Vitiliginous Lesions Research Articles

Facial involvement is reflective of patients' global perception of vitiligo extent.

The involvement of visible areas in vitiligo has been found to be correlated with increased psychiatric morbidity. Although multiple tools have been developed to assess vitiligo, no cutoff for improvement or worsening of vitiligo from a patient's perspective has been established. To determine the minimal clinically important difference (MCID) of the Self-Assessment Vitiligo Extent Score (SA-VES) in patients with vitiligo and to evaluate, from the patient's perspective, the importance of the change in the involvement of visible areas (face and hands) in patients' overall perception of disease worsening or improving. This was a cross-sectional study in the context of the ComPaRe e-cohort. Adult patients with vitiligo were invited to answer online questionnaires. They completed the SA-VES twice, 1 year apart. In addition, patients answered a 5-point Likert anchor question aimed at assessing their perception of the evolution of the extent of their vitiligo. The MCID was calculated using distribution- and anchor-based approaches. Using ordinal logistic regression, the change of vitiliginous lesions on the face or hands was compared to the overall extent of vitiligo (patches on all body areas). In total, 244 patients with vitiligo were included in the analyses; 20 (8%) were found to have an improvement in their vitiligo. The MCID in worsened patients was equal to a 1.3% body surface area [95% confidence interval (CI) 1.01-1.43] increase in the SA-VES. For participants with improved vitiligo, the MCID was equal to a decrease in total SA-VES of 1.3% (95% CI 0.867-1.697). Patients' perceptions of change in their vitiligo was increased sevenfold when it affected the face vs. the rest of the body. Changes in the facial SA-VES were highly correlated with patients' impressions of the extent of vitiligo.

Simvastatin and non-segmental vitiligo: A new potential treatment option?

There is a paucity of data about the impact of systemic statins on vitiliginous lesions in non-segmental vitiligo (NSV) patients. To the best of our knowledge, no other studies have considered the correlation between lipid disturbances in vitiligo and vitiligo disease activity (VIDA) score. We sought in this study to evaluate the influence of simvastatin on vitiliginous lesions in NSV patients with dyslipidemia and study the correlation between VIDA score and lipid profile. This clinical trial started with 120 patients with NSV, 79 patients had dyslipidemia and received simvastatin 80 mg daily (till normalization of lipid profile or for 4months, which came first) and only 63 patients continued till the end of the study. Lipid profile, vitiligo area severity index and VIDA were assessed before and 6months after the end of simvastatin use. Serum total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein, and LDL/HDL ratio showed statistically significant increases in the NSV than in the control group (p˂0.001). There was a statistically significant positive correlation between VIDA and serum levels of TC and LDL and with LDL/HDL ratio. Simvastatin significantly improved the lipid profile and significantly decreased VIDA (p < 0.011). Negative moderate correlation was found between the decrease in VIDA and duration of disease (r=-0.562, p < 0.001). Simvastatin 80 mg daily could be a helpful treatment for NSV patients with dyslipidemia, controlling the vitiligo activity and protecting against the hazardous effects of dyslipidemia. Better results can be obtained in patients with short duration of the disease.

Evaluation of E- cadherin and Hydrogen Peroxide in Skin of Patients with Vitiligo

Abstract Background Vitiligo is acquired depigmentary disorder characterized by destruction of the epidermal melanocytes leading to the loss of the skin color. Oxidative stress has a major role in the aetiopathogenesis and in melanocytic destruction due to its accumulation in the melanocytes and the hazardous effects to all compartments of the cell. Objective The aim of the work was to evaluate the level of E-cadherin and H2O2 level in vitiligo versus controls. Subjects This is a case control study which was carried out at Department of Dermatology, Venereology and Andrology,New Cairo Police Academy Hospital on 20 Subjects were divided into two groups, Group I included 10 patients having non segemental vitiligo. Group II included 10 non vitilignous controls were included in the study. Results We found that H2O2 level is increased in NSV patients when compared with healthy individuals. While E-cadherin level is significantly decreased in vitiligo skin compared to normal skin. Conclusion As compared to controls, increased H2O2 levels levels were suggestive of oxidative stress in patients of vitiligo in our study. From our results we can conclude that vitiligo is not a disease confined to melanocytes only, keratinocytes also showed certain pathological changes in vitiliginous lesions. As functional and structural units with melanocytes, keratinocytes in depigmented epidermis may constitute a different microenvironment compared to those in normally pigmented epidermis. These differences include obvious loss of cell to cell adhesion between keratinocytes and melanocytes and between keratinocytes and each other, which in turn may affect the pigmentary system of the skin.

