Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm.

BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed. OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients. CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Oral tranexamic acid lightens refractory melasma.

BACKGROUND/OBJECTIVES: Melasma is a common acquired hyperpigmentary disorder, particularly among Asians and Hispanics, but its exact pathomechanism is poorly understood. Tranexamic acid has been found to lighten melasma by interfering with the interaction of melanocytes and keratinocytes by inhibiting the plasminogen/plasmin system. The aim was to evaluate the therapeutic effects of oral tranexamic acid in the treatment of melasma refractory to topical skin-lightening agents. METHODS: This retrospective study analyses patients with melasma recruited from a tertiary dermatological centre in Singapore between 1 August 2009 and 31 March 2011. The patients chosen had refractory melasma treated with oral tranexamic acid 250 mg twice daily in addition to pre-existing combination topical therapy. Objective assessment using the physician's global assessment and melasma area and severity index (MASI) scores were performed based on a post-hoc analysis of photographic records by three independent physicians. A paired t-test was used to evaluate the changes in the MASI scores pre-therapy and post-treatment. Statistical significance was defined as P < 0.05. RESULTS: Altogether 25 patients were treated with tranexamic acid for a mean period of 3.7 ± 0.33 months, in addition to combination topical therapy. Their mean age was 47.2 ± 1.61 years. The mean MASI scores after tranexamic acid treatment (2.7 ± 1.6) were significantly lower (P < 0.01) than those prior to treatment (8.8 ± 4.2). The mean improvement in scores was 69%. The follow-up period was up to 6 months. CONCLUSION: Low-dose oral tranexamic acid can serve as a safe and useful adjunct in the treatment of refractory melasma.

Twelve-month and sixty-month outcomes of noncultured cellular grafting for vitiligo.

BACKGROUND: Noncultured cellular grafting is a known surgical technique for vitiligo. OBJECTIVE: This study evaluated our center's 12-month repigmentation outcome and its maintenance up to 60 months, factors influencing repigmentation and safety data. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSION: Noncultured cellular grafting was successful in allowing more than 80% of patients to achieve good to excellent repigmentation for at least 60 months.

Investigating factors associated with quality of life of vitiligo patients in Singapore.

Skin disease is often visible to others. People who have dermatological condition may also suffer from its psychological consequences. The purpose of this study is to explore the quality of life of patients with vitiligo and to identify factors associated with their quality of life. A descriptive correlational study was conducted with 222 patients with vitiligo recruited from two skin centres in Singapore from 2009 to 2011. Data were collected by a structured questionnaire. Three outcome variables were measured in the study: predisposal, clinical and psychological outcomes. Results showed that almost two-thirds of the participants reported vitiligo had moderate to extreme impact on their quality of life. Multiple regression analyses showed that patients who were depressed, had thyroid disease and had not used multiclear treatment were more likely to report poor quality of life. It is recommended that providing health care consultation for patients with vitiligo may help reduce depressive symptoms and maintain their psychological health, thus enhance their quality of life.

Investigating factors associated with depression of vitiligo patients in Singapore.

AIMS: To explore the depression level of a group of vitiligo patients in Singapore and to identify factors associated with depression. BACKGROUND: Unlike most internal illness, skin disease is often immediately visible to others and therefore people suffers from dermatological conditions may suffer psychological consequences. DESIGN: A descriptive survey was conducted during the period October 2009-August 2010 in Singapore; 145 vitiligo patients aged 21+ completed a structured questionnaire. METHODS: Three main outcome variables were employed in the study: demographic characteristics, clinical and psychosocial outcomes. RESULTS: Among the patients, 17·2% (n = 25) had been identified as depressed. Multiple logistic regression analyses were used to identify a model to predict vitiligo patients who will have depression. The results showed that females (p = 0·05), aged below 50 years old (p = 0·016), having 5+ years of illness (p = 0·021) and with low self-esteem (p = 0·002) and poor quality of life scores (p = 0·004) were significant risk factors for depression. CONCLUSION: Providing a suitable health care consultation for vitiligo patients may reduces depressive symptoms and maintaining their psychological health may be crucial for preventing suffering from depressive symptoms. Apart from the findings, these conclusions resonate with recent Singapore guidance on managing depression in vitiligo patients. This stresses the importance of prevention, early detection and stepped care with a multifaceted approach to management. RELEVANCE TO CLINICAL PRACTICE: It is important to regularly screen for depressive symptoms among vitiligo patients. Focusing on vitiligo patients with enhancing self-esteem and improving quality of life should help in both the prevention and recognition of onset of depression among vitiligo patients.

