Differentiating active from stable vitiligo: The role of dermoscopic findings and their relation to CXCL10.

BACKGROUND: Distinguishing vitiligo activity/stability status is pivotal in the management of patients with vitiligo. CXCL10 is a chemokine released in the tissues and sera of patients with vitiligo and an indicator of disease activity. AIM: This study aimed to assess the role of dermoscopy in detecting active and stable vitiligo by comparing the dermoscopic signs in vitiligo with Vitiligo Disease Activity Score (VIDA), clinical activity, and CXCL10 activity. METHODS: Ninety-seven patients with vitiligo were enrolled in this cross-sectional study. Vitiligo activity/stability was assessed using VIDA scores, clinical examination, dermoscopy, and serum CXCL10 levels measured by enzyme-linked immunosorbent assay technique. Dermoscopic scores were calculated using BPLeFoSK score. RESULTS: The dermoscopic score was concordant with the VIDA score in 83.5% of patients (n = 81), clinical assessment in 97.9% (n = 95), and serum CXCL10 level in 70.1% (n = 68). Dermoscopic signs of ill-defined border, satellite lesions, and micro-Koebner and starburst appearance were more common in active vitiligo, while a well-defined border was more common in stable lesions. CONCLUSION: Dermoscopic examination is a practical, reliable, noninvasive, semi-objective tool in the assessment of vitiligo activity/stability that helps reach an informed decision on the disease status to choose the appropriate therapeutic modality.

Different methods of enhancing the efficacy of topical tacrolimus in extra-facial vitiligo: A comparative study.

BACKGROUND: Vitiligo is an acquired pigmentation disorder due to loss of melanocytes. Topical tacrolimus is effective in vitiligo treatment with minimal effect on extra-facial lesions. OBJECTIVE: To assess different methods of enhancing the absorption of topical tacrolimus in extra-facial vitiligo sites using microneedling and occlusion. METHODS: This study included 20 adult patients of both sexes with non-segmental vitiligo. Four extra-facial vitiligo lesions in each patient were randomly labeled A, B, C, and D and treated as follows: area A: tacrolimus ointment (0.03%) application twice/day, area B: microneedling once/week and tacrolimus ointment application directly after microneedling and twice/day the rest of the week, area C: microneedling once/week alone, and area D: tacrolimus ointment application twice/day under occlusion by polyethylene foil. The evaluation was done clinically by calculating the re-pigmentation percent after 6 months of treatment. RESULTS: Responders in area B were 45%, and 35% in area C, and 25% in both areas A and D. No statistically significant difference was detected regarding the re-pigmentation percent between the four areas (p > 0.05). No correlations were detected between re-pigmentation percent and patients' data. CONCLUSION: Combination of microneedling and topical tacrolimus has an edge over monotherapy in vitiligo, and further studies are needed to verify such results.

Analysis of symmetricity in the three different (sagittal, transverse and frontal) planes in generalized nonsegmental vitiligo.

BACKGROUND: Nonsegmental vitiligo is defined as being "often symmetrical", however, no work has tackled the point as to how valid it is to depend upon the concept of symmetricity in generalized nonsegmental vitiligo. AIMS: To investigate vitiligo symmetry, taking into account sites of predilection, the clinical characteristics of patients were studied. METHODS: This multicentric study included 712 nonsegmental vitiligo patients with 2876 examined lesions. Three models were drawn for each patient. Sagittal, transverse and frontal planes were drawn to divide the body into right/left, upper/lower and anterior/posterior halves respectively. Patients were examined by Wood's light and analyzed for symmetry. RESULTS: Bilateral involvement was present in 78% (P < 0.001). Studying the similarity of clinical involvement in the upper and lower body parts revealed that such similarity was present in 38%, with a significant positive association in some areas. Studying clinical similarity in the anteroposterior distribution pattern revealed a significant positive association in 11%. LIMITATIONS: Relatively low number of patients. CONCLUSIONS: We found significant bilateral symmetry in the lesions of 78% of vitiligo patients. Our work could aid in drawing the anticipated vitiligo map in patients with active disease, helping in increasing our understanding of the clinical behaviour of this disease.

Efficacy and tolerability of chemical peeling as a single agent for melasma in dark-skinned patients: A systematic review and meta-analysis of comparative trials.

