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.

Expert opinion about laser and intense pulsed light (IPL)-induced leukoderma or vitiligo: a cross-sectional survey study.

Vitiligo patients may desire laser hair removal, skin rejuvenation, vascular treatments, and other laser or intense pulsed light (IPL) assisted treatments. However, there is a risk of inducing new depigmented patches (Koebner phenomenon). In absence of guidelines on the safe use of laser or IPL in vitiligo patients, dermatologists tend to be reluctant to administer these treatments. The aim of this survey study was to provide an estimation of the occurrence and related risk factors of laser/IPL-induced leukoderma or vitiligo. A cross-sectional survey study was performed among 15 vitiligo experts from 11 countries, with 14 questions about affected patients, involved laser/IPL treatments and the physicians' approach. In a total of 11,300 vitiligo patients, laser/IPL-induced leukoderma or vitiligo was reported in 30 patients (0.27%). Of these, 12 (40%) patients had a medical history of vitiligo and seven (58%) of these patients had stable (> 12 months) vitiligo before the treatment. Most frequently reported were hair removal procedures and localization of the face and legs. Side effects like blistering, crusting, and erosions occurred in 56.7% of the cases. These vitiligo experts based their advice on the risk of the laser treatment on stability of the vitiligo (43%) and activity signs (50%), and 50% discuss the risks before starting a laser treatment. Relevant activity signs are the Koebner phenomenon (57.1%), confetti-like lesions (57.1%) and hypochromic borders (50%). Laser-induced leukoderma or vitiligo is an uncommon phenomenon. Remarkably, a minority had a medical history of vitiligo of which 58% were stable. Consequently, most cases could not have been prevented by not treating vitiligo patients. However, a majority had laser/IPL-induced skin damage. Therefore, caution is advised with aggressive settings and test-spots prior to the treatment are recommended. This study showed significant variation in the current recommendations and approach of vitiligo experts regarding laser/IPL-induced leukoderma or vitiligo.

Different vitiligo characteristics as predictors of increased risk of metabolic syndrome and insulin resistance: A case-control study.

BACKGROUND: Autoimmune and metabolic disturbances have been reported in association with vitiligo, highlighting possible systemic associations that should be considered. AIMS: To assess the possible association of metabolic syndrome (MetS) as well as insulin resistance (IR) with vitiligo in different age groups. METHODS: This case-control study included 142 patients with vitiligo aging ≥ 6 years and 142 age- and sex-matched controls. Participants were assessed for MetS using the International Diabetes Federation (IDF) criteria in addition to IR via homeostasis model assessment of IR (HOMA-IR). The study was registered at Clinical Trials.gov, Identifier: NCT03622320, on August 9, 2018. RESULTS: As per the IDF criteria, patients with vitiligo showed significantly more frequent association with high fasting plasma glucose levels, high blood pressure readings, central obesity, dyslipidemia, and MetS than controls (p = 0.020, p = 0.034, p = 0.014, p < 0.001, and p = 0.002, respectively). Moreover, patients with vitiligo have significantly higher levels of fasting insulin and HOMA-IR (p ≤ 0.001). Results obtained from patients with vitiligo and controls with coexistent MetS/IR demonstrated vitiligo as a risk factor for both MetS and IR. Univariate and multivariate logistic regression highlighted that older age was the significant independent predictor for MetS and IR. CONCLUSION: Patients with vitiligo showed a significantly higher incidence of MetS than controls. Vitiligo per se can be considered a risk factor for MetS and IR. Therefore, regular follow-up and early metabolic derangement diagnoses are mandatory.

Evaluation of needling/microneedling as an adjunct to phototherapy in the treatment of stable acral vitiligo: a comparative clinical and immunohistochemical study.

OBJECTIVES: To evaluate the efficacy and tolerability of needling/microneedling as an adjunct to NB-UVB phototherapy in the treatment of stable refractory patches of acral vitiligo, based upon clinical and immunohistochemical assessment of melanocyte count and distribution in response to needling/microneedling. MATERIALS AND METHODS: Twenty patients with stable acral vitiligo (≥2 patches) were enrolled. One of the two index patches was randomized to receive needling or microneedling in conjunction with NB-UVB. Patients received phototherapy sessions 3 times weekly, while needling was carried out on biweekly basis for 6 months. Assessment was done clinically using point counting method, VESTA, and global patients' satisfaction, and immunohistochemically by quantitative assessment of melanocyte count by Melan-A. RESULTS: No statistically significant difference was observed between NB-UVB monotherapy and either of the combined therapy regimens as regards the mean percentage change in vitiligo surface area (p = .451), mean change in absolute melanocyte count from baseline (p = .589), and mean VESTA (p = .916). Patches subjected to adjuvant microneedling/needling were afflicted by koebnerization in 50% and 20% of cases, respectively. CONCLUSION: Neither microneedling nor needling appear to confer an added therapeutic value to NB-UVB phototherapy in the treatment of stable acral vitiligo. Moreover, both carry the risk of koebnerization.