Effect of Narrow Band Ultraviolet B Therapy on Tissue Levels of Interleukin-33 in Egyptian Vitiligo Patients

Abstract Background Vitiligo is an acquired pigmentary disorder of unknown etiology, affecting approximately 1 % of the world population, without predilection for race or sex. It is characterized by white macules and patches, whose size increases over time, due to the loss of melanocytes. Vitiligo can appear at any time, and it significantly impairs the patients’ quality-of-life. Objectives The aim of the work was to study the influence of the NB-UVB radiation therapy on tissue level of IL-33 in patients with vitiligo. Patients and Methods This prospective study was carried out on 10 patients diagnosed as having non -segmental vitiligo stable for 6 months duration. All patients were selected from the dermatology outpatient clinic of vitiligo, Ain-Shams University Hospitals. All patients were subjected to full history taking, general examination and dermatological examination. The disease characteristics of vitiligo were recorded as regards stability, duration and extent of vitiliginous lesions. The activity of the disease was evaluated according to VIDA score, and the disease severity was evaluated according to VASI score. Digital photographic documentation was done. Results Hydropic degeneration of lower epidermis was also detected in (40%) of them and apoptotic keratinocytes were found in (10%) of them. After therapy, these inflammatory changes were significantly reduced this can be partially explained by immunosuppressive properties of NB-UVB as it is believed to cause a reduction of T cells by inducing apoptosis and impairs in-vitro antigen presentation by both murine DCs and human Langerhans cells. The main limitation of our study was the small cohort of the studied patients. Further large-scale studies are needed. Investigatory techniques other than immunohistochemical analysis may be also used to evaluate abnormalities of keratinocytes in vitiligo skin. Conclusion We concluded that NB-UVB has no effect on tissue expression of IL-33 and and that NB-UVB was effective in treating vitiligo as manifested by VASI score change after treatment with NB-UVB. Based on our results we recommend further studies with larger sample size and studying the effect of treatment on IL-33 expression in active vitiligo cases is also recommended.

Evaluation of phosphodiesterase 4 enzyme levels in lesional skin and serum of vitiligo patients

Background Vitiligo is the most commonly acquired depigmenting disorder. It has a negative psychological impact on affected individuals. The pathogenesis of vitiligo is complex and not yet fully revealed. Phosphodiesterase (PDE) inhibitors are widely used in many medical diseases and dermatological conditions, for example, psoriasis and atopic dermatitis. Recently, a case report showed that Apremilast (PDE4 inhibitor) resulted in significant repigmentation in a female patient with recalcitrant vitiligo. Objective To evaluate PDE4 levels in the tissues and serum of vitiligo patients and to compare them to the levels of controls to assess its role in the pathogenesis of the disease. Patients and methods In this case-control study, skin biopsies of vitiliginous lesions and blood samples were taken from 20 vitiligo patients and 20 controls. The PDE4 enzyme level was measured in both skin and serum samples. Results PDE4 enzyme levels in both the skin and serum of vitiligo patients were significantly higher than those in controls. PDE4 enzyme tissue levels were significantly higher than serum levels of both groups (patients and controls). A significant positive correlation was found between PDE4 tissue and serum levels of vitiligo patients. Conclusion High PDE4 levels in tissue and serum of vitiligo patients compared with controls suggest that it may contribute to the pathogenesis of vitiligo. Hence, PDE4 inhibitors may be a promising therapeutic modality of this disease.

Skin pigmentation and its control: From ultraviolet radiation to stem cells.