BACKGROUND: Chemical peelings are used on a wide scale in cosmetic field including melasma treatment. They often provide clinicians with flexibility in tailoring treatments according to patient needs and satisfaction. OBJECTIVE: To evaluate safety and efficacy of chemical peeling as single agents in melasma management in patients with darker skin types. METHODS: We included randomized controlled trials (RCTs) and prospective studies that assessed efficacy and safety of chemical peeling as single agents for facial melasma. An online bibliographic search was conducted, and data were extracted from the included studies. RESULTS: Ten RCTs and three prospective comparative studies (No. of patients = 478) were included. The overall effect estimate favored Glycolic acid (GA) over trichloroacetic acid peel in terms of melasma activity and severity index (MASI) (mean difference [MD] -1.89, 95% CI [-3.26, -0.52], P = .007). On the other hand, the overall effect estimates did not favor GA over tretinoin (MD 0.53, 95% CI [-0.46, 1.52], P = .3), vitamin C iontophoresis (MD 1.50, 95% CI [-0.50, 3.50], P = .14), and amino fruit acid (MD 0.39, 95% CI [-0.64, 1.42], P = .46) in terms of MASI. The overall effect estimates favored trichloroacetic acid peel (MD -5.30, 95% CI [-6.41, -4.19], P < .001) and Jessner's solution (MD -3.20, 95% CI [-5.35, -1.05], P = .004) over topical hydroquinone in terms of MASI. CONCLUSION: In conclusion, chemical peelings are effective as single agents for management of melasma in patients with darker skin types, with the use of topicals as maintenance treatment.

Effect of Different Methods of Trypsinization on Cell Viability and Clinical Outcome in Vitiligo Patients Undergoing Noncultured Epidermal Cellular Suspension.

BACKGROUND: Noncultured Epidermal Cell Suspension (NCECS) is a surgical modality used in treating stable vitiligo. Trypsinization of the epidermis may be done either at 4°C overnight (cold) or at 37°C for 30 to 50 minutes (warm). Recently, trypsinization was done at room temperature (25°C) in an in vitro trial. OBJECTIVE: To compare different trypsinization techniques in NCECS regarding cell viability and clinical outcome. METHODS: This comparative multicenter study was conducted on 20 patients with stable nonsegmental vitiligo. In each patient, 3, nonacral vitiligo lesions were randomly assigned for treatment by NCECS prepared by warm, room temperature, and cold trypsinization techniques, respectively. A perilesional biopsy was taken from each of the 3 treated lesions as an objective measure of disease stability. After transplantation, all patients received narrow-band ultraviolet B twice weekly for 6 months. Cell viability was assessed in each technique, as well as clinical outcome in all treated lesions. RESULTS: Warm and room temperature trypsinization techniques were comparable with each other. Both were significantly better than the cold technique regarding viability and repigmentation. CONCLUSION: Room temperature trypsinization can be used as a convenient substitute to warm trypsinization. Cold trypsinization is not recommended because of its poor results and poor patient satisfaction.

Estimation of Homocysteine Level and Methylenetetrahydrofolate Reductase (MTHFR) Gene and Cystathionine B Synthase (CBS) Gene Polymorphisms in Vitiligo Patients.

BACKGROUND: Vitiligo is an acquired, multifactorial disorder of the skin and mucous membranes. An elevated homocysteine level has been described in vitiligo. Methylenetetrahydrofolate reductase (MTHFR) and cystathionine B synthase (CBS) are major determinants of the homocysteine metabolism. OBJECTIVES: Determine serum homocysteine levels in vitiligo patients as well as the association between MTHFR (C677T, A1298C) and CBSgene polymorphisms and susceptibility to vitiligo in a sample of those populations. METHODS: Homocysteine levels were estimated by radioimmunoassay while MTHFR (C677T, A1298C) and CBSgene polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism technique in 100 vitiligo patients and 80 healthy controls. RESULTS: The homocysteine level was significantly higher in vitiligo patients than controls (p = 0.000). Significant differences in the genotype and allele distributions of single nucleotide polymorphisms of the MTHFR (C677T, A1298C) with the mutant genotypes are more common in the controls than patients (p = 0.001, 0.029, respectively). CBS gene mutant genotypes and alleles are more common in vitiligo patients than controls (p = 0.002). CONCLUSION: CBSand MTHFRgene polymorphisms may play a major role in the genetic susceptibility to vitiligo.

A clinical and immunological study of phototoxic regimen of ultraviolet A for treatment of alopecia areata: a randomized controlled clinical trial.

Background: Various therapeutic agents have been described for alopecia areata but none is satisfactory. The use of ultraviolet A phototherapy in phototoxic regimens has emerged lately with promising results. Objective: To determine the efficacy and safety of phototoxic regimen of psoralen ultraviolet A (PUVA) in comparison to conventional therapy with intralesional corticosteroids in patients with alopecia areata. Methods: In this randomized controlled clinical trial, 40 patients were randomized to either phototoxic regimen of psoralen ultraviolet A group or potent intralesional corticosteroids group for three months. Study ended at six months. The primary outcome was treatment success: sustained regrowth of hair in ≥80% of the affected areas at six months. Tissue cytokines were assessed at zero and three months. Results: At six months, treatment success was achieved by 45% of patients, similarly in both groups. Tissue cytokine expression correlated well with clinical response. Conclusion: Phototoxic regimen of topical PUVA deserves a place among therapeutic tools used in management of alopecia areata especially in more extensive conditions where intralesional corticosteroids would not be suitable. Trial registration: https://clinicaltrials.gov/ct2/show/record/NCT01559584.

Do Prolactin and its Receptor Play a Role in Alopecia Areata?

CONTEXT: Studying the link between prolactin and autoimmunity has gained much ground over the past years. Its role played in alopecia areata (AA) is not clear yet, as previous reports yielded controversial results. AIMS: This study aimed to measure the serum level of prolactin and to detect the expression of its receptor in AA, in an attempt to highlight its possible role in the pathogenesis of this disease. SUBJECTS AND METHODS: A case-control study of 30 AA patients and 20 controls from outpatient clinic were undertaken. Every patient was subjected to history taking and clinical examination to determine the severity of alopecia tool (SALT) score. Blood samples were taken from patients and controls to determine the serum prolactin level. Scalp biopsies were obtained from the lesional skin of patients and normal skin of controls for assessment of the prolactin receptor. STATISTICAL ANALYSIS: Depending upon the type of data, t-test, analysis of variance test, Chi-square, receiver operator characteristic curve were undertaken. RESULTS: On comparing the serum prolactin level between patients and controls, no significant difference was found, while the mean tissue level of prolactin receptor was significantly higher in patients than in controls. In patients, a significant positive correlation was found between the prolactin receptor and the SALT score. CONCLUSIONS: Prolactin plays a role in AA, and this role is probably through the prolactin receptors rather than the serum prolactin level.

Increased tenascin C and DKK1 in vitiligo: possible role of fibroblasts in acral and non-acral disease.

Recently, multiple culprits-in addition to melanocytes-have been implicated in the pathogenesis of vitiligo. Among those factors are fibroblasts. However, their exact role has not been clearly elucidated. The aim of the study was to evaluate the possible role played by fibroblasts in vitiligo via studying the expression Tenascin C and DKK1 in acral versus non-acral vitiligo lesions. This case-control study included 19 non-segmental vitiligo patients and ten controls. All patients were subjected to thorough clinical evaluation. Both Tenascin C and DKK1 were measured in lesional and peri-lesional skin of acral and non-acral lesions using ELISA technique. The measured levels of Tenascin C and DKK1 were significantly higher in the vitiligo group when compared to controls in all assessed sites (P < 0.05). Tenascin C was found to be significantly higher in lesional areas compared to peri-lesional ones only in the acral sites. DKK1 was significantly higher in lesional areas in all assessed sites (P < 0.05). The current work suggests a malfunction of fibroblasts in vitiligo, through demonstrating significant up-regulation of two melanogenesis inhibitory products (Tenascin C and DKK1) in patients compared to controls. Larger scale studies are warranted to detect the possible implications of such findings on vitiligo treatment.

Low level light-minoxidil 5% combination versus either therapeutic modality alone in management of female patterned hair loss: A randomized controlled study.

BACKGROUND: Female pattern hair loss (FPHL) is the most common form of hair loss in women. Nevertheless, its management represents a real challenge. Among the FDA approved therapeutic modalities for FPHL are topical minoxidil and more recently low-level light therapy (LLLT). AIM OF WORK: Assess the efficacy and safety of LLLT in comparison to topical minoxidil 5% and to a combination of both therapies in the treatment of FPHL. PATIENTS AND METHODS: This study included 45 female patients with proven FPHL. They were randomly divided into three equal groups, where group (i) patients were instructed to apply topical minoxidil 5% twice daily, group (ii) patients received LLLT using the helmet iGrow® device for 25 minutes 3 days weekly, and group (iii) patients received a combination of both topical minoxidil 5% twice daily and LLLT for 25 minutes 3 days weekly for 4 months (study duration). Evaluation was done according to clinical, dermoscopic (folliscopic), and ultrasound bio-microscopic (UBM) parameters. Patient satisfaction and side effects were reported. RESULTS: The efficacy and safety of both topical minoxidil and LLLT were highlighted with comparable results in all parameters. The combination group (iii) occupied the top position regarding Ludwig classification and patient satisfaction. UBM and dermoscopic findings showed significant increase in the number of regrowing hair follicles at 4 months in all groups, whereas only UBM showed such significant increase at 2 months in the combination group (iii). A non-significant increase in the hair diameter was also documented in the three groups. CONCLUSION: LLLT is an effective and safe tool with comparable results to minoxidil 5% in the treatment of FPHL. Owing to the significantly better results of combination therapy, its usage is recommended to hasten hair regrowth. Lasers Surg. Med. 49:835-843, 2017. © 2017 Wiley Periodicals, Inc.

