Vitiligo Patches Research Articles

Direct Transplant of Melanocytes from Normal Donor Area into Vitiligenous Recipient Area by Intralesional Injection of Melanocytes Using Spade Like Needle Technique

Background: Vitiligo is a common autoimmune inflammatory skin disease, where there are different surgical techniques for treatment of stable patches of vitiligo .Objective: To find non-costly, minimally invasive, simple technique by direct melanocytes transplant by spade needle technique in treatment of vitiligo. Patients and Methods: This interventional, therapeutic, comparative study was done in Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq from April 2014-March 2015. Twenty patients with localized, generalized and segmental vitiligo were included. Full history and examination for each patient was done with 4 (20%) males and 16 (80%) females and their ages ranged from 9 - 40 (23.15 ± 11.44) years. Forty one patches in 20 patients treated by spade grafting technique and the donor and recipient sites were demarcated and anesthesia done by xylocaine 2% with adrenalin 1:100,000. Transplantation was started by using disposable needle gauge 18 (the sharp end of needle was cut by a scissor to make it a spade like) with medical syringe 5 ml supplied with normal saline. The micro-pieces were taken from donor site and transplanted directly, easily and rapidly into dermis of recipient site and followed by pushing normal saline and the procedure was repeated to cover all recipient sites with 5 mm distance between injection points. The surface area of the lesions was calculated and the reduction rate was estimated every month till the end of the 4th month period of the treatment. Results: Including 41 patches in 20 patients with the surface area of the patches ranged from 1.5 - 90 cm2 (13.78 ± 17.57) cm2. The mean ±SD of surface area of lesions was decreased from 13.78 ± 17.57 cm2 at baseline visit to 13.61 ± 17.48 cm2 at the second visit (after 2 weeks ) which was statistically significant (p value ≤ 0.001). The mean surface area continued to be reduced till reaching 12.20 ± 15.68 cm2 at the third visit and 12.01 ± 15.55 cm2 at the fourth visit. All were statistically significant when compared to baseline visit. There was reduction in surface area 1.1% at two weeks, 9.93%, and 12.5% at the 2nd, 4th months respectively. Conclusions: Intradermal injection of melanocytes in patients with vitiligo by spade like needle was very quick and simple non-costly technique, and gave 12.5% reduction which could be repeated at different times until satisfactory re-pigmentation of vitiligenous skin is achieved.

Validation of the Vitiligo noticeability scale: a patient-reported outcome measure of Vitiligo treatment success

Background: Patient-reported outcome measures are rarely used in vitiligo trials. The Vitiligo Noticeability Scale (VNS) is a new patient-reported outcome measure assessing how ‘noticeable’ the vitiligo patches are after treatment. The noticeability of vitiligo after treatment is an important indicator of treatment success from the patient’s perspective. Objectives: This study aimed to evaluate the construct validity, acceptability and interpretability of the VNS. Our main hypothesis was that the VNS would be a better and more consistent indicator of treatment success than percentage repigmentation. Methods: Clinicians (n=33) and patients with vitiligo (n=101) examined 39 image pairs, each depicting a vitiligo lesion pre- and post-treatment. Using an online questionnaire, respondents gave a global assessment of treatment success and a VNS score for treatment response. Clinicians also estimated percentage repigmentation of lesions ( 75). Treatment success was defined as ‘Yes’ on global assessment, a VNS score of 4 or 5, and more than 75% repigmentation. Agreement between respondents and the different scales was assessed using kappa statistics. Results: VNS scores were associated with both patient- and clinician-reported global treatment success (κ = 0.54 and κ = 0.47, respectively). Percentage repigmentation showed a weaker association with patient- and clinician-reported global treatment success (κ = 0.39 and κ = 0.29, respectively). VNS scores of 4 or 5 can be interpreted as representing treatment success. Images depicting post-treatment hyperpigmentation were less likely to be rated as successful. Conclusions: The VNS is a valid patient-reported measure of vitiligo treatment success. Further validation of the VNS is required, using larger sets of clinical pre- and post-treatment images, affecting a wider range of anatomical sites.

