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Accurately diagnosing and describing the severity of vitiligo is crucial for prognostication, treatment selection and comparison. Currently, disease severity scores require dermatologists to estimate percentage area of involvement, which is subjected to inter and intra-assessor variability. Previous studies focus on pure skin but vitiligo on the face, which has a more serious impact on patients’ quality of life, was completely neglected. Convolutional neural networks (CNNs) have good performance on many segmentation tasks. However, due to data privacy, it is hard to have a large clinical vitiligo face image dataset to train a CNN. To address this challenge, images from two different sources, the Internet and the proposed vitiligo face synthesis algorithm, are employed in training. 843 vitiligo images taken from different viewpoints were collected from the Internet. These images are hugely different from the target clinical images collected according to a newly established international standard. To have more vitiligo face images similar to the target clinical images to enhance segmentation performance, an image synthesis algorithm is proposed. Both synthetic and Internet images are used to train a CNN which is modified from the fully convolutional network (FCN) to segment face vitiligo lesions. The results show that 1) the synthetic images effectively improve segmentation performance; 2) the proposed algorithm achieves 1.06 $\%$ error for the face vitiligo area estimation and 3) it is more accurate than two dermatologists and all the previous automated vitiligo segmentation methods, which were designed for segmentation vitiligo on pure skin.

Background We developed the first-of-its-kind handheld confocal Raman spectroscopy (CRS) system to quantify the concentration of natural moisturizing factors in the skin. Objective To evaluate the feasibility of our handheld CRS system and propose a novel quantitative index to measure skin barrier function. Methods This prospective study included 30 atopic dermatitis (AD) patients and 14 healthy volunteers. All AD participants were assessed using the Scoring Atopic Dermatitis (SCORAD) severity instrument, a vapometer for trans-epidermal water loss and a moisture meter for skin surface moisture. A handheld CRS operating at 785 nm laser was used to measure the biochemical constituents of the skin up to a depth of ∼100 μm. We trained a linear kernel-based support vector machine (SVM) model for eczema classification based on the water, ceramide and urocanic acid content. A novel Eczema Biochemical Index (EBI) was then formulated using the skin constituents measured from the AD participants to stage disease severity. Results The SVM model used to classify healthy participants and AD patients obtained high cross-validated area under the curve of 0.857 and accuracy of 0.841, with high sensitivity and specificity values of 0.857 and 0.833 respectively. EBI can be used to stratify AD patients of varying severity, based on the biochemical constituents in the skin. Conclusion As compared to the standard CRS system, the handheld CRS offers higher portability and provides Raman measurements at various body regions with similar sensitivity. This suggests that a handheld CRS device could be a valuable point-of-care resource in both research and clinical use.

Glucose is critical to all organisms. Herein, we developed a wire electrode embedded microneedle patch (WEMNP) for in situ real-time detection of glucose in the interstitial fluid (ISF) of skin or plant tissues with minimal invasiveness. WEMNP is made of proline treated silk fibroin proteins, which provide good mechanical strength (0.75 N/microneedle) for tissue penetration and desirable bioelectronic interface for fast and high-fidelity detection. WEMNP shows specific and linear response to glucose between 3 and 18 mM for detection in skin ISF with a sensitivity of 21.21 nA/mM and between 30 and 180 mM for detection in plant ISF with a sensitivity of 1.22 nA/mM. Such self-administrable WEMNP could be instrumental to long-term home-based management for chronic diseases and to smart agriculturing. Ministry of Education (MOE) Submitted/Accepted version This research was financially supported by AcRF Tier-1 Grants (RG110/20 and RT02/20) and AcRF Tier-2 grant (MOE2019-T2-2-004) from Singapore Ministry of Education.

Hyperpigmentation is a major cosmetic concern that results from the overproduction of melanin from melanocyte cells in the skin. Current formulations of therapeutic drugs and active molecules that are intended to be delivered to the melanocytes are not targeted, leading to inefficient delivery and undesirable side effects. There is a compelling need for delivery vehicles that target melanocytes to effectively regulate melanin production. Self‐assembling protein nanocages (PNCs) have been shown to offer safe and efficient delivery of active molecules. They are versatile protein nanoparticle platforms that can be engineered to display functional ligands to impart specific biological functions. In this work, E2 PNCs are engineered to display alpha‐melanocyte‐stimulating hormone (AlphaMSH) peptides as ligands for targeting and enhancing uptake by melanocytes. At 500 pM, the AlphaMSH‐modified E2 PNCs show 4‐fold increase in melanocyte cell uptake compared to bare E2 PNCs in 2 hours. This increase was less pronounced in keratinocytes. Competitive inhibition assay proves that the MC1R melanocyte cell surface receptor facilitates the uptake of E2 PNCs by mediating interaction with the displayed AlphaMSH peptides. PNCs can thus be used as targeted delivery vehicles of drugs and active molecules to melanocytes for the management of hyperpigmentation.

