic acid. These results suggest that S. mukorossi seed oil can effectively inhibit melanogenesis and has the potential for future development as a de-hyperpigmentation product within a waste utilization context.

Melanocytes are the major cells responsible for skin and fair pigmentation in vertebrates. They localize to hair follicles(HFs) and the epidermis during embryonic development. A reduced number or dysfunction of melanocytes results in pigmentation disorders.Thus, methods for isolation, culture, and identification of melanocytes in mouse hair follicles provide an experimental basis for thestudy of of pigmentation disorders. In the current work, we harvested the melanocytes from the anagen phase dorsal skin of C57BL/6 mice.After its separation from the skin, the dermis was digested, and the HFs were released. HFs were then also digested, and the cells released from HFs were cultured in melanocyte growth medium. Immunofluorescence and immunohistochemistry staining were used to localize the distribution of melanocytes in HFs . Reverse transcription polymerase chain reaction was performed to detect the expression of specific melanocyte marker genes. Immunofluorescence, immunohistochemistry, flow cytometry, and western blot were carried out to detect the expression of marker proteins in cells. 3,4-Dihydroxy-L-phenylalanine (L-DOPA) staining was used to detect the pigmentation functionality of melaonocytes. Based on our results, we conclude that mature and functional melanocytes can be successfully obtained from theHFs, providing a cell model to study pigmentation disorders. The current findings provide novel insights for the treatment of pigmentation disorders by autologous cell transplantation. Further, we believe that issues related to skin damage, insufficient numbers of autologous cells, and autoimmune problems can be resolved in future though the use of functional melanocytes.

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.

Background Cutaneous mosaicism is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding of the conditions in this field, and to an ongoing paradigm shift in the approach to management of mosaic skin disorders. Objectives To lay out the general principles of mosaicism as they are currently understood, summarize the known cutaneous mosaic abnormalities of the skin with associated phenotypic and genotypic information, review the latest trials on targeted therapies and propose guidelines for the general approach to a patient with suspected mosaicism. Methods This was a consensus expert review as part of the European Reference Network project (ERN-Skin). Conclusions This study provides clinicians with a practical approach to the patient with suspected mosaicism, redefines mosaicism for the modern genetic era, and proposes a new classification system based on genetic mechanism. What's already known about this topic? Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes. Some cutaneous patterns are known to be seen in mosaicism. Very few treatment options are available for most mosaic abnormalities of the skin. Recent high-sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature. What does this study add? Expert consensus from the European Reference Network project. Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype. Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential. Practical tips on correct sample collection and genetic investigation. Review of trials of targeted therapies. Guidelines for a practical clinical approach to the patient with suspected mosaicism.

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.

Aging skin is subject to morphological change due to both intrinsic (skin tone, genetics, endogenous hormones) and extrinsic (chronic sun exposure, medications, exogenous pigments) factors. The broad spectrum of transformation includes both hypo- and hyperpigmentation. Although cutaneous pigmentary disorders are common in younger individuals, certain disorders are more prevalent in the geriatric population. This article reviews the epidemiology, pathophysiology, clinical appearance, treatment, and prognosis of pigmentary lesions that are predominant in the elderly.

Since the first edition of this textbook, the nomenclature has been revised after an extensive international work within the Vitiligo Global Issues Consensus Conference (VGICC). Vitiligo/nonsegmental vitiligo (NSV) is a consensus umbrella term for all forms of generalized vitiligo. It is an acquired chronic pigmentation disorder characterized by white patches, often symmetrical, which usually increases in size with time, corresponding to a substantial loss of functioning epidermal and sometimes hair follicle melanocytes. The two other subsets of vitiligo defined by the international consensus are segmental vitiligo and unclassified/undetermined vitiligo which correspond to focal disease and rare variants. A series of hypopigmented disorders may masquerade as vitiligo, and some of them need to be ruled out by specific procedures including a skin biopsy.

Beta thalassemia is a disease that affects many organs and leads to mortality and morbidity. We also aimed to investigate the skin findings in children with beta-thalassemia major. Between April 2016 and September 2016, cross-sectionally 24 children with beta-thalassemia who were followed-up and transfused with blood at the Thalassemia Center of Mugla Sitki Kocman University were included in the study. The dermatological examinations of the patients were performed by two dermatologists. In addition to dermatological examinations, additional diseases, iron chelator agents and other treatments, hemoglobin, hematocrit, ferritin levels, accompanying skin, hair and nail findings were recorded. Seventeen of the 24 beta-thalassemia patients were male (70.8%), seven were female (29.2%) evaluated in our study. When we assessed the skin, hair and nail findings of patients; 62.5% of the patients had xerosis, 54.2% had pigmentation disorders, 33.3% had nevi, 33.3% had splenectomy scar, 25% had dermatoses, 16.7% nail involvement, 16.7% had pruritus, tinea versicolor in 8.3% and other skin findings in 37.5%. As a result, xerosis was detected as the most common skin finding in our study. The second most common disorders were pigmentation diseases. Ferritin levels were found to be significantly increased in patients with impaired pigmentation. Patients with thalassemia disease should be followed for xerosis and pigmentation diseases. Moisturizing creams and sunscreens should be recommended to patients by hematology and dermatology doctors. Our study is limited with few cases, and multi-centered studies are needed in the future.