In the light of substantial discoveries in epithelial and hair pigmentation pathophysiology, this review summarizes the current understanding of skin pigmentation mechanisms. Melanocytes are pigment-producing cells, and their key regulating transcription factor is the melanocyte-specific microphthalmia-associated transcription factor (m-MITF). Ultraviolet (UV) radiation is a unique modulator of skin pigmentation influencing tanning pathways. The delayed tanning pathway occurs as UVB produces keratinocyte DNA damage, causing p53-mediated expression of the pro-opiomelanocortin (POMC) gene that is processed to release α-melanocyte-stimulating hormone (α-MSH). α-MSH stimulates the melanocortin 1 receptor (MC1R) on melanocytes, leading to m-MITF expression and melanogenesis. POMC cleavage also releases β-endorphin, which creates a neuroendocrine pathway that promotes UV-seeking behaviours. Mutations along the tanning pathway can affect pigmentation and increase the risk of skin malignancies. MC1R variants have received considerable attention, yet the allele is highly polymorphic with varied phenotypes. Vitiligo presents with depigmented skin lesions due to autoimmune destruction of melanocytes. UVB phototherapy stimulates melanocyte stem cells in the hair bulge to undergo differentiation and upwards migration resulting in perifollicular repigmentation of vitiliginous lesions, which is under sophisticated signalling control. Melanocyte stem cells, normally quiescent, undergo cyclic activation/differentiation and downward migration with the hair cycle, providing pigment to hair follicles. Physiological hair greying results from progressive loss of melanocyte stem cells and can be accelerated by acute stress-induced, sympathetic driven hyperproliferation of the melanocyte stem cells. Ultimately, by reviewing the pathways governing epithelial and follicular pigmentation, numerous areas of future research and potential points of intervention are highlighted.

A comparative study of fractional carbon dioxide laser, narrowband ultraviolet B and topical tacrolimus 0.1% ointment versus narrowband ultraviolet B, topical tacrolimus 0.1% ointment in stable vitiligo

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Vitiligo, an acquired pigmentary disorder of skin and mucous membrane characterized by well circumscribed depigmented macules that occur secondary to selective destruction of melanocytes. Fractional CO&lt;sub&gt;2&lt;/sub&gt; laser system is a recent advancement in the treatment of vitiligo which works on the concept of fractional photo-thermolysis, in which microscopic treatment zones are created which help in increasing the penetration of topically applied agent which indirectly improves drug efficacy.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A comparative study was conducted on 40 patients of stable vitiligo attending OPD, Dept of DVL with fractional CO&lt;sub&gt;2&lt;/sub&gt; laser, narrowband ultraviolet B (NBUVB) and topical tacrolimus 0.1% vs NBUVB, topical tacrolimus 0.1% for a duration of 4 months and patients were followed up for 12 weeks post treatment.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Patients on Fractional CO&lt;sub&gt;2&lt;/sub&gt; laser in combination with NBUVB and topical tacrolimus 0.1% ointment showed &amp;gt;50% improvement compared with other group, with duration for initiation of pigmentation being comparatively less.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The treatment protocol with CO&lt;sub&gt;2&lt;/sub&gt; laser in combination with topical tacrolimus 0.1% cream and NBUVB for stable vitiligo was more effective than NBUVB and topical tacrolimus 0.1% alone and this study demonstrates that adding fractional CO&lt;sub&gt;2&lt;/sub&gt; laser improves repigmentation rate of vitiliginous lesions.&lt;/p&gt;

Clinical Observation and Proposed Classification of Vitiliginous Patches by a Wood’s Lamp

Although vitiligo lesion especially in static state is characterized as sharply demarcated and complete depigmented macule, we encounter patients who have various manners of hypopigmented lesions. We examined the 81 lesions using the newly released Wood’s lamp (Woody®) and investigated whether or not vitiliginous lesions could be uniformly classified under Wood’s lamp illumination and also this classification helped to estimate the tendency of repigmentation after treatment. As result, the vitiliginous lesions were categorized into 4 types on intra- and peri-lesions prior to treatment by using the Wood’s lamp. The inside and border of the lesions were classified as follows: clear white, faint, multi-dot, and perifollicular for the inside, and sharp, blunt, confetti, and trichrome for the border. Suggestive residual pigmentation was detected in 73.6% of patients at the first visit and repigmentation was observed in 67.9% of patients at least 3 months after treatment. Lesions with the “clear white” inside pattern showed significantly lower repigmentation frequency in 38.5% of patients compared to others. The borders with 4 enlarged lesions were composed of 3 of confetti-type and one of sharp-type. This preliminary study demonstrated that detailed observation with a Wood’s lamp could be the basis to classify vitiliginous lesions and might be useful for predicting not only disease progression but also repigmentation prior to treatment.

