Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2023;13(3):e2023186 1 Comparative Analysis of the Most Used Versus the Recently Developed Vitiligo Activity and Extent Scores and Their Change with Treatment Randa Youssef1, Nourhan Emad1, Rania M Mogawer1 1 Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Key words: VES plus, VASI, VIDA, VSAS, vitiligo assessment Citation: Youssef R, Emad N, Mogawer RM. Comparative Analysis of the Most Used Versus the Recently Developed Vitiligo Activity and Extent Scores and Their Change With Treatment. Dermatol Pract Concept. 2023;13(3):e2023186. DOI: https://doi.org/10.5826 /dpc.1303a186 Accepted: February 6, 2023; Published: July 2023 Copyright: ©2023 Youssef et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Rania M Mogawer, Lecturer of Dermatology, Faculty of Medicine, Cairo University, 15 D4, Maadi Grand City, Cairo, Egypt. Telephone: +201068165330 Postal code: 11427 Orchid ID: https://orcid.org/0000-0002-9929-5413 Email: Raniamogawer@kasralainy.edu.eg Introduction: There are diverse assessment tools for vitiligo, with no standardized approach that helps unify treatment outcome measures. Thus, comparing different treatment modalities and develop- ing evidence-based recommendations for vitiligo management has been quite challenging. Objectives: We compared the most commonly used tools assessing both vitiligo activity and extent, namely, Vitiligo Disease Activity Score (VIDA) and Vitiligo Area and Severity Index (VASI) score to their newly developed counterparts, namely, Vitiligo Extent Score Plus (VES plus) and Vitiligo Signs of Activity score (VSAS), to provide insights that would help set recommendations for a unified outcome assessment protocol for vitiligo patients. Methods: Thirty-six active non-segmental vitiligo cases were recruited, 30 of whom completed 48 ses- sions of narrow band ultraviolet B (NB-UVB). Patients were assessed for both extent and activity both before and after treatment with NB-UVB. Scores were correlated. Additionally, VES plus was assessed for its reliability in comparison to VASI score. Results: Both extent (VASI and VES plus) and activity scores (VIDA and VSAS) showed significant improvement following treatment. Additionally, VES plus and VASI were positively correlating both before and after treatment as well as their percent change. Furthermore, VES plus proved as reliable as VASI. Regarding activity scores, total, hypochromic and Koebner VSAS only correlated with VIDA following treatment. Confetti VSAS neither correlated with VIDA before nor after treatment. Conclusions: VES plus and VASI scores have proven of comparable reliability. While examination-based VSAS score comes as an additive tool to the history-based VIDA score. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2023;13(3):e2023186 Introduction Vitiligo is a chronic depigmenting skin disorder that can be cosmetically disfiguring with high psychological burden [1]. Treatment is quite challenging [2] with no standardized as- sessment tools for its evaluation and follow-up of treatment response as well as for comparing different treatment modal- ities. This, in turn, hinders comparison of different clinical trials and the development of evidence-based recommenda- tions [3-7]. Various tools are currently available for assessing vitiligo extent and response to treatment. Since re-pigmentation is the most important reported treatment outcome [4], limita- tion to the previously developed Vitiligo Extent Score (VES score) was disregarding pigmentation [7]. Thus, Vitiligo Ex- tent Score Plus (VES plus score) was developed that consid- ered both extent and follicular pigmentation [8]. Accordingly, VES plus score stands as an alternative tool to Vitiligo Area and Severity Index (VASI), which is the most cited and used vitiligo extent assessment tool [9,10]. Both VES plus and VASI scores consider extent as well as follicular pigmentation. However, VASI score, despite being widely used [3], is more time-consuming [9,10] since it is manually calculated [9], in comparison to VES plus score, which is calculated online [7]. Additionally, VES plus has been pointed out to detect small changes in the extent of vitiligo, which adds to its privilege [11,12]. Regarding vitiligo activity, history-based Vitiligo Disease Activity Score (VIDA) has been the most used tool [13]. It was only in 2020, when examination-based Vitiligo Signs Activity Score (VSAS) was introduced taking into account different signs of vitiligo activity [14]. Objectives The aim of this work is to provide some insights in the most recently introduced vitiligo extent score; namely, VES plus [8] in comparison to the most used one; namely, VASI score [9]. Additionally, we aimed at evaluating examination based VSAS, which is the first vitiligo assessment tool that consid- ers solely clinical signs of vitiligo activity [14] in compari- son to the most used and validated tool; VIDA score [13]. This study provides a cohort of vitiligo patients to evalu- ate change in the aforementioned extent and activity scores to allow for a deeper understanding and interpretability of change in these scores and their utility in follow up of vitiligo patients. Methods The study was conducted at the Vitiligo Clinic, Cairo Uni- versity Hospitals. Thirty-six active Non segmental vitiligo (NSV) patients aging ≥ 18 years old were recruited. A VIDA score ≥2 was set as an inclusion criterion to ensure recent vitiligo activity and monitor its change following treatment. Of the 36 patients, only 30 patients completed the study. Thorough history was taken for different vitiligo character- istics including duration and age of onset. Baseline assessments for vitiligo activity and extent as well as pigmentation were carried out. Vitiligo activity was evaluated using total VSAS, Koebner VSAS, confetti VSAS and hypochromic VSAS [14], together with the history-based VIDA score [13]. Vitiligo ex- tent and pigmentation were evaluated using both VES plus [8] and VASI scores [9]. Both VSAS and VES plus, available through online vit- iligo calculator https://www.vitiligo-calculator.com, depend upon diagrammatic representation of different body sites. In VES plus, diagrams representing different extents of vitil- igo with option of adding extent of follicular pigmentation within each site are available. Final VES plus score is de- veloped by automatically summing the extent in different affected sites after deducting extent of follicular pigmenta- tion [8]. In VSAS, the three main signs of vitiligo activity; koebnerization type IIB, confetti-like depigmentation and hypochromic/ ill-defined edges, are recorded for different body sites giving a total activity score out of 15, for all signs as total VSAS, where one or more signs of activity within one site scores 1 out of 15, and for each sign separately as Koebner, hypochromic and confetti VSAS [14]. Regarding VIDA score, it is mainly based on the duration since the date of last activity, which is essentially given by history, in the form of expansion of old lesions, koebneriza- tion or development of new lesions [13]. As for VASI, extent of vitiligo as per hand units is multiplied by extent of depig- mentation in different body sites, which are added together to get total VASI score [9]. Total body narrow band ultraviolet B (NBUVB) was chosen as a unified treatment protocol that achieves both re-pigmentation and stabilization [15]; thus, offering change in both extent and activity scores. Sessions were delivered by a UV 100 L; Waldmann GmbH cabinet with 40 narrow band UVB fluorescent tubes (Philips TL 01, 100 W, Philips company), an emission spectrum of 310-315 nm was used. Patients received 3 sessions per week on non-consecutive days for a total of 48 sessions. Following 48 sessions of NB-UVB, patients were reas- sessed for both activity using VIDA and VSAS scores and extent using VES plus and VASI scores. Statistical Methods Data were coded and entered using the statistical package for the Social Sciences (SPSS) version 28 (IBM Corp.). Data was summarized using mean, standard deviation, median, minimum, and maximum in quantitative data and using Original Article | Dermatol Pract Concept. 2023;13(3):e2023186 3 frequency (count) and relative frequency (percentage) for categorical data. For comparison of serial measurements within each patient, the non-parametric Wilcoxon signed rank test was used. Correlations between quantitative vari- ables were done using Spearman correlation coefficient. Testing for across items reliability (internal consistency) was done using the Intra Class Coefficient (ICC) and Cronbach’s alpha reliability coefficient with their 95% confidence inter- val (95%CI). P values less than 0.05 were considered as sta- tistically significant. Results Thirty-six patients were recruited, of whom 30 patients com- pleted the 48 sessions of NB-UVB. Of those who completed the NB-UVB sessions, nine were males and twenty-one were females. Patients had mean age of 29.6 ± 13.7 and an aver- age disease duration of 92.17 ± 83.08 months. The demo- graphic data of the patients are summarized in Table 1 Baseline assessment for vitiligo extent revealed a VES plus score area of 3.39 ± 3.66 and a VASI score of 4.38 ± 4.11. Regarding vitiligo activity, twenty-four patients (80%) had a VIDA score of +4 and mean VIDA score was 3.77±0.5. Re- garding VSAS score, patients had a mean total VSAS, confetti VSAS, Koebner VSAS and hypochromic VSAS of 6.63 ± 2.9, 1.47 ± 1.46, 1.67 ± 1.77 and 6.1 ± 3.03 respectively. After completing 48 sessions of NB-UVB, significant improvement was evident in both activity and extent scores (P = 0.01). Patients had a mean VES plus score of 1.86 ± 2.15 and a mean VASI score of 2.81 ± 2.58; while mean VIDA score was 2.5 ± 0.82 and mean total VSAS, Koebner VSAS, hypochromic VSAS and confetti-VSAS were 0.83 ± 1.34, 0.23 ± 0.57, 0.63 ± 1.22 and 0.13 ± 0.35 respectively. The clinical data of the patients are summarized in Table 1. On correlating both extent scores, namely, VES plus and VASI, they were strongly positively correlating both before and after NB-UVB as well as their percent change (r = 0.936, 0.97 and 0.723, respectively, P < 0.001) (Figure 1). Table 1. Clinical and Demographic Data of the Patients Who Completed the Study (N = 30). Characteristics Sex (%) Females 21 (70%) Males 9 (30%) Age (years) Mean ± SD (Range) 29.6 ± 13.7 (18–61) Age of onset (years) Mean ± SD (Range) 22 ±13.01 (6–56) Duration of disease (months) Mean ± SD (Range) 92.17 ± 83.08 (3–360) Skin phototype (%) III 14 (46.7%) IV 16 (53.3%) Associated with stress or trauma (%) 24 (80%) Family history of vitiligo (%) 10 (33.3%) Family history of autoimmune disease (%) 4 (13.30%) Clinical assessment scores Cases Before NB-UVB After NB-UVB P-value Mean ± SD (Range) Mean ± SD (Range) VIDA score 3.77±0.5 (2-4) 2.5 ± 0.82 (2–4) < 0.001 VIDA score (%) 2 1(3.33%) 20(66.66%) 3 5(16.66%) 3(10%) 4 24(80%) 6(20%) VASI score 4.38 ± 4.11(0.33–15.85) 2.81 ± 2.58 (0.17–10.62) < 0.001 VES plus score 3.39 ± 3.66 (0.33 –13.33) 1.86 ± 2.15 (0.07–9.31) < 0.001 Total VSAS score 6.63 ± 2.9 (2–14) 0.83 ± 1.34 (0–5) < 0.001 Confetti VSAS score 1.47 ± 1.46 (0–6) 0.13 ± 0.35 (0–1) < 0.001 Koebner VSAS score 1.67 ± 1.77 (0–6) 0.23 ± 0.57 (0–2) < 0.001 Hypochromic VSAS 6.1±3.03 (2-14) 0.63±1.22 (0-5) < 0.001 NB-UVB = narrow band ultraviolet B; SD = standard deviation; VIDA = Vitiligo Disease Activity Score; VES = Vitiligo Extent Score; VSAS = Vitiligo Signs of Activity score. 4 Original Article | Dermatol Pract Concept. 2023;13(3):e2023186 treatment outcome [11], comparing the different available scores would help provide insights in their application. This, in turn, will aid in the process of unifying vitiligo assess- ment, which would help give way for a better analysis of different treatment modalities as well as comparing different clinical trials, which has currently been an urging need for the development of evidence -based recommendations for vitiligo [3-7]. When assessing vitiligo, both vitiligo activity and ex- tent, together with lesional pigmentation are to be consid- ered, where both pigmentation and cessation of spread of vitiligo are main treatment outcomes, from both patients’ and physicians’ perspectives [16]. Both VES plus [8] and VASI [9] scores consider extent and follicular pigmenta- tion; thus, they stand as alternative tools, but the first is less time consuming, while the latter is most used. Regard- ing