Periorbital hyperpigmentation in Asians: an epidemiologic study and a proposed classification.

BACKGROUND: Periorbital hyperpigmentation (POH) presents with a dark area surrounding the eyelids. It is an ill-defined condition, and the pathogenesis can be multifactorial. OBJECTIVE: This epidemiologic study was conducted to assess the prevalence of periorbital hyperpigmentation in Singapore in an attempt to propose a classification. MATERIALS AND METHODS: One thousand consecutive patients attending the general dermatology clinic at the National Skin Center were enrolled in the study to assess for POH, of whom 200 with POH were examined and investigated to define the cause of POH. The possible causes were determined according to a detailed history, clinical examination, and assessment by three dermatologists. The extent of the POH was measured using a mexameter. RESULTS: The commonest form of POH was the vascular type (41.8%), followed by constitutional (38.6%), postinflammatory hyperpigmentation (12%), and shadow effects (11.4%). The vascular type was seen predominantly in Chinese, whereas as the constitutional type was most common in Indians and Malays. CONCLUSION: The vascular form of POH was the predominant type. We propose a comprehensive classification for POH that we hope will influence the choice of treatment modalities used in managing POH in the future.

Treatment of progressive macular hypomelanosis with narrow-band ultraviolet B phototherapy.

Treatment for progressive macular hypomelanosis (PMH) has been disappointing. Recently, Propionibacterium acnes had been postulated as the causative agent and narrow-band ultraviolet B (NBUVB) had been shown to stimulate melanogenesis and has antibacterial properties. The aim of this study was to evaluate the effectiveness of NBUVB in the treatment of PMH. A retrospective analysis of PMH cases diagnosed and treated with NBUVB treatment from 1 January 2007 to 30 April 2009 at the National Skin Centre (NSC) was conducted. The diagnosis of PMH was clinical. Treatment with NBUVB (311 nm) was given twice to thrice weekly. The initial treatment dose was determined as 70% of the patients' individual 311 nm UVB minimal erythema dose. The dose was increased by 10-20% if previous treatment had caused no or slight erythema. Percentage repigmentation from baseline was assessed at each follow-up. A total of six patients diagnosed with PMH were treated with NBUVB in NSC in the past 2 years. Three patients had good improvement and the remainder had moderate improvement. Recurrence did occur. No adverse events were documented. The success of NBUVB as a monotherapy provides a viable and relatively safe, albeit temporary relief, for these individuals.

Simplified cellular grafting for treatment of vitiligo and piebaldism: the "6-well plate" technique.

BACKGROUND: Vitiligo is a disfiguring depigmenting dermatosis that affects approximately 0.5% to 1% of the general population regardless of race and sex. In patients with stable vitiligo who fail conventional therapies, surgical transplant offers a viable alternative. Noncultured cellular grafting offers the advantage of repigmenting vitiligo 5 to 10 times the size of the donor skin and can be completed on the same day on an outpatient basis. In recent years, ways to simplify this procedure have been explored, including the use of commercially available kits. OBJECTIVES: To simplify the extraction of epidermal cells from donor skin using a 6-well plate and to evaluate the clinical efficacy of this simplified technique in repigmenting stable vitiligo and piebaldism. METHODS: Four patients with focal or segmental vitiligo and one with piebaldism were treated using the simplified noncultured cellular grafting protocol. Percentage of repigmentation 6 months after grafting was objectively measured using digital contour mapping. RESULTS: Patients with stable segmental or focal vitiligo achieved 65% to 92% repigmentation 6 months after grafting; the treated sites involved face or limbs. The patient with piebaldism achieved 86% repigmentation. One year after grafting, the extent of repigmentation remained for all patients. CONCLUSION: This set-up is simple and inexpensive; it reduces cell preparation time, amount of reagents used, and costs, and obviates the need of a laboratory for extraction of epidermal cells.

Vitiligo occurring after halo formation around congenital melanocytic nevi.

We present two cases wherein vitiligo developed after the onset of halo formation involving congenital melanocytic nevi to emphasize the possibility of this finding as a potential albeit unusual presentation of vitiligo.