&lt;p&gt;Effect of Topical 5-Fluorouracil Alone versus Its Combination with Erbium:YAG (2940 nm) Laser in Treatment of Vitiligo&lt;/p&gt;

PurposeTo compare the efficacy of topical 5-FU as monotherapy to combined therapy of topical 5-FU and Er:YAG (2940 nm) laser in the treatment of non-segmental vitiligo (NSV).MethodsThis is a prospective randomized comparative study. Thirty patients diagnosed with NSV were recruited from the dermatology outpatient clinics of the Medical Research Centre of Excellence, the National Research Centre and the National Institute of Laser Enhanced Sciences. Our study group was divided into two subgroups, Group 1 was subjected to ablative Er:YAG and 5-FU cream and Group 2 applied topical 5-FU cream. Three treatment sessions were repeated every 4 to 6 weeks and patients were followed up to 9 months. Repigmentation was assessed by digital photography and subsequent computer based image analysis.ResultsRepigmentation of Group 1 patients ranged from 0 to 70% (mean 12±7%) whilst in Group 2 this ranged from 0 to 5% (mean 1.4±0.8%). In Group 1 repigmentation was mild in 22/30 (73.3%) and moderate to severe in 3/30 (10%) starting after 3 months and persisted or increased during the period of follow up to 9 months. Groups 1 and 2 were subdivided into A and B, vitiligo involving non-resistant and resistant areas respectively. Group 1A showed more repigmentation (mean 13.8±8.5%) than Group 1B (mean 9.8±4.5%) and Group 2A showed more repigmentation (mean 1.5±1%) than Group 2B (mean 1.3±0.5%).ConclusionThe combination of Er:YAG with 5-FU is safe and effective in treating and improving outcome in vitiligo especially of non-resistant areas. Computer based image analysis of vitiliginous lesions and assessing post-therapy response is an easy, quick, and reliable method.

Using the blue screen of a smartphone as an alternative to Wood’s lamp for examination of vitiligo

The Wood’s lamp is an instrument that is commonly used as a bedside investigative modality. Vitiligo is a common, autoimmune disorder characterized by depigmentation of the skin and mucosal surfaces. When the radiation (wavelength, 320-400 nm) from a Wood’s lamp falls on a vitiliginous lesion, the lack of epidermal melanin facilitates visible autofluorescence of dermal collagen, thereby accentuating the lesion. This accentuation is used to differentiate vitiligo from other disorders with hypopigmentation and depigmentation.

Role of Anti-oxidants in the Treatment of Vitiligo

Introduction: The role of free radicals and oxidative damage in the pathophysiology of vitiligo has been documented in recent studies. Antioxidant supplementation has been reported to be useful in the treatment of vitiligo.&#x0D; Objective: To evaluate the role of oral antioxidants supplementation therapy in the treatment of vitiligo by assessing the onset of repigmentation and oxidative stress.&#x0D; Materials and Methods: A total of 80 cases of vitiligo randomized into two groups: antioxidant and placebo comprising 40 patients each and were followed up for 8 weeks for the assessment of onset of repigmentation of vitiliginous lesions as primary outcome. The activities of Malondialdehyde (MDA), Vitamin C, and Vitamin E in serum and of Catalase (CAT) in erythrocytes of patients at baseline and at end of eight weeks were also assessed by using the spectrophotometric assay.&#x0D; Results: The onset of repigmentation was noted significantly earlier among the anti-oxidant group as compared to the placebo group (p=0.015). At the baseline, between the two groups, no significant difference was found in the different biochemical parameters. However, at the end of 2 months the level of MDA (p&lt;0.001) was found to be significantly lower and that of Vitamin E (p&lt;0.001) and CAT (p=0.005) was significantly higher among the anti-oxidants group as compared to the placebo group.&#x0D; Conclusion: Antioxidant supplementation carried a better response in terms of early onset of repigmentation and significant decrease in the oxidative stress, in the short follow up of two months.

Comparison Between (311-312 nm) Narrow Band Ultraviolet-B Phototherapy and (308 nm) Monochromatic Excimer Light Phototherapy in Treatment of Vitiligo: A Histopathological Study.