Autologous platelet-rich plasma versus readymade growth factors in skin rejuvenation: A split face study.

BACKGROUND: The escalating urge for a youthful-looking skin instigates continuous innovations with minimally invasive procedures. Readymade growth factors and autologous platelet-rich plasma (PRP) represent such therapeutic interventions. OBJECTIVE: Compare the efficacy and safety of PRP to readymade growth factors in skin rejuvenation. PATIENTS AND METHODS: Twenty adult females with Fitzpatrick skin types III-IV and Glogau photoaging types II and III were enrolled in this study. They underwent a split face therapy where each side was randomly assigned to treatment by either readymade growth factors (area A) or autologous PRP (area B). All patients received six sessions at 2-weeks interval. Evaluation was carried out using Global Aesthetic Improvement Scale (GAIS) and optical coherence tomography (OCT). Patients were followed up for 6 months. RESULTS: Both procedures yielded significant improvement regarding both GAIS (skin turgor and overall vitality) and OCT (epidermal and dermal thickness) assessment. Significant negative correlation was detected between patients' age, sun exposure, and GAIS. Burning sensation was significantly higher in area A. Patient satisfaction was significantly higher in area B. Improvement was more sustained in area B on follow-up. CONCLUSION: Platelet-rich plasma is effective and safe for skin rejuvenation, comparable to readymade growth factors with noticeable higher longevity.

Phototherapy and Combination Therapies for Vitiligo.

Vitiligo is a disease characterized by disappearance of melanocytes from the skin. It can negatively influence the physical appearance of affected individuals, and may profoundly affect a person's psychosocial function and quality of life. Therefore, vitiligo should not be considered as merely a condition that affects a patient's appearance, but needs to be actively treated in patients who seek medical help. Phototherapy has been used as the main treatment modality for patients with vitiligo. Different forms of phototherapy for vitiligo include broadband UVB, narrowband UVB, excimer light and excimer laser, and psoralen plus UVA.

Vitiligo - The story from within: A transmission electron microscopic study before and after narrow-band ultraviolet B.

Melanocyte loss is the main feature of vitiligo, but evidence refers to pathological multiplayers. Transmission electron microscopy was utilized to further explore vitiligo before and after narrow-band ultraviolet B (NB-UVB) therapy. Skin biopsies were retrieved from lesional and perilesional skin and compared to normal control skin. Sections were examined for melanocytes and keratinocytes and the number of melanosomes and thickness of basal lamina were measured. In lesional skin, keratinocytes revealed two types of degeneration with a significant increase in the mean thickness of basal lamina and decrease in the number of melanosomes. After treatment, lesional and perilesional skin showed variable ultrastructural features.

Phototherapy: The vitiligo management pillar.

Phototherapy has been the mainstay of vitiligo therapy for several decades. A variety of wavelengths and modalities are available, but narrowband ultraviolet B remains the safest and most commonly used treatment. Acting on multiple steps in vitiligo pathogenesis, narrowband ultraviolet B is one of the few therapies that can effectively induce stabilization and stimulate repigmentation. Achievement of optimal results involves using a combination of appropriate treatment protocols, careful patient selection, and patient education to set expectations. Individual patient characteristics, including disease activity, vitiligo phenotype, lesion location, and skin phototype, should all be considered, along with combination therapies.

Serum Vitamin D and Vitamin D Receptor Gene Polymorphism in Mycosis Fungoides Patients: A Case Control Study.