Background The visual assessment and severity grading of acne vulgaris by physicians can be subjective, resulting in inter- and intra-observer variability. Objective To develop and validate an algorithm for the automated calculation of the Investigator's Global Assessment (IGA) scale, to standardize acne severity and outcome measurements. Materials and methods A total of 472 photographs (retrieved 01/01/2004-04/08/2017) in the frontal view from 416 acne patients were used for training and testing. Photographs were labeled according to the IGA scale in three groups of IGA clear/almost clear (0-1), IGA mild (2), and IGA moderate to severe (3-4). The classification model used a convolutional neural network, and models were separately trained on three image sizes. The photographs were then subjected to analysis by the algorithm, and the generated automated IGA scores were compared to clinical scoring. The prediction accuracy of each IGA grade label and the agreement (Pearson correlation) of the two scores were computed. Results The best classification accuracy was 67%. Pearson correlation between machine-predicted score and human labels (clinical scoring and researcher scoring) for each model and various image input sizes was 0.77. Correlation of predictions with clinical scores was highest when using Inception v4 on the largest image size of 1200 × 1600. Two sets of human labels showed a high correlation of 0.77, verifying the repeatability of the ground truth labels. Confusion matrices show that the models performed sub-optimally on the IGA 2 label. Conclusion Deep learning techniques harnessing high-resolution images and large datasets will continue to improve, demonstrating growing potential for automated clinical image analysis and grading.

Background: Smartphone apps could support patients and caregivers in disease self-management. However, as patients’ experiences and needs might not always align with clinical judgments, the eliciting and engaging of perspectives of all stakeholders in the smartphone app design process is of paramount importance. Objective: The aims of this study are to better understand the needs of and challenges facing caregivers and health care professionals (HCPs) who care for children with atopic dermatitis (AD) and to explore the desirable features and content of a smartphone app that would support AD self-management. Methods: This study adopted a qualitative participatory co-design methodology involving 3 focus group discussions: workshop one focused on caregivers; workshop two engaged with HCPs; and in the last workshop, caregivers and digital health experts were asked to design the wireframe prototype. The participants completed a sociodemographic questionnaire, a technology acceptance questionnaire, and a workshop evaluation form. Results: Twelve caregivers participated in the first workshop, and 10 HCPs participated in the second workshop. Eight caregivers and 4 digital health experts attended the third workshop. Three superordinate themes that reflected caregivers’ and HCPs’ challenges and needs were identified: empowerment by education, confusion over treatment, and emotional impact. Workshop participants also raised a series of suggestions on the features and contents of the AD self-management app, which informed the last co-design workshop, and described their needs and challenges. In the last workshop, the participants developed a wireframe prototype of the app following the identified requirements and recommendations. Conclusions: The co-design approach was found to be a successful way of engaging with the participants, as it allowed them to express their creativity and helped us to articulate the root of the clinical problems. The co-design workshop was successful in creating and generating new ideas and solutions for smartphone app development. Nanyang Technological University Published version This research was funded by a principal investigator start-up grant (Lee Kong Chian School of Medicine, Nanyang Technological University). JC’s post at Imperial College London is supported by the National Institute for Health Research NW London Applied Research Collaboration.

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin condition that affects about 10–20% of children and 2-15% of adults in developed countries (1). In Singapore, the prevalence among children and adolescents is 20.8% (2). Itchiness, the most common complaint, results in behavioural and social impairments among paediatric AD patients, which in turn impacts on the wellbeing of caregivers, particularly family members (3, 4). A sick child can markedly affect normal family life and the mental and social wellbeing of other family members (5). Their family members, namely parents, may experience feelings of helplessness and stress as they struggle to treat their child’s symptoms, and this can lead to feelings of guilt as they feel they are failing in their duty to care for their offspring (6). In return, family quality of life can greatly influence patient-related outcomes. Previous studies have demonstrated that paediatric atopic eczema can significantly affect family life; however, they provide limited quantitative data on the factors influencing family life and functions (6). Therefore, we conducted this study in an effort to gain in-depth insights into the family burden caused by paediatric AD, and to explore the social and clinical factors potentially impacting family life and function.