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.

Early localized vitiligo, a medical emergency: Long-term follow-up study.

In spite of multiple therapeutic regimens for vitiligo, disease relapse remains a challenge. Most guidelines consider systemic treatments only in rapidly progressive disease with wider surface areas. This delay in halting the immune attack, may give the chance for further disease progression as well as establishment of resident memory T-cell population predisposing to future relapses. To assess the ability of early systemic therapy of localized (<2% BSA), recent onset (<6 months) vitiligo to control disease activity and minimize the possibility of recurrence. Twenty-five patients with recent onset (<6 months), localized (<2% BSA) vitiligo were included. Patients received pulse dexamethasone therapy for 6 months plus topical treatments and NB-UVB sessions. Patients were followed monthly as regards percent of repigmentation and VIDA score. To detect recurrence, biannual assessment was done for 4 years. Eighty-four percent of patients had acrofacial lesions and 44% had facial lesions. Arrest of activity was achieved after 3.65 ± 2.19 months. Complete repigmentation was achieved in a mean duration of 6.88 ± 0.2 months. At the end of the 4-year follow up, recurrence occurred in 32% of patients. In spite of recurrence, localized disease (<2% BSA) was secured. A significantly higher incidence of recurrence was associated with cases with bilateral distribution of lesions. Early systemic immunomodulation for recent localized vitiligo is a successful approach to achieve early control of disease activity and minimize the incidence of recurrence. Such cases should not be overlooked but managed as early as possible; it is a race against time.

Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, randomized, placebo-controlled, prospective, multicenter study.

BACKGROUND: NB-UVB has long been the vitiligo management pillar with capability of achieving the main treatment outcomes; repigmentation and stabilization. Its stabilizing effect in dark skin has been debatable. However, randomized controlled trials regarding NB-UVB ability to control disease activity are lacking. PURPOSE: To assess stabilizing effect of NB-UVB in comparison to systemic corticosteroids, the mainstay in vitiligo stabilization, in skin photo-types (III-V). METHODS: This is a multicenter, placebo-controlled, randomized, prospective study. Eighty patients with active nonsegmental vitiligo (NSV) (Vitiligo disease activity (VIDA) ≥2) were randomized to either NB-UVB and placebo (NB-placebo) or NB-UVB and dexamethasone oral mini-pulse (OMP) therapy (NB-OMP) for 6 months. Sixty four patients completed the study, 34 in the NB-OMP group and 30 in the NB-placebo group. Patients were evaluated fortnightly according to presence or absence of symptoms/signs of activity. RESULTS: In spite of earlier control of disease activity observed in the NB-OMP group, it was comparable in both groups by the end of the study period. Disease activity prior to therapy, but not extent, was found to influence control of activity in both groups. Thus, NB-UVB is a safe sole therapeutic tool in vitiligo management. Not only does it efficiently achieve repigmentation, but also it is a comparable stabilizing tool for systemic corticosteroids in spite of slightly delayed control. CONCLUSION: NB-UVB is the only well-established vitiligo therapy that can be used solely whenever corticosteroids are contraindicated or immune-suppression is unjustified. Nonetheless, its combination with corticosteroids expedites response and improves compliance.

Automated Microneedling Versus Fractional CO2 Laser in Treatment of Traumatic Scars: A Clinical and Histochemical Study.

BACKGROUND/OBJECTIVES: Microneedling has shown satisfactory effects in scar rejuvenation. Comparisons of its results with fractional laser are limited. This study aims to compare the efficacy and safety of automated microneedling versus fractional carbon dioxide (CO2) laser in treatment of traumatic scars on clinical and histochemical bases. MATERIALS AND METHODS: Thirty patients with traumatic facial scars were randomized to treatment with 4 monthly sessions of either automated microneedling or fractional CO2 laser. Assessment of scars was performed at baseline and 3 months after the last treatment session, clinically by the modified Vancouver Scar Scale (mVSS) and histochemically by quantitative assessment of collagen and elastic fibers. RESULTS: Both groups showed improvement in mVSS, collagen, and elastin contents after treatment. Percentage improvement of collagen and elastin content was higher after treatment by a laser compared with microneedling, in case of the collagen content. Percentage increase in the collagen content after treatment was higher in atrophic scars of the laser group than those of the microneedling group. CONCLUSION: In this small study, microneedling was as safe as fractional CO2 laser for rejuvenation of traumatic scars with comparable clinical effects. Fractional CO2 laser is more powerful in stimulating neocollagenesis. Automated microneedling is effective for treatment of hypertrophic scars.