Maintenance Therapy of Adult Vitiligo with 0.1% Tacrolimus Ointment: A Randomized, Double Blind, Placebo–Controlled Study

The risk of relapse after successful repigmentation in vitiligo is estimated to 40% within the first year. It has been shown in atopic dermatitis that continuous low-level use of topical corticosteroids and calcineurin inhibitors in previously affected skin can prevent new flares. We hypothesized that a twice-weekly application of 0.1% tacrolimus ointment might be effective for maintaining repigmentation in therapeutically repigmented lesions of vitiligo patients. After randomization, sixteen patients with 31 patches were assigned to the placebo group and 19 patients with 41 patches were assigned to the tacrolimus group. In the intention-to-treat analysis, 48.4% of lesions showed depigmentation in the placebo group, whereas 26.8% did in the tacrolimus group (P=0.059). The intention-to-treat results did not remain significant after adjustment for within-patient clustering, odds ratio (OR) 2.55; 95% confidence interval (CI; 0.65-9.97); P=0.1765. The per-protocol analysis (n=56) showed that 40% of lesions had some depigmentation in the placebo group, whereas only 9.7% did in the tacrolimus group (P=0.0075). The per-protocol results remained significant after adjustment for within-patient clustering: OR 6.22; 95% CI (1.48-26.12); P=0.0299. Our study shows that twice-weekly application of 0.1% tacrolimus ointment is effective in preventing the depigmentation of vitiligo patches that have been previously successfully repigmented.

Dermatophyte infection encircling vitiligo.

Dermatophyte infection encircling vitiligo.

The changes in melanocyte number and melanin density occurring in vitiligo patches during 180 days of narrow band-ultraviolet B therapy

The changes in melanocyte number and melanin density occurring in vitiligo patches during 180 days of narrow band-ultraviolet B therapy

A Study of Hair Follicular Transplantation as a Treatment Option for Vitiligo.

Background:Repigmentation of vitiligo is closely related to hair follicles. Hence, replenishing melanocytes in vitiliginous patches utilizing undifferentiated stem cells of the hair follicles using follicular unit transplantation (FUT) is a possible treatment option.Objectives of the Study:To study the efficacy of FUT in cases of segmental/stabilized vitiligo as a treatment option for leukotrichia.Materials and Methods:Fifty patients with 63 lesions of stable vitiligo over nonglabrous areas were treated with follicular unit grafts. Reduction in the size of vitiligo patches as well as improvement in the associated leukotrichia were evaluated using subjective and objective assessments.Results:Of the 63 patches, good to excellent response was seen in 39 (61.9%), fair in 16 (25.4%), and poor in eight (12.7%) lesions. No repigmentation was seen in two (4.8%) lesions. The mean improvement seen was 61.17%. Excellent color match was observed in 44 lesions (69.8%). Repigmentation of the depigmented hairs occurred in 11 out of 46 patients with associated leukotrichia.Conclusion:FUT is a safe and effective method for treating localized and segmental vitiligo, especially on hairy parts of the skin. Though labor intensive, it was found to be associated with a quick patient recovery time, very low morbidity, and good color match.

New Winning Strategies for Vitiligo: The Low Dose Cytokines Therapy Approach

Vitiligo is a dermatologic pigmentary disorder triggered by melanocytes’ loss and sustained by a deep immune imbalance which induce chronic inflammation and excessive oxidative stress phenomena at skin level. Current therapies are mainly symptomatic and designed in order to inhibit the inflammatory mediators at vitiligo patches level. To restore the correct immune balance between Th1/Th17 and Th2/Treg response and concomitantly rebalancing the inflammatory response represents an innovative and effective approach for Vitiligo treatment; Low Dose Medicine theories and the availability of specific low dose SKA interleukins, antibodies and growth factors allows researchers and clinicians to act simultaneously against all the main etiologic causes of vitiligo and makes possible to design new therapeutic approaches for vitiligo.

Induction of vitiligo after imiquimod treatment of condylomata acuminata

BackgroundCondylomata acuminata (genital warts) is the most common sexually transmitted disease, and imiquimod is the sole FDA-approved medication for combating this condition. Vitiligo associated with imiquimod treatment of condylomata acuminata is rare.Case presentationA 28-year-old male with condylomata acuminata of the penis presented to our clinic. After removing his condylomata acuminata, we advised him to use imiquimod 5% cream to prevent relapse. When he presented to our clinic again about 12 weeks later, he complained of vitiligo patches on his penis and scrotum. Physical examination showed vitiligo patches involving the glans penis, shaft of the penis, and scrotum, and remaining pigmented areas within the plaques of vitiligo.A skin biopsy of the dorsal surface of the penis showed a complete absence of melanocytes and melanin granules in the basal layer; the dermis was normal.ConclusionThis is the first report of a case of imiquimod-induced vitiligo diagnosed by histopathological examination. This adverse effect should be considered when dermatologists prescribe this medication.

Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo – Part II: Rheological characterization and in vivo assessment through dermatopharmacokinetic and pilot clinical studies

Vitiligo is a non contagious acquired pigmentation disorder with limited treatment possibilities. Clobetasol propionate (CP) is the drug-of-choice for vitiligo which suppresses the immune system by reducing immunoglobulin action and causes the restoration of melanocytes leading to repigmentation of skin. However, despite being effective, its low and variable bioavailability prompt for development of novel carrier that could effectively target CP to site of action without producing undesirable side-effects. Low solubility of CP in subsequent poor in vivo bioavailability was overcome by formulating microemulsion based gel of CP (MBC) which would enhance the percutaneous transport of CP into and across the skin barrier. Comprehensive characterization of MBC was carried out for viscosity, gel strength and rheological behavior. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to control (Cream of CP). In vitro and in vivo occlusion studies demonstrated similar occlusiveness for MBC and control. MBC exhibited 3.16 times higher stratum corneum CP levels compared to control. Visualization of cutaneous uptake in vivo using laser scanning microscopy confirmed targeting of CP to epidermis and dermis. Dermatopharmacokinetic studies of MBC showed enhanced drug deposition of CP in skin layers. MBC was assessed for in vivo efficacy by single blind randomized pilot clinical study. The efficacy was assessed by vitiligo area scoring index (VASI) method. After completion of trial, repigmentation of vitiligo patches in patients were evaluated and scored. MBC was superior in terms of faster repigmentation and efficacy when compared with control (p value<0.5). Hence, it was concluded that CP loaded MBC possess enhanced skin localization as well as therapeutic activity in vitiligo patients.

Clinical and treatment characteristics determining therapeutic outcome in patients undergoing autologous non‐cultured outer root sheath hair follicle cell suspension for treatment of stable vitiligo

Autologous non-cultured outer root sheath hair follicle cell suspension (NCORSHFS) is a recently described novel cellular graft technique for the treatment of stable vitiligo. There is lack of data about various factors determining the repigmentation rate in vitiligo patients undergoing this novel surgical therapy. To study the clinical characteristics and treatment variables determining therapeutic outcome in patients of stable vitiligo undergoing NCORSHFS. Non-cultured outer root sheath hair follicle cell suspension was prepared from anagen hairs extracted from the occipital area. The number of melanocytes and hair follicle stem cells (HFSC) in the suspension was quantified by staining with anti-HMB45 and anti-CD200 antibody, respectively. In all patients, a 2mm punch skin biopsy was taken from one of the vitiligo patch to be treated prior to surgery for assessment of histomorphological features. Post surgery patients were followed up at regular intervals for 24weeks. Thirty patients (21 females, 9 males) with a clinical diagnosis of stable vitiligo, with a total of 60 target lesions were included in this study. The mean age of the study population was 21.10±5.64years. The number of melanocytes (P=0.04) and HFSC (P=0.01) transplanted were significantly higher among patients achieving optimum repigmentation (>75% repigmentation). There was a strong correlation between repigmentation at 24week and number of melanocytes and HFSC transplanted. Number of HFSC transplanted and absence of dermal inflammation were significant predictors of achieving optimum repigmentation. The number of melanocytes and HFSC transplanted and absence of dermal inflammation were important determents of optimal repigmentation in patients undergoing NCORSHFS for treatment of stable vitiligo. Hence, refining the technique of NCORSHFS on the basis of these factors would help in achieving better surgical outcomes.

A comparative study of the mini-punch grafting and hair follicle transplantation in the treatment of refractory and stable vitiligo

Some vitiligo lesions are resistant to all medical treatments. We sought to compare the efficacy of hair follicle transplantation and mini-punch grafting for the treatment of refractory vitiligo lesions. A total of 25 patients with stable and resistant vitiligo participated in the study. In each patient, a resistant vitiligo patch was divided into 2 equal parts. One part was treated with hair follicle transplantation and the other part with mini-punch grafting. Postsurgically, the recipient areas were exposed to narrowband ultraviolet B twice a week for 6 months. The diameter of the repigmentation around each graft was measured monthly. At the end of the sixth month, 68% of follicle grafts, and 72% of mini-punch grafts, had repigmentation. The mean diameter of repigmentation around follicle grafts was 5 ± 1.7 mm and aroundpunch grafts was 5.3±1.6 mm. There was no significant difference between the 2 groups statistically (P= .18). Small sample size and short time of follow-up are limitations. Because the results of the 2 methods are not statistically different and mini-punch grafting is much easier to do than follicular transplantation, we recommend mini-punch grafting to treat drug-resistant vitiligo.