This study examined concordance between caregiver-reported and physician-rated estimates of severity of atopic dermatitis (AD) in paediatric patients and explored potential explanatory factors. Physician-reported severity of AD was retrieved from medical records, while caregiver-reported disease severity and sociodemographic data were obtained through a survey that also collected information on out-of-pocket expenses due to AD. There was 38.5% (95% confidence interval (95% CI) 30.1, 43.5) disagreement between physician and caregivers with regards to both underestimating and overestimating the condition. A duration since AD diagnosis shorter than 6 months showed higher concordance (kappa: 44.4%; 95% CI 30.6, 58.2) between caregiver and physician estimates of AD severity compared with a duration of 6 months or longer. Caregivers underestimating their child’s AD accounted for 27.7% among all participants, while 10.8% overestimated the severity of AD compared with physicians. Factors significantly associated with caregiver’s underestimation of disease severity were age of the child and time since disease diagnosis. Comparison of concordance between caregiver-reported and physician-rated estimates of severity of AD in paediatric patients revealed a tendency amongst caregivers to underestimate severity of AD. This information may have clinical implications for treatment outcomes if caregivers fail to adhere to medical advice. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University Skin Research Institute of Singapore (SRIS) Published version The authors would like to thank all children and caregivers that responded to the questionnaire and made this study possible. This research was supported through the Skin Research Grant by the Skin Research Institute of Singapore (SRIS), a tripartite partnership between the Agency for Science, Technology, and Research (A*STAR), National Healthcare Group through its National Skin Centre (NHG) and the Nanyang Technological University (NTU). Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the legally authorized representative (LAR) of the child prior to enrolment in the study.

Background Childhood atopic dermatitis can often have a negative impact on quality of life for affected children and their caregivers. The condition contributes to increased healthcare costs and can pose heavy economic burdens on healthcare systems and societies. Objectives The objective of this study is to provide a comprehensive estimate of the economic burden of childhood atopic dermatitis in a Singaporean sample and to investigate associated factors. Methods This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with a physician-confirmed diagnosis of atopic dermatitis were recruited and sociodemographics, clinical characteristics, health service utilization data and time spent on caregiving were collected from all eligible participants. Results The average annual cost per child with atopic dermatitis was estimated at U.S. dollars (USD) 7943 (mild USD 6651, moderate USD 7935 and severe USD 14 335) in 2017 prices. The major cost was for informal caregiving (46% of the total cost) followed by out-of-pocket expenses (37%). Healthcare utilization contributed to 17% of the total cost of which 43% was for medications. Conclusions Childhood atopic dermatitis imposes substantial costs with a large proportion arising from informal caregiving and out-of-pocket expenses. The costs related to atopic dermatitis are also strongly related to disease severity. This information is important for policy makers and other health planners when considering how to better support affected families. What's already known about the topic? Childhood atopic dermatitis is a costly disease for society. However, comprehensive cost estimations are lacking. Previous cost studies are old, based on small sample sizes or are healthcare-setting specific. What does this study add? This study comprises a health economic evaluation assessing different levels of care and includes various categories of costs. The result showed that informal caregiving was the most prominent cost for children with atopic dermatitis.

Background: Eczema is a prevalent complex skin condition requiring active disease monitoring and personalized education. No studies have assessed the quality of apps that aim to support eczema self-management. Objectives: To evaluate the quality and comprehensiveness of English, Chinese and Spanish self-management eczema smartphone apps for patients and/or their caregivers. Methods: A systematic assessment of eczema apps from July 2018 to November 2018. The assessment criteria were based on conformance with international eczema guidelines. The following domains were assessed: consistency and comprehensiveness of eczema-specific educational information; quality and comprehensiveness of eczema-specific tracking functions; compliance with health information best practice principles. Results: In total, 98 apps were assessed: 82 (84%) provided educational information; 38 (39%) tracking functions; and 13 (13%) both. We found that 34% (28/82) of apps provided misleading information, particularly regarding aspects of treatment and disease progression of eczema. Only 15% (12/82) provided international guideline supported information on pharmacological therapies and 16% (13/82) on nonpharmacological therapies. Among 38 apps with a tracking function, 82% (31/38) measured specific symptoms, disease severity or current skin condition and 89% (34/38) helped users to record medication usage including application of topicals. Environmental or dietary allergens were recorded by 34% (13/38). None of the included apps complied with all criteria for educational information, tracking functions or health information principles. Conclusions: Eczema apps have not yet reached their potential. The large variance in quality of eczema apps highlights the need for quality assurance mechanisms for health apps and guidance for clinicians that would enable them to make personalized recommendations for patients and caregivers. What's already known about this topic?. There is limited information about the quality of eczema self-management smartphone apps on the global market. What does this study add?. This systematic assessment evaluated all English, Chinese and Spanish language apps that support eczema self-management. The majority did not conform with information in guidelines and insufficiently support evidence-based self-management. The large variance in the quality of eczema apps highlights the need for mechanisms to ensure app quality and to guide personalized app selection for patients, caregivers and doctors.

