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Since the eighteenth century&#44; dermatologists have described the &#8220;external characteristics of individual skin lesions&#8221; in an entirely subjective way&#46; Over time&#44; they developed other methods&#44; including the use of analogous measurements based on the comparison of lesion size or shape with objects such as pins&#44; peas&#44; beans&#44; nuts&#44; lentils&#44; and coins&#46; The difficulties faced by dermatologists are also reflected in the morphometric devices they have developed&#46; These include the transparent grids used to measure the extent of the affected area and the length or shape of the lesion and&#44; more recently&#44; instruments designed to quantify no less important subjective or complex information&#44; such as quality of life&#44; activity&#44; severity&#44; burden of disease&#44; and clinical course&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Why Do We Need to Know More About the Clinical Course of Nonsegmental Vitiligo&#63;</span><p id="par0010" class="elsevierStylePara elsevierViewall">It is not unusual to see statements in the literature to the effect that the clinical course of nonsegmental vitiligo &#40;NSV&#41; &#8220;is unpredictable&#8221;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> and&#44; while this is true&#44; the reason for this unpredictability is that&#44; to date&#44; we have not acquired or generated the knowledge we need to define the clinical course of the condition&#46; Greater knowledge about the clinical course of NSV will facilitate more accurate prediction of prognosis&#44; which will be very useful for patients families&#44; and physicians as well as for the health services&#46; This better understanding will&#44; in turn&#44; serve to generate more knowledge&#44; leading in time to further improvement in prognosis and treatment&#46; This is a process that has already been shown to be successful in oncology&#44; the field that pioneered prognostic studies&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Knowledge is needed to answer many questions&#58; the possible role of NSV as an indicator of other conditions &#40;for example&#44; thyroid disease&#41;&#44; whether such conditions can be prevented or their course modified by treating vitiligo&#44; and whether the associated morbidity influences the course of NSV&#46; These and many other questions need to be answered if we are to gain a better understanding of the course of this disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">How To Define the Clinical Course of a Disease&#63;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Prognostic studies can be divided into three phases depending on the knowledge currently available about the factors that determine the course of the disease under study&#46; When very little information is available&#44; as in the case of NSV today&#44; the optimum design is a cohort study&#46; In the second phase&#44; when the factors influencing the course of the disease have been identified&#44; cohort studies are undertaken to determine the weight of each one of the independent variables&#46; In the third phase&#44; when the results of the multivariate analyses carried out in the phase 2 studies are available&#44; researchers can test methods for developing prediction instruments or algorithms&#46; Each of these 3 stages has a different purpose&#58; exploration&#44; confirmation&#44; and the development of understanding&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Descriptive prognostic studies &#40;phase 1&#41; allow us to generate hypotheses about the factors that may influence a good or a bad prognosis&#44; to identify patients with a high probability of a bad prognosis&#44; and to provide the data needed to make more objective clinical decisions&#46; Analytical studies &#40;phases 2 and 3&#41; serve to ascertain the weight of each prognostic factor and to compare the effects of each factor and each treatment on the course of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A special methodology called survival analysis has been developed for prognostic studies&#58; it is important because the outcome is a composite endpoint &#40;time-to-event&#41;&#46; This analysis is accompanied by a graphic representation of how the probability of the outcome decreases over time&#46; These survival curves&#44; calculated using the Kaplan-Meier method&#44; are a descriptive tool used to summarize the history of a series of patients in terms of the risk of an endpoint occurring&#46; While&#44; in oncology the endpoint is the probability of survival&#44; in the case of NSV it could be the probability of achieving disease stability&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Another question that can be investigated using the cohort study design is the incidence of comorbidities&#44; such as alopecia areata and other associated diseases&#46; Survival studies can also be used to determine how the clinical course of the disease is affected by these comorbidities or by other factors&#44; such as smoking&#44; stressful life events&#44; etc&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">What Resources Do We Need to Carry Out Prognostic Studies in Patients With NSV&#63;</span><p id="par0040" class="elsevierStylePara elsevierViewall">It should be borne in mind that this type of study is relatively costly in terms of time&#44; money&#44; and effort&#46; While&#44; the investment is&#44; of course&#44; fully justified by the results obtained&#44; it is essential&#44; before starting&#44; to ensure that adequate measurements can be