Squamous cell carcinoma in a patient with vitiligo of photo-covered skin

Ultraviolet radiation is an important risk factor for the development of skin cancers. Melanin is known to protect the skin against harmful effects of ultraviolet radiation. Hence, vitiligo patients are at higher risk of developing such malignancies. But few reports of occurrence of skin cancers in vitiligo lesions suggest that their occurrence in vitiligo is rare. There are reports of development of Squamous cell carcinoma (SCC) in vitiligo lesions, following long-term Psoralen and Ultraviolet-A (PUVA) therapy. But there are no reports of occurrence of SCC in a vitiligo patch located in photo-covered area. We describe a patient with SCC in a vitiligo patch present in photo-covered skin.

Therapeutic wounding - 88% phenol in idiopathic guttate hypomelanosis

Context:Therapeutic wounding includes wounding the skin to induce pigmentation of the depigmented skin patches that was earlier used for repigmenting small patches of stable vitiligo. In this study, we have used the same principle to induce pigmentation in idiopathic guttate hypomelanosis (IGH) by spot peel with 88% phenol.Aims:To study the efficacy of phenol in causing repigmentation in IGH and its adverse effect profile.Settings and Design:Open prospective study.Materials and Methods:Twenty patients with 139 IGH macules were subjected to spot peel. Eighty-eight percent phenol was applied with an ear bud once a month for two sittings. Patients were assessed both subjectively and objectively after every session and at the end of 3 months of initiation of therapy.Results:Repigmentation was noted in 64% of IGH macules. More than 75% improvement was seen in 45% of the total IGH macules, while 41.5% showed 50-75% improvement at the end of three months. Persistent scabbing was the common adverse effect noted in 17.26% of lesions.Conclusion:Spot peel with 88% phenol is a safe, simple, cost-effective, outpatient procedure for IGH, which can be combined with other medical therapies.

New Insights in Mixed Vitiligo: Initial Non Segmental Vitiligo can precede the Onset of Segmental Vitiligo (Cases Report and Review of Theories)

Recently, mixed vitiligo (MV) was defined by Mulekar as the association of segmental vitiligo (SV) and nonsegmental vitiligo (NSV) in the same patient. Until now, SV and generalized NSV were considered to be separate entities with a different distribution (unilateral or bilateral). Generalized vitiligo seemed to be more frequently associated with other autoimmune diseases than SV. From the pathophysiological standpoint, it was hypothesized that NSV was an autoimmune disease, while SV may result of a sympathetic dysfunction. The first pediatric case of SV associated with NSV was reported in 2003 and 36 other observations were subsequently reported. In all these cases, segmental involvement associated usually in a second step with the onset of bilateral vitiligo patches. In this article, we describe, for the first time, two atypical cases of mixed vitiligo in which NSV involvement preceded the onset of SV. In the light of these remarkable cases, different possible aetiopathogenetic mechanisms of MV are discussed which may provide new insights into the pathogenesis of vitiligo.

308 nm excimer lamp in combination with topical tacrolimus: A retrospective study of its efficacy and safety in childhood vitiligo

Background: Vitiligo is a chronic, polygenic dyschromia that presents with multiple depigmented macules and patches. Among the various therapeutic modalities for treatment of vitiligo in children, phototherapy as one of the mainstay treatments has varying therapeutic efficacy. There is limited data regarding the use of combination of tacrolimus and 308 nm excimer lamp for treatment of vitiligo in children. Aim: The aim of the present study is to retrospectively assess the efficacy and tolerability of 308 nm Excimer lamp in combination with topical tacrolimus to treat vitiligo in children below 17 years with skin type III, IV and V. Methods: Case sheets and photographs of 47 vitiligo patches from 24 children (male = 9, female = 15), Results: Of the 47 patches, 35 patches achieved repigmentation accounting to 74.4% of the total patches. The repigmentation response was good in ultraviolet (UV) sensitive areas but minimal in UV resistant areas. All the patches retained pigmentation during the follow-up period of 12-18 months. Conclusion: The degree of repigmentation achieved with topical tacrolimus and excimer lamp in a period of 4-6 weeks is much higher than other contemporary vitiligo therapies in children. This dual therapy of topical tacrolimus and 308 nm Excimer lamp is a safe and effective therapy showing an early response, for localized vitiligo in children.