Population studies suggest that atopic dermatitis (AD) is associated with an increased risk of obesity, however a causal relationship between these two conditions remains to be established. We therefore use Mendelian randomization (MR) to evaluate whether obesity and AD are causally interlinked. We used summary statistics extracted from genome wide association studies of Body Mass Index (BMI) and AD. MR analysis was performed in both directions to establish the direction of causality between BMI and AD. We find that genetically determined increase in adiposity is associated with increased risk of AD (odds ratio of AD 1.08 [95% CI 1.01 to 1.14; p = 0.015] per unit increase in BMI). Conversely, genetically determined increased risk of AD is not associated with a higher BMI (change in BMI attributable to AD based on genetic information: 0.00; 95% CI − 0.02 to 0.02; p = 0.862). There was no evidence for confounding of these genetic analyses by horizontal pleiotropy. Our results indicate that the association of AD with obesity is likely to reflect a causal role for adiposity in the development of AD. Our findings enhance understanding of the etiology of AD, and the basis for experimental studies to evaluate the mechanistic pathways by which adiposity promotes AD.

Non-tumorous skin pigmentation disorders can have a huge negative emotional impact on patients. The correct diagnosis of these disorders is essential for proper treatments to be instituted. In this paper, we present a computerized method for classifying five non-tumorous skin pigmentation disorders (i.e., freckles, lentigines, Hori's nevus, melasma and nevus of Ota) based on probabilistic linear discriminant analysis (PLDA). To address the large within-class variance problem with pigmentation images, a voting based PLDA (V-PLDA) approach is proposed. The proposed V-PLDA method is tested on a dataset that contains 150 real-world images taken from patients. It is shown that the proposed V-PLDA method obtains significantly higher classification accuracy (4% or more with p< 0.001 in the analysis of variance (ANOVA) test) than the original PLDA method, as well as several state-of-the-art image classification methods. To the authors' best knowledge, this is the first study that focuses on the non-tumorous skin pigmentation image classification problem. Therefore, this paper could provide a benchmark for subsequent research on this topic. Additionally, the proposed V-PLDA method demonstrates promising performance in clinical applications related to skin pigmentation disorders. Accepted version

The ability to monitor oxygen delivery in microvasculature plays a vital role in measuring the viability of skin tissue and the probability of recovery. Using currently available clinical imaging tools, it is difficult to observe non-invasive hemodynamic regulation in the peripheral vessels. Here we propose the use of a novel multispectral raster-scanning optoacoustic mesoscopy (RSOM) system for noninvasive clinical monitoring of hemodynamic changes in the skin microvasculature’s oxy- (HbO2) and deoxy-hemoglobin (Hb), total hemoglobin (HbT) and oxygen saturation (rsO2). High resolution images of hemoglobin distribution in the skin microvasculature from six healthy volunteers during venous and arterial occlusion, simulating systemic vascular diseases are presented. During venous occlusion, Hb and HbO2 optoacoustic signals showed an increasing trend with time, followed by a drop in the values after cuff deflation. During arterial occlusion, an increase in Hb value and decrease in HbO2 values was observed, followed by a drop in Hb and jump in HbO2 values after the cuff deflation. A decrease in rsO2 values during both venous and arterial occlusion was observed with an increase in value after occlusion release. Using this proof of concept study, hereby we propose multispectral RSOM as a novel tool to measure high resolution hemodynamic changes in microvasculature for investigating systemic vascular diseases on peripheral tissues and also for monitoring inflammatory skin diseases, and its therapeutic interventions.

Summary The Vitiligo Global Issues Consensus Conference (VGICC), through an international e-Delphi consensus, concluded that “repigmentation” and “maintenance of gained repigmentation” are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation and the second summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over three years. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus. This article is protected by copyright. All rights reserved.