Introduction: Recently, the monochromatic excimer light (MEL) of 308 nm wavelength has shown some advantages in comparison to narrow band ultraviolet B (NB-UVB) for the treatment of vitiligo. To histopathologically compare the early effects of NB-UVB and 308-nm MEL phototherapy on vitiliginous patches using H&E and HMB-45. Methods: Thirty subjects with non-segmental vitiligo lesions were treated twice a week for 6 weeks with 308-nm MEL, while NB-UVB was used to treat lesions contra laterally. Skin biopsies were taken from lesional areas before and after 6 weeks of treatment by either modality. It was prepared for light microscopy and immunohistochemical study (HMB-45). This study was performed as a clinical trial (Trial registration: http://www.pactr.org; Identifier: PACTR201705002279419) Results: All lesions before treatment had labeling index (number of pigmented cells/non-pigmented cells) of 0.0 (0%). After treatment the LI for MEL was 4.2 ± 2.6, while for NB-UVB LI it was 0.3 ± 0.7. MEL showed higher statistical significance regarding increase of basal pigmented cells, and significant decrease in vacuolated keratinocytes and basal membrane thickness than NB-UVB. Conclusion: Although NB-UVB is considered as treatment of choice for vitiligo, MEL is acknowledged as an effective treatment modality for vitiliginous lesions that induces more repigmentation than NB-UVB, and more rapidly, as confirmed by our study.

Prevalence and Clinical Characteristics of Itch in Vitiligo and Its Clinical Significance.

Objective Vitiligo usually presented as asymptomatic depigmented macules and patches. Little is known regarding itch in vitiligo. This study aimed to evaluate the prevalence and characteristics of itch in vitiligo patients. Patients and Methods A cross-sectional study was conducted on vitiligo patients. Itch character and intensity were determined through questionnaires. Evaluation was also made by dermatologists to define vitiligo subtype, body surface area, Koebner phenomenon (KP), and so on. Data were assessed by computer software. Results were considered statistically significant if p < 0.05. Results Among 402 patients, itch on vitiliginous lesion presented in 20.2%. Prevalence of itch was most common in focal vitiligo (29.4%), followed by segmental vitiligo (20.3%) and nonsegmental vitiligo (19.6%), respectively. Tingling sensation was the most common itch-related symptom (82.7%). The median itch intensity is 5 by 10-point visual analog scale. Daily activity and sleep disturbance were observed in 60.5% and 39.5% of patients who experience itch. Itch occurred approximately 3 days prior to the development of lesions in 48.1% of patients. Thirty-two patients (78.1%) with both itch and KP type IIb had active disease. Conclusions Itch in vitiligo is not uncommon. The presence of itch with KP type IIb may warrant the active vitiligo.

A Case of Segmental Vitiligo with Generalized Morphea Stabilized by Antimalarial Medication.

Dear Editor: A 10-year-old girl presented with a round, brown to whitish, atrophic plaque on the right side of her back, which she has had for 5 years. Histologic findings showed thick collagen bundles with lymphocytic infiltrations around the vessel in the dermo-subcutaneous tissue, which are consistent with morphea. Only topical calcipotriol was used due to the limited localization of the plaque and the young age of the patient. However, after 6 months, a new morphea lesion developed on the left side of the back and linear scleroderma occurred on the forehead. The patient was diagnosed with generalized mixed-type morphea, with two circumscribed morphea on the right and left sides of the back (Fig. 1A) and linear scleroderma on the forehead (Fig. 1B). Hypopigmented lesions were also present on her left leg and on the left side of the trunk (Fig. 1C). Based on Wood's light examination and clinical findings, the patient was diagnosed with segmental vitiligo (SV). Fig. 1 (A) Two circumscribed morphea on the right and left sides of the back. (B) Linear scleroderma on the left side of the forehead. (C) Vitiliginous lesions on the left side of the trunk. The vitiliginous lesions and linear scleroderma on the forehead showed progression despite the combination therapy using intermittent oral steroid, topical calcineurin inhibitor, and narrowband ultraviolet B phototherapy for 1 year. To block the progression of morphea, hydroxychloroquine sulfate (200 mg/day) was used. Skin lesions of morphea and vitiligo stabilized within 6 weeks. In addition, the vitiliginous lesions showed 70% repigmentation after 5 months from start of medication. Skin lesions of morphea also showed no more progression. The patient tolerated the 7-month treatment period with no side effects (Fig. 2). Fig. 2 Flow diagram during the follow-up period. NBUVB: narrowband ultraviolet B. Although the pathogenesis of vitiligo remains unknown, an immunological mechanism is strongly considered. However, SV is associated with a neurogenic mechanism. Furthermore, an immune-mediated mechanism known as the three-step theory has been reported to be involved in the pathogenesis of SV, according to a case report showing simultaneous occurrence of SV, alopecia areata, psoriasis, and halo nevus1. The association of SV with scleroderma has been rarely reported2. Bonifati et al.3 reported the case showing linear scleroderma on the left limb and homolateral SV on the trunk. Contrary to previous reports, our patient had generalized morphea lesions on the right and left sides of the back and linear scleroderma on the left side of the forehead, which was on the same side of the body where SV was located. Our case study suggested that hydroxychloroquine is effective not only in blocking the progression of scleroderma4 but also in treating vitiligo. Walsh et al.5 reported two systemic lupus erythematosus patients with exextensive widespread vitiligo-like depigmentations who showed rapid responses to hydroxychloroquine. Although we cannot exclude the possibility of coincidental development of SV and scleroderma, our case suggested that vitiligo and scleroderma that have the same autoimmune background can occur at the same time because they occurred during the same period and progressed in parallel for several years. In addition, this concomitant presence could support the theory that SV is associated with an autoimmune background. Moreover, our report suggested that an antimalarial drug could be used as a promising option for the treatment of vitiligo.