activity, VIDA [13], which is essentially history based, is the most used prior to the introduction of the VSAS [14], which is examination based. Thus, this work aimed at comparing the most recently developed vitiligo assessment tools for extent and activity in comparison to the most commonly used ones, at baseline, following treatment as well as their change with treatment. In the current study, all scores have proven to change sig- nificantly with disease regression, which in turn points out to their utility as outcome measures for vitiligo follow up and comparison of different treatment modalities. On correlating both history-based VIDA score and exam- ination based total VSAS, Koebner VSAS, hypochromic VSAS and confetti VSAS, none of the VSAS scores correlated with the VIDA score before NB-UVB treatment (r = - 0.007, -0.132, -0.106 and -0.015, respectively) (P = 0.97, 0.488, 0.576 and 0.938, respectively). Similarly, percent change in both scores did not correlate with one another (r = 0.03, -0.103, -0.005 and -0.140, respectively) (P = 0.876, 0.589, 0.98 and 0.462, respectively). After NB-UVB treatment, total, hypochromic and Koebner VSAS positively correlated with history-based VIDA score (r = 0.846, 0.873 and 0.427, respectively) (P < 0.001, < 0.001 and 0.018, respectively) (Figure 2). On the other hand, confetti VSAS did not correlate with VIDA score after NB-UVB treatment (r = 0.211, P = 0.263). For assessing reliability of VES plus score in comparison to VASI, which is the most commonly used and cited extent score, reliability score was done for all readings of VES plus in com- parison to VASI (both before and after treatment with NB-UVB) including the readings of the six patients who were dropped out making a total of 66 readings. It revealed an Intraclass Correla- tion Coefficient of 0.962 and Cronbach Alpha score of 0.981, P < 0.001 denoting high reliability of both scores (Table 2). Conclusions In the light of the challenging nature of vitiligo treatment [2], together with the diversity of the available tools for assessing Figure 1. Strong Positive correlation between Vitiligo Extent Score plus (VES plus) and Vitiligo Area and Severity Index (VASI) scores both before and after narrow band Ultraviolet B (NB-UVB) treatment as well as percent change in the scores following treatment (r = 0.936, 0.97, 0.723). Original Article | Dermatol Pract Concept. 2023;13(3):e2023186 5 previously compared to VASI score, which have simulated patient reported activity to flipping a coin, due to lack of cor- relation to physician reported VASI score [17]. Since VIDA score is essentially history based [13], patients can easily miss activity especially prior to starting treatment when he is not much concerned about change in his disease. While on treat- ment, patients are more likely to be concerned about their disease and its progression which could explain why scores correlated only after treatment but not prior to treatment. Regarding confetti VSAS, it did not correlate with VIDA neither before nor after treatment being a difficult clinical sign that patients are very likely to miss until the small mac- ules coalesce in a well-recognized lesion. This highlights the fact that an examination-based assessment tool for vitiligo activity is indispensable to accurately identify vitiligo activity status and to meticulously follow up vitiligo activity. A significant positive correlation was detected between VES plus score and VASI before and after NB-UVB as well as their percent change following treatment. Additionally, both VES plus and VASI scores were found equally reliable. Thus, VES plus score stands as an easy, less time-consuming tool, to assess vitiligo extent taking into account perifollicular pig- mentation which was one of the drawbacks of the original VES score [7,10]. Regarding activity scores, a significant positive correla- tion was detected between VIDA score and total VSAS score, Koebner VSAS and hypochromic VSAS after NB-UVB. How- ever, VIDA score did not correlate with either VSAS scores before treatment with NB-UVB or with confetti VSAS after treatment. To the best of our knowledge, no