Classification of non-tumorous facial pigmentation disorders is an important but overlooked problem. Recently, a voting-based probabilistic linear discriminant analysis (V-PLDA) method was developed to address this problem by extracting hand-craft features from a given image set of rather small size, with limited classification accuracy. In this paper, we propose an improved Synthetic Minority Over-sampling Technique (improved SMOTE) with several parameters tuned to fully utilize the available images. Moreover, transfer learning is applied to reduce the data size requirement of the deep learning model. By combining the improved SMOTE and transfer learning, a classification accuracy gain (10%) is attained compared to the state-of-the-art V-PLDA method.

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.

Vitiligo usually begins in childhood or in young adults with some studies recording around half of patients with disease onset before the age of 20 years old. Childhood vitiligo tends to present more with segmental vitiligo and is associated with higher incidences of thyroid dysfunction as well as family history of autoimmune disease, significant psychological morbidity and quality of life (QOL) impairment in the patient and in the parent. Prepubertal onset of vitiligo associates with atopic dermatitis, halo naevi, family history of vitiligo and premature hair greying. When treating children with vitiligo, special considerations would include the need to coordinate treatments with school schedules and the significant psychosocial impact of the disease on children especially if they have visible lesions. Patients with vitiligo have possibly a higher incidence of worsening during pregnancy and 6 months’ post-partum. Treatment of vitiligo during pregnancy is largely influenced by how treatment may affect the foetus in utero, and treatment has to be balanced with possible adverse effects to foetus in utero. Late-onset vitiligo is an interesting subgroup of patients with vitiligo, and its prevalence ranges from 6.8% in Northern India to 14.7% in Singapore; they seem to progress faster than childhood vitiligo, and the disease progression is significantly associated with a stressful event.

Raster Scanning Optoacoustic Mesoscopy (RSOM) is a novel optoacoustic imaging modality that offers non-invasive, label-free, high resolution (~7 mu m axial, ~30 mu m lateral) imaging up to 1 to 2 mm below the skin, providing novel quantitative insights into skin pathophysiology. As the RSOM image contrast mechanism is based on light absorption, it is expected that the amount of melanin present in the skin will affect RSOM images. However, the effect of skin tone in the performance of RSOM has not been addressed so far. Herein, we present the efficiency of RSOM for in vivo skin imaging of human subjects with Fitzpatrick (FP) skin types between II to V. RSOM images acquired from the volar forearms of the subjects were used to derive metrics used in RSOM studies, such as total blood volume, vessel diameter and melanin signal intensity. Our study shows that the melanin signal intensity derived from the RSOM images exhibited an excellent correlation with that obtained from a clinical colorimeter for the subjects of varying FP skin types. We could successfully estimate the vessel diameter at different depths of the dermis. Furthermore, our study shows that there is a need to compensate for total blood volume calculated for subjects with higher FP skin types due to the lower signal-to-noise ratio in dermis, owing to strong absorption of light by melanin. This study sheds light into how RSOM can be used for studying various skin conditions in populations with different skin phenotypes.

Better understanding of atopic dermatitis' effect on quality of life could enhance current management and therapeutic strategies. Studies investigating factors related to the health-related quality of life (HRQOL) of children with atopic dermatitis and their caregivers are limited. This cross-sectional study included 559 children (

Atopic dermatitis (AD) is a skin inflammatory disease affecting 10% of the population worldwide. Raster-scanning optoacoustic mesoscopy (RSOM) has recently shown promise in dermatological imaging. We conducted a comprehensive analysis using three machine-learning models, random forest (RF), support vector machine (SVM), and convolutional neural network (CNN) for classifying healthy versus AD conditions, and sub-classifying different AD severities using RSOM images and clinical information. CNN model successfully differentiates healthy from AD patients with 97% accuracy. With limited data, RF achieved 65% accuracy in sub-classifying AD patients into mild versus moderate-severe cases. Identification of disease severities is vital in managing AD treatment.