Can Vemurafenib Induce Vitiligo in Metastatic Melanoma Patients?

To the Editor, Melanoma is a mucocutaneous or ocular, sporadic or familial, neoplasm that is associated with a range of genetic factors. Environmental predisposing factors include the exposure to intense sunlight associated with sunburn, as well as a type II phototype. Between 1.5% and 20% of patients with melanoma may have vitiligo-like lesions. From a clinical point of view, the latter may be classified as: a) lesions adjacent to the primary melanoma or metastatic regression; b) development of a melanocytic nevi nevus halo on pre-existing nevi; or c) vitiliginous lesions at sites distant to the melanoma, whether isolated or associated with the ocular findings of Vogt-Koyanagi-Harada syndrome. We report this relationship of vitiligo-like lesions in a patient with a metastatic melanoma who attended our Unit for treatment with vemurafenib. A 56 year-old male, with no past medical history, was referred to our outpatient clinic complaining about a cutaneous lesion on his back, which had developed abnormal changes for 2 years. With a clinical diagnosis of typical nevi, the patient had the lesion excised. Histological examination revealed superficial spreading melanoma (SSM), absence of ulceration, a 1.9 mm Breslow Depth Index, and a Clark IV Level with positive sentinel node. An elective lymph node dissection was required, and the presence of micrometastases was observed in three nodes (Stage IIIA). BRAF (Serine Threonine kinase B raf) V600E mutation in primary tumor and lymph node were analyzed, with a positive result in both cases. After evaluation of the case by our Hospital Oncological Committee, treatment with 960 mg Vemurafenib (Roche; Basel, Switzerland) twice daily was started. Eight weeks later, vitiligo-like depigmented macules developed on the patient’s neckline (Figure 1). The examination with a Wood’s lamp revealed similar lesions on the periocular and perioral area. A skin biopsy was then performed, showing a loss of melanocytes on the basal layer in the excised area. FIG. 1. Vitiligo-like lesion on the neckline of our patient After ten months of treatment, the patient remains tumor-free, according to the imaging tests performed, and is under periodic follow-ups by the Units of Dermatology and Oncology. Ethics committee approved the presentation of this case report with academic and research purpose under signed of the informed consent by our patient. Vitiligo-like lesions occur most commonly in the setting of untreated metastatic melanoma, although they also develop in association with immunomodulatory therapies, such as INFa2b, IL2A, and the new biologics drugs (BRAF inhibitors, anti–CTLA-4 antibody therapy and anti MEK-MAPkinse ERK kinase-drugs). In these cases, they are usually considered grade 1 toxicity, i.e. a mild adverse effect, and therefore, no further action is required. Drug-induced vitiligo shows different characteristics to classical vitiligo from the epidemiological point of view: an absent family history, partial discoloration, a wayward patchy distribution and a rapid development after the introduction of the drug, as in our case (1). The etiology of the occurrence of this phenomenon remains unclear, although the main theory considers it the result of metabolic dysregulation and damage by direct cytotoxicity against melanocytes as well (2). On the other hand, the use of these drugs that selectively alter the immune system may explain the appearance of vitiligo as an immune-related adverse event. The development of vitiligo-like lesions in metastatic melanoma under treatment with interferon has also been described (3), and more recently, with the BRAF inhibitor Vemurafenib, adding further complexity to the association of both diseases (4). However, what it does seem clear is that the development of vitiligo-like lesions in both untreated patients and patients on biological therapy or interferon-α2β improves the survival rates for metastatic melanoma (5).