A global consensus statement on ashy dermatosis, erythema dyschromicum perstans, lichen planus pigmentosus, idiopathic eruptive macular pigmentation, and Riehl's melanosis.

Ashy dermatosis (AD), lichen planus pigmentosus (LPP), erythema dyschromicum perstans (EDP), and idiopathic eruptive macular pigmentation are several acquired macular hyperpigmentation disorders of uncertain etiology described in literature. Most of the published studies on these disorders are not exactly comparable, as there are no clear definitions and different regions in the world describe similar conditions under different names. A consensus on the terminology of various morphologies of acquired macular pigmentation of uncertain etiology was a long-felt need. Several meetings of pigmentary disorders experts were held to address this problem. A consensus was reached after several meetings and collation of e-mailed questionnaire responses and e-mail communications among the authors of publications on the above conditions. This was achieved by a global consensus forum on AD, LPP, and EDP, established after the 22nd International Pigment Cell Conference held in Singapore in 2014. Thirty-nine experts representing 18 countries participated in the deliberations. The main focus of the deliberations was terminology of the conditions; as such, we present here the consensus statement of the forum and briefly review the available literature on the subject. We have not attempted to discuss treatment modalities in detail.

Halo congenital naevus in a middle-aged patient with vitiligo.

A case of halo congenital naevus is reported on the chest of a 56-year-old Asian woman with pre-existing vitiligo. The naevus measured 3.5 cm x 2 cm and underwent depigmentation around its periphery. Dermoscopic examination showed coarse pigment in the darker centre of the naevus and depigmentation in the surrounding halo. Light microscopy showed well-formed naevus cell nests with coarse melanin granules in the papillary dermis, and surrounding fibrosis. Melanocytes extended into reticular dermis, consistent with a congenital growth pattern. There was no evidence of malignancy. The epidermis was of normal appearance. S100 staining highlighted melanocytes in the dermis. Basal melanocytes were retained at the periphery of the naevus. Based on the clinical history and histological findings, a diagnosis of halo congenital naevus was made. The naevus was not excised.

Frontiers in pigment cell and melanoma research.

In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution.

Presentations, Signs of Activity, and Differential Diagnosis of Vitiligo.

Vitiligo has a variety of presentations, including focal, acrofacial, segmental, and generalized forms. Thorough knowledge of these presentations is important to make the correct diagnosis. Signs of activity are important to recognize so that treatment is optimized. Clinical findings of confettilike depigmentation, trichrome and inflammatory vitiligo, and the Koebner phenomenon should alert the clinician that a patient's disease is likely to worsen. These patients may require systemic treatment to stabilize their disease. Many other skin disorders present with hypopigmentation or depigmentation and must be distinguished to determine the right diagnosis, advise the patient on prognosis, and prescribe the correct treatment.

Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference.

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 section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. 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.

Exogenous ochronosis in a Chinese patient: use of dermoscopy aids early diagnosis and selection of biopsy site.

The diagnosis of exogenous ochronosis is often challenging and requires a high index of suspicion. Herein, we report a case of exogenous ochronosis in a Chinese patient. The condition was caused by the use of bleaching agents, including creams containing hydroquinone. We demonstrate the use of dermoscopy as an invaluable tool for the early recognition of the condition, as well as in the selection of an appropriate site for a skin biopsy.

Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

A Review of Non-cultured Epidermal Cellular Grafting in Vitiligo.

Non-cultured epidermal cellular grafting is an innovative surgical technique that can be used for the treatment of stabilized leucoderma, including vitiligo. Many reports have been published since its introduction in 1992, including several modifications and simplification of the original technique. This systematic review gives an overview of the literature.

Case of primary localized cutaneous amyloidosis with protean clinical manifestations: lichen, poikiloderma-like, dyschromic and bullous variants.

Primary localized cutaneous amyloidosis (PLCA) commonly presents as macular and lichen variants. We present a case of a 27-year-old Chinese woman with cutaneous features of the rarely reported poikiloderma-like, dyschromic and bullous forms of PLCA, and the commoner lichen variant. There were no syndromic associations or systemic involvement, and the various morphological subtypes occurred in isolation from one another. We review the clinical spectrum of PLCA, highlight its protean clinical manifestations in this patient, and discuss its postulated pathogenesis in relation to its histopathological features.