Recent advances in technology have enabled the development of various non-invasive skin imaging tools to aid real-time diagnosis of both benign and malignant skin tumours, minimizing the need for invasive skin biopsy. Multispectral optoacoustic tomography (MSOT) is a recently developed non-invasive imaging tool, which offers the unique capacity for high resolution three dimensional (3D) optical mapping of tissue by further delivering highly specific optical contrast from a depth of several millimetres to centimetres in living tissues. MSOT enables volumetric, spectroscopic differentiation of tissue, both in vivo and in real time, with and without the application of biomarker-specific probes, and is further able of providing spatial maps of skin chromophores, as well as underlying blood vasculature.Three patients with suspicious skin tumours consented to have their lesions imaged with MSOT prior to excision. The histological findings and measurements were compared.We demonstrated the first in vivo clinical use of MSOT for 3D reconstruction of skin tumours in three patients with good histological correlation.Our findings confirm the potential benefit of the new imaging method in guiding surgical intervention to achieve a more precise excision with better clearance and lower relapse rates. It can also potentially help to shorten the duration of Mohs' micrographic surgery. Further large-scale studies are necessary to ensure correlation between MSOT and histology.

Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Skin barrier defects contribute to disease initiation and development; however, underlying mechanisms remain elusive. Objective To understand the underlying cause of barrier defect, we investigated aberrant expression of specific microRNAs (miRNAs) in AD. Delineating the molecular mechanism of dysregulated miRNA network, we focused on identification of specific drugs that can modulate miRNA expression and repair the defective barrier in AD. Methods A screen for differentially expressed miRNAs between healthy skin and AD lesional skin resulted in the identification of miR-335 as the most consistently downregulated miRNA in AD. Using in silico prediction combined with experimental validation, we characterized downstream miR-335 targets and elucidated the molecular pathways by which this microRNA maintains epidermal homeostasis in healthy skin. Results miR-335 was identified as a potent inducer of keratinocyte differentiation; it exerts this effect by directly repressing SOX6. By recruiting SMARCA complex components, SOX6 suppresses epidermal differentiation and epigenetically silences critical genes involved in keratinocyte differentiation. In AD lesional skin, miR-335 expression is aberrantly lost. SOX6 is abnormally expressed throughout the epidermis, where it impairs skin barrier development. We demonstrate that miR-335 is epigenetically regulated by histone deacetylases; a screen for suitable histone deacetylase inhibitors identified belinostat as a candidate drug that can restore epidermal miR-335 expression and rescue the defective skin barrier in AD. Conclusion Belinostat is of clinical significance not only as a candidate drug for AD treatment, but also as a potential means of stopping the atopic march and further progression of this systemic allergic disease.

This randomized clinical trial evaluates the use of atorvastatin combined with narrowband UV-B therapy vs narrowband UV-B therapy alone in adult patients with active vitiligo.

Herein, Multispectral Optoacoustic Tomography (MSOT) was utilized to map non-melanoma skin cancers on Asian patients to obtain their lesion dimensions. The dimensions were then correlated from the measurements acquired from histology, showing good correlation via intraclass correlation coefficient.

Background/objectives Controversy persists as to whether lichen planus pigmentosus and ashy dermatosis are separate clinical entities. This study was conducted to examine the clinicopathological features and treatment outcome of the two conditions. Methods A retrospective medical chart review of all patients who were diagnosed with lichen planus pigmentosus or ashy dermatosis was conducted. The information collected included the participants' age at onset, site of onset, duration of disease, presence of precipitating factors, distribution of disease, pigmentation and presence of symptoms. In patients from whom a biopsy was taken the histopathological reports were included. Results Altogether 26 patients with ashy dermatosis and 29 with lichen planus pigmentosus were included in the study. Compared with ashy dermatosis, lichen planus pigmentosus had a more localised distribution with a preponderance for facial involvement, compared with the truncal preponderance in ashy dermatosis. Ashy dermatosis tended to have a more stable clinical course than lichen planus pigmentosus, which was more likely to wax and wane. The utility of histopathology in differentiating between the two conditions is low. Conclusion Ashy dermatosis and lichen planus pigmentosus, as defined in this study, appear to be two separate clinical entities with distinguishable clinical features and natural histories.

Melasma is a widely spread skin pigmentation disease and accurate assessments of the disease severity is crucial during its treatment. Recently, several computerized methods have been developed to overcome the shortcomings of the conventional clinical assessment method. As a key step in algorithm, image segmentation has extensive impacts on the accuracy of the assessment. Currently, the optimal hybrid thresholding (oHybrid) segmentation method that adaptively combines both local and global thresholding methods has obtained reasonable results in solving the melasma assessment problem. Nevertheless, the distance measure adopted in the oHybrid method is empirically selected and its influence is not well discussed. In this paper, a generalized distance measure is introduced and applied to improve the hybrid thresholding image segmentation method. The proposed method is tested on a data set of melasma patients to determine the lesion severity and it shows the best overall performance among the methods compared.