A Randomized Comparative Study of Oral Corticosteroid Minipulse and Low-Dose Oral Methotrexate in the Treatment of Unstable Vitiligo

Background: Despite continued progress towards elucidation of the biochemical, genetic and immunopathological pathways in vitiligo, a definitive cure remains elusive. The initial therapy must be directed to arrest disease progression. Oral minipulse therapy (OMP) with betamethasone/dexamethasone has been tried and shown to be an effective modality to arrest the disease progression in vitiligo. Objectives: Methotrexate (MTX) is a time-tested effective treatment extensively used in various autoimmune disorders with good efficacy, safety and tolerability on a long-term basis. We intended to compare the efficacy of MTX with that of OMP in patients with unstable vitiligo vulgaris. Patients and Methods: In a prospective randomized open label study, 52 patients with vitiligo were divided into two groups. Patients in group 1 received 10 mg methotrexate weekly. Group 2 patients received corticosteroid OMP which comprised tablets of dexamethasone 2.5 mg (5 tablets), taken on 2 consecutive days in a week (total weekly dose of 5 mg dexamethasone). Results: In the MTX group, among 25 patients analyzed, during the course of treatment for 24 weeks, overall 6 patients developed new vitiliginous lesions. In the OMP group, 7/25 patients developed new lesions. Statistical correlation between the two groups showed no significance in the number of patients who developed new lesions (increasing disease activity) in either of the groups. At the end of the study, it was demonstrated that patients in both groups had a similar reduction in the vitiligo disease activity score. Conclusion: Our study demonstrated that both drugs are equally effective in controlling the disease activity of vitiligo. MTX can be used in patients with active vitiligo, wherever corticosteroids are contraindicated.

Effects of a preceding fractional carbon dioxide laser on the outcome of combined local narrowband ultraviolet B and topical steroids in patients with vitiligo in difficult-to-treat areas.

Conventional treatment of vitiligo on hands and feet often produces an unsatisfactory result. Various ablative treatment methods were tried with favorable results in facial, neck, and truncal areas. The aim of this study is to evaluate the efficacy and safety of combined fractional CO2 laser, narrowband UVB (NB-UVB) phototherapy, and topical clobetasol propionate in managing stable vitiligo in difficult-to-treat areas. A prospective randomized-intraindividual study was conducted on 27 patients with 27 pair-lesions of non-segmental vitiligo on both hands. The lesions were randomized to receive treatment with fractional CO2 laser, NB-UVB phototherapy, and 0.05% clobetasol propionate cream (Group A) or NB-UVB phototherapy and 0.05% clobetasol propionate cream (Group B). Fractional CO2 laser was performed at 1-week interval for 10 sessions. NB-UVB phototherapy was administered twice weekly for 20 sessions. Patients were evaluated 12 weeks after the last treatment. Outcome was evaluated objectively based on standard digital photographs, patient satisfaction, and adverse events. Twenty-six patients completed the study. Six vitiligious lesions (23.1%) in group A achieved good to excellent repigmentation compared with one lesion (3.9%) in group B (P = 0.065). The overall mean improvement score was 1.35 (± 1.38) in group A and 0.50 (± 0.95) in group B (P = 0.0004). Patients' satisfaction score was significantly higher for the lesions in group A than group B. Lesions on the dorsum of the hand showed a higher response rate than those on the fingers. No serious side-effects were noted. This study demonstrates that adding fractional CO2 laser treatment to NB-UVB phototherapy and topical steroids improves the repigmentation rate of vitiliginous lesions on hands in some patients. This technique may be offered to vitiligo patients who are unresponsive to other treatments.

