Dermoscopy in vitiligo, diagnostic clues and markers of disease activity: a review of the literature.

Dermoscopy is a noninvasive, efficient and inexpensive tool used to aid diagnosis of skin conditions such as vitiligo. Furthermore, it aids in tracking patient progress, treatment response and disease activity. Vitiligo can be diagnosed on dermoscopy by the presence of white structureless areas signifying hypopigmentation with a typical glowing appearance. Other typical features are perilesional and perifollicular hyperpigmentation, pigmentation networks and leucotrichia. In total, 15 studies were reviewed to determine the dermoscopic signs of the three main stages of disease activity: active, stable and repigmenting vitiligo. Features that differentiate active, stable and repigmenting vitiligo are reviewed and discussed in this article. Notably, there is a conflict in the literature between various dermoscopic features and which type of vitiligo they are truly indicative of. However, dermoscopy can be coupled with other clinical, biological and physiological markers to strengthen diagnostic accuracy.

Ultrasound Patterns of Vitiligo at High Frequency and Ultra-High Frequency.

OBJECTIVES: To detect ultrasonographic anatomical alterations in all the skin layers in patients with vitiligo. METHODS: A prospective observational color Doppler ultrasound study was performed in nonsegmental face and/or neck vitiligo patients without a history of previous treatments. Two sites, a lesional area and a contralateral clinically healthy region, were ultrasonographically studied and compared in the same patient. All cases were studied in high-frequency (24 MHz) and ultra-high-frequency (70 MHz) ultrasound devices with the highest axial spatial resolution available in the market. Demographic data of the sample, ultrasound grayscale, and color Doppler features were recorded and analyzed. RESULTS: Ten patients met the study criteria (60% females; mean age 49 years). All cases presented ultrasonographic undulation of the epidermis in the affected zones vs 50% in the healthy control regions, being more prominent in the vitiligo areas. Eighty percent demonstrated intense hypoechoic thin plaques in the upper dermis (subepidermal). All vitiligo areas presented thickening and hypoechogenicity of the regional hair follicles and/or pilosebaceous units. Ninety percent showed prominent sebaceous glands, and 20% demonstrated a hypoechoic cap surrounding the sebaceous glands in the lesional areas. Dermal hypervascularity was detected in 100% of the affected regions and 40% of the clinically healthy areas. CONCLUSION: Ultrasound can identify subclinical inflammatory cutaneous patterns in the epidermis, dermis, hair follicles, pilosebaceous units, and sebaceous glands in vitiligo. This noninvasive information can support early detection, monitoring, and research, including the clinical trials of drugs used to manage this devastating disease.

Novel ultraviolet-dermoscopy: Early diagnosis and activity evaluation of vitiligo.

BACKGROUND/OBJECTIVE: Polarized dermoscopy, Wood's lamp, and reflectance confocal microscopy were currently commonly used auxiliary technology in vitiligo clinic diagnosis. To improve the efficiency and accuracy of different periods of lesions of vitiligo, we used a novel ultraviolet (UV)-dermoscopy (Model CH-UVDS30, Ultraviolet wavelength range of 360<390nm, Chuanghong Science and Technology Company, China) in clinical observation. MATERIALS AND METHODS: Three cases of different periods of vitiligo patients were included in this study. Polarised dermoscopy and novel UV-dermoscopy (UV wavelength range of 360 nm < λ < 390 nm) were performed at 20 × magnification in polarized and UV modes. Characteristic manifestations of different periods of vitiligo lesions were captured and compared. RESULTS: The depigmented and pigmented junctional zone and perifollicular pigmentation areas could be easier and simultaneously identified via UV-dermoscopy. In a progressive vitiligo patient (woman, 42 years old, face) enhanced perifollicular pigmentation and blurred border were clearly observed. In a stable vitiligo patient (man, 27 years old, right foot) sharply demarcated border and perifollicular depigmentation could be found. In a re-pigmenting vitiligo patient (woman, 41 years old, neck) telangiectasias and pigmentation reservoirs were observed. CONCLUSION: Novel UV-dermoscopy, as a miniature and portable device, might help early diagnosis, active/progress judgment, and treatment effect evaluation of vitiligo in the clinic.

Reflectance Confocal Microscopy for Identification of Vulvar Lichen Sclerosus et Atrophicus and Vitiligo.