A comparative study of efficacy of cultured versus non cultured melanocyte transfer in the management of stable vitiligo

BackgroundReplenishing melanocytes by autologous melanocytes selectively in vitiliginous macules is a novel and promising treatment. With expertise in culturing autologous melanocytes, it has now become possible to treat larger recipient areas with smaller skin samples. To determine the relative efficacy of cultured versus non cultured melanocyte transfer in the management of stable vitiligo. MethodsThe melanocytes were harvested as an autologous melanocyte rich cell suspension from a donor split thickness graft. Cultured or non cultured melanocytes were then transplanted to the recipient area that had been superficially dermabraded. 100 patches of vitiligo in patients reporting to this hospital were randomly allocated into 2 groups to receive either of the interventions. ResultsAn excellent response was seen in 62.17% cases with the autologous melanocyte rich cell suspension technique and in 52% with the melanocyte culture technique. ConclusionAutologous melanocyte transplantation can be an effective form of surgical treatment in stable but recalcitrant lesions of vitiligo. Large areas of skin can be covered with a smaller donor skin using melanocyte culture technique; however culture method is more time consuming, and a labour intensive process, requiring state of the art equipments with a sterile lab setup.

Targeted Gene Disruption in theXenopus tropicalisGenome using Designed TALE Nucleases

Transcription activator-like effector nucleases (TALENs) are attractive and powerful molecular tools for targeted gene disruption because of their simple design and quick assembly. To evaluate the utility of TALENs in genome editing in Xenopus tropicalis, we prepared nine pairs of TALENs for the tyrosinase, noggin and MMP-9TH genes. All of the TALENs had some activity in a single-strand annealing assay using a cultured frog cell line, suggesting double-stranded DNA cleavage activity by the TALENs at their target site. The injection of mRNAs encoding TALENs into fertilized X. tropicalis embryos resulted in Cel-1 cleavage of the PCR fragment containing the target site amplified from embryo genomic DNA, indicating that a mutation in the target gene had occurred during embryogenesis. These mutations were confirmed by the sequencing of clones derived from the PCR fragments of genomic DNA. Patches of vitiligo were observed in tadpoles raised from fertilized eggs that had been injected with mRNAs of TALENs for the tyrosinase gene. TALENs containing the repeat variable di-residue (RVD) NN appeared to show more activity than TALENs containing RVD NK, although both RVD NN and NK preferentially associate with a G nucleotide.

Body hair transplantation in vitiligo

Hair transplantation has been used to repigment a stable vitiligo patch. Body hair transplant was done for a 28-year-old male with stable vitiligo with scarring. Peri-folllicular repigmentation was noted at 4 weeks and complete repigmentation of vitiligo patch was achieved at 12 weeks. No recurrence was noted at the end of 3-month follow-up with a good colour match with surrounding skin. To the best of our knowledge, this is the first case report highlighting the effectiveness of body hair transplantation by FUE in focal vitiligo patch with leukotrichia.

Lymphocytic Expression of Fas and FasL Apoptotic Markers in Vitiligo

Background. Lymphocytic dermal infiltrations accompany the melanocytes loss in depigmenting vitiligo skin. These lymphocytes are incriminated during the pathogenesis of the disease. Fas receptor is a death receptor on the surface of cells that leads to programmed cell death (apoptosis) and FasL is its ligand. Fas/FasL system plays a crucial role in modulating apoptosis. Objectives. This study investigates the lymphocytic expression of apoptotic markers Fas/FasL in vitiligo. Methods. The present study was conducted on 45 vitiligo samples obtained from 15 vitiligo patients including 8 females (53.3%) and seven males (46.7%). Biopsies were obtained also from control volunteers. All specimens were routinely stained with Hematoxylin &Eosin and immunohistochemically for Fas & FasL apoptotic markers. Results. Fas & FasL were significantly expressed by infiltrating lymphocytes in vitiligo biopsies compared to control. Lymphocytic expression of Fas & FasL was higher on the edge biopsies than the center. Considerable lymphocytic infiltration and attack of B.M. were associated with higher lymphocytic Fas and FasL expression. During vitiligo activity lymphocytic Fas & FasL expression was also significantly higher. Conclusions. Lymphocytic Fas and FasL are significantly expressed in vitiligo patches which may trigger epidermal apoptosis and loss of melanocytes. At the same time these factors have a role in switching-off of the immune responses and cell mediated cytotoxicity.

Follicular unit extraction as a therapeutic option for Vitiligo

Follicular unit extraction (FUE) is a surgical procedure, which can be used to transplant follicular units into vitiliginous areas. Such follicular unit transplant has been recently used to repigment stable vitiligo patches. FUE was done for a 12-year-old female with a stable vitiligo patch with leukotrichia on the eyebrow. Repigmentation was noted in 6 weeks and complete pigmentation seen at 12 weeks. Leukotrichia resolved over a period of 6 months. No recurrence was noted at the end of 6 months follow-up with excellent colour match. This case is presented to highlight the simplicity, safety and effectiveness of FUE in stable vitiligo patches with leukotrichia.