studies have yet compared VSAS to VIDA score. However, VIDA has been Figure 2. Positive correlation between Vitiligo Disease Activity Score (VIDA) and total, Koebner and hypochromic Vitiligo Signs Activity Score (VSAS) after narrow band Ultraviolet B (NB-UVB) treatment (r = 0.846, 0.427 and 0.873 respectively) (P < 0.001, 0.018 and < 0.001, respectively). Table 2. Reliability of Vitiligo Extent Score Plus score in Comparison to Vitiligo Area and Severity Index score (N = 66). Value 95% Confidence Interval Lower Bound Upper Bound P value Intraclass Correlation Coefficient 0.962 0.939 0.977 <0.001 Cronbach alpha 0.981 0.968 0.988 <0.001 6 Original Article | Dermatol Pract Concept. 2023;13(3):e2023186 6. Wolkerstorfer A. The long road to valid outcomes in vitiligo.  Br J Dermatol. 2019;180(3):454-455. DOI:10.1111/bjd.17409. PMID: 30821367. PMCID: PMC6850450. 7. van Geel N, Lommerts J, Bekkenk M, et al. Development and Val- idation of the Vitiligo Extent Score (VES): an International Col- laborative Initiative.  J Invest Dermatol. 2016;136(5):978-984. DOI: 10.1016/j.jid.2015.12.040. PMID: 26827762. 8. van Geel N, Wolkerstorfer A, Lommerts JE, et al. Validation study of the Vitiligo Extent Score-plus.  J Am Acad Dermatol. 2018;78(5):1013-1015. DOI: 10.1016/j.jaad.2017.11.032. PMID: 29180094. 9. Hamzavi I, Jain H, McLean D, et al. Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quan- titative tool: the Vitiligo Area Scoring Index. 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DOI:10.1001/archderm.135.4.407. PMID: 10206047. 14. van Geel N, Passeron T, Wolkerstorfer A, Speeckaert R, Ezzedine K. Reliability and validity of the Vitiligo Signs of Activity Score (VSAS). Br J Dermatol. 2020;183(5):883-890. DOI: 10.1111 /bjd.18950. PMID: 32064583. PMCID: PMC7687072. 15. Esmat SM, El-Mofty M, Rasheed H, et al. Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, random- ized, placebo-controlled, prospective, multicenter study.  Pho- todermatol Photoimmunol Photomed. 2022;38(3):277-287. DOI:10.1111/phpp.12749. PMID: 34726808. 16. van Geel N, Desmedt V, De Schepper S, Boone B, Lapeere H, Speeckaert R. Cessation of spread as a treatment objective in vitiligo: perception from the patients’ point of view. Br J Der- matol. 2016;174(4):922-924. DOI:10.1111/bjd.14283. PMID: 26556484. 17. Coias J, Hynan LS, Pandya AG. Lack of correlation of the patient-derived Vitiligo Disease Activity Index with the clinician-derived Vitiligo Area Scoring Index. J Am Acad Derma- tol. 2018;78(5):1015-1016. DOI: 10.1016/j.jaad.2017.11.034. PMID: 29180097. 18. van Geel N, Depaepe L, Vandaele V, et al. Assessing the dy- namic changes in vitiligo: reliability and validity of the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improve- ment Score (VDIS). J Eur Acad Dermatol Venereol. 2022;36(8): 1334-1341. DOI :10.1111/jdv.18134. PMID: 35398942; PMCID: PMC9543188. In the context of vitiligo follow up and assessment of its dynamic change in terms of both pigmentation and activ- ity, it is noteworthy to mention that Vitiligo Disease Activ- ity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS) have been recently introduced. Vitiligo Sings of Ac- tivity Score is suggested for a single point static assessment, while VDAS and VDIS scores for dynamic assessments on follow ups, where the same 15 body sites assessed in VSAS are reassessed for improvement (repigmentation) or wors- ening (activity) and scored accordingly [18]. However, this score is not readily available for implementation, but worth assessment and comparison to utilizing separate scores for assessing vitiligo extent and activity in the follow up. Limitations to this study include failure to compare the newly developed semi-subjective scores; VES plus and VSAS to objective ones, which are essentially lacking for vitiligo activity. Additionally, our study has been conducted in a sin- gle tertiary center and all patients were either skin phototype III or IV. Thus, further studies involving larger cohorts as well as both active and stable vitiligo patients and different skin photo-types would help ascertain our findings. 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