made&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The first task is to decide what endpoint should be measured and determine the most objective method of measurement&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The authors of a 2010 systematic review on the treatment of vitiligo commented that the endpoint most frequently measured was repigmentation &#40;96&#37;&#41;&#44; using 48 different scales&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> They concluded that no consensus had been reached on the methods used to measure the results of interventions in patients with vitiligo&#46; This led to the publication of guidelines for clinical trials in vitiligo&#46; These recommend measuring quality of life&#44; percentage of repigmentation&#44; cessation of spread or stabilization of disease &#40;defined by the absence of an increase in the size and&#47;or number of lesions and the persistence of the repigmentation achieved with treatment for at least 2 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The treatment guidelines establish that repigmentation alone is not an appropriate endpoint since&#44; without stabilization&#44; it is very probable that the pigmentation regained will later be lost and that&#44; overall&#44; the size and number of lesions will continue to grow&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In light of the above&#44; we believe that three outcomes should be measured&#58; progression&#44; regression &#40;repigmentation&#41;&#44; and relapse &#40;loss of regained pigmentation&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The second task is to decide which measurement method should be used&#46; The ideal method should combine the 3 principal characteristics of an adequate measurement instrument&#58; feasibility&#44; consistency&#44; and validity&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">With respect to feasibility and consistency&#44; it is important to consider the characteristic of the disease under study&#58; in a patient with vitiligo it is common to see progression in some lesions&#44; stability in others&#44; and repigmentation in others&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> a circumstance that limits the usefulness of methods based on measuring the percentage of the body surface area affected&#46; Another difficulty facing dermatologists in the follow-up of patients with vitiligo is the task of monitoring the patient&#39;s lesions over time&#44; a complicated undertaking even when imaging is used because the number of lesions can vary from 1 to countless&#46; Moreover&#44; lesion counts are likely to be inconsistent over time because of the tendency towards confluence&#46; Measuring the area of each lesion is also an imprecise method because of the variable number and irregular and confluent nature of the macules&#44; which range in size from a dot to large areas&#46; Finding a practical recording method that is easy to use is important because the course of each lesion must be documented over time&#46; Finally&#44; all of these problems are encountered in both patients with very little vitiligo and those with involvement of most of the body surface&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Eleven instruments for measuring outcomes in patients with vitiligo were identified in a systematic review published in 2012&#44; covering the period from 1948 to July 2011&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> Three of these are based on the clinician&#39;s assessment&#58; Vitiligo European Task Force assessment &#40;VETFa&#41;&#44; Vitiligo Area Scoring Index &#40;VASI&#41;&#44; and the point counting method&#46; Six are patient reported&#58; Skindex-29&#44; Skindex-16&#44; Skindex-teen&#44; Dermatology Life Quality Index &#40;DLQI&#41;&#44; Patient Benefit Index &#40;PBI&#41;&#44; and Pictorial Representation of Illness and Self Measure &#40;PRISM&#41;&#46; The clinician-reported instruments assess the extent of disease by measuring lesion size&#59; VETF also seeks to determine disease stage and spreading or progression&#46; Of the patient-reported instruments mentioned above&#44; the first 4 measure quality-of-life in patients with skin disease&#44; the PBI combines data on the patient&#39;s treatment needs and response to therapy&#44; and PRISM combines pictorial representation of the disease with the patient&#39;s perception of suffering&#46; One of the 2 computer-based tools was developed to determine the affected area by combining manual methods and software&#44; and the other uses digital images to measure repigmentation&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Of the instruments mentioned&#44; only the software-based and clinician-reported tools provide ways to measure the percentage of body surface area affected and&#47;or depigmentation by body area&#46; However&#44; because of their lack of precision&#44; these methods are not useful in prognostic studies&#46; Although the VETF was designed to assess disease stage and spread or progression&#44; it was determined in later studies that the tool is not reliable for these variables&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">13&#8211;15</span></a> None of the instruments mentioned measure relapse &#40;depigmentation of previously repigmented areas&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">An updated evaluation of the instruments available for measuring disease in patients with vitiligo is underway&#44; including tools published between 2010 and January 2017&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Which Variables Have Been Proposed as Prognostic Factors in NSV&#63; What Level of Evidence Supports