Combining Low Power Fractional CO2 With QS-NdYAG Toning in the Treatment of Melasma Reduces the Incidence of Punctate Leukoderma.

BACKGROUND AND OBJECTIVES: Q-switched Nd:YAG (QS-Nd:YAG) toning (low fluence, large spot size, and high frequency) has been used successfully for the treatment of melasma, especially in dark skin phototypes. Punctate leukoderma was found to be a frequent complication that reduced the safety of this procedure. Combining low power fractional CO2 laser, which is another effective melasma laser therapy, might improve the efficacy and safety of this procedure. The aim of this study was to evaluate  the effect of combining low power fractional CO2 laser with QS-Nd:YAG toning in the treatment of melasma. STUDY DESIGN/MATERIALS AND METHODS: A randomized comparative split-face study included a total of 30 patients with bilateral, symmetrical melasma. All patients received QS-Nd:YAG toning on one randomly selected side of the face, while the other side randomly received either low power fractional CO2 alone (group A) or combined QS-Nd:YAG toning with low power fractional CO2 (group B). QS-Nd:YAG toning sessions were scheduled every two weeks for nine consecutive sessions, and low power fractional CO2 sessions were received every 4 weeks for three consecutive sessions. The assessment was done using the modified melasma area and severity index (mMASI) score, spectrophotometry (melanin index [MI] and erythema index [EI]), photography, blinded physician assessment, and patient satisfaction (at baseline, 1 week and 8-12 weeks after the last treatment sessions). RESULTS: A significant reduction in the mMASI score and MI was obtained with all treatment regimens. On comparing different modalities, group A reduction in mMASI and MI was significantly greater on the side receiving QS-ND:YAG toning (64.03% and 8.27%, respectively), than the side receiving low power fractional CO2 laser alone (36.02%. 2.64%, respectively). On the other hand, reduction of mMASI score and MI showed no statistical significance between the side receiving QS-Nd:YAG toning alone and the combined modality. Punctate leukoderma occurred in four cases (13%) on the side receiving QS-Nd:YAG toning. CONCLUSION: QS-Nd:YAG toning is significantly more effective than low power fractional CO2 in the treatment of melasma when used separately. Although combining low power fractional CO2 with QS-Nd:YAG toning does not increase its efficacy, it minimizes the incidence of the undesirable punctate leukoderma complication and achieves lower recurrence. This combination can thus be recommended as a safe and effective measure for the treatment of melasma. © 2021 Wiley Periodicals LLC.

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.

Cosmetic camouflage as an adjuvant to vitiligo therapies: Effect on quality of life.

BACKGROUND: Vitiligo is a pigmentary disorder associated with considerable psychological imbalance. Partial response to therapy and long duration for repigmentation are common. Meanwhile, camouflage may help through concealing vitiligo lesions and improving patient confidence and self-esteem. AIM: To assess the Dermatology Life Quality Index (DLQI) in vitiligo patients, and to determine the patients' acceptance and willingness to utilize camouflage regularly and the impact of using camouflage as an adjuvant modality. PATIENTS/METHODS: The study was carried out on 100 vitiligo patients who underwent thorough history taking, clinical examination, and DLQI assessment. Forty patients were randomly chosen, taught how to apply camouflage, and followed up over 1 month of regular application. RESULTS: Dermatology Life Quality Index in the 100 vitiligo patients was found to be 12.2 ± 3.9, denoting the very large effect on quality of life vitiligo has. It was significantly worse in female patients, adolescents, students, and high-socioeconomic level patients, in visible sites and genitalia, and in unstable cases. There was a significant positive correlation between the DLQI and disease duration (r = 0.75, P < .001) and VES (r = 0.79, P < .001). The 40 cases on camouflage showed a significant percent reduction in their DLQI when compared to noncamouflage users (P: .00). CONCLUSIONS: Dermatology Life Quality Index is significantly affected by vitiligo. Camouflaging is a technique that needs to be taught to the patient to overcome the anticipated problems that drive them away from using it; especially, it significantly improves their DLQI in their devastating disease.