ABSTRACT: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disease. The clinical presentation is clustered distribution of porcelain white spots that can be fused together. Early diagnosis of LSA is difficult, especially in the vulva, where it is difficult to distinguish from vitiligo. Traditional diagnostic methods mainly rely on histopathology. In this study, we used reflectance confocal microscopy (RCM) to study the characteristics of LSA and vitiligo. We investigated the clinical and confocal features of 40 cases of histopathologically proven genital LSA or vitiligo, and correlated the features with histopathologic findings. Through the analysis of the results, by RCM, we can easily distinguish genital LSA from vitiligo, which are clinically indistinguishable. This can reduce the number of unnecessary biopsies, and help with early diagnosis and timely treatment.

Proposing a novel unsupervised stack ensemble of deep and conventional image segmentation (SEDCIS) method for localizing vitiligo lesions in skin images.

BACKGROUND: Vitiligo is an acquired pigmentary skin disorder characterized by depigmented macules and patches which brings many challenges for the patients suffering from. For vitiligo severity assessment, several scoring methods have been proposed based on morphometry and colorimetry. But, all methods suffer from much inter- and intra-observer variations for estimating the depigmented area. For all mentioned assessment methods of vitiligo disorder, accurate segmentation of the skin images for lesion detection and localization is required. The image segmentation for localizing vitiligo skin lesions has many challenges because of illumination variation, different shapes and sizes of vitiligo lesions, vague lesion boundaries and skin hairs and vignette effects. The manual image segmentation is a tedious and time-consuming task. Therefore, using automatic image segmentation methods for lesion detection is necessarily required. MATERIALS AND METHODS: In this study, a novel unsupervised stack ensemble of deep and conventional image segmentation (SEDCIS) methods is proposed for localizing vitiligo lesions in skin images. Unsupervised segmentation methods do not require prior manual segmentation of vitiligo lesions which is a tedious and time-consuming task with intra- and inter-observer variations. RESULTS: Our collected dataset includes 877 images taken from 21 patients with the resolution of 5760*3840 pixels suffering from vitiligo disorder. Experimental results show that SEDCIS outperforms the compared methods with accuracy of 97%, sensitivity of 98%, specificity of 96%, area overlapping of 94%, and Dice index of 97%. CONCLUSION: The proposed method can segment vitiligo lesions with highly reasonable performance and can be used for assessing the vitiligo lesion surface.

Reference method for digital surface measurement of target lesions in vitiligo: a comparative analysis.

BACKGROUND: Objective measurement of target lesions in vitiligo is important for clinical practice and trials, yet no preferred tool has been defined. Reported digital tools have shortcomings related to feasibility aspects and often lack information on validity, reliability and responsiveness. Moreover, studies are not yet based on ultraviolet (UV) photography. OBJECTIVES: To assess the reliability, validity and feasibility of two functions in ImageJ for measurement of target lesions, based on three different types of images including UV pictures. METHODS: Planimetric measurements were performed on photographs with and without UV, and lesion contours on transparent sheets of 52 vitiligo lesions from 10 patients with vitiligo. The ImageJ functions 'wand' and 'threshold' were used by three and four assessors, respectively. Inter- and intrarater reliability, hypothesis testing for construct validity, and feasibility were evaluated. RESULTS: The inter- and intrarater reliability for the 'wand' and 'threshold' functions were excellent [intraclass correlation coefficient (ICC) > 0·9] for measurement on pictures (with or without UV). The highest agreement (ICC > 0·95) and lowest variance were obtained for measurements on transparent sheets. All four hypotheses for construct validity were confirmed for all measurements. Overall, all measurement methods scored satisfactorily for user-friendliness. However, measurements on transparent sheets were preferred and the completion time was significantly faster. CONCLUSIONS: This study confirmed the reliability, validity and feasibility of two functions in ImageJ to measure target lesions in vitiligo. Based on the feasibility and included three-dimensional aspects, transparent sheets measured with the ImageJ 'wand' function can be proposed for future trials as a reference method to investigate the criterion validity of other digital instruments.

Comparison of 311-nm Titanium:Sapphire laser and 308-nm excimer laser treatment for vitiligo: A randomized controlled non-inferiority trial.