These Proposals&#63;</span><p id="par0090" class="elsevierStylePara elsevierViewall">History of autoimmune disease&#44; family history of vitiligo&#44; Ko&#235;bner phenomenon&#44; age of onset&#44; mucosal involvement&#44; leucotrichia&#44; and confetti-like depigmentation have all been proposed as prognostic factors in NSV&#46; However&#44; to date there is insufficient evidence to support the hypothesis that these factors can predict the clinical course of vitiligo&#44; and if so&#44; how and in what time frame&#46; Moreover&#44; none of these studies include survival analysis and they are all subject to the problems mentioned above relating to outcome measurement&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; the phrase &#8220;the course of disease in a patient with nonsegmental vitiligo is unpredictable&#8221; only serves to underscore the need for prospective research using appropriate methodologies&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Glossary</span><p id="par0100" class="elsevierStylePara elsevierViewall">Consistency or reliability&#58; The property of producing similar&#44; error-free results on repeated measurements provided the conditions under which the scale is applied and the outcome measured do not change&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Validity&#58; The capacity of a tool to measure what it was designed to measure&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Viability or feasibility&#58; The degree to which an instrument is acceptable to the user&#44; expressed as the level of difficulty in answering the questionnaire or applying the tool&#44; the time required&#44; the resources used&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Interpretability&#58; is the degree to which the results produced by the instrument provide real insight into the health outcome being measured&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Peralta-Pedrero M&#44; Jurado Santa-Cruz F&#46; Experiencia de un investigador y un dermat&#243;logo sobre el conocimiento del curso cl&#237;nico del vitiligo no segmentario&#46; Actas Dermosifiliogr&#46; 2018&#59;109&#58;767&#8211;770&#46;</p>"
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Opinion Article
What We Know About the Clinical Course of Nonsegmental Vitiligo: Experience of a Researcher and a Dermatologist
Experiencia de un investigador y un dermatólogo sobre el conocimiento del curso clínico del vitiligo no segmentario
M.L. Peralta-Pedrero
Autor para correspondencia
luisa.peraltap@gmail.com

Corresponding author.
, F. Jurado Santa-Cruz
Centro Dermatológico Dr. Ladislao de la Pascua, Ciudad de México, Mexico
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">One of the defining characteristics of dermatology is the fact that the clinical manifestations of skin diseases&#8212;while difficult to measure&#8212;are nonetheless visible and&#44; therefore&#44; observable&#46; This has led to the development of numerous clinimetric instruments that allow us to assess many aspects of the disease process&#44; such as its impact on the patient&#39;s quality of life&#44; the response to treatment&#44; or the value of a diagnostic test&#46; However&#44; many skin diseases are chronic disorders with a multifactorial&#44; autoimmune&#44; or even an unknown etiology&#46; This poses a challenge for the dermatologist and gives rise to considerable interindividual variation in the description of diseases&#44; their manifestations&#44; and the response to therapy&#46; V&#225;zquez-L&#243;pez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> have clearly and concisely summarized the efforts made throughout the history of our specialty to refine the methods used to measure skin disease&#46; Since the eighteenth century&#44; dermatologists have described the &#8220;external characteristics of individual skin lesions&#8221; in an entirely subjective way&#46; Over time&#44; they developed other methods&#44; including the use of analogous measurements based on the comparison of lesion size or shape with objects such as pins&#44; peas&#44; beans&#44; nuts&#44; lentils&#44; and coins&#46; The difficulties faced by dermatologists are also reflected in the morphometric devices they have developed&#46; These include the transparent grids used to measure the extent of the affected area and the length or shape of the lesion and&#44; more recently&#44; instruments designed to quantify no less important subjective or complex information&#44; such as quality of life&#44; activity&#44; severity&#44; burden of disease&#44; and clinical course&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Why Do We Need to Know More About the Clinical Course of Nonsegmental Vitiligo&#63;</span><p id="par0010" class="elsevierStylePara elsevierViewall">It is not unusual to see statements in the literature to the effect that the clinical course of nonsegmental vitiligo &#40;NSV&#41; &#8220;is unpredictable&#8221;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> and&#44; while this is true&#44; the reason for this unpredictability is that&#44; to date&#44; we have not acquired or generated the knowledge we need to define the clinical course of the condition&#46; Greater knowledge about the clinical course of NSV will facilitate more accurate prediction of prognosis&#44; which will be very useful for patients families&#44; and physicians as well as for the health services&#46; This better understanding will&#44; in turn&#44; serve to generate more knowledge&#44; leading in time to further improvement in prognosis and treatment&#46; This is a process that has already been shown to be successful in oncology&#44; the field that