Vitiliginous lesions during contact immunotherapy for alopecia in a patient with autoimmune thyroiditis

Vitiliginous lesions during contact immunotherapy for alopecia in a patient with autoimmune thyroiditis

Efficacy of autologous cultured melanocyte transplantation for and its relationship with the levels of interleukin-6 and soluble interleukin-6 receptor in suction blister fluid from patients with vitiligo

Objective To investigate the relationship between the efficacy of autologous cultured melanocyte transplantation for and the levels of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) in suction blister fluid from patients with vitiligo.Methods Fifty-three patients with stable vitiligo were included in this study,and received autologous cultured melanocyte transplantation.Clinical efficacy was evaluated at six months after the transplantation.Suction blister fluid was collected from vitiliginous and non-vitiliginous skin in these patients before and six months after the transplantation.Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of IL-6 and sIL-6R in the blister fluid.Statistical analysis was done using paired t test and two independent samples t-test.Results Significant differences were observed in the blister fluid levels of IL-6 ((113.22 ± 81.20) vs.(84.40 ± 48.78) ng/L,P ＜ 0.01) and sIL-6R ((56.28 ± 24.87) vs.(53.96 ± 25.67) ng/L,P ＜ 0.05) between vitiliginous and non-vitiliginous skin.The unsuccessfully treated patients showed higher levels of IL-6 in vitiliginous skin ((153.61 ± 100.26) vs.(88.75 ± 55.75) ng/L,P ＜ 0.05) but similar levels of IL-6 in non-vitiliginous skin ((100.26 ± 55.17) vs.(74.78 ± 42.50) ng/L,P ＞ 0.05) as well as of sIL-6R in both vitiliginous and non-vitiliginous skin compared with the successfully treated patients.The level of IL-6 in the suction blister fluid from both vitiliginous and non-vitiliginous skin was significantly higher in patients with vitiligo stable for less than one year than in those stable for one or more years ((148.46 ± 88.00) vs.(93.54 ± 71.07) ng/L, P ＜ 0.05; (114.82 ± 64.66) vs.(67.40 ± 25.23) ng/L,P ＜ 0.01),but no significant differences were observed for the level of sIL-6R in vitiliginous or non-vitiliginous skin between the two groups of patients (both P ＞ 0.05).Decreased blister fluid level of IL-6 was observed in vitiliginous skin from patients with segmental vitiligo compared with those with non-segmental vitiligo ((77.33 ± 61.70) vs.(131.68 ± 84.54) ng/L,P ＜ 0.05),but there was no significant difference in the level of IL-6 in non-vitiliginous skin or the level of sIL-6R in vitiliginous and non-vitiliginous skin between the patients with segmental vitiligo and those with non-segmental vitiligo (all P ＞ 0.05).Moreover,significant differences were observed in the level of IL-6 in vitiliginous skin ((96.27 ± 53.390) vs.(178.90 ± 96.48) ng/L,P ＜ 0.01) and non-vitiliginous skin ((78.25 ± 40.30) vs.(107.02 ± 42.48) ng/L,P ＜ 0.05),but not in the level of sIL-6R (both P ＞ 0.05) in vitiliginous or non-vitiliginous skin,between the successfully and unsuccessfully treated patients with non-segmental vitiligo.Conclusions The abnormal expression of IL-6 may somewhat affect the microenvironment in vitiliginous lesions of patients,which seems to be associated with the efficacy of autologous cultured melanocyte transplantation. Key words: Vitiligo; Interleukin-6 receptors; Interleukin-6; Melanocytes; Transplantation; Treatment outcome

Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: An implication for pathogenesis

The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully understood. Notch signaling is required for development and maintenance of melanocyte lineage and acts as a key component among keratinocyte-melanocyte interactions. The current study aimed to investigate the possible role of Notch signaling and its effect on the whole melanocyte lineage in vitiligo and correlating it with the different clinicopathologic parameters. Using immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional and 20 perilesional biopsies of patients with vitiligo in comparison with 20 normal skin biopsies as a control group. Lesional biopsies were stained with human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor of control and perilesional skin, whereas cytoplasmic expression appeared only in vitiliginous lesions (P < .05). Membranous and/or nuclear expression of Notch-1 was significantly associated with epidermal human melanoma black-45 positivity (P = .01) and percentage of expression in both epidermis (P = .02) and hair follicles (P = .03) of lesional skin. Cytoplasmic pattern of Notch-1 expression in epidermis was significantly found in lesions with white hair (P = .04) and in cases with marked keratinocyte vacuolization (P = .03). Segmental and acrofacial vitiligo were associated with mild to moderate Notch-1 intensity, whereas generalized vitiligo was associated with strong intensity of expression (P = .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling in vitiliginous white hair and acral and segmental vitiligo may be the cause of their treatment resistance.