Fractional Carbon Dioxide Laser is Effective in Amelioration of Pruritus in Primary Cutaneous Amyloidosis: A Clinical and Biochemical Study.

BACKGROUND AND OBJECTIVES: Primary cutaneous amyloidosis (PCA) is a pruritic disease characterized by amyloid deposition in the skin. Interleukin-31 (IL-31) is a pruritus-mediating cytokine. Fractional carbon dioxide (CO2 ) laser has shown efficacy in the treatment of PCA regarding the clinical appearance, histological pattern, and pruritus. The aim of this study is to assess the effect of fractional CO2 laser on pruritus associated with PCA, and analyze whether this effect is related to IL-31 and IL-31 receptor (R) expression. STUDY DESIGN/MATERIALS AND METHODS: The study included 24 patients with PCA and 24 healthy controls. Each patient received four fractional CO2 laser sessions, 4 weeks apart, using the superficial ablative mode. Skin biopsies were taken from patients before and after treatment, as well as controls, for assessment of IL-31 and IL-31R by real-time polymerase chain reaction. RESULTS: Treatment resulted in significant improvement of all clinical parameters, including pruritus (P < 0.001). Patients before treatment had significantly higher IL-31 and IL-31R than controls (P = 0.000 for both). In addition, there was a statistically significant decrease in IL-31 and IL-31R after treatment than their values before treatment (P = 0.000 for both). CONCLUSION: This study confirms the therapeutic efficacy of fractional CO2 laser in treatment of PCA. Reduction of IL-31 and its receptor seems to be one of the involved mechanisms; however, its relation to improvement of pruritus is still not clear. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Recipient site preparation by cryoblebbing in melanocyte keratinocyte transplantation procedure over the fingers in vitiligo: A pilot study.

Surgical treatment of vitiligo lesions over the fingers has poor outcome. In this intra-patient comparative study, 12 patients with stable non-segmental vitiligo (NSV) affecting the middle three fingers of one hand were included. Three variations were used in treatment of finger vitiligo lesions: minipuch grafting, melanocytes keratinocyte transplantation procedure (MKTP) preceded by cryoblebbing or full CO2 laser resurfacing of the recipient site. Liquid nitrogen was used to create blebs in one finger 24 hours before therapy. On the following day, the second finger was treated by minipunch grafting and the third finger was resurfaced by CO2 laser. A suspension was prepared and 0.1 mL was injected into each cryobleb. It was also applied to the resurfaced skin. All patients underwent topical PUVA therapy and were followed-up for 12 months. Ten cases with 52 lesions completed the follow-up period. About 4/18 lesions treated by cryoblebbing followed by MKTP showed ≥75% repigmentation while only 1/17 lesions treated by laser resurfacing + MKTP and 1/17 lesions treated by minipunch grafting showed 30% and 10% repigmentation, respectively. No complications occurred in MKTP treated lesions. Cryoblebbing of the recipient site seems to improve the outcome of MKTP in lesions over the fingers in stable NSV.

Studying the effect of adding growth factors to the autologous melanocyte keratinocyte suspension in segmental vitiligo.

Addition of different growth factors to the medium used in autologous melanocyte-keratinocyte transplantation procedure (MKTP) was reported in the literature. The aim of the current study was comparison of response to MKTP in segmental vitiligo (SV) with and without adding growth factors to the suspension medium. Eighteen cases with SV were randomly divided into two groups. In group A: Ham F12 medium was used for suspension and in group B: 5 ng/mL recombinant basic fibroblast growth factor (bFGF) and 25 mg/500 mL 3'5' cyclic adenosine monophosphate (cAMP) were added to the medium. All cases received NB-UVB twice weekly for 24 weeks. The area of vitiligo lesions was measured before and after therapy by point-counting technique and complications were recorded. Excellent response (90%-100% repigmentation) occurred in 5/9 cases (56%) in group A and 7/9 cases (78%) in group B (with growth factors). A significant decrease in the area of treated lesions before and after therapy was found in both groups A and B (P = .0012 and .0004, respectively), however, a higher percentage of reduction in area of vitiligo was seen in group B cases (70% in group A vs 90% in group B; P value: .028). Marginal halo was seen in five cases in group A and six in group B. In conclusion addition of bFGF and cAMP to MKTP medium improved the results of the procedure. It could be considered if economically feasible.