pioneered prognostic studies&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Knowledge is needed to answer many questions&#58; the possible role of NSV as an indicator of other conditions &#40;for example&#44; thyroid disease&#41;&#44; whether such conditions can be prevented or their course modified by treating vitiligo&#44; and whether the associated morbidity influences the course of NSV&#46; These and many other questions need to be answered if we are to gain a better understanding of the course of this disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">How To Define the Clinical Course of a Disease&#63;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Prognostic studies can be divided into three phases depending on the knowledge currently available about the factors that determine the course of the disease under study&#46; When very little information is available&#44; as in the case of NSV today&#44; the optimum design is a cohort study&#46; In the second phase&#44; when the factors influencing the course of the disease have been identified&#44; cohort studies are undertaken to determine the weight of each one of the independent variables&#46; In the third phase&#44; when the results of the multivariate analyses carried out in the phase 2 studies are available&#44; researchers can test methods for developing prediction instruments or algorithms&#46; Each of these 3 stages has a different purpose&#58; exploration&#44; confirmation&#44; and the development of understanding&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Descriptive prognostic studies &#40;phase 1&#41; allow us to generate hypotheses about the factors that may influence a good or a bad prognosis&#44; to identify patients with a high probability of a bad prognosis&#44; and to provide the data needed to make more objective clinical decisions&#46; Analytical studies &#40;phases 2 and 3&#41; serve to ascertain the weight of each prognostic factor and to compare the effects of each factor and each treatment on the course of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A special methodology called survival analysis has been developed for prognostic studies&#58; it is important because the outcome is a composite endpoint &#40;time-to-event&#41;&#46; This analysis is accompanied by a graphic representation of how the probability of the outcome decreases over time&#46; These survival curves&#44; calculated using the Kaplan-Meier method&#44; are a descriptive tool used to summarize the history of a series of patients in terms of the risk of an endpoint occurring&#46; While&#44; in oncology the endpoint is the probability of survival&#44; in the case of NSV it could be the probability of achieving disease stability&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Another question that can be investigated using the cohort study design is the incidence of comorbidities&#44; such as alopecia areata and other associated diseases&#46; Survival studies can also be used to determine how the clinical course of the disease is affected by these comorbidities or by other factors&#44; such as smoking&#44; stressful life events&#44; etc&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">What Resources Do We Need to Carry Out Prognostic Studies in Patients With NSV&#63;</span><p id="par0040" class="elsevierStylePara elsevierViewall">It should be borne in mind that this type of study is relatively costly in terms of time&#44; money&#44; and effort&#46; While&#44; the investment is&#44; of course&#44; fully justified by the results obtained&#44; it is essential&#44; before starting&#44; to ensure that adequate measurements can be made&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The first task is to decide what endpoint should be measured and determine the most objective method of measurement&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The authors of a 2010 systematic review on the treatment of vitiligo commented that the endpoint most frequently measured was repigmentation &#40;96&#37;&#41;&#44; using 48 different scales&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> They concluded that no consensus had been reached on the methods used to measure the results of interventions in patients with vitiligo&#46; This led to the publication of guidelines for clinical trials in vitiligo&#46; These recommend measuring quality of life&#44; percentage of repigmentation&#44; cessation of spread or stabilization of disease &#40;defined by the absence of an increase in the size and&#47;or number of lesions and the persistence of the repigmentation achieved with treatment for at least 2 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The treatment guidelines establish that repigmentation alone is not an appropriate endpoint since&#44; without stabilization&#44; it is very probable that the pigmentation regained will later be lost and that&#44; overall&#44; the size and number of lesions will continue to grow&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In light of the above&#44; we believe that three outcomes should be measured&#58; progression&#44; regression &#40;repigmentation&#41;&#44; and relapse &#40;loss of regained pigmentation&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The second task is to decide which measurement method should be used&#46; The ideal method should combine the 3 principal characteristics of an adequate measurement instrument&#58; feasibility&#44; consistency&#44; and validity&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">With respect to feasibility and consistency&#44; it is important to consider the characteristic of the disease under study&#58; in