Currently, imaging technologies that enable dermsurgeons to visualize non-melanoma skin cancers (NMSC) in vivo preoperatively are lacking, resulting in excessive or incomplete removal. Multispectral optoacoustic tomography (MSOT) is a volumetric imaging tool to differentiate tissue chromophores and exogenous contrast agents, based on differences in their spectral signatures and used for high-resolution imaging of functional and molecular contrast at centimeter scale depth. We performed MSOT imaging with two- and three-dimensional handheld scanners on 21 Asian patients with NMSC. The tumors and their oxygenation parameters could be distinguished from normal skin endogenously. The lesion dimensions and depths were extracted from the spectral melanin component with three-dimensional spatial resolution up to 80μm. The intraclass correlation coefficient correlating tumor dimension measurements between MSOT and ex vivo histology of excised tumors, showed good correlation. Real-time 3D imaging was found to provide information on lesion morphology and its underlying neovasculature, indicators of the tumor's aggressiveness.

This paper proposes a new method for melasma pigmentary area segmentation utilizing re action-diffusion based level set model (RDLSM) together with local entropy thresholding. In the adopted level set model, a diffusion term is used to regularize the level set function while a reaction term with anticipated sign property is used to force the zero level set towards desired locations. Then local entropy thresholding is applied to address the over-segmentation issue of RDLSM and to extract desired boundaries with higher overall local entropy. As a result, the melasma pigmentary areas and the normal skin areas can be better identified. Experimental results show that the proposed method performs well for melasma image segmentation, especially for cases with severe non-uniform illumination distribution.

Background: Progressive macular hypomelanosis is an acquired disorder characterized by hypopigmented macules mostly on the trunk and upper extremities. Although many treatment modalities have been proposed for this condition with variable success rates, there are few reports comparing their efficacy and relapse rates. Aim: To compare the efficacy and relapse rates of different treatment modalities for progressive macular hypomelanosis. Methods: Case records of patients diagnosed with progressive macular hypomelanosis and treated in National Skin Centre for a six year period between 2008 and 2014 were reviewed. Patient demographics, distribution of hypopigmented macules, treatment efficacy and relapse rates were noted. Results: A total of 108 patients were seen for progressive macular hypomelanosis over the study period; of these, 40 opted for no treatment but were followed up. Thirty-six were treated with topical antimicrobials and 32 with phototherapy. Of those untreated, 23% recovered spontaneously while 38% in the antimicrobial group and 90% in the phototherapy had remission of their hypopigmentation. After 2 years of follow-up, relapse occurred only in the phototherapy group. Limitations: The main limitation is the retrospective design whereby diagnosis is dependent on the attending dermatologist. Conclusions: Narrow-band ultraviolet B therapy appears to be the most effective treatment for progressive macular hypomelanosis but also has the highest potential for relapse. Response rates for antimicrobial therapy are lower and slower, but patients who responded did not relapse. A combination of topical/systemic antimicrobials with narrow-band ultraviolet B therapy might be the best option to hasten recovery and minimize relapse.