BACKGROUND: Vitamin D has been considered a key player in various malignancies including cutaneous cancers. To date, mycosis fungoides (MF) has been the least studied in relation to vitamin D. Furthermore, the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) have not been tackled before in the context of MF, despite their incrimination in numerous diseases. AIM OF STUDY: To assess the role of vitamin D in MF by measuring its serum level, and studying VDR SNPs (TaqI, BsmI, FokI) in different stages of MF. PATIENTS AND METHODS: 48 patients with various stages of MF, and 45 healthy controls were included. Complete history, full clinical examination and a five mm punch skin biopsy were performed to all recruited patients. Venous blood samples were withdrawn from both patients and controls to determine the serum vitamin D level and VDR gene polymorphisms. RESULTS: Serum vitamin D level was significantly lower in patients (5.3-33.7 nmol/L)] compared to controls (8.3-90.1 nmol/L)] (P<0.001). A significant difference was observed between patients and controls regarding the FokI polymorphism only, being higher in patients (P = 0.039). Also Vitamin D serum levels differed significantly in patients with FokI genotypes (P = 0.014). No significant correlations were detected between any of the studied parameters and the demographic and clinical data of the included subjects. CONCLUSION: Depressed vitamin D and FokI polymorphism are potentially involved in the context of MF. VDR gene polymorphisms warrant further larger scale investigations to detect the exact genes involved in the pathogenesis of such an enigmatic disease.

B cell activating factor and T-helper 17 cells: possible synergistic culprits in the pathogenesis of Alopecia Areata.

The role of T-helper 17 cells (Th17) and regulatory T-cells (Tregs) in the pathogenesis of alopecia areata (AA) has not been clearly elucidated. B cell activating factor (BAFF) being a regulator of T cell activation could be involved in this pathologic process as well. The current study evaluated the expression of IL-17, IL-22, Foxp3 and BAFF in tissue and sera of AA patients. Forty AA patients and 40 age and sex matched healthy controls were included. Tissue and serum levels of IL-17, IL-22, BAFF as well as serum level of Foxp3 were measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining was used for assessment of tissue level of Foxp3. Tissue and serum levels of IL-17, tissue levels of IL-22 and BAFF were significantly higher in patients. Serum levels of IL-22, Foxp3 and BAFF were non-significantly higher in patients. Foxp3 immunostaining showed negativity in tissue of patients and controls. A significant positive correlation was found between both tissue levels of IL-17 and BAFF (r = 0.474, P = 0.035) and tissue level of IL-22 and disease duration (r = 0.766, P < 0.001) in AA patients. Th17 cells and BAFF are synergistically involved in the pathogenesis of AA. BAFF represents a promising therapeutic target for such a challenging disease. Defective Tregs number and/or function in AA warrants further studies.

Propranolol versus captopril in the treatment of infantile hemangioma (IH): A randomized controlled trial.

BACKGROUND: Renin-angiotensin system components have been demonstrated in the biology of infantile hemangioma (IH). Captopril, an angiotensin-converting enzyme inhibitor, is proposed as a therapeutic alternative to oral propranolol. OBJECTIVES: We sought to compare the benefit of propranolol and captopril in the treatment of IH, and to assess angiotensin-converting enzyme gene polymorphism in patients with IH and in control subjects. METHODS: Thirty patients with IH and 35 healthy control subjects were enrolled in this study. Patients were randomly assigned to treatment with either propranolol or captopril. Assessment was done clinically and by measurement of serum vascular endothelial growth factor and angiotensin II in patients and control subjects. Angiotensin-converting enzyme gene polymorphism was also studied. RESULTS: Clinical improvement was significantly better and faster in the patients treated with propranolol. Both groups showed reduced vascular endothelial growth factor and angiotensin II levels posttreatment, with a significantly higher percentage reduction in the propranolol-treated group. Cardiac side effects were reported only in the captopril-treated group. Baseline vascular endothelial growth factor level was significantly higher, and baseline angiotensin II level was significantly lower, in patients than control subjects. LIMITATIONS: We studied a relatively small number of patients and control subjects. CONCLUSION: Propranolol shows greater benefit than captopril in the treatment of IH.

Vitamin D and the skin: Focus on a complex relationship: A review.

The "sunshine" vitamin is a hot topic that attracted ample attention over the past decades, specially that a considerable proportion of the worldwide population are deficient in this essential nutrient. Vitamin D was primarily acknowledged for its importance in bone formation, however; increasing evidence point to its interference with the proper function of nearly every tissue in our bodies including brain, heart, muscles, immune system and skin. Thereby its deficiency has been incriminated in a long panel of diseases including cancers, autoimmune diseases, cardiovascular and neurological disorders. Its involvement in the pathogenesis of different dermatological diseases is no exception and has been the subject of much research over the recent years. In the current review, we will throw light on this highly disputed vitamin that is creating a significant concern from a dermatological perspective. Furthermore, the consequences of its deficiency on the skin will be in focus.