a patient with vitiligo it is common to see progression in some lesions&#44; stability in others&#44; and repigmentation in others&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> a circumstance that limits the usefulness of methods based on measuring the percentage of the body surface area affected&#46; Another difficulty facing dermatologists in the follow-up of patients with vitiligo is the task of monitoring the patient&#39;s lesions over time&#44; a complicated undertaking even when imaging is used because the number of lesions can vary from 1 to countless&#46; Moreover&#44; lesion counts are likely to be inconsistent over time because of the tendency towards confluence&#46; Measuring the area of each lesion is also an imprecise method because of the variable number and irregular and confluent nature of the macules&#44; which range in size from a dot to large areas&#46; Finding a practical recording method that is easy to use is important because the course of each lesion must be documented over time&#46; Finally&#44; all of these problems are encountered in both patients with very little vitiligo and those with involvement of most of the body surface&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Eleven instruments for measuring outcomes in patients with vitiligo were identified in a systematic review published in 2012&#44; covering the period from 1948 to July 2011&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> Three of these are based on the clinician&#39;s assessment&#58; Vitiligo European Task Force assessment &#40;VETFa&#41;&#44; Vitiligo Area Scoring Index &#40;VASI&#41;&#44; and the point counting method&#46; Six are patient reported&#58; Skindex-29&#44; Skindex-16&#44; Skindex-teen&#44; Dermatology Life Quality Index &#40;DLQI&#41;&#44; Patient Benefit Index &#40;PBI&#41;&#44; and Pictorial Representation of Illness and Self Measure &#40;PRISM&#41;&#46; The clinician-reported instruments assess the extent of disease by measuring lesion size&#59; VETF also seeks to determine disease stage and spreading or progression&#46; Of the patient-reported instruments mentioned above&#44; the first 4 measure quality-of-life in patients with skin disease&#44; the PBI combines data on the patient&#39;s treatment needs and response to therapy&#44; and PRISM combines pictorial representation of the disease with the patient&#39;s perception of suffering&#46; One of the 2 computer-based tools was developed to determine the affected area by combining manual methods and software&#44; and the other uses digital images to measure repigmentation&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Of the instruments mentioned&#44; only the software-based and clinician-reported tools provide ways to measure the percentage of body surface area affected and&#47;or depigmentation by body area&#46; However&#44; because of their lack of precision&#44; these methods are not useful in prognostic studies&#46; Although the VETF was designed to assess disease stage and spread or progression&#44; it was determined in later studies that the tool is not reliable for these variables&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">13&#8211;15</span></a> None of the instruments mentioned measure relapse &#40;depigmentation of previously repigmented areas&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">An updated evaluation of the instruments available for measuring disease in patients with vitiligo is underway&#44; including tools published between 2010 and January 2017&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Which Variables Have Been Proposed as Prognostic Factors in NSV&#63; What Level of Evidence Supports These Proposals&#63;</span><p id="par0090" class="elsevierStylePara elsevierViewall">History of autoimmune disease&#44; family history of vitiligo&#44; Ko&#235;bner phenomenon&#44; age of onset&#44; mucosal involvement&#44; leucotrichia&#44; and confetti-like depigmentation have all been proposed as prognostic factors in NSV&#46; However&#44; to date there is insufficient evidence to support the hypothesis that these factors can predict the clinical course of vitiligo&#44; and if so&#44; how and in what time frame&#46; Moreover&#44; none of these studies include survival analysis and they are all subject to the problems mentioned above relating to outcome measurement&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; the phrase &#8220;the course of disease in a patient with nonsegmental vitiligo is unpredictable&#8221; only serves to underscore the need for prospective research using appropriate methodologies&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Glossary</span><p id="par0100" class="elsevierStylePara elsevierViewall">Consistency or reliability&#58; The property of producing similar&#44; error-free results on repeated measurements provided the conditions under which the scale is applied and the outcome measured do not change&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Validity&#58; The capacity of a tool to measure what it was designed to measure&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Viability or feasibility&#58; The degree to which an instrument is acceptable to the user&#44; expressed as the level of difficulty in answering the questionnaire or applying the tool&#44; the time required&#44; the resources used&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Interpretability&#58; is the degree to which the results produced by the instrument provide real insight into the health outcome being measured&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p></span></span>"
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