Marcel Bekkenk

Development and Validation of the Vitiligo Extent Score (VES): an International Collaborative Initiative.

The clinical assessment of vitiligo involves an estimation of the affected body surface area. The most commonly used method is the palm of hand 1% rule as integrated in the Vitiligo Area Scoring Index. However, this method can be challenging and time consuming. In this study, we introduce a global Vitiligo Extent Score (VES). In the first part of the study, this measurement instrument was developed and subsequently optimized during a pilot scoring session. In a subsequent stage, the inter- and intrarater reliability of the instrument were tested. Live scoring showed an excellent interrater reliability for the VES (intraclass correlation VES: 0.924 vs. Vitiligo Area Scoring Index: 0.846). Subsequent scoring on pictures was comparable with the live evaluation and demonstrated an excellent intrarater reliability. A high intraclass correlation forxa0the VES (intraclass correlation VES: 0.923 vs. Vitiligo Area Scoring Index: 0.757) was also found in anxa0additional subgroup of patients with extensive vitiligo. Moreover, user-friendliness and timing were scored veryxa0favorably. In conclusion, this measurement instrument allows us to monitor accurately andxa0easily thexa0affected body surface area in a standardized way. Moreover, our results provide evidence that the VESxa0can be proposed as a promising tool to measure the vitiligo extent in clinical trials and in daily practice.

Treatment of Basal Cell Carcinoma Using a One-Stop-Shop With Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

Background Basal cell carcinoma (BCC) is the most common cancer diagnosed in white populations worldwide. The rising incidence of BCC is becoming a major worldwide public health problem. Therefore, there is a need for more efficient management. Objective The aim of this research is to assess the efficacy and safety of a one-stop-shop (OSS) concept, using real-time in vivo reflectance confocal microscopy (RCM) (Vivascope 1500; Lucid Technologies, Henrietta, NY, USA) as a diagnostic tool, prior to surgical management of new primary BCCs. Methods This is a prospective non-inferiority multi-center RCT designed to compare the “OSS concept using RCM” to current standards of care in diagnosing and treating clinically suspected BCC. Patients ≥ 18 years attending our outpatient clinic at the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Department of Dermatology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (Amsterdam, The Netherlands) with a clinically suspected new primary BCC lesion will be considered for enrollment using predefined inclusion and exclusion criteria, and will be randomly allocated to the experimental or control group. The main outcome parameter is the assessment of incomplete surgical excision margins on the final pathology report of confirmed BCC lesions (either by punch biopsy or RCM imaging). Other outcome measures include diagnostic accuracy (sensitivity and specificity) of RCM for diagnosing BCC and dividing between subtypes, and throughput time. Patient satisfaction data will be collected postoperatively after 3 months during routine follow-up. Results This research is investigator-initiated and received ethics approval. Patient recruitment started in February 2015, and we expect all study-related activities to be completed by fall 2015. Conclusions This RCT is the first to examine an OSS concept using RCM for diagnosing and treating clinically suspected BCC lesions. Results of this research are expected to have applications in evidence-based practice for the increasing number of patients suffering from BCC and possibly lead to a more efficient disease management strategy. Trial Registration ClinicalTrials.gov: NCT02285790; https://clinicaltrial.gov/ct2/show/NCT02285790 (Archived by WebCite at http://www.webcitation.org/6b2LfDKWu).

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

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e‐Delphi consensus, concluded that ‘repigmentation’ and ‘maintenance of gained repigmentation’ are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e‐surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e‐surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.

Melanoma-associated leukoderma and vitiligo cannot be differentiated based on blinded assessment by experts in the field

BACKGROUNDnMelanoma-associated leukoderma (MAL) is a depigmenting disorder that can occur spontaneously in patients with melanoma. The differences in clinical presentation between MAL and vitiligo are not well defined. This may lead to misdiagnosing MAL as vitiligo, resulting in delayed detection of melanoma.nnnOBJECTIVEnThe objective of this study was to assess whether experts in the field can distinguish between MAL and vitiligo, and to assess if discriminative features can be identified.nnnMETHODSnWe designed an image comparison study in which 4 experts in the field blindly assessed photographs followed by medical history of 11 patients with MAL and 33 with vitiligo.nnnRESULTSnThe assessors misdiagnosed 72.7% of MAL cases and marked 80.0% of them as typical vitiligo. The median age at onset of the leukoderma was higher (55xa0years, Pxa0=xa0.001) in MAL. No discriminative features were found.nnnLIMITATIONSnSampling bias because of inclusion in tertiary referral center is a limitation.nnnCONCLUSIONnThe clinical presentation of leukoderma in patients with melanoma resembles that of vitiligo. We propose melanoma-associated vitiligo as the more appropriate term for leukoderma in patients withxa0melanoma. Clinicians should be aware that depigmentation in vitiligo can also be caused by melanoma-associated vitiligo and a total body inspection should be performed.