OBJECTIVES: The 308-nm excimer laser (EL) has been widely used for localized vitiligo. The recently developed Titanium:Sapphire laser, emits a wavelength of 311 nm, would be expected to be as effective as excimer laser in treatment of vitiligo but few controlled trials have been reported. We sought to compare the efficacy and safety of the TSL and EL as vitiligo treatments. METHODS: A randomized controlled non-inferiority trial based on split-body was conducted. Patients with stable vitiligo between June 2016 and May 2017 were enrolled. Paired symmetrical vitiligo lesions were randomized to either the EL or TSL treatment group, and treated with a 308-nm EL or a 311-nm TSL twice weekly for 12 weeks. The extent of repigmentation was assessed every 4 weeks, and the non-inferiority margin was set to 10%. We also recorded any adverse events. RESULTS: Seventy-four paired lesions in 21 patients were assigned to both the EL group or TSL group. The mean difference between two groups (EL minus TSL) was -2.862%, and the 95% confidence interval (-6.531% to 0.807%) was lower than the non-inferiority margin. No serious adverse events were noted in either group. CONCLUSIONS: The Titanium:Sapphire laser showed similar therapeutic effect to excimer laser in localized vitiligo with good safety profiles in this non-inferiority randomized controlled trial. The Titanium: Sapphire laser can serve as an alternative treatment option for localized vitiligo. Lasers Surg. Med. 51:239-244, 2019. © 2019 Wiley Periodicals, Inc.

UV light set-ups for vitiligo photography, a comparative study on image quality and ease of use.

BACKGROUND: Ultraviolet (UV) light is an essential tool to assess the extent, spreading and staging of vitiligo. Different UV light set-ups are used for vitiligo photography, including the following: (i) hand-held Wood's lamps; (ii) soft boxes with UV lamps; (iii) UV flash attached to the camera; and (iv) high output UV flash. OBJECTIVE: Our objective was to compare UV light set-ups for vitiligo photography regarding image quality and ease of use. METHODS: Patients with vitiligo lesions with unclear borders were included. Two images were made with all four UV set-ups per patient, for a large and a small area. Image quality was scored separately by three blinded vitiligo experts on five criteria: overall quality, clearness of borders, contrast and sharpness and for larger areas the shadows. The two professional medical photographers were asked to score the ease of use for each set-up. RESULTS: A total of 88 photos were assessed from 11 patients. For larger areas, the frequency of a 'good' or 'very good' overall quality rating was 12.1% (Wood's), 6.1% (soft boxes), 15.2% (camera flash) and 78.8% (high output flash). For smaller areas, the score 'good' or 'very good' was given to 54.5%, 3%, 66.6% and 84.8% in the same order. For the shadow criteria, each set-up scored below 40% on a 'good' or 'very good' score. The high output flash was scored as most easy to use by the photographers. CONCLUSION: When comparing four different UV light set-ups for vitiligo photography, we concluded that the UV set-ups strongly influenced the quality scores of the obtained images. The high output flash scored best for both small and large areas and for ease of use. For small areas, Wood's lamp and camera flash were acceptable. All set-ups scored badly for shadows, and more research is needed to find the optimal exposure to avoid shadows.

Clinical markers of vitiligo activity.

BACKGROUND: Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. OBJECTIVE: We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. METHODS: In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8+ T lymphocytes, and E-cadherin. RESULTS: The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8+ T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). LIMITATION: The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. CONCLUSION: The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion.

Vitiligo of the Face in a Patient Treated With Vemurafenib for Metastatic Melanoma.

Vemurafenib is a potent and selective BRAF inhibitor, which is effective on patients with BRAF V600E mutated late-stage melanoma. Common and less common adverse skin reactions include photosensitivity, maculo-papular exanthema, hand-foot skin reactions, hyperkeratotic follicular rash, pruritus, benign verrucous papillomas, plantar hyperkeratosis, keratoacanthomas, squamous cell carcinomas, infections, and melanoma. To our knowledge, vitiligo has been reported in 2 cases only. This paper reports the case of a 63-year-old man with metastatic melanoma, who developed sudden facial depigmentation after 4 weeks of treatment with vemurafenib 960 mg twice daily. Features consistent with vitiligo were evident at clinical and ultraviolet light examination, as well as at in vivo reflectance confocal microscopy. The latter examination showed lack of normal brightly refractile papillary rings at the dermo-epidermal junction in lesional skin, as well as decreased brightness and half-rings with "scalloped border-like" features in adjacent non-lesional skin. Vitiligo is an adverse reaction to be expected in patients treated with vemurafenib and whether its occurrence may be associated with a positive outcome, as suggested by previous investigations, is still a matter of debate.

J Drugs Dermatol. 2016;15(6):766-768.

Objective assessment of vitiligo with a computerised digital imaging analysis system.

An objective tool to quantify treatment response in vitiligo is currently lacking. This study aimed to objectively evaluate the treatment response in vitiligo by using a computerised digital imaging analysis system (C-DIAS) and to compare it with the physician's global assessment (PGA). Tacrolimus ointment 0.1% (Protopic; Astellas Pharma Tech,Toyama, Japan) was applied twice daily on selected lesions which were photographed every 6 weeks for 24 weeks. The primary efficacy end-point was the mean percentage of repigmentation (MPR), as assessed by the digital method (MPR-C-DIAS) or by the PGA. The response was categorised into none (0%), mild (1-25%), moderate (26-50%), good (51-75%) and excellent (76-100%). MPR-C-DIAS: Out of 56 patients, 44 (79%) responded. Overall, the response was mild in 22 (39%), moderate in 21(40%) and good in one (2%) patient(s). A total of 39 (70%) patients responded as measured by PGA. The repigmentation was mild in 27(48%), moderate in 10 (18%) and good to excellent in two (4%) patients. The κ test of consistency was 0.17 (P = 0.053), which shows poor agreement between the two assessment methods, although this is not statistically significant. The C-DIAS can be used to perform an objective analysis of repigmentation or depigmentation in vitiligo skin lesions in response to treatment.

Bridging the Gap Between Vitiligo Segmentation and Clinical Scores.

Quantitative evaluation of vitiligo is crucial for assessing treatment response. Dermatologists evaluate vitiligo regularly to adjust their treatment plans, which requires extra work. Furthermore, the evaluations may not be objective due to inter- and intra-assessor variability. Though automatic vitiligo segmentation methods provide an objective evaluation, previous methods mainly focus on patch-wise images, and their results cannot be translated into clinical scores for treatment adjustment. Thus, full-body vitiligo segmentation needs to be developed for recording vitiligo changes in different body parts of a patient and for calculating the clinical scores. To bridge this gap, the first full-body vitiligo dataset with 1740 images, following the international vitiligo photo standard, was established. Compared with patch-wise images, full-body images have more complicated ambient light conditions and larger variances in lesion size and distribution. Additionally, in some hand and foot images, skin can be fully covered by either vitiligo or healthy skin. Previous patch-wise segmentation studies completely ignore these cases, as they assume that the contrast between vitiligo and healthy skin is available in each image for segmentation. To address the aforementioned challenges, the proposed algorithm in this study exploits a tailor-made contrast enhancement scheme and long-range comparison. Furthermore, a novel confidence score refinement module is proposed to manage images fully covered by vitiligo or healthy skin. Our results can be converted to clinical scores and used by clinicians. Compared to the state-of-the-art method, the proposed algorithm reduces the average per-image vitiligo involvement percentage error from 3.69% to 1.81%, and the top 10% per-image errors from 23.17% to 8.29%. Our algorithm achieves 1.17% and 3.11% for the mean and max error for the per-patient vitiligo involvement percentage, which is better than an experienced dermatologist's naked-eye evaluation.

In-depth study of Wood's lamp examination combined with reflective confocal laser scanning microscopy for the guidance of vitiligo staging and treatment.

BACKGROUND: Both Wood's lamp and reflective confidential laser scanning microcopy are helpful for the diagnosis and treatment of vitiligo. However, there is few research that contains large samples and consistent observations. AIMS: To analyze the characteristics of Wood's lamp images and reflectance confocal microscopy (RCM) images of vitiligo lesions and to evaluate their significance in vitiligo staging. METHODS: We analyzed the characteristics of RCM images, Wood's lamp images, the vitiligo disease activity (VIDA) score, and clinical features to guide vitiligo staging and treatment. RESULTS: The expert consensus based on the clinical features, VIDA score, Wood's lamp findings, and isomorphic response was consistent with the Wood's lamp findings (χ2 = 3.63, p > 0.05) and RCM findings (χ2 = 3.60, p > 0.05) in diagnosing vitiligo and assessing the disease stage. There was a correlation between the three lesion grades based on the Wood's lamp findings and the stage of vitiligo (p < 0.01). Lesions that appeared porcelain white under the Wood's lamp were in the slowly progressive stage; lesions that appeared gray-white or trichromatic under the Wood's lamp were in the rapidly progressive stage; lesions with clear borders under the Wood's lamp needed further analysis by RCM for the stage to be determined; lesions with blurred borders under the Wood's lamp were in the rapidly progressive stage; lesions that were visible under the naked eye and under the Wood's lamp were in the rapidly progressive stage. CONCLUSION: The study demonstrates a reliable correlation between the findings of RCM (a sophisticated expensive tool) and Wood's lamp examination (a simple, readily available, inexpensive tool) in the assessment of the disease activity of vitiligo lesions.

Evaluation of diagnostic accuracy of dermoscopy in some common hypopigmented skin diseases.

BACKGROUND: Diagnosis of cutaneous hypopigmentation can sometimes be challenging. Dermoscopy may play a role in identifying hypo or-depigmented dermatoses. The aim was to investigate which dermoscopic criteria represent potent indicators for the diagnosis of vitiligo, nevus depigmentosus, pityriasis alba, hypopigmented pityriasis versicolor, idiopathic guttate hypomelanosis, hypopigmented mycosis fungoides (MF), lichen sclerosus et atrophicus and ash leaf hypopigmented macules of tuberous sclerosis, and evaluate their diagnostic accuracy. 168 individuals diagnosed with one of these hypopigmented disorders were evaluated for the presence or absence of predetermined dermoscopic criteria. Evaluation of dermatoscopic characteristics in each condition and analysis for sensitivity and specificity of dermatoscopic diagnosis in these hypopigmented lesions was performed. The starburst pattern, micro-koebnerization, and trichrome pattern were unique to vitiligo diagnosis. Vitiligo had higher comet-tail appearance, perifollicular pigmentation, and perilesional hyperpigmentation than other hypopigmented illnesses. Other hypopigmented lesions had greater incidence of amoeboid pattern, faint or diminished pigment network, islands of pigmentation, ill-defined boundaries, pseudopods, and widespread scaling than vitiligo. Finally, perifollicular scaling, comedo-like openings, blue-gray specks, and fibrotic regions excluded vitiligo. Dermoscopy can help identify common hypopigmented skin lesions and reduce the need for skin biopsy. Nevus depigmentosus, pityriasis alba and idiopathic guttate hypomelanosis were the top three hypopigmented dermatoses that could be diagnosed by dermoscopy with 100% sensitivity. Vitiligo was in the second rank (94.7%), followed by lichen sclerosis et atrophicus (93.3%) then hypopigmented MF at 81.2% sensitivity. Dermoscopy sensitivity was lowest in pityriasis versicolor and ash leaf macules of tuberous sclerosis (52.6% and 46.7%, respectively).

Poisson-based image editing for semi-supervised vitiligo lesion segmentation with limited annotations.

Vitiligo lesion segmentation is crucial for the assessment and treatment of vitiligo. There are two significant challenges in this problem, namely, the availability of dense segmentation annotations and the collection of large amounts of vitiligo images, which are also major challenges in medical image analysis (MIA). However, most existing methods often heavily rely on the availability of large-scale labeled datasets and high-quality annotations. Consequently, the performance of these models may not be easily reproducible or transferable to those domains with limited data availability. As a result, there is a need to develop alternative approaches that can leverage unlabeled datasets for segmentation with a small-scale training set. In this paper, we propose a data augmentation strategy based on image editing, which can synthesize a large number of samples using a small number of annotated data. The synthesized examples are of high visual quality and enforce the segmentation performance without any cost. Besides, we also adapt the Mean-Teacher framework for reliable predictions mining from unlabeled samples to alleviate the demands of densely annotated segmentations. We obtain pseudo-labels for unlabeled samples by utilizing highly confident pixels. On the other hand, we proposed a new Bimodal Vitiligo Lesions Segmentation (BVLS) dataset containing fine-grain segmentation masks and bimodal images usually used for vitiligo diagnosis to mitigate the lack of a vitiligo segmentation dataset. Extensive experiments conducted on the BLVS dataset demonstrate that our approach can achieve significant improvements (+17.27%) compared with previous data augmentation methods on the UNet backbone. Furthermore, the semi-supervised framework can reach an IoU of 49.71% with only 10% annotated images. Our code and dataset are availabel at https://github.com/JcWang20/BLVS.