Introduction Les donnees recentes sur la physiopathologie du vitiligo soulignent l’importance de la voie de l’IFNg et des chimiokines CXCL9 et CXCL10. Les anticorps anti-CXCL10 ont donne des resultats encourageants dans des modeles murins de vitiligo. Les statines protegent les melanocytes humains du stress oxydatif et diminuent le nombre de lymphocytes T autoreactifs dans la peau. Il a egalement ete montre que l’atorvastatine peut diminuer le taux plasmatique de CXCL10 dans la maladie de Crohn. Le but de notre etude etait d’evaluer l’efficacite d’un traitement par atorvastatine associe a une phototherapie UVB vs phototherapie UVB seule dans le vitiligo evolutif. Materiel et methodes Cette etude interventionnelle, prospective, en simple insu, bicentrique a ete realisee au CHU de Nice et au National Skin Center de Singapour. Les patients atteints de vitiligos evolutifs non segmentaires (definis par des bords flous en lumiere de Wood et/ou une depigmentation en confetti) ont ete randomises (randomisation equilibree, centralisee et stratifiee sur le centre) en deux groupes : phototherapie UVB-TL01 avec atorvastatine 80 mg par jour ou phototherapie UVB-TL01 pendant 6 mois. Les patients etaient suivis a 1 mois, 3 mois et 6 mois avec examen clinique, photographies et prise de sang. Le critere de jugement principal etait l’evolution du Vitiligo Area Scoring Index (VASI) entre j0 et m6 evalue par 3 dermatologues independants sur photographies en insu du traitement. Les criteres secondaires etaient les scores VETF, VES, PGA, DLQI. Resultats Trente patients (16 a Nice, 14 a Singapour) ont ete inclus, 15 dans le groupe A et 15 dans le groupe B. En ITT, l’evolution moyenne dans le groupe UVB+ atorvastatine etait de −2,95 ± 1,39 (−5,81 a −0,09) ; p = 0,0434 et de −4,38 ± 1,44 ; (−7,35 a −1,42), p = 0,0054, dans le groupe UVB seul. La difference d’evolution moyenne entre les 2 groupes etait de 1,43 (−2,76 a 5,62). Cette difference n’est pas significative ( p = 0,49, Ancova ajustee sur le centre et la valeur du score VASI a j0). L’analyse en perprotocole ne montre egalement pas de difference entre les 2 groupes. Discussion Dans les 2 groupes, le traitement a permis de diminuer significativement le score de severite du vitiligo et de stopper l’evolutivite. Cependant, la combinaison atorvastatine-UVB n’a pas montre de superiorite par rapport aux UVB seuls. Cela est concordant avec une etude recente ayant evalue la symvastatine 80 mg en monotherapie vs placebo dans des vitiligos souvent non evolutifs. Il est possible qu’aux doses utilisees l’action sur CXCL10 soit trop modeste pour impacter significativement l’evolution du vitiligo. Conclusion L’association de l’atorvastatine a la phototherapie UVB n’a pas montre de superiorite par rapport a la phototherapie pour re-pigmenter des vitiligos tres evolutifs. Ces resultats confirment cependant l’interet de la phototherapie dans ce sous-groupe de patients tres actifs.

Noncultured cellular grafting is a known surgical technique for vitiligo.This study evaluated our center's 12-month repigmentation outcome and its maintenance up to 60 months, factors influencing repigmentation and safety data.Clinicoepidemiologic and repigmentation data were reviewed for patients with vitiligo who had undergone noncultured cellular grafting from March 2006 to December 2012 at the National Skin Center, Singapore.All 177 patients who received noncultured cellular grafting during the study period were included. For those with available data, good to excellent repigmentation was present in 83% at 60 months. At 12 months, 88% of patients (n = 52) with segmental vitiligo achieved good to excellent repigmentation compared with 71% (n = 55) with nonsegmental vitiligo (P .05). More patients on collagen dressings (82%) achieved good to excellent repigmentation compared with those who received hyaluronic acid (63%) (P .05). Sites of lesions and postgrafting phototherapy did not significantly affect repigmentation outcome. Adverse reactions were uncommon and mild.The study is limited by its retrospective nature, the progressive loss to follow-up of patients, the absence of blinding, and the lack of use of standardized assessment tools.Noncultured cellular grafting was successful in allowing more than 80% of patients to achieve good to excellent repigmentation for at least 60 months.

© 2015 The Authors. doi: 10.2340/00015555-2104 Journal Compilation © 2015 Acta Dermato-Venereologica. ISSN 0001-5555 Primary localized cutaneous amyloidosis (PLCA; MIM 105250) is a chronic itchy skin disorder associated with amyloid deposits in the superficial dermis (1). Clinically, most skin lesions comprise small, flat-topped papules (lichen amyloidosis) or brown-grey macules (macular amyloidosis). Recently, proteins containing a considerable amount of β-sheet structures, such as galectin-7 and actin, have been reported as amyloidogenic in PLCA (2, 3). Most cases of PLCA are sporadic, but familial cases (FPLCA) with autosomal dominant inheritance also exist (4–6). Pathogenic mutations in OSMR and IL31RA have been reported as the major cause of FPLCA (5, 7); both of these genes belong to the family of interleukin (IL)6 family cytokine receptors. OSMR encodes oncostatin M receptor-beta (OSMRβ), a component of both the OSM type II receptor and the interleukin (IL)-31 receptor (8, 9), whereas IL31RA encodes the IL-31 receptor alpha, which combines with OSMRβ to form the IL-31 receptor (7). To date, 10 heterozygous missense mutations in OSMR and 1 heterozygous missense mutation in IL31RA have been reported in FPLCA, with all cases showing autosomal dominant inheritance (5–7, 10). In this study, we examined 2 large pedigrees with FPLCA originating from Pakistan (family A) and Malaysia (family B) (Fig. 1a, b). Unusually, however, the occurrence of FPLCA in both families is consistent with autosomal recessive, rather than dominant, inheritance.