Meeting report: Vitiligo Global Issues Consensus Conference Workshop “Outcome measurement instruments” and Vitiligo International Symposium, Rome, Nov 30–Dec 3rd

The international vitiligo community had last December its first vitiligo only research meeting in the Eternal City. Vitiligo is a well-recognized but poorly addressed public health concern worldwide. The Vitiligo International Symposium (VIS) is a strong signal for the medical world of the coming of age of vitiligo as a major research field. Because of the gathering of the majority of world experts, the meeting was preceded by a clinical research methodology workshop held at the San Gallicano Institute. This report gives a combined account of the two parts. This article is protected by copyright. All rights reserved

Development and validation of a patient-reported outcome measure in vitiligo: The Self Assessment Vitiligo Extent Score (SA-VES)

Background: The Vitiligo Extent Score (VES) has recently been introduced as a physicians score for the clinical assessment of the extent of vitiligo, but a good patient self‐assessment score is lacking. Objective: The objective is to develop and validate a simplified version of the VES as a patient‐reported outcome measure (PROM). Methods: After extensive pilot testing, patients were asked to score their vitiligo extent twice with an interval of 2 weeks using the Self Assessment Vitiligo Extent Score (SA‐VES). The scores were compared with the physicians evaluation (VES). Results: The SA‐VES demonstrated very good test‐retest reliability (intraclass correlation = 0.948, 95% confidence interval [CI]: 0.911‐0.970) that was not affected by age, skin type, or vitiligo distribution pattern. According to patients, this evaluation method was easy to use (22% very easy; 49% easy; 29% normal) and required <5 minutes in the majority of patients (73%, <5 minutes; 24%, 5‐10 minutes; 2%, 10‐15 minutes). Comparison of the SA‐VES and the VES demonstrated excellent correlation (r = 0.986, P <.001). Limitations: Few patients had a dark skin type. Conclusion: The results demonstrate excellent reliability of the SA‐VES and excellent correlation with its investigator‐reported counterpart (VES). This patient‐oriented evaluation method provides a useful tool for the assessment of vitiligo extent.

Vitiligo‐like depigmentations as the first sign of melanoma: a retrospective case series from a tertiary vitiligo centre

patients with melanoma may develop vitiligo-like skin depigmentation referred to as melanoma-associated leukoderma (MAL), melanoma-associated hypopigmentation (MAH), melanoma-associated depigmentation (MAD) or melanoma-associated vitiligo (MAV) 1-3. Many dermatologists are not aware of the diagnosis MAL and may easily diagnose and treat these patients as having non-segmental vitiligo, thereby overlooking the underlying (metastatic) melanoma. At present, the prevalence of MAL and its clinical characteristics are not well established. n nThis article is protected by copyright. All rights reserved.

Validation study of the Vitiligo Extent Score-plus (VESplus)

Fig 1. Vitiligo. Correlation analysis between the Vitiligo Extent Score (VES) and Modified Vitiligo Extent Score (VESplus) for total body surface area. REFERENCES 1. Sekulic A, Migden MR, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017;17(1):332. 2. Lear JT, Migden MR, Lewis KD, et al. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol. August, 28 2017. https://doi.org/10.1111/jdv.14542 [Epub ahead of print]. 3. Gonnissen A, Isebaert S, Haustermans K. Targeting the hedgehog signaling pathway in cancer: beyond smoothened. Oncotarget. 2015;6:13899-13913. 4. Buonamici S, Williams J, Morrissey M, et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med. 2010;2: 51ra70. 5. Rajurkar M, De Jesus-Monge WE, Driscoll DR, et al. The activity of GLI transcription factors is essential for KRAS-induced pancreatic tumorigenesis. Proc Natl Acad Sci U S A. 2012;109: E1038-E1047. 6. Zhou J, Zhu G, Huang J, et al. Non-canonical GLI1/2 activation by PI3K/AKT signaling in renal cell carcinoma: a novel potential therapeutic target. Cancer Lett. 2016;370:313-323. 7. Chang ALS, Oro AE. Initial assessment of tumor regrowth after vismodegib in advanced basal cell carcinoma. Arch Dermatol. 2012;148(11):1324-1325. 8. Zelenetz AD, Barrientos JC, Brown JR, et al. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017;18: 297-311.

Autologous cell suspension grafting in segmental vitiligo and piebaldism: a randomized controlled trial comparing full surface and fractional CO2 laser recipient-site preparations

Autologous noncultured cell suspension transplantation is an effective treatment for repigmentation in segmental vitiligo and piebaldism. Full surface laser ablation is frequently used to prepare the recipient site before cell suspension transplantation, even though the optimal laser settings and ablation depth are unknown.

The Vitiligo Extent Score (VES) and the VESplus are responsive instruments to assess global and regional treatment response in patients with vitiligo

From the Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah; Department of Dermatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Dermatology, Emory University, Atlanta, Georgia; Division of Dermatology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia; University of Arizona Cancer Center, Tucson, Arizona; Scully-Welsh Cancer Center, Indian River Medical Center, Vero Beach, Florida; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Dermatology, Oregon Health Sciences University, Portland, Oregon; Dermatology Service, Memorial Sloan Kettering Skin Cancer Center, Hauppage, New York; Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center, Stanford, California; Cancer Institute, Stanford, California; Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Inova Schar Cancer Institute, Department of Medicine, Virginia Commonwealth University, Fairfax, Virginia; and Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania