Skip to main content

Vitiligo Scientific Study

Quality of life of adult vitiligo patients using camouflage: A survey in a Chinese vitiligo community




Vitiligo is an acquired depigmented skin disease resulting in white macules, which may significantly impair the quality of life (QoL) of the patients.



To estimate the QoL in Chinese vitiligo patients using camouflage with a more detailed description, and to identify the possible risk factors related to poor QoL.



An online survey was conducted in vitiligo patients using camouflage from a vitiligo community. Survey questions included demographic, clinical information, dermatology- and vitiligo-specific QoL questionnaires. Multivariate logistic analysis was performed to identify risk factors that related to poor QoL.



In total, 884 respondents were included in the analyses, of which 413 (46.7%) were male. The score of DLQI was 5.83±5.75 (mean± SD). Age, gender, marriage status, occupational status, anogenital involvement, patient-perceived severity (presented by VAS score), symptoms as itching, pain, sunburn and koebner phenomenon, total cost of treatment and degree of satisfaction in camouflage therapy were independently associated with DLQI score (p<0.05).



Vitiligo has considerable impact on QoL of affected patients in Chinese population even when they were using camouflage. Camouflage might be helpful to improve QoL of the patients.


Vitiligo is an acquired chronic depigmenting disorder of the skin, predominantly asymptomatic, manifested by circumscribed depigmented macules and patches due to the disappearance of melanocytes from the epidermis. Vitiligo was recognized in ancient times and is still confused with leprosy in some countries[1]. Numerous studies have revealed that vitiligo has a major effect on the patients’ quality of life (QoL) and negatively affects sexual relations[2].

Cosmetic camouflage is an alternative and complementary option to the traditional standard treatment options, since the effectiveness of the latter are often disappointing with only partial results, and the treatment may last for months or years, before re-pigmentation occur. Preliminary studies have reported that camouflage for patients with vitiligo could improve their quality of life[3,4]. However, all these studies were conducted in small populations, therefore this effect remains to be observed in a larger population. Furthermore, the effect of camouflage on QoL can be significantly influenced by social-psychological factors but has not been studied in Chinese population.

We conducted this study to determine the dermatology-specific QoL in a group of adult vitiligo patients using camouflage in a large Chinese vitiligo community, especially to identify the possible risk factors for poor QoL. We also used a vitiligo-specific QoL questionnaire to illustrate the vitiligo-specific QoL aspects that haven’t been covered by DLQI.



An online survey was conducted from September to December 2016 to assess QoL of adult vitiligo patients using camouflage, and to identify risk factors that related to poor QoL.



An online questionnaire was formulated and sent to 8602 consecutive adult patients (age ≥18 years) with vitiligo, in WeChat groups and QQ groups of a vitiligo community, “Leukoplakia Common Home”. Before taking the survey, participants had to sign the online consent form first. Patients who had been using camouflage for more than 1 month were invited. Patients who were younger than 18 years, and who had not been diagnosed by dermatologists were excluded from the study. Information that could identify individual participants was not collected.

The study protocol was approved by the ethics committee of Beijing Tsinghua Changgung Hospital.




Demographic and clinical Information.

Demographic and clinical information was collected including gender, age, residential location, marital status, fertility status, educational level, employment status, income, duration of the disease, localizations of vitiligo (e.g. face, neck, scalp, upper arms, forearms, hands, thighs, legs, feet, chest, upper back, waist, axillae, groins, anogenital area), percentage of body surface area (BSA) affected, symptoms, duration of camouflage therapy, degree of satisfaction in camouflage therapy, other previous treatment, and total cost of treatment, as well as visual analogue scale (VAS) to assess the patient-perceived severity.


Quality of life.

  We used a dermatology-specific QoL questionnaire, Dermatology Life Quality Index (DLQI) and a vitiligo-specific QoL questionnaire, Vitiligo Impact Scale-22 (VIS-22), to assess the impact of vitiligo. The DLQI contains 10 questions related to patients’ symptoms and feelings, daily activities, leisure, work or school, personal relationships, and treatment over the previous 1 week, and each question has four possible answers scored from 0 to 3. The VIS-22 comprises 22 items covering domains of self-confidence, anxiety, depression, marriage, family worries, social interactions, school/college-related, occupation-related, treatment-related and attitude. Each question has four possible answers scored from 0 to 3. The QoL impairment could be classified into 5 levels according to the total score of DLQI. A DLQI score of 0–1 means no effect at all, 2–5 means a small effect, 6–10 moderate effect, 11–20 large effect, and 21–30 extremely large effect on patient’s life.


Statistical analysis

The data was carefully checked for consistency and plausibility to guarantee the quality of data. Normally distributed data were expressed as means±SD, whereas variables with a skewed distribution were reported as median (range). Categorical variables were represented by frequency and percentage. Univariate associations were calculated using Mann-Whitney U test or Kruskal-Wallis test with Bonferroni correction. The outcome variables were the sum score of DLQI. Independent variables were the sociodemographic and clinical characteristics. The independent variables that were univariately associated with the outcome variables (P <0.10) were entered into a stepwise multivariate logistic regression models with dichotomized DLQI (6–30 vs. 0–5) as dependent variable. A value of P < 0.05 was considered significant. All calculations were performed with the statistical package Stata 12.0 (Stata Corp., College Station, Tex.).



One thousand nine hundred and twenty four patients had shown a willingness to participate in this study. Of whom 1198 completed the questionnaires. However, 314 were excluded after plausibility checking (Fig 1). Therefore, 884 respondents were included in the final analyses.

Fig 1. Flow diagram of patient enrollment, exclusion, data quality control and data analysis.

(Online completion ensured that there were no missing data in completed questionnaires).

Demographic and clinical characteristics of respondents

The median age of these 884 respondents was 36 years (range 18–83); 413 (46.7%) were male. The visible body areas, such as face, scalp, neck, hands, were affected in most of the patients (n = 829, 93.8%). All but one patient had received previous treatment. The median duration of camouflage therapy was 50 months (range 1–216). The demographic and clinical characteristics were presented in Table 1.

Table 1. Demographic and clinical characteristics of the study group.

Quality of life


The DLQI score (mean± SD) was 5.83±5.75 (range 0–30), and 228 (25.8%) patients reported DLQI scores between 0–1, which mean no effect at all; 294 (33.3%) reported small effects; 198 (22.4%), moderate effects; 164 (18.5%), large to extremely large effects. The mean± SD score for the six domains of DLQI were 1.47±1.52 for daily activities, 1.47±1.53 for leisure, 1.25±1.14 for symptoms and feelings, 0.63±1.22 for personal relationship, 0.51±0.88 for work and school, and 0.49±0.79 for treatment. The frequency of the answers to each item of the DLQI and VIS-22 were shown in Fig 2.



Impact of QoL of vitiligo and the assessment tools

Vitiligo is often perceived as a cosmetic disease, whereas it has a profound and permanent impact on patients’ quality of life (QoL). Numerous studies had revealed the association of stigmatization, distress, depression, anxiety, low self-esteem, social isolation and impact on sexual life with vitiligo[5,6]. DLQI is one of the most widely used dermatology-specific QoL instruments in vitiligo, and the DLQI scores reported by previous studies showed obvious geographical differences, with the highest mean DLQI score of 15.00 reported in a Turkish study[7], followed by two Arab studies (mean score 11.86) [8,9], and ten Indian studies (mean score 9.51)[1016], while the lowest score was 1.82 in one Italian study[17,18]. Therefore, QoL of vitiligo patients is considerably variable according to different skin phototypes and cultures. However, few studies have reported the impact of vitiligo on Chinese patients’ QoL. Although preliminary studies have shown that camouflage can help improving QoL of the patients[3,4], this have never been studied in Chinese patients.

This is the first study to evaluate the impact of vitiligo on Chinese patients who had been using camouflage. To obtain a more comprehensive profile of QoL, we conducted the study in a large vitiligo community using both dermatology-specific and vitiligo-specific QoL instruments.

Since disease-specific instruments could be more sensitive to disease-specific issues, there were four vitiligo-specific Qol instruments had been developed in recent years, including Vitiligo-specific Quality-of-Life instrument (VitiQoL) in the U.S.[19], Vitiligo Impact Patient Scale (VIPs) in France[20], Vitiligo Life Quality Index (VLQI) in Turkey[7], and Vitiligo Impact Scale-22 (VIS-22) in India[13]; and since China and India shared many similarities in culture and belief, we chose the VIS-22 to estimate the vitiligo-specific Qol in our participants. Compared with DLQI, VIS-22 covered the attitude and anxiety about the disease, as well as family worries. Nevertheless, VIS-22 did not have any questions concerned about the symptoms and sexual life.

Impairment of QoL found in Chinese vitiligo patients

Eight hundred and eighty four vitiligo patients who had been using camouflage for more than 1 month were available for final analyses. The mean total score of DLQI was 5.83. There were more than one third of the vitiligo patients experiencing a significant impairment of QoL, as 40.9% of the patients reported a moderate to extremely large QoL impairment assessed with DLQI (score 6–30).

The highest DLQI score was found in ‘daily activities’, followed by ‘leisure’ and ‘symptoms and feelings’. The high scores of VIS-22 added more detailed information of QoL in domains of attitude and anxiety about the disease, such as ‘disease incurable’, ‘worried about new lesions’, ‘the worst disease’, and ‘keep thinking about this disease’; and treatment-related burdens, such as ‘difficulties in adhering to treatment’, ‘the amount of money spent on treatment’; then ‘problems in getting married’ and the feelings of ‘embarrassment’ and ‘helpless’, while there were only small impacts on work/school life or personal relationship.

Risk factors related to QoL

The impact of vitiligo on QoL varies in patients with different clinical and demographic characteristics. In the majority of previous studies, women showed more QoL impairment than men did[18], as did young patients compared to elderly ones[10], married women with vitiligo than singles[21], and patients with involvement on exposed sites than those on unexposed sites[18,2224]. Our results showed that female patients, patients aged less than 30 y/o, patients who were single and without a committed relationship (compared with who were married), patients who were working or seeking work (compared with who retired), patients with anogenital involvement, patients who experienced pruritus or pain, with symptoms as sunburn or koebner phenomenon, and patients who had spent more than 10,000RMB (vs. <10,000 RMB) on treatment had more impaired QoL. Intriguingly, the presence of vitiligo on visible sites, such as face, neck, scalp was not associated with a poor dermatology-specific QoL, which was inconsistent with the previous studies. Several studies showed that patients had higher scores of QoL when having lesions on visible sites[22,23,25,26]. Nevertheless, there were also several studies did not find any relationship between DLQI score and visibility of lesions[6,10,27]. In our study, since most of participants had visible sites involvement (n = 829, 93.8%), the sample size of those without visible sites involvement may be too small (n = 55, 6.2%) to reach statistical significance. Meanwhile, all of our participants had been using camouflage for more than 1 month. QoL has been shown to be improved in vitiligo patients who had lesions on visible sites after use of camouflage[3,4]. Therefore, we supposed that the effectiveness of hiding the visible vitiligo lesions might have abrogated the impact on the patient’s QoL.

We found that the patients with lesions on hands had poor QoL (p = 0.052). These might be explained by the fact that acral lesions of vitiligo were usually resistant to conventional treatment[2830] as well as surgical interventions[31], and the effect of camouflage on these visible sites could not sustain for long because of frequent hand-washing.

Camouflage use and QoL in vitiligo patients

Our result showed a less QoL impairment than that reported by Wang et al.[22], who reported a mean total DLQI score of 8.40 in 101 Chinses vitiligo patients. This may be due to the difference between the target populations of these two studies, as we recruited the patients who had been using camouflage for at least one month, from the community, while in the previous study, dermatology clinic outpatients were enrolled.

There were 67 patients who finished the questionnaire were excluded from our primary analysis, as they used camouflage for less than one month. The mean DLQI score of them was higher than those who had been using camouflage for at least one month (7.22±6.83vs. 5.83±5.75), although the differences between the two groups did not reach statistically significance. One possible reason for the difference might be that continuous camouflage application improved the QoL of vitiligo patients who had lesions on visible sites[3,4]. As another evidence, in our multivariate analysis, the degree of satisfaction after camouflage therapy was positively correlated with QoL of the patients.

Several limitations in our study should be addressed. Firstly, it was an online survey, thus the clinical characteristics such as type of vitiligo, disease activity, and vitiligo extent were unable to be assessed clinically. Secondly, there might be some non-serious respondents participated in the survey, and therefore would increase noise and reduce experimental power of the study[32]. For this reason, we performed a consistency and plausibility check to make sure most of the low-quality data sets submitted by non-serious respondents were excluded from the final analysis[32,33]. Thirdly, although China and India shared many similarities in culture and belief, we found that some items in VIS-22 may not be suitable for our patients, further modification and validation is needed. Furthermore, family history was not assessed and should be considered in future studies.

Despite these limitations, our study demonstrated that vitiligo has a considerable impact on the QoL of affected patients in Chinese population even when they had been using camouflage for at least one month, and camouflage might be helpful to improve QoL of the patients.


Mental Health and Psychosocial Quality-of-Life Burden Among Patients With Vitiligo Findings From the Global VALIANT Study

Kristen Bibeau, PhD, MSPH; Khaled Ezzedine,MD, PhD; John E. Harris, MD, PhD; Nanja van Geel, MD, PhD;
Pearl Grimes, MD; Davinder Parsad, MD; Mukta Tulpule, MBBS; Jackie Gardner, BA; Yan Valle, MSc, MBA;
Gaone Tlhong Matewa, BBA; Christine LaFiura, BA; Anouk Lindley, MBA; Haobo Ren, PhD; Iltefat H. Hamzavi, MD

IMPORTANCE Patients with vitiligo often have impaired quality of life (QOL) and experience
substantial psychosocial burden.
OBJECTIVE To explore the global association of vitiligo with QOL and mental health from the
patient perspective.
DESIGN, SETTING, AND PARTICIPANTS This qualitative study of the cross-sectional
population-based Vitiligo and Life Impact Among International Communities (VALIANT)
study was conducted from May 6, 2021, to June 21, 2021. Potential participants for this
qualitative study were recruited from an online panel in 17 countries. Of 5859 surveyed adults
(aged18 years) who reported a vitiligo diagnosis, 3919 (66.9%) completed the survey, and
3541 (60.4%) were included in the analysis.
EXPOSURES Patients were asked questions regarding their emotional well-being, including
QOL and mental health.
MAIN OUTCOMES AND MEASURES Reported analyses are descriptive and hypothesis
generating. Vitiligo Impact Patient scale (VIPs) scores ranged from 0 to 60, with higher scores
indicating more psychosocial burden.
RESULTS The median age of the 3541 patients was 38 years (range, 18-95 years), and 1933
(54.6%) were male; 1602 patients (45.2%) had more than 5%affected body surface area
(BSA; Self-Assessment Vitiligo Extent Score assessed), and 1445 patients (40.8%) had
Fitzpatrick skin types IV to VI (ie, darker skin). The mean (SD) global short-form VIPs score
was 27.3 (15.6) overall; patients from India (mean [SD], 40.2 [14.1]) reported the highest
scores (ie, most burden). The QOL burden according to the scale was profound for patients
with more than 5%affected BSA (mean [SD] score, 32.6 [14.2]), darker skin (mean [SD] score,
31.2 [15.6]), and lesions on the face (mean [SD] score, 30.0 [14.9]) or hands (mean [SD], 29.2
[15.2]). At least 40% of patients globally reported that vitiligo frequently affected aspects of
their daily lives, including choosing clothes to wear (1956 of 3541 [55.2%]). Most patients
(2103 of 3541 [59.4%]) reported concealing their vitiligo frequently. More than half of
patients (2078 of 3541 [58.7%]) reported diagnosed mental health conditions, including
anxiety (1019 of 3541 [28.8%]) and depression (866 of 3541 [24.5%]). The Patient Health
Questionnaire–9 depression screener showed that 55.0%of patients (1948 of 3541) had
moderate to severe depressive symptoms; the highest rates were in India (271 of 303
[89.4%]) and among patients with more than 5%affected BSA (1154 of 1602 [72.0%]) and
darker skin (987 of 1445 [68.3%]).
CONCLUSIONS AND RELEVANCE This qualitative study found that, globally, patients with
vitiligo reported being substantially affected in their emotional well-being, daily lives, and
psychosocial health; the burden was typically greatest among patients with more than 5%
affected BSA, darker skin types, and lesions on the face or hands. Survey findings suggest
that patients reported having altered their behavior, expressed clear discontent, and have
symptoms consistent with depression, which may be underdiagnosed.

Vitiligo is a chronic autoimmune disease characterized by the destruction of melanocytes, resulting in pale or
white patches of skin.1 Patients with vitiligo encounter significant quality-of-life (QOL) impairment in routine activities, employment, and psychosocial health.2,3 Previous reports suggest that patients with greater body surface area (BSA) involvement and visible lesions experience greater psychosocial burden.4,5 Patients with vitiligo are also more likely to have depression and anxiety than individuals without vitiligo serving as controls.6,7 Psychosocial stressors are associated with vitiligo onset or flares.8,9

There is a need to further understand the global burden of vitiligo from the patient’s perspective. Here we explore sociodemographic characteristics and QOL and describe differences in psychosocial burden across geographic regions and subgroups of disease characteristics among patients surveyed in the Vitiligo and Life Impact Among
International Communities (VALIANT) study.


Study Participants
This cross-sectional observational qualitative study provided a survey that was administered to adults (aged ≥18 years) who received a diagnosis of vitiligo from a health care professional and were recruited via an online panel from 17 countries between May 6 and June 21, 2021, using a general population sampling approach (eAppendix in Supplement 1). The study protocol received an exemption from informed consent from the Western Institutional Review Board based on survey procedures and use of deidentified data. Participants
completed a brief online screener before continuing to the 25-minute survey. The survey was designed to assess self-reported emotional well-being, QOL, and depressive symptoms in a target sample of approximately 3500 patients. Additional assessment instruments (eg, theVitiligoImpactPatient scale [VIPs] and the Patient Health Questionnaire–9 depression screener) are described in the eAppendix and eTable 1 in Supplement 1.Datawere summarizedwith descriptive statistics. This qualitative study followed the Standards forReporting Qualitative Research (SRQR) reporting guidelines.

Statistical Analysis
Analyses included comparison of the 17 countries, 7 geographic regions, and demographic and clinical characteristic
subgroups, with t tests for comparisons of mean values and χ2 tests for categorical counts. Statistical significance was conferred at P < .05 (2-sided). The software used for analysis was WinCross, version 20 (The Analytical Group).


Patient Demographic Characteristics

Of 5859 participants who reported a vitiligo diagnosis were directed to the survey, 3919 (66.9%) completed the survey, 378 (6.5%)were excluded fordata quality issues (eTable2inSupplement 1), and 3541 (60.4%) were included in the analysis. The median age was 38 years (range, 18-95years); 1933 (54.6%)were male, 1603 (45.3%)were female, and 5 were nonbinary (0.1%). Race and ethnicity were not solicited in France (n = 250) or Germany (n = 250). A total of 929 of the 3041 patients with available datawere Asian (30.5%), 283were Black (9.3%), 144 were Central or South American (4.7%), 135 were Middle Eastern or North African (4.4%), and 1555were White (51.1%).

A total of 75 patients (2.5%) reported race and ethnicity as “other,” as categorized within the survey, with no further breakdown available. Thirteen patients (0.4%) preferred not to report race and ethnicity. A total of 1445 patients (40.8%) had Fitzpatrick skin types IV toVI (ie, darker skin), and1602(45.2%)
reported more than 5% affected BSA (Table).

QOL and EmotionalWell-Being

Globally, the mean (SD) total 12-itemVIPs score was 27.3 (15.6) (Figure 1). Scale scores ranged from0to 60,with higher scores indicating more psychosocial burden. Patients in India (mean [SD] score,40.2 [14.1]), Brazil (mean [SD] score, 29.7 [17.1]), and theUS(mean[SD] score,29.4 [12.8]) reportedthe highest scores (ie, the greatest burden) among countries surveyed (eFigure 1 in Supplement 1).

Worse QOL was observed among patients with more than 5%affected BSA(Vitiligo Impact Patient scale
mean [SD] score, 32.6 [14.2] vs 24.1 [13.9] for 1%-5% BSA and 21.6 [16.4] for <1%BSA; both P < .001), darker skin (mean [SD] score, 31.2 [15.6] vs 24.5 [15.0] for fairer skin; P < .001), and facial lesions (mean [SD] score, 30.0[14.9] vs 21.8 [14.9] for no facial lesions; P < .001) or hand lesions (mean [SD] score, 29.2 [15.2] vs 22.5 [14.8] for no hand lesions; P < .001).

More than 30% of patients (range across questions, 32.8%  [1160 of 3541] to 53.5% [1893 of 3541]) reported agreeing or strongly agreeing that vitiligo affected multiple aspects of their emotional well-being, including self-esteem or stigma, relationships, and careers (eFigure 2 in Supplement 1). Among all domains evaluated, patientswith more than 5% affected BSA consistently reported being more greatly affected compared with those with less extensive disease. A total of 49.0%of patients (1735 of 3541) agreed that having vitiligo made them feel
less confident or more self-conscious. Furthermore, 46.6% of patients (1649of 3541) believed that “no one understands what it’s like to live with vitiligo.” Patients also felt frustrated with their career prospects,with 41.9%(1483 of 3541) reporting that they believed that they would have been further along in their
careers if they did not have vitiligo. In contrast, 35.5% (1258 of 3541) reported that having vitiligo made them feel
empowered, suggesting that the question may have been misinterpreted.

Abbreviation: BSA, body surface area.
a Multiple answers were accepted.
bRace and ethnicity were not solicited in France (n = 250) or Germany
(n = 250).
c Category taken from the survey with no further breakdown available.
d Fitzpatrick skin types are defined as follows: type I, pale white skin; type II,
white skin; type III, light brown skin; type IV, moderate brown skin; type V,
dark brown skin; and type VI, deeply pigmented dark brown to black skin.

More than 40% of patients (range across questions, 42.9%[1520 of 3541] to 55.2% [1956 of 3541]) reported that aspects of their daily lives were frequently affected by vitiligo. Among the most
stressful daily activities were making clothing choices, attending social activities, shaking hands, and being intimate with their partner (Figure 2).Furthermore,59.4%ofpatients (2103of 3541)
reported that they frequently concealed their vitiligo with makeup or concealer or clothing, the rates of which were higher among patients with more than 5% affected BSA (1164 of 1602 [72.7%]), darker skin (955 of 1445 [66.1%]), and facial or hand lesions (1690 of 2712 [62.3%]).

Mental Health
More than half of patients (2078 of 3541 [58.7%]) reported diagnosed mental health conditions, most commonly anxiety disorder (1019 of 3541 [28.8%]) and depression (866 of 3541 [24.5%]) (eFigure 3 in Supplement 1). Rates of diagnosed mental health conditions were highest for patients with more than 5% affected BSA (73.8% [1183 of 1602] vs 52.0% [497 of 955] for 1%-5% BSA and 40.4% [398 of 984] for <1% BSA; both P < .001), darker skin (73.4%[1061 of 1445] vs 48.5%[1017 of 2096] for fairer skin; P < .001), and facial lesions (67.2%[1441 of 2143] vs 45.8% [600 of 1311] for no facial lesions; P < .001) or hand lesions (67.2% [1527 of 2274] vs 43.6% [514 of 1180] for no hand lesions; P < .001) and for those from India (90.1% [273 of 303]; P < .05 vs other countries).

Globally, 55.0% of patients (1948 of 3541) reported moderate to severe symptoms of depression according to the Patient Health Questionnaire–9, with the highest rates among patients from India (271 of 303 [89.4%]) (eFigure 4 in Supplement
1). Rates of moderate to severe depressive symptoms were greater among patients with more than 5%affected BSA (1154 of 1602 [72.0%]), darker skin (987 of 1445 [68.3%]), and facial or hand involvement (1607 of 2712 [59.3%]) than among their counterparts (eFigure 5 in Supplement 1). previous findings, the VALIANT study demonstrated frequent avoidance behavior and concealment strategies.11,12 One quarter of patients in the VALIANT study reported diagnosed depression and approximately three-tenths reported anxiety, which may substantially affect health care resources.13Furthermore, depression may be underdiagnosed, possibly owing to lack of access to mental healthcare, with more than half of patients in theVALIANT study reporting symptoms consistent
with moderate to severe depression. Regional differences were observed in the burden of vitiligo and were particularly notable in India. There is reportedly a highly negative perception of vitiligo in India, with patients reporting how having vitiligo has affected their marriage prospects, education, and employment.14 These perceptions may be a reason why patients in India reported the greatest burden among all countries



In this first international survey to date exploring the burden of vitiligo, patients, especially those with more than 5% affected BSA, darker skin, and facial or hand involvement, reported that this burden profoundly affected their emotional well-being, daily activities, and mental health. Smaller studies have reported a higher burden for patients at least 25% affected BSA or darker skin,2,10 supporting our findings that QOL impairment was greater among patients with more than 5% affected BSA and darker skin vs their counterparts. Lesion location was also associated with disease burden, with greater QOL impairment and higher prevalence of depressive symptoms among patients with vs. without facial or hand involvement, expanding on previous results.3,11 Corroborating previous findings, the VALIANT study demonstrated frequent avoidance behavior and concealment strategies.11,12

One quarter of patients in the VALIANT study reported diagnosed depression, and approximately three-tenths reported anxiety, which may substantially affect health care resources.13Furthermore, depression may be underdiagnosed, possibly owing to lack of access to mental health care, with more than half of patients in theVALIANT study reporting symptoms consistent with moderate to severe depression. Regional differences
were observed in the burden of vitiligo and were particularly notable in India. There is reportedly a highly negative
perception of vitiligo in India,with patients reporting how having vitiligo has affected their marriage prospects, education, and employment.14 These perceptions may be a reason why patients in India reported the greatest burden among all countries surveyed.


This study has some limitations. For example, the VALIANT survey is limited by factors observed with other online surveys, including selection and recall biases and reliance on self-report of physician diagnosis. Also, patients with lower disease burden may have been less likely to complete the survey. Some questions may also have been misread or misunderstood by patients. For example, 35.5% of patients (1258 of 3541) reported feeling empowered by their vitiligo in contrast to clinical experience, in which most patients express considerable disempowerment.15 This result could be because the terminology was interpreted differently across ethnic and national groups; therefore, translated survey validation across groups is warranted. Nonetheless, stratifications by BSA and skin type demonstrated similar trends in emotional well-being despite the fact that the questions were a mix of positive and negative characteristics. Finally, multivariate analysis was not undertaken; thus, confounding
cannot be excluded.



In this qualitative study, the results of the VALIANT survey indicate that vitiligo affects patients’ daily lives, emotional well-being, and careers. Patients altered their behavior, expressed clear discontent, and had symptoms consistent with depression, which may be underdiagnosed. Patients with more than 5% affected BSA, darker skin, and facial or hand lesions reported being more affected than their counterparts. Findings highlight the need to prioritize reduction in the psychosocial burden of vitiligo and increase efforts to educate patients and health care professionals on vitiligo, particularly in countries where patients experience the highest burden.


The relationship between stress and vitiligo: Evaluating perceived stress and electronic medical record data


Vitiligo is a T-cell mediated skin disorder characterized by progressive loss of skin color. In individuals genetically predisposed to the disease, various triggers contribute to the initiation of vitiligo. Precipitating factors can stress the skin, leading to T-cell activation and recruitment. Though hereditary factors are implicated in the pathogenesis of vitiligo, it is unknown whether precipitating, stressful events play a role in vitiligo. To understand this, we utilized a validated perceived stress scale (PSS) to measure this parameter in vitiligo patients compared to persons without vitiligo. Additionally, we probed a clinical database, using a knowledge linking software called ROCKET, to gauge stress-related conditions in the vitiligo patient population. From a pool of patients in an existing database, a hundred individuals with vitiligo and twenty-five age- and sex-matched comparison group of individuals without vitiligo completed an online survey to quantify their levels of perceived stress. In parallel, patients described specifics of their disease condition, including the affected body sites, the extent, duration and activity of their vitiligo. Perceived stress was significantly higher among vitiligo individuals compared to those without vitiligo. ROCKET analyses suggested signs of metabolic-related disease (i.e., ‘stress’) preceding vitiligo development. No correlation was found between perceived stress and the stage or the extent of disease, suggesting that elevated stress may not be a consequence of pigment loss alone. The data provide further support for stress as a precipitating factor in vitiligo development.


Vitiligo is an acquired skin disorder characterized by a progressive loss in skin pigmentation due to the loss of melanocytes, the pigment producing cells in the skin. Among other tissues, melanocytes are present in the inner ear, eye and mucosal membranes [13] and, are therefore, also affected due to vitiligo [4]. Vitiligo affects around 0.5% of the global population and, although all ethnic groups are similarly affected, it is more noticeable and more severe in dark-skinned individuals [56]. While the onset of vitiligo usually occurs during adolescence [6], individuals developing vitiligo during adulthood have been reported [78]. Though hereditary factors predispose patients to depigmentation, in adult onset vitiligo, a relatively greater contribution to disease etiology can be attributed to stress [910].

Vitiligo predisposition is defined by variant sequences at loci associated with both the innate and adaptive immune system as well as to loci associated with melanogenesis and apoptosis [1115]. Precipitating factors have been acknowledged, including exposure to sunlight or skin trauma, leading to oxidative stress in melanocytes [1619] and T-cell mediated autoimmune responses [2021]. Indeed, while vitiligo has been established as an autoimmune entity, [21], the mechanism connecting the initiating event(s) to the induction of anti-melanocyte T-cell immunity is unknown.

Physical or environmental stressors are reported in the onset and disease progression of vitiligo [2224]. In the event of a sunburn or exposure to certain chemicals or skin trauma, free radicals and hydrogen peroxide are generated [25], and in individuals who are predisposed to vitiligo, this leads to an activation of the immune system that generates melanocyte-specific cytotoxic responses. Heat shock proteins (HSP) are cellular stress response proteins that protect a cell under stressful conditions [26]. Notably, among the family of HSP, inducible HSP70 (HSP70i) is secreted by live cells under stress [27]. Previous work from our lab showed a critical role of HSP70i from the melanocytes in accelerating autoimmune vitiligo [2829]. Stressed cells secrete HSP70i and in the extracellular milieu, HSP70i can activate dendritic cells (DCs) and aid in antigen cross-presentation [30], resulting in cytotoxic T cell responses to melanocytic antigens.

Psychological stressors also play a role in vitiligo [2324]. Events such as death of a family member, work and financial problems have been associated as preceding factors to the onset of vitiligo [24]. In addition, vitiligo patients experience severe psychological effects [3132] and exhibit anxiety [33], depression [13], social stigma [34] and impaired quality of life [3536]. Stress increases the levels of catecholamines, neuropeptides, and cortisol that are higher in vitiligo patients [3739] suggesting their role in the pathogenesis of vitiligo.

To understand the association of stress in vitiligo patients, in this study, we used a validated questionnaire [40] to assess levels of perceived stress (PSS) [41] in vitiligo and healthy age- and gender- matched individuals. Patients were asked some additional questions about their condition, and ROCKET software was used to probe a patient database to explore the prevalence and chronology of stress related conditions among vitiligo patients. The data serve to correlate stress and vitiligo, providing support for the concept that stress can influence progressive depigmentation of the skin.


Sample size

One-hundred vitiligo patients who previously emailed us about our vitiligo research efforts were contacted and invited to participate in this study. The study was approved by the Loyola University Chicago Institutional Review Board. They were also asked to identify a person in their direct environment (not a blood relative) of the same sex and of the same age +/- 5 years. Though some patients provided personal contact information, the questionnaire responses could not be linked to the submitter.

Vitiligo questionnaire

A previously published questionnaire was provided to the patients to assess and record their disease etiology [42]. Patients diagnosed with vitiligo by a physician were requested to answer questions related to their condition including their sex, disease activity, and lesional distribution. Data are shown in S1 Table.

Perceived stress scale (PSS) and scoring

The PSS is a 10-item scale, which asks participants to rate the degree to which life experiences over the past 30 days are perceived as uncontrollable. PSS is a widely used measure of general perceived stress [40]. Reliability (stability) is 0.85 and Cronbach alphas range from 0.75–0.86 [43]. The threshold for stressed individuals is set to a PSS score of 15 as described [44]. Data are shown in S1 Table.

Questionnaire administration

The vitiligo and PSS questionnaires were electronically uploaded to Google Drive. Study participants were given access to the Drive to record their own responses, while maintaining anonymity.

Relationship of clinical knowledge and events tool (ROCKET)

ROCKET software can be used to probe the Clinical Research Database or ‘CDRB’ to query a limited dataset (LDS) repository of electronic patient records without personal identifiers, covering about 9 million encounters between 1/1/2007 and 9/30/2015. The software allows the investigator to locate information related to a particular patient population (here: vitiligo patients) and compare outcomes to those among unaffected controls. All patients at all encounter types where an ICD9 code of 709.1 or an ICD10 code of L80 was assigned are included. This covers a target population of just over 1000 subjects. As psychological stress and metabolic syndrome (metabolic stress) are associated with vitiligo [4547], anemia and depression (markers for psychological stress) and hypertension and hyperlipidemia (markers for metabolic stress [48]) conditions were probed. The requested information can include demographics, encounter information, order codes, chronic disease status and calculation of comorbidities, medication and clinical lab results.

Statistical analysis

PSS among healthy and vitiligo patients, and among male and female vitiligo patients were compared. The responses from the vitiligo questionnaire were correlated to outcomes from the PSS questionnaire. Unadjusted odds ratios (OR), a measure of association between an exposure and an outcome, and 95% confidence intervals (CI) were computed for stress-related conditions in the vitiligo group compared to the general population group. A paired t-test or Mann-Whitney U-test was used to determine differences between two groups, whereas ANOVA was used to determine differences among three or more groups. Pearson’s correlation coefficients were computed to determine associations between continuous variables. Statistical analysis was performed using GraphPad Prism Software (V8), and the odds ratio were computed using STATA.


Vitiligo patients experience an increase in perceived stress

We hypothesized that vitiligo patients experience more stress than individuals without vitiligo. Among 102 participating patients, 54.8% were male and 45.2% were female. At the time of completion of the PSS, 63.5% of patients described their disease activity as active, while 31.7% described their disease as stable disease and the remainder (4.8%) reported regressing disease. As patients are most distressed about vitiligo developing in the more visible, sun-exposed areas of their skin (unpublished), we tallied vitiligo development in different body parts. Among participants, 75% or more of patients developed vitiligo of their hands and of their face, which is commonly perceived as the most impactful by patients. Other commonly visible body parts include the extremities, which affected 50% or more of the sample at the time of data collection. The mean PSS score for vitiligo patients was 19.3, whereas, age and sex-matched controls had a mean PSS score of 13.8 (Fig 1, n = 22; P = 0.0396 in a paired t-test). A 2009 US probability sampling of adults documented a mean PSS score of 15.2 [44], suggesting that the present cohort of vitiligo patients had elevated PSS scores. That is, they perceived events in their life to be less manageable. We thus probed the full population of participating vitiligo patients for a more in-depth evaluation of levels of perceived stress.


PSS scores of healthy versus and vitiligo age-matched patients were compared. Sample includes both males and females (n = 25). The dashed line indicates the cutoff score for stressed individuals (at PSS = 15). Statistical significance for PSS among the populations was determined by paired two-tailed t-test, P = 0.0396.


Female vitiligo patients perceive more stress than affected males

Among all vitiligo participants, we compared the PSS scores between males and females (n = 55 and 47, respectively). While both groups reported a mean PSS score indicating stressed population (Fig 2A, PSS males 19.4 and PSS females 21.53), female patients perceived significantly more stress compared to male patients (P = 0.0143). An evaluation of the relationship between PSS scores per group relative to either duration of vitiligo (Fig 2B) or age (Fig 2C), revealed no significant correlations in either male or female patients.


(A) PSS scores were compared between male (n = 56) and female (n = 47) vitiligo patients. Statistical significance was determined by Mann-Whitney test, P = 0.0143. (B-C) Scatter plot illustrates relationship between PSS scores and vitiligo duration (B, P = 0.7955); and between PSS scores and age (C, P = 0.8746). (B) and (C) include both male and female vitiligo patients. Dashed line indicates the PSS cutoff score for stressed individuals (at PSS = 15).


Perceived stress is not related to disease activity

Almost two-thirds of patients evaluated were in an active phase of their disease, with others experiencing disease stability or regression. There was no difference in PSS values among patients experiencing differences in disease activity (Fig 3A); thus, we next examined the possibility as to whether perceived stress may be associated with self-reported extent of depigmentation (Fig 3B). The percentage of self-reported depigmentation was divided into four categories, based on percent of depigmentation (0–25; 25–60; 51–75; and 76–100). Although no significant correlation was observed between percentage of depigmentation and PSS scores, interestingly, a wide distribution of PSS among the 0–25% depigmentation group was observed. This figure also demonstrates that PSS scores are not related to the age of participating patients. As vitiligo development is commonly believed to initiate most frequently in the second decade of life, this would suggest that patient age might reflect the duration of disease. To determine if this is the case, we probed the anonymized clinical database available at Loyola using ROCKET software.



  • PPT
    PowerPoint slide
  • PNG
    larger image
  • TIFF
    original image
Fig 3. Perceived stress is not associated with disease progression and self-reported depigmentation.

(A) Violin plots depicting the distribution of PSS among the three stages of vitiligo progression. Colored dashed line and number indicate the median values. (B) Violin plots depicting the distribution of PSS in the four categories of self-reported depigmentation. Dashed line indicates the PSS cutoff score for stressed individuals (at PSS = 15).

Vitiligo is primarily diagnosed between two distinct age groups

To understand how the timing of other diagnoses and treatment relate to vitiligo development, we probed and plotted the age at diagnosis among vitiligo patients in the ROCKET database (Fig 4). The results revealed a biphasic pattern, the first one covering the first 2 decades of life peaking slightly later among males, than among females and the second peaking in the 5th decade of life. This is not dependent on the number of patients registered in the system for every age group, as the biphasic peaks were not observed for other conditions (unpublished). Instead, the distinct peaks would suggest that different etiologic factors prevail in different phases of life. This provided a framework to use the ROCKET database to probe other parameters among vitiligo patients.



  • PPT
    PowerPoint slide
  • PNG
    larger image
  • TIFF
    original image
Fig 4. Bi-phasic age groups of vitiligo diagnosis.

The ROCKET database was probed to determine the number of patients diagnosed with vitiligo. Total, male and female vitiligo populations are shown.

The timing of metabolic stress and not psychological stress can support a causative relationship among vitiligo patients

Hypothyroidism is the most common autoimmune disorder associated with vitiligo [4950]. To confirm this, we initially probed the database to determine whether hypothyroidism is increasingly prevalent among vitiligo patients (not as a marker for metabolic stress). Consistent with previous literature, we observed that the percentage of patients (11.69% in vitiligo vs 3.19% in general) and the odds (OR 4.02, CI 3.29 to 4.88) of hypothyroidism diagnosis is higher among vitiligo patients (Fig 5A). We then probed the database for the prevalence of hypertension and hyperlipidemia among vitiligo patients compared to the general patient population as a possible sign of metabolic stress among patients [51]. Indeed, the percentage of being diagnosed with hypertension (20.30%; OR 2.09, CI 1.79 to 2.44) and hyperlipidemia (22.90%; OR 2.81, CI 2.42 to 3.26) were higher among vitiligo patients (Fig 5A). Upon probing the timing of diagnosis, more patients were diagnosed with these metabolic disorders prior to their vitiligo diagnosis than after, suggesting a causative factor for vitiligo (Fig 5B). As a possible sign of psychological stress, the database was probed for patients diagnosed with depression and anemia [5255]. Interestingly, while the percentage of patients and the odds of being diagnosed with depression (9.18%; OR 2.3, CI 1.84 to 2.85) and anemia (16.62%; OR 2.62, CI 2.22 to 3.1) were high among vitiligo patients (Fig 5A), the timing prior to and after vitiligo showed a similar percentage of patients diagnosed (Fig 5B). This would suggest that both conditions might involve common etiologic factors.



  • PPT
    PowerPoint slide
  • PNG
    larger image
  • TIFF
    original image
Fig 5. Prevalence and timing of metabolic stress parameters among vitiligo patients.

(A) The odds of expressing a comorbidity among vitiligo patients, compared to the general patient population expressed as an odds ratio. A value of 1 indicates odds equal to the general patient population. Values greater than 1 indicates greater, and lower than 1 indicates smaller odds. The error bars indicate the upper and lower confidence intervals (B) Timing of diagnosis for indicated comorbidities compared to the diagnosis of vitiligo among patients.

To further support the role of metabolic stress in vitiligo, we probed the database for patients prescribed beta-blockers and statins [5657]. In line with our above findings, we observed that the percentage of patients and the odds of statins (17.49%; OR 1.93, CI 1.64 to 2.27) and beta-blockers (16.14%, OR 5.07, CI 3.37 to 7.33) prescription were higher among vitiligo patients (Fig 6A). In addition, more patients were prescribed the drugs prior to their vitiligo diagnosis, than after (Fig 6B). These differences are even more impressive when accounting for patient age at vitiligo diagnosis (Fig 4). Taken together, these results indicate that signs of (metabolic) stress are more frequently observed among vitiligo patients, and largely precede disease diagnosis. Thus, patients in part develop disease following signs of stress, producing a dataset informative of a potentially causative relationship.


Fig 6. Prevalence and timing of prescription drugs for metabolic stress.

(A) Odds ratio depicting the odds of being prescribing statins of beta blockers among vitiligo patients compared to the general patient population. The error bars indicate upper and lower confidence intervals. (B) Timing of first drug prescription compared to the timing a vitiligo diagnosis was made among patients.


To understand whether vitiligo associates with stress, the PSS and ROCKET analyses in our study newly revealed that ‘metabolic’ stress precedes and might thus contribute to vitiligo. Indeed this is in line with studies suggesting environmental and psychological stressors are triggers for the onset and progression of vitiligo [24]. Although the exact mechanism(s) by which stress influences vitiligo remains unknown, as discussed earlier, both environmental and psychological stress result in autoimmune vitiligo [21].

The PSS questionnaire is a validated tool to measure perceived stress and several studies have used this tool to estimate perceived stress in patients, including those with autoimmune disease [5859]. Among the vitiligo patients who participated in this study, female patients perceived significantly more stress than male patients did. Other studies have also found female patients to be increasingly impacted by stress [2231]. Whether women are more conscious of their stress or there are other underlying factors that attribute to their perception remains uncertain. In vitiligo, the depigmentation itself can also cause stress and in fact, self-reported depigmentation was the highest on the face and hands (S1B Fig) supporting this former notion. In the current study, neither age, nor duration of vitiligo or disease status were associated with perceived stress. PSS only measures a person’s perception of stress over the past month. It does not capture cumulative stress and it does not capture the quantity of negative life events. Thus, this limits the ability to make any inferences as to the role of cumulative life stress, which is more likely to influence vitiligo development and/or progression. It is also likely that social support and adaptive coping may buffer the impact of stress associated with vitiligo, which may explain why levels of perceived stress did not associate with vitiligo duration or characteristics.

Stress and stressors can have a profound impact on autoimmunity [60]. The timing and release of stress hormones regulate the pro- and anti-inflammatory cytokine balance that dictate immunoprotective or immunosuppressive activity [6162]. Acute or short-term stress results in an immunoprotective environment whereas chronic or long-term stress commonly result in an immunosuppressive environment [63]. Chronic stressors can, however, also promote a proinflammatory environment, resulting in dysregulated immune responses that might lead to autoimmunity [6364]. A limitation in this study is that no biochemical assays or cytokine profiles were investigated for these patients to correlate them to the PSS or vitiligo questionnaire. However, perceived stress did not correlate with disease state or duration. As stress hormones are increased in vitiligo patients [3738] and a cytokine imbalance has been assigned to oxidative stress in melanocytes, the data collectively prompt studies of a role for chronic stress in disease development.

The ROCKET analyses revealed a bimodal age of vitiligo diagnosis with the first age group peaking around 10–20 years and the second age group peaking around 50–60 years. First presented by us at the International Pigment Cell and Melanoma Research Conference in 2017, a recent GWAS study has since solidified this finding regarding vitiligo onset [65]. Diagnosis occurring at two different phases of life could implicate different etiological factors. Frequency of a stressful event was higher among adult patients compared to childhood onset [9], suggesting that stress is a precipitating factor particularly for adult onset vitiligo. In fact, the death of a loved one and work/financial problems are the most common stressful life events reported among adult vitiligo patients, and such events are consistently associated with a poor quality of life and depression [1366]. While the percentage of population affected and the odds of having depression were higher among vitiligo patients, the percentage of patients that were diagnosed with depression prior to and after vitiligo were similar in our study. This suggests that depression is neither a causative factor nor a consequence of vitiligo, but rather these conditions may share a common etiological factor. Metabolic syndrome is a cluster of disorders presenting with aberrant metabolism resulting in an increased risk of cardiovascular disease [51]. Chronic stress and stressful events present with a high risk of metabolic syndrome [6769], and vitiligo patients are at a higher risk of developing metabolic syndrome [4670]. Consistent with previous findings, the ROCKET analyses revealed that the percentage of patients and the odds of developing metabolic disorders, hypertension and hyperlipidemia, were higher among vitiligo patients (Fig 5), and these disorders are linked to oxidative stress and autoimmunity [7175]. Similarly, the odds for being prescribed statins and beta-blockers for cardiovascular disease, the major risk for metabolic syndrome, were higher for vitiligo patients. Taking into account the timing of diagnosis, patients were more frequently diagnosed with hypertension and hyperlipidemia, and more frequently so prior to their vitiligo diagnosis. This was accompanied by a greater percentage of patients prescribed statins and beta-blockers prior to their vitiligo diagnosis. A limitation of the current ROCKET analyses was that only a subset of comorbidities were available for analysis of the vitiligo patient cohort. Further, lifestyle factors, such as health behaviors, are important factors that contribute to the chronic diseases we probed, and must be considered in future studies investigating any associations of these diseases with onset and progression of vitiligo. Collectively, our data suggest that metabolic stress might be involved with the onset and progression of vitiligo. This prompts further analysis, including measurement of physiologic parameters.

In conclusion, the findings from this study indicate that vitiligo patients have high levels of perceived stress. In patients predisposed to vitiligo, metabolic and psychological stress might influence the onset and progression of vitiligo.


Image Credit: Polina Tankilevitch

Iltefat Hamzavi, MD, Reviews Surgical Treatment Advances for Vitiligo

The 2023 Pigmentary Disorders Exchange Symposium held in Chicago, Illinois, from May 5th to May 6th, covered numerous hot topics in managing pigmentary disorders. Hosted by conference co-chairs Pearl Grimes, MD, and Jill Waibel, MD, faculty members met for the 2-day conference to discuss the pathogenesis of vitiligo, hyperpigmentation, medical and surgical treatments for vitiligo, cosmeceuticals for photodamage, and more.

Iltefat Hamzavi, MD, spoke with Dermatology Times® to review key highlights of his session, “Vitiligo Surgical Treatment Advances,” including punch graft techniques and non-cultured epidermis suspension.

Hamzavi: I’m Iltefat Hamzavi from Henry Ford Hospital, Hamzavi Dermatology, and Dermatology Specialists, and a dermatologist in the Detroit area. And we’ll get jump into some of the points of the talk today. So, I had the good fortune of joining as inaugural faculty with Pearl Grimes and the rest of the group to look at vitiligo surgery. So, we had a session on hypo and depigmentation, and I was charged with the responsibility of talking about vitiligo surgery. So, at the meeting, we talked about the role of the immune system on causing vitiligo. But the melanocytes also are an area of destruction and dysfunction. And so in order to really repigment individuals, you have to manage the immune system, but then you have to create the milieu for the melanocytes to come back into the skin. Sometimes melanocytes just don’t want to come back in there.So there’s a role for vitiligo surgery. Vitiligo surgery can provide rates of repigmentation you can almost never get with phototherapy, topical agents or systemic agents. But if you don’t manage the immune system, the transplant procedure will not work. And we covered a variety of different transplant options. There is the traditional punch grafting where you take a larger punch, then you take another punch of the recipient site that’s smaller, and you place a larger punch in that area. That can give you good results for smaller areas. Talked about blister grafting where you create a blister and transplant the blister on the recipient side. We talked about split-thickness skin grafting, which is basically what sounds like, when you take a split-thickness graft, you dermabrade the vitiligo area and place it on top.

We spent most of our time talking about non cultured epidermal suspension technique also known as MKTP, melanocyte keratinocyte transplant procedure. These non-cultured epidermal suspension techniques have become the preferred technique for many of us. It allows you to treat a larger area with a smaller donor area. And so if you’ve managed the immune system, or you have segmental vitiligo, you can often use that. So as many of the attendees knew, we categorized the ideal surgical patient as somebody whose immune system is stable, their vitiligo is not progressing. And within that group, there’s 2 subgroups. There’s the segmental vitiligo where it only covers one segment of their body, and there’s nonsegmental, vitiligo. Nonsegmental vitiligo often has an immune activity, it’s active, but it goes through active and quiescent phases, versus segmental often is burnt out. Segmental patients tend to have a better response than nonsegmental, partly because the immunomodulation that’s occurring in the skin. And so with both of these types of subgroups, if you pick the right patient and location, you can have some dramatic results. And we talked about the rates of the repigmentation, they approached anywhere from 71% to 92% repigmentation in segmental vitiligo, and around 54% to 60% for nonsegmental. And that pigmentation tends to hold over 2 years based on some studies that have been presented, and again in this systematic reviews, it showed that split-thickness skin grafts and non-cultured epidermis suspensions were the most successful techniques. But our data is still generating, it doesn’t have the same robust nature as the pharmaceutical trials.

The ideal treatment also involves an awareness of where you can treat. So generally we want to treat 40 to 100 square centimeter locations, we would like to use an appropriate dressing process. And then you also have to have a nursing team. The nursing team’s role is to help you obtain the graft where you often from the hip, you process that tissue with the non-cultured epidermis suspension technique and the MKTP technique by heating it in an incubator and stripping off the collagen and dermal cells. And then you will continue to process that until the point where you are able to scrape the dermal components from the epidermal cells and you end up with a mix of keratinocytes and melanocytes. You spin those cells down and we suspend them in a solution and you convert that solid graft into a liquid solution. And then you dermabrade or laser abrade the recipient site, let’s say in the face, and you spray that solution over there and then place a collagen dressing or a gauze dressing and over 6 to 7 days, we leave that dressing in place. And we showed pictures of the face, the legs, and arms, having significant degrees of repigmentation.

And then we talked a little bit about adjunct techniques to preserve the level of pigmentation. But there is nothing that we have today for vitiligo that repigments to the degree and the speed that the vitiligo surgery can offer. We finished up by talking about some new commercial options, which are going to FDA review, using kits that will allow this technique to be much more accessible. And we presented an FDA-approved trial, where I believe it’s around 56% of patients had greater than 75% pigment. They’re not able to use a VASI score yet for these areas. But we’re working on that. But the VASI is the primary outcome measure for many of the topical systemic trials. But this measure of degree of repigmentation, more than 56% of people achieved that more than 75% pigmentation rate versus 0% in one arm, and about 12% was given to the other arm. So a great degree of improvement that was sustained with very few side effects ever noted. And we showed pictures of that. The patients served as their own control in these trials. And so this was comparing the area that did not receive treatment compared to treatment area that did receive treatment. So we finished the lecture summarizing the appropriate candidates, we talked about the appropriate expectations of the degree response. We talked about what patients to avoid, we talked about the upcoming new research. And we talked about how to continue to maintain the immunostability of the patient so that you don’t get a recurrence of vitiligo after you do the surgery. And hopefully at the end of it, the audience was able to at least have an understanding of vitiligo surgery. And then hopefully, over time, develop the techniques we can apply that to that patient whose immune systems is managed, they just cannot repigment them.

Dermatology Times: What are a few highlights from the 2023 Pigmentary Disorders Exchange Symposium?

Hamzavi: I’m just so excited that we are able to actually have a conference on pigmentation. So there are some excellent talks on dermal pigmentation done by Dr. Heather Woolery Lloyd, and she talked about the different classifications and different agents that we can use. She talked about oral agents that might trigger pigmentation. This is very disfiguring pigmentation that can occur. We had some great talks on melasma options and treatment of hyperpigmentation with Dr. Andrew Alexis. And he gave us an extensive summary of treatment options and other from the therapeutic ladder of photoprotection, topical intervention, systemic interventions and procedural based interventions. And then we also had some great lectures by Dr. Berson, and she spoke about the numerous agents that help manage hyperpigmentation and where they might be useful. And Pearl Grimes also gave a very, very strong overview of these pigmentary options across the different disease states. And those are the portions that I was able to attend. But really an in-depth conference. If you really want to improve your ability to treat hyperpigmentation and depigmentation, I haven’t seen a conference like this.

[Transcript edited for clarity]

Image Credit: Envato Elements


Advancing Medical Treatments for Vitiligo With Amit Pandya, MD, FAAD

Pandya gives an in-depth overview of his vitiligo treatment pearls from the 2023 Pigmentary Disorders Exchange Symposium.

The 2023 Pigmentary Disorders Exchange Symposium held in Chicago, Illinois, from May 5th to May 6th, covered numerous crucial topics in managing pigmentary disorders and featured a powerhouse list of faculty members. Hosted by conference co-chairs Pearl Grimes, MD, and Jill Waibel, MD, faculty members and attendees met for the 2-day conference to discuss the pathogenesis of vitiligo, hyperpigmentation, medical and surgical treatments for vitiligo, cosmeceuticals for photodamage, and more.

Amit Pandya, MD, FAAD, a dermatologist in Sunnyvale, California, the president of the Global Vitiligo Foundation, and director of the pigmentary disorders clinic at the Palo Alto Medical Foundation, spoke with Dermatology Times® to review his session, “Vitiligo Medical Treatment Advances,” as well as important topics from the meeting that he enjoyed.


Pandya: Hello, my name is Amit Pandya. I’m the director of the pigmentary disorders clinic at the Palo Alto Medical Foundation in Sunnyvale, California. And I’m also an adjunct professor in the department of dermatology at UT Southwestern in Dallas, Texas.

Dermatology Times: What are a few key highlights from your session, “Vitiligo Medical Treatment Advances?”

Pandya: I was excited to present advances in medical treatments for vitiligo at the recently concluded Pigmentary Disorders Exchange in Chicago. I talked about the exciting advances in JAK inhibitors for vitiligo with the recent approval of a topical JAK inhibitor ruxolitinib last year by the FDA. I talked about the phase 2 studies for this medication, which showed excellent results after one year, 50% of the patients got 75% of the color back on their face, and 1 out of 3 got 90% back on their face. The results on the body was that half the patients got 50% of the color back on their body. And this is with no phototherapy. This is simply with the cream and just normal sun exposure. I also showed that the responses were better on the head and neck, the trunk and the proximal extremities. But there was still a significant number that got improvement on the hands and feet. The side effects were very minimal, with less than 10% getting acne or pruritis. And the rest of the side effects were equal to placebo. So, it seemed to be very safe. And when we added narrowband UVB to ruxolitinib in a separate study, which was recently published, we got even better results, even better repigmentation. I showed the results of the phase 3 study which led the FDA to approve it. And that showed very similar results to the phase 2 study with again, half the patients getting 75% of their color back on their face. And the side effects again being very minimal with less than 10% getting acne. I then went on to talk about the exciting oral treatments, ritlecitinib, a JAK3 inhibitor, and that one was used to treat patients with active vitiligo, so it was a higher bar. And in that one, when they looked at the F-VASI75 or the improvement of 75% in the face, 1/3 of the patients reached that result after one year. And overall, there was a 66% improvement on the face and lower on the whole body. And then finally, I talked about the very recent results that were released on povorcitinib, a JAK1 inhibitor, and in this one, the patients who are treated for 36 weeks so far, these are like hot off the press, we don’t even have the 52 week results available. But in this one, it was similar in that F-VASI75, 1/3 of the patients achieved that F-VASI75. And then when it came to the T-VASI50, it was about 1/3 achieved 50% improvement on their body. Again, side effects for this one, just like the ritlecitinib, were very similar to placebo. So, these were the exciting results I was able to show with the medications, especially JAK inhibitors that are approved and also in the pipeline.

Dermatology Times: What did you enjoy about the 2023 Pigmentary Disorders Exchange Symposium?

Pandya: The Pigmentary Disorders Exchange was the first meeting that I’ve been to that was solely devoted to pigmentary disorders. It covered the wide spectrum of lectures on each of these disorders, including vitiligo, melasma, post-inflammatory hyperpigmentation, and photodamage. And what I really loved about it is that it really covered everything from A to Z, from the pathogenesis of the condition to medical treatments, to procedural treatments of these conditions. And they really went into the science of the pathogenesis. And then that helped you understand why these treatments work and which treatments should be selected. And of course, I can’t help but mention the camaraderie and just the social activities and meeting all my friends and leaders in pigmentary disorders. And a chance to talk to the audience one on one about these disorders was really a real treat for me. I really enjoyed going there.


Image Credit: Envato Elements

The use of Janus kinase inhibitors and narrowband ultraviolet B combination therapy in non-segmental vitiligo


Vitiligo is a depigmentation disorder of the skin that occurs secondary to the destruction of melanocytes by an immune-mediated process. Vitiligo clinically presents with depigmented macules and patches, most commonly on the face, acral sites, and genitalia. It can be characterized as generalized or localized based on distribution. The localized form can be further divided into segmental (linear, band-like, or Blaschkoid) and non-segmental vitiligo. The classical treatment of vitiligo includes topical steroids, pulsed oral steroids in unstable vitiligo, phototherapy, a combination of steroid therapy and phototherapy, surgical grafting, as well as intentional depigmentation therapy in severe cases. However, recent advances in understanding the immune mechanisms implicated in the pathogenesis of vitiligo have led to the use of an FDA-approved topical Janus kinase (JAK) inhibitors for vitiligo. Despite this novel therapy advancement, we recommend the addition of narrowband ultraviolet B (NB-UVB) to JAK inhibitors in patients with extensive and progressive lesions, or those not fully responsive to JAK inhibitor monotherapy.

Vitiligo is a depigmentation disorder of the skin that occurs secondary to the destruction of melanocytes by an immune-mediated process. Vitiligo can be associated with various autoimmune diseases such as hypothyroidism, pernicious anemia, alopecia areata, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), among others.12 Vitiligo clinically presents with depigmented macules and patches, most commonly on the face, acral sites, and genitalia. It can be characterized as generalized or localized based on distribution. The localized form can be further divided into segmental (linear, band-like, or Blaschkoid) and non-segmental vitiligo.1 The diagnosis of vitiligo is made clinically, and examination with Wood’s Lamp shows “milky-white fluorescence” of the depigmented patches.1 This helps differentiate vitiligo from conditions with hypopigmentation rather than depigmentation such as pityriasis alba. The classical treatment of vitiligo includes topical steroids, pulsed oral steroids in unstable vitiligo, phototherapy, a combination of steroid therapy and phototherapy, surgical grafting, as well as intentional depigmentation therapy in severe cases.138 However, recent advances in understanding the immune mechanisms implicated in the pathogenesis of vitiligo have led to the use of an FDA-approved topical Janus kinase (JAK) inhibitors for vitiligo.9 JAK inhibitors are small molecules that disrupt the JAK–STAT (Signal Transducer and Activator of Transcription) signaling pathways, leading to inhibition of immune-mediated inflammatory pathways.4810In March of 2022, Opzelura™ (ruxolitinib), a topical JAK inhibitor was approved by the FDA for the treatment of non-segmental vitiligo in patients 12 and older.9 In the largest clinical trial for this medication, a total of 674 patients with non-segmental vitiligo were enrolled in phase 3 clinical trials of TRuE-V1 and TRuE-V2, ( Identifier: NCT04052425 and NCT04057573).9 Ruxolitinib therapy showed 75% improvement in Total Vitiligo Area Scoring Index (T-VASI) at 24 weeks posttreatment.9 Topical ruxolitinib addresses melanocyte dysfunction through inhibiting cytokines which lead to immune-mediated destruction of melanocytes by T cells.9 The safety profile of topical ruxolitinib has been studied in these trials and has been shown to have fewer adverse effects than the systemic route of administration.89 Patients with oral JAK inhibitors are at risk of developing serious bacterial, fungal, and viral infections that may result in hospitalization or death.4Despite this novel therapy advancement, we recommend the addition of narrowband ultraviolet B (NB-UVB) to JAK inhibitors in patients with extensive and progressive lesions, or those not fully responsive to JAK inhibitor monotherapy. In Opzelura clinical trials, 25% of patients did not respond to treatment.10 Subsequently, in the study by Leu et al, treatment with topical tofacitinib led only to re-pigmentation when there was concomitant light exposure.4 Topical JAK inhibitor monotherapy might not be an appropriate choice for extensive (>5%–10% of BSA) progressive non-segmental vitiligo, therefore we recommend the addition of an optimized aggressive NB-UVB regimen to topical ruxolitinib due to its paucity of side effects.3 In NB-UVB devices, the starting safe dose (200 mJ) 2–3 times per week can be increased by a 10%–20% dose increment to achieve light pink erythema or development of skin burning, sensitivity, peeling, or thickening.5 Furthermore, the 308-nm excimer laser therapy can be considered for smaller lesions.7 There have been several studies that have investigated the use of JAK inhibitors with various adjunctive therapy, including NB-UVB and excimer laser (Table 1).8 The maximum dose depends on Fitzpatrick’s skin phototype, photosensitive, and lesion location.6 After stabilization of progression and distribution of vitiligo through NB-UVB and topical ruxolitinib combination therapy, maintenance of regimentation may be achieved with JAK inhibitor monotherapy.

TABLE 1. Vitiligo treatment modalities with JAK inhibitors and various adjunctive therapy options in different studies
Investigator Number Of subjucts JAK inhibitor dosage and frequency Study duration Adjunct therapy Outcome Adverse events
Rothstein et al (2017) 11 Ruxolitinib 1.5% cream BID 20 weeks None Face: 76% VASI improvement

Non-acral upper extremity: 3.6% VASI improvement

Lower extremity/trunk (undefined): 0% VASI improvement


Peripheral hyperpigmentation

Transient acne

Rothstein et al (2017) 8 Ruxolitinib 1.5% cream BID 32-week extension (52 weeks total) NB-UVB Face: 92% VASI improvement

Non-acral upper extremity: 12.6% VASI improvement

Trunk: 16.7% VASI improvement

Erythema Transient acne
McKesey et al (2019) 11 Tofacitinib 2% cream BID 8–16 weeks NB-UVB 3 times weekly 70% VASI improvement N/A
Rosmarin et al (2020) 1 Tofacitinib 2% cream BID 24 weeks NB-UVB (3 times weekly, home unit) Face:100 repigmentation None
Ferreira et al (2021) 2 Delgocitinib cream BID 36 weeks NB-UVB (3 times weekly) Face: Significant repigmentation, Erythema Transient acne

The psychosocial and cosmetic burden from this chronic autoimmune disease can lead to patients’ isolation. The cost and access of this recent FDA-approved topical JAK inhibitor for non-segmental vitiligo can pose a burden on patients to be compliant and receive appropriate treatment. Adjuvant light exposure treatment can overcome these challenges with effective targeted treatment. Topical JAK inhibitors found their place in the treatment of vitiligo after years of investigation. Prospective clinical trials are needed to further assess adjuvant light therapy and the future formulation of topical JAK inhibitors for the treatment of non-segmental rapidly progressive vitiligo.



Image source: Envato Elements


Current Status of Cell-Based Therapies for Vitiligo


Vitiligo is a chronic pigmentary disease with complex etiology, the signs of which are caused by the destruction of melanocytes in the epidermis, leading to the lack of melanin pigment responsible for skin coloration. The treatment of vitiligo, which aims at repigmentation, depends both on the clinical characteristics of the disease as well as on molecular markers that may predict the response to treatment. The aim of this review is to provide an overview of the clinical evidence for vitiligo cell-based therapies taking into account the required procedures and equipment necessary to carry them out as well as their effectiveness in repigmentation, assessed using the percentage of repigmentation of the treated area. This review was conducted by assessing 55 primary clinical studies published in PubMed and between 2000 and 2022. This review concludes that the extent of repigmentation, regardless of the treatment method, is highest in stable localized vitiligo patients. Moreover, therapies that combine more than one cell type, such as melanocytes and keratinocytes, or more than one method of treatment, such as the addition of NV-UVB to another treatment, increase the chances of >90% repigmentation. Lastly, this review concludes that various body parts respond differently to all treatments.

1. Background

Vitiligo is a chronic pigmentary disease that affects approximately 1% of the world’s population. This dermatological condition affects skin and hair and manifests itself by characteristic white macules and patches. The disease can be segmental, localized in one area of the body, or generalized, affecting a broader area. It can also be stable or unstable, depending on the appearance of new decoloration. Non-segmental vitiligo is prone to reactivation but, as in many of the studies, patients are required to have stable vitiligo, those with the segmental type of the disease are more likely to be selected for treatment. The loss of skin pigmentation is caused by the destruction of melanocytes in the epidermis, leading to the lack of melanin pigment responsible for skin coloration. The published data suggest that the causes of melanin deficiency are multifactorial; mostly, it has an autoimmune origin with an underlying genetic tendency.
The disease has vast deleterious consequences beyond the aesthetical aspect, negatively affecting the patient’s emotional well-being and self-esteem. It is reported that around 75% of vitiligo patients have a psychological disorder, and female vitiligo patients experience significantly more significant impairment of general and psychological health, intimate relationships, and sexual function compared to healthy women.
The standard treatment for vitiligo varies based on the patient’s tolerance and consists of topical steroid therapy, immunosuppressant, sun protection, phototherapy, vitamin D, or narrow-band ultraviolet B (UVB) phototherapy (Figure 1). While these treatment options can be successful for certain patients, for others, they do not bring satisfactory results. Moreover, some patients are resistant to conventional medical treatments, probably due to polymorphisms in the genes involved in the immune response and melanogenesis , which motivates the search for novel combination therapy.
Figure 1. Standard and cell-based therapies for vitiligo. The figure was created with, accessed on 3 November 2022.
Therefore, there is a great interest in introducing other novel therapies that are effective and safe for vitiligo patients (Figure 1).
This narrative literature review aims to bring a comprehensive knowledge of cell-based therapies in the treatment of vitiligo. In the present study, we discuss the development of these methods in recent years and point out various technical aspects affecting the effectiveness of the given methods for a better understanding of which procedure could be recommended, taking into account the characteristics of vitiligo and the patient’s age as well as facilities available in the clinic. Different transplantation approaches using keratinocytes and melanocytes or both cell types are presented with a description of the most applicable techniques such as hair follicle cell transplantation, the ReCell system, the Jodhpur Technique, and an approach where cell transplantations are combined with narrowband ultraviolet B (NB-UVB) or autologous platelet-rich plasma.
This literature review aims to bring knowledge of cell-based therapies by assessing 55 of the most effective primary clinical studies published in PubMed (, accessed on 20 November 2022)  and (, accessed on 20 November 2022)  between 2000 and 2022 with the oldest studies being discussed for historical relevance. Moreover, this review aims to give an indication of the therapies depending on the vitiligo type and location. Only human-based clinical studies and case reports were included in this review.
This review is divided into five sections, each considering a different cell-based therapy, its background, studies, and effects. It should be stated that the studies presented here have been conducted on several different ethnic groups. It is known that people of varying skin colors respond differently to vitiligo treatment; thus, this must be kept in mind when analyzing the results of clinical trials.

2. Melanocytes and Keratinocytes as the Targets for Vitiligo Therapy

Neural crest cell-derived melanocytes are the melanin-producing cells of the skin; several melanocyte cell death mechanisms have been proposed to explain the origin of vitiligo. As such, the transplantation of healthy cells shows great promise for treating vitiligo patients. Several methods for the delivery of non-cultured melanocytes into the affected skin areas of patients have been attempted , including transplantation onto dermabraded or laser-abraded areas. In this approach, the skin sample is shortly incubated with trypsin and centrifuged before spreading on the recipient area. As the number of melanocytes in this method is not increased in culture, its efficacy might be lower compared to cultured melanocyte transplantation. This is suggested by the relatively low (57.4%) number of patients achieving >50% repigmentation in the study by Ghorbani et al. Melanocytes only account for up to 10% of skin cells and thus should be amplified in vitro prior to transplantation to maximize the chances of success .
Therefore, there are numerous approaches for transplanting pure cultured melanocytes. For example, in the Chen et al. study, 25 segmental vitiligo patients were treated with cultured autologous melanocytes. The cells were transplanted into laser-denuded areas at a density of 70,000 to 100,000 melanocytes per cm2. Complete repigmentation was seen in most patients in less than one month, although in some cases, a thin vitiliginous line at the junction between normal skin and the transplant was visible. Hair follicles, the outer root sheath, are rich in melanocytes with potential proliferative ability. Thus, this offers a potential donor site for autologous cell transplants and was recently explored in several studies. In the study by Shi et al. [23], the occipital area was used to obtain a scalp specimen containing at least 15 hair follicles. Following the removal of adipose tissue, the remaining hair follicles and dermal papillae were incubated, and a single-cell suspension was created. The sterilized recipient area was then abraded superficially using a motorized dermabrader or a CO2 laser and covered with the cell suspension and a hyaluronic acid dressing. In the nine months following treatment, 22 of the 26 patients achieved >75% repigmentation, and of those, 9 individuals achieved >90% repigmentation. Moreover, hair follicle transplantation using the hair follicular unit transplantation (FUT) technique is a cheap, simple method requiring minimal infrastructure, which makes it suitable for small stable lesions affecting hairy body parts [24].
Melanocytes can also be transplanted using dermarolling treatment, which involves microneedles piercing the epidermis for cell delivery. Melanocytes can be obtained with superficial shaving of scalp skin, as this is another area known to be particularly rich in these cells. Following incubation in a trypsin solution, the epidermis can easily be separated from the dermis using forceps. The epidermis is then centrifuged, the supernatant removed, and the pellet suspended in plasma. Following cleaning with an antiseptic spray, the recipient site can be dermarolled to deliver the melanocytes. Benzekri and Gauthier [25] have shown that after 24 h, nearly all holes had closed up without signs of infection, and melanocytes had been observed in the basal layer of the epidermis. After six months, 40% of the patients had an excellent response (76–100%) to the treatment. Autologous melanocytes can also be obtained from the thigh or buttock areas with normal skin color, which was explored in generalized vitiligo patients. The autologous material was incubated with trypsin then mixed with patients’ serum and centrifuged. The cell suspension mixed with hyaluronic acid was then evenly spread on recipient areas, previously injected with lidocaine, and shaved with a curate device. The success of the treatment was highly dependent on the recipient area, with the highest proportion of excellent and good results achieved in various areas of the face (57.4% on the face compared to the overall success of 50%) [14]. Using eyelid skin to harvest melanocytes and subsequent transplantation of the autologous melanocytes yielded similar results, with >80% repigmentation in 56% of the cases. The high success rate could be in part due to the selective growth of melanocytes while inhibiting fibroblasts and keratinocyte cells, as their faster growth and high proportion prevent the growth of melanocytes. The best results and even coloration were achieved in the legs, trunk, and face, and it was observed that sunlight could promote pigment production of transplanted cells [26]. Even though the results of the three latter studies are satisfactory, using hair root melanocytes appears to be the most effective solution. Moreover, it is clear that the choice of melanocyte donor area for melanocytes should be influenced by the recipient area affected by vitiligo, as the different methods showed varying success in various locations on the body [27]. Interestingly, Zhu et al. [26] found a higher level of anti-melanocyte antibodies in the vitiligo patients’ serum, indicating that humoral immunological mechanisms could play a role in the development of the disease.
The clinical characteristic of vitiligo is another important aspect determining the effectiveness of transplantation. One hundred and twenty cases of vitiligo patients were studied, and it was investigated whether stable localized vitiligo, stable generalized vitiligo, and active generalized vitiligo show different outcomes after cultured autologous pure melanocytes transplantation. In this study, similar to previous work of this group [16], 60,000 to 100,000 melanocytes/cm2 were applied on the skin after carbon dioxide laser abrasion of the vitiligous areas. The best outcome was observed in the stable localized vitiligo group, where 84% of patients achieved 90% to 100% repigmentation. An excellent percentage of coverage was shown in 54% of patients in the stable generalized vitiligo group and none in patients suffering from active generalized vitiligo. This study proved the validity of the treatment of stable vitiligo with cultured autologous pure melanocytes [28]. The clinical applications of melanocyte cell transplantation in vitiligo are summarized in Table 1 and Figure 2. However, most clinical trials attempt to transplant keratinocytes in co-culture with melanocytes [29,30].
Figure 2. CT-cell therapy. The highest percentage of repigmentation depending on the cell-based therapy used (based on papers presented in Table 1).

3. Melanocyte–Keratinocyte Cell Transplantation (MKCT)

It should be clarified that MKCT is the complete clinical grafting procedure which includes harvesting epithelium from the donor site, preparing the recipient site, and applying the suspension and dressing the wound, whereas non-cultured epidermal suspension (NCES) refers to a prepared cell suspension used in MKCT. The first introduction of non-cultured epidermal cellular grafting in the treatment of stable vitiligo took place in 1992 [31] after several successful attempts under experimental conditions on piebald guinea pig skin [32]. In this treatment, both melanocytes and keratinocytes are transferred, as melanocytes grow better in the presence of keratinocytes and produce better repigmentation. For instance, Phillips et al. [33] demonstrated the significance of improving the method of maintaining melanocyte numbers by introducing a feeder layer. The use of a hyaluronic acid-enriched cellular graft gave a repigmentation rate of over 70% in the vitiligous areas in 77% of patients after 12 months compared to a placebo in a double-blind study [1]. For a change, Khodadadi et al. [34] replenished the missing melanocytes and keratinocytes using a different route of their administration: the cell suspension was injected intraepidermally into vitiligous lesions. In the 6-month follow-up, 4 out of 10 patients had achieved moderate repigmentation (76–100%) and one patient’s patch was fully repigmented. The authors found no correlation between the number of transplanted cells and the outcome. Further development of this technique gave a repigmentation rate of over 50% in 32.2% of treated patches, whereas acquired repigmentation remained stable in 79.3% of treated patches during the 30-month-long follow-up period. Observing 300 patients, the first pigmentation loss in treated patches started around 9 months post-transplantation and mostly occurred during the first year (68.5%, n = 150) after treatment [35]. It is worth mentioning the results of the study by Budania et al. [34] and Bao et al. [36] which compared the NCES method with suction blister epidermal grafting (SPEG) and showed a better extent of repigmentation after NCES. Interestingly, in the study by Budania et al. [37], no melanocyte culture media, trypsin inhibitor, or hyaluronic acid was used, and only simple syringe-base suction was applied. Moreover, a comparison between an autologous non-cultured extracted hair follicle outer root sheath cell suspension (NCORSHFS) and NCES showed comparable efficacy in repigmentation [38,39], although, patients in the NCES group were significantly more satisfied than the patients in the NCORSHFS group [38]. However, there is also a study that suggests that cultured melanocyte transplantation (CMT) may give better repigmentation as compared with NCES in the case of stable generalized and segmental vitiligo [40]. Interestingly, a superior repigmentation to NCES or NCORSHFS alone was achieved when those two techniques were combined. The authors suggested that this approach may be a good alternative for the more resistant-to-treatment acral vitiligo [41].
The MKCT grafting procedure was also substantially developed since its discovery by Olsson and Juhlin in 1998 [42]. Initially, the sample of superficial skin was removed, and cells were isolated, separated, and cultured in a melanocyte growth medium. To carry out this procedure in one day, the next step was to apply the melanocyte-enriched epidermal cell suspension directly on dermabraded depigmented skin. Some of the changes proposed by Mulekar [43] concern the use of Dulbecco’s Modified Eagle’s Medium (DMEM) and Ham’s F-12 Nutrient Mixture for cell separation procedure and CO2 incubator substitution with an ordinary incubator. The CO2 incubator helps to maintain the pH in the cell cultures; however, it makes the procedure more expensive. Currently, melanocyte–keratinocyte cell transplantation (MKCT) involves obtaining a skin biopsy from the donor site one-tenth of the recipient area size. This is followed by soaking it in trypsin-EDTA solution, separating the dermis from the epidermis, and disposing of the dermis. The sample is then centrifuged, and the stratum corneum is discarded. Finally, the cell suspension is transplanted onto the deep epidermis of the dermabraded recipient area, which is then covered with a dry collagen sheet. The whole treatment can be conducted as a 2 to 4 h outpatient procedure.
In this technique, repigmentation can be seen between 2 weeks and 2 months after surgery . Many patients show hyperpigmentation, but it usually blends with the surrounding skin in 6 to 8 months, and the likelihood increases when patients expose the transplanted areas to sunlight. This method is most effective in segmental and focal vitiligo patients, for whom a scarring or cobblestone appearance is unlikely. Interestingly, the only post-operative pain that can be observed is in the feet and ankles. Six months following the surgery, 84% of the patients showed good to excellent repigmentation, and in the long term, six years after the surgery, the treatment results remained positive for patients with segmental, stable vitiligo with the absence of fingertip involvement. Mulekar et al also evaluated the effects of this treatment in 49 patients with segmental vitiligo and 15 patients with focal vitiligo who were followed up for up to 5 years. Overall, 95% to 100% of repigmentation was achieved in 84% of patients with segmental vitiligo and 73% of those with focal vitiligo, while a poor outcome was observed in 10% and 20%, respectively. Another study using MKCT reported that in the 12 to 72 months post-treatment, good to excellent repigmentation remained in 71% and 54% of patients with stable and non-stable vitiligo, respectively, confirming the success of this treatment for stable vitiligo patients. Interestingly, at 12 months, 62% of patients showed additional repigmentation that was not present before, and only 26% showed partial or complete regression. It was noted that improvement peaked at 10 months post-surgery and stabilized by up to a year, plateauing at around 18–24 months. In another paper by Mulekar et al, 142 patients were followed up to 6 years after autologous, non-cultured melanocyte-keratinocyte cell transplantation. Complete repigmentation was shown in 56% of patients, while poor pigmentation was observed in 24%. Another group presented data concerning three cases of patients with stable genital vitiligo. A 26-year-old male with the loss of pigmentation on the penis glans and neck, and 24- and 39-year-old males with depigmentation of the glans and shaft of the penis, all of whom were treated with autologous, non-cultured MKCT. All of the patients achieved almost complete repigmentation. In another study, patients with stable vitiligo were treated using the same method as Mulekar and co-workers.  The outcome of the treatment of eight vitiligous patches treated with autologous non-cultured melanocyte–keratinocyte transplantation was compared to six control lesions, which were only dermabraded. The results were evaluated after 4 months. Over 95% repigmentation was observed in 50% and 0% to 24% repigmentation in 37% of patients treated with MKT. Five out of six control patches failed to show repigmentation, and one patch resulted in hyperpigmentation following inflammation.
Vazques-Martinez et al and Quezada et al compared the efficacy of the transplantation of melanocyte and keratinocyte (MKCT) cell suspension after dermabrasion (DA) or with dermabrasion only. In the 12-month follow-up period in Vazquez-Martinez’s study there was no statistically significant difference between MKCT + DA and DA alone in the area of depigmentation but clinically MKCT + DA showed slightly better results. Quezada et al analyzed the results 3 months after transplantation and observed no significant differences between the treatments. It should be noted that the two latter studies indicate that MKCT + DA and DA alone are similar in terms of efficacy, whereas Mulekar and co-workers have found MKCT to be significantly better. This highlights the differences between methods and samples used in different studies even when, in principle, the technique used is the same.
Huggins et al performed 29 MKCT procedures in 23 patients with focal, generalized, or segmental vitiligo with no control group. Overall, 52% of the vitiligous lesions were localized on the extremities. Patients were evaluated monthly between the 3rd and 6th month after the procedure. Excellent repigmentation was achieved in 17% and poor in 41% of patients. The presence of vitiligo on the face/neck was associated with a better response to the treatment, with 19% of patients showing excellent repigmentation and 50% good.
Ebadi et al conducted a study where patients with stable generalized vitiligo, with a total of 39 patches, were divided into four groups. Nine patches were treated with MKCT alone, ten patches with MKCT and excimer laser, ten patches with excimer laser alone, and ten patches served as controls and did not receive any treatment. The authors reported that excimer laser combined with non-cultured MKCT improves the repigmentation rate, with an average of 41.9% reduction in the depigmented area surface. For comparison, it was only 4.7% for patients treated with excimer laser alone, 15.9% for those treated with MKCT alone, and 0.1% for the control group.
Lastly, it has been observed that the ethnicity of patients must be considered in the choice of MKCT treatment, for instance, Asian patients are more prone to hypertrophic scarring. Even though vitiligo affects all ethnic groups similarly, it may be more noticeable in people with darker skin, and some treatments may show varying efficacy between the different groups.
It is worth mentioning that the response to NCES treatment may depend on the location of the lesions. The best results were observed in face and neck lesions (88% of satisfactory responses) and the worst in the extremity lesions (33% of satisfactory responses). However, based on their results, Mulekar et al. concluded that the concept of a “difficult-to-treat site” is a relative term and depends upon the technique used. The non-cultured MKCT seems to be favorable as this technique does not require special precautions to treat these anatomical sites. According to some authors, using a higher density of melanocytes in the suspension , a strict immobilization procedure for the treated areas, and post-operative phototherapy in the form of sun exposure might improve the results in such a “difficult-to-treat site”. Others reported that a better response was achieved in segmental vitiligo patients compared to non-segmental ones (84% compared to 63%). Moreover, NCES was also successfully used in the repigmentation of leucotrichia in vitiliginous patches. The proposed mechanism of this process is a retrograde migration of transplanted melanocytes or interfollicular epidermal stem cells to the hair bulb and/or their production of cytokines, which stimulates melanogenesis in the follicular bulbs. It should also be mentioned that skin grafting may be considered to treat localized vitiligo in children In this group of patients, an MKTP is favorable as it does not require a long surgical time, and there is no need for absolute immobility and any special precautions to treat ‘‘difficult-to-treat’’ sites. The clinical applications of MKCT in vitiligo are summarized in Table 1 and Figure 2.

4. ReCell System in Vitiligo Therapy

ReCell is a robust point-of-care autologous therapy designed to treat skin defects such as small and large thermal burn wounds using a patient’s regenerative cells. The ReCell system enables the harvesting of autologous cells, processing them, and delivering them using a spray applicator. Three clinical trials analyzed the results of treating patients with stable vitiligo with ReCell (a cell suspension with keratinocytes, melanocytes, dermal papillary fibroblasts, and Langerhans cells sprayed over the wound). Mulekar et al compared the efficacy of the ReCell system and melanocyte–keratinocyte transplantation 4 months after the procedure. In both methods, the cell suspension was spread to previously dermabraded areas, and the results of the treatments were comparable.
Due to efficacy, time, and cost, surfaces that can be covered with cultured melanocytes are larger than those that can be covered with non-cultured cells. Cervelli et al treated 15 patients, and 12 of them (80%) achieved more than 75% repigmentation. The authors observed an excellent color match in 66% of patients.
In 2010, the same group presented a case report of a 30-year-old man suffering from stable vitiligo on his hands. Before undergoing ReCell therapy, he had vitamin A, C, E, and UVB therapy, none of which were beneficial. Treatment with the ReCell system gave excellent results, both in the extent of repigmentation and the skin color match. The clinical applications of the ReCell system in vitiligo are summarized in Table 1 and Figure 2.

5. Autologous Non-Cultured, Non-Trypsinized Epidermal Cell Grafting

This method is also known as the Jodhpur Technique (JT) (the first time was carried out in the Medical College in Jodhpur in India) and is a modification of the autologous non-cultured, non-trypsinized keratinocyte–melanocyte cellular graft technique. The grafting material is rich in melanocytes and is obtained following the dermabrasion of the donor area. The epidermal particles fragmented during dermabrasion become entangled in an ointment, and a paste-like material is obtained. This material is laid out over the recipient lesion area using a graft spreader. This technique is very low-cost and does not need any sophisticated equipment.
The study by Tyagi et al with the use of the JT technique revealed that in both epidermal cell suspension and epidermal curettes, over 75% repigmentation was achieved in 60% of lesions. Moreover, the color matching with surrounding skin and yield of grafts was not significantly different between these techniques. Even better results were presented in the study by Lamoria et al, where excellent repigmentation (>75%) was observed in 70% of lesions. In terms of the repigmentation rate, side effects, patient satisfaction, and dermatology life quality index reduction, this method was superior to FUT. The clinical applications of non-cultured epidermal cell grafting in vitiligo are summarized in Table 1 and Figure 2.

6. Cell Transplantations in Combination Therapy with a Narrowband Ultraviolet B (NB-UVB) or Autologous Platelet-Rich Plasma

Narrowband ultraviolet B (NB-UVB) is one of the treatment options for patients suffering from active vitiligo. It promotes the proliferation and migration of cultured melanocytes. Zhang et al collected a group of 473 patients and investigated the effect of NB-UVB in combination with autologous melanocyte transplantation. The patients were divided into four groups: group 1 underwent NB-UVB sessions before melanocyte transplantation, group 2 was NB-UVB treated after transplantation, group 3 received NB-UVB before and after transplantation, while group 4 did not undergo NB-UVB sessions and received only transplantation. The best results were observed in group 3, where ≥90% repigmentation was achieved in 81% of patients, which suggests that NB-UVB given before and after transplantation of the melanocytes gives the best chance of repigmentation in active vitiligo patients. Interestingly, Yao et al. demonstrated more than 90% repigmentation at the 1-year follow-up in all patients treated with low-density cultured autologous melanocytes combined with NB-UVB treatment after cell transplantation. Excellent repigmentation (85–100%) was also achieved in the small four-patient study where the non-cultured autologous melanocytes and keratinocytes transplantation was combined with UVA or UVB therapy after grafting .
Platelet-rich plasma (PRP) originates from the collection of venous blood, which is then centrifuged in the presence of anticoagulants. After centrifugation, autologous platelets are suspended in a small amount of plasma. Topical application using an intradermal injection of PRP through the secretion of platelet’s alpha granules increases the release of growth factors (especially basic fibroblast growth factor, bFGF), adhesion molecules, and chemokines, which, by interacting with the local environment, stimulate melanocyte migration along with the stimulation of keratinocyte and fibroblast proliferation. Moreover, PRP promotes the release of inflammatory mediators and modulators through the release of numerous anti-inflammatory cytokines, such as interleukins (IL-4, IL-10, IL-13), IL-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor (TNF) receptor (sTNF-R) I, and interferon-gamma (IFN-γ). Although intralesional injection of PRP alone did not induce repigmentation, a combination of PRP with NB-UVB induced statistically significant repigmentation in a series of 60 patients from Egypt  An interesting and promising study was performed with NCES suspended in PRP. Parambath et al compared the extent of repigmentation achieved using the transplantation of NCES in PRP and NCES in phosphate-buffered saline (PBS) in 21 patients with stable vitiligo. After 6 months, the repigmentation was 75.6% after NCES in PRP and 65% after NCES and PBS treatment (p = 0.0036). Moreover, the suspension in PRP was better assessed by patients in the visual analog scale. The clinical applications of combination therapy for vitiligo are summarized in Table 1 and Figure 2.

7. Are Cell-Based Therapies Appropriate for All Vitiligo Patients? Limitations and Challenges

Although vitiligo cell-based therapy is safe, well-tolerated, and effective at repigmentation with matching color and texture in appropriate candidates, it is still an underperformed treatment. There are several reasons for this: a limited number of practitioners know the technique details, a lack of awareness on the part of physicians, and a lack of insurance coverage for vitiligo because many consider it a cosmetic disease. Moreover, not all patients are willing to undergo this type of therapy. Parambath et al found that 11 out of 38 patients screened for the study were not willing to undergo surgery. When asked about the reasons for refusal, patients indicated the desire to receive a trial of medical therapy from a tertiary care center, fear of surgery, unwillingness for follow-up visits, and high costs. It should also be noted that not every vitiligo patient is eligible for surgical therapy. Depending on the clinical practice, most patients must have clinically stable vitiligo for 6 months to one year to qualify. Clinically stable vitiligo is determined by the non-appearance of new lesions and by the absence of changes in the existing ones. Patients with segmental or focal vitiligo are better candidates because they tend to achieve greater repigmentation than those with generalized disease. Higher rates of repigmentation were also reported in young patients compared to older ones.
It is also very important to note that it is difficult to estimate the overall percentage of people who have recovered from vitiligo, as only a fraction of them undergo treatment. Moreover, even though combination therapy is more effective than monotherapy, recurrence affects up to 40% of patients.
Patients are excluded from surgery if they had a history of koebnerization, hypertrophic scarring, keloids, or are susceptible to poor wound healing. According to Ramos et al., isolated scalp leukotrichia is an adverse prognostic sign, and the presence of significant distal fingertip, periorificial, or acrofacial involvement is also an exclusion criterion because these disease variants typically respond poorly to the melanocyte–keratinocyte transplantation procedure . However, as we discuss below, patients with leucotrichia in vitiliginous patches may also have a chance for successful treatment. Recently, molecular markers were suggested for better predictions of vitiligo diagnosis and response to treatment. The RNA sequencing in vitiligo patients showed differences in expression levels of 470 genes between the skin specimens of responder versus non-responder patients. Two hundred sixty-nine upregulated genes were involved in processes, such as fatty acid omega oxidation, whereas down-regulated genes (two hundred and one) were related to PPAR and estrogen signaling pathways.

8. Conclusion

In conclusion, cell therapies undergo continuous improvements both toward better re-pigmentation effects and simplifying the methods, making them more accessible to dermatological clinics. Modifications of procedures involving simplifying cell collection, ensuring their good transplantation potential, as well as using less sophisticated laboratory equipment, reduce the cost of the procedure and make it more accessible to patients. Another important factor when considering cell-based vitiligo treatment is the selection of appropriate candidates. In the meta-regression analyses by Ju et al, the successful outcome (>90% repigmentation) was associated with younger age, segmental vitiligo, and a non-acral area.
It should also be mentioned that repigmentation after cell therapy progresses gradually and may continue beyond 12 months following the procedure. Thus, there is a great need for more extended follow-up studies (minimum 6 months) for evaluation of the effectiveness and real cost that the patients must undertake on their way along the treatment of vitiligo.







Vitiligo in Children: A Review of Conventional Treatments



Vitiligo is an acquired, chronic, maybe autoimmune, pigmentary disorder characterised by white macules and patches, due to the progressive loss of cutaneous melanocytes and to an abnormality in their normal function [1].

Usually, it starts in childhood or young adult: it has been estimated that about 50% of patients develop vitiligo before the age of 20 years and about 25% of them develop the disease before the age of 8, with a mean age of 4 – 5 years [2].

In pediatric age, vitiligo may represent a psychological trauma for both patients and their parents, resulting in emotional disorders (e.g. anxiety, depression), poor quality of life scores, and low self-esteem [3].

Treating vitiligo and supporting patients to live their stigmatising condition, is the first aim of a dermatologist. Fortunately, nowadays different treatments, both medicals and surgical, are available.

Table 1

Current traditional therapeutic options for vitiligo in children

Treatment modality Drugs Mechanism of actions Side effect
Topical treatments Calcineurin inhibitors Immunomodulation Burning sensation, erythema, transient pruritus; risk of malignancies?
Calcipotriol Repigmentation, immunosuppression Transient burning or irritation
Corticosteroids Immunomodulation Epidermal atrophy. striae, telangiectasia, glaucoma, tachyphylaxis, hypothalamus-pituitary axis suppression, Cushing’s syndrome, growth retardation
Systemic treatments Corticosteroids Immunomodulation Glaucoma, tachyphylaxis, hypothalamus-pituitary axis suppression, Cushing’s syndrome, growth retardation
Phototherapies PUVA (12yo), Topical PUVA, Topical PUVA sol, nbUVB Repigmentation, immunomodulation Erythema, itching or burning sensation; chronic actinic damage; psoralen toxicity (nausea, vomiting, abdominal pain, liver toxicity, cataracts)

Other therapeutic options:

Combined therapies Camouflage

Depigmentation therapy (monobenzyl ether of hydroquinone)

Cognitive therapy and psychological support

Topical treatments

Topical corticosteroids (TCs)

The efficacy of topical corticosteroids in the treatment of vitiligo, especially of localised forms on the face and other body’s area, is well – known since long time [4].

Steroids act as anti-inflammatory and immunosuppressant agents. Even if different classes of steroids are now available, the mid- potent ones (e.g. betamethasone dipropionate 0.05% cream, 0.05% clobetasol propionate ointment) are usually preferred for the treatment of young patients. The drugs may be applied once or twice a day, in consecutive or on alternate days. Different studies report a response rate of 45 – 60% in childhood vitiligo, with best outcome in inflammatory vitiligo [5].

Even if their use should be prolonged for several months, TCs are quite safe only if used for few weeks, not more than 2 – 4 months, to avoid local side effects (e.g. atrophy, striae, telangiectasia, hypertrichosis, acneiform eruption) and systemic ones due to the percutaneous absorption (e.g. tachyphylaxis, suppression of hypothalamic-pituitary-adrenal axis, Cushing’s syndrome and growth retardation). In detail, the use of TCs on vitiligo patches of the face should be avoided or limited in time because of the higher risk of topical side effects, including glaucoma [6][7].

Topical calcineurin inhibitors (TCI)

Topical calcineurin inhibitors (tacrolimus and pimecrolimus) are considered valid alternatives to TCs for the treatment of localised forms of vitiligo. They act as immunomodulator agents: by blocking calcineurin, they inhibit the cytokines expression [8].

As TCs, TCIs are indicated for the treatment of localised forms of vitiligo, also for the facial lesions where they seem to be safer than steroids. Usually, TCIs are prescribed twice a day.

Tacrolimus 0.1% seems to be more effective than pimecrolimus 1%, achieving a repigmentation rate similar to that of topical clobetasol propionate (0.05%) [9]. Pimecrolimus 1% is another valid option for the treatment of facial lesions, especially on the thinnest cutaneous areas, such as eyelids [10].

Usually, TCIs are safe and well tolerated. The most common side effects are burning sensation, transient pruritus and erythema at the side of the application. Because of the potential risk of malignancies (e.g. skin cancers and lymphoma), TCIs cannot be used in children < 2 years. The major limit to treat vitiligo with CIs is due to their costs [6].


Calcipotriol is a synthetic vitamin D3 analogue, which has been used for many years in the treatment of psoriasis for its ability to regulate the epidermal turnover.

Its use in vitiligo patients, start with the observations that its topical application, on psoriatic lesions, may cause perilesional hyperpigmentation. Even if the exact mechanism of action has to be elucidated, calcipotriol seems to stimulate melanogenesis and to halt the melanocytes destruction by T – cells [11].

Calcipotriol is applied once a day. It seems to be less effective than TCs, with variable results in term of repigmentation rate. Interesting, calcipotriol seems to stimulate repigmentation in both treated and untreated skin, and to continue its action also after treatment termination, leading to hypothesise a systemic effect of the drug applied topically [12].

The drug is well tolerated, and the most common side effects are represented by a transient burning sensation or irritation at the site of application. The treated sites should not be exposed to phototherapy to avoid cutaneous hyperpigmentation.

Systemic treatment

Systemic corticosteroids (SCs)

In patients affected by unstable vitiligo, another therapeutic option is the systemic administration of corticosteroids (e.g. betamethasone, methylprednisolone), which seem to be useful to stop the progression of the disease and to induce repigmentation. Due to the potential well-described side effects, SCs are usually administered for a short period or in pulsed a regimen [13][14]. The dosages of SCs are usually decided by the patient’s characteristics. Recently, an oral mini-pulse therapy (OMP) has been proposed [15]. It consists of the morning intake of betamethasone (0.1 mg/kg body weight) on two consecutive days in a week for 12 weeks. After that, patients have to assume 1 mg/month for the following three months. The clinical results seem to be good, with minimal risk of side effects.


Ultraviolet radiations (UVR), both in the range of UVB and UVA, are considered as a first line therapy especially for extensive vitiligo, because of their good efficacy and tolerance. The effects of UVR are both immunosuppression and stimulation of the melanocytes activity [16].

Today, a range of phototherapies are now available: oral PUVA; topical cream PUVA, bath PUVA; PUVA sol; narrow-band UVB. Broad band UVB should no longer be used because of the sunburn risk and low efficacy.

PUVA therapy

PUVA therapy consists of the oral intake of a photosensitizing psoralen (e.g. 8 – methoxypsoralen, 5 – methoxysporalen or 4, 5, 8 – trimethylpsoralen) followed by exposure to photoactivating UVA light (320 – 400 nm). Treatment is performed 2 – 3 times a week, increasing the dose of UVA on the base of patient’s response. Because of psoralen’s toxicity (e.g. gastric and ocular damage), PUVA therapy should not be performed in children < 12. The rate of repigmentation after oral PUVA is about 75% in 50-60% of the children with vitiligo [4]. The possible side effects are due to both radiations and psoralens. While the most common short- time side effects are erythema, pruritus, xerosis and phototoxic reactions; the long-term ones include chronic actinic damage and carcinogenesis [16].

Topical PUVA

A valid therapeutic option for children with vitiligo is the topical PUVA. It consists of the application of 0.1 – 0.01% 8-methoxypsoralen in hydrophilic petrolatum or ethanol onto the vitiligo skin, followed by exposure to UVA-irradiated with a dose of 0.12 – 0.25 J/cm². The treatment is done 1 – 3 times a week, increasing the UVA dose until mild erythema will develop. The treatment provides good results, similar to the systemic PUVA [4]. The acute and chronic side effects, due to UV radiations, are well described.

Topical PUVA sol

Similar treatment is the topical PUVA sol: after the topical application of a psoralen cream, the patient will be exposed to sunlight. Although the proven efficacy of the treatment, the risk of acute and chronic actinic damage are well documented [17].


Patients take a warm bath with 0.5 -1.0 mg/l 8 – MOP for 20 min before they are exposed to UVA [18][19].

Narrow – band UVB (nb – UVB)

Today, narrow-band UVB (nb – UVB, 311 nm) is considered a valid and safeness therapy for vitiligo, especially for children due to the lack of psoralens. It consists in the exposure to nb – UVB at the starting dose of 0.1 mJ/cm², followed by 20% increasing dose of UVR on a weekly basis, accordingly to the clinical response. Treatment is well – tolerated. The commonest acute side effects are pruritus and erythema. Apart from supposed photo-damages, long-term side effects are yet to be determined [16]. Recent studies show how nb – UVB is more active than topical and oral PUVA, and that the repigmentation achieved with nb – UVB is more persistent and more similar to the colour of the unaffected skin [20].

Combined treatments

In the last years, different types of combined therapies have been proposed for the treatment of vitiligo in children.

Topical corticosteroids may be used in combination with calcipotriol [20]. This type of association seems to provide better clinical results in term of repigmentation and fast response, also in patients who did not have a response to the use of steroids alone. Moreover, the combination calcipotriol -corticosteroids reduce the side effects due to each drug, leading to a safer treatment.

In progressive vitiligo, TCs may be associated to the oral ones [21]. Apart from the risks due to the steroids therapy, the protocol seems to be effective in halting the progression of the disease and in inducing skin repigmentation. Finally, a study underlines also how the combination of OMP to nb – UVB phototherapy should be superior in the treatment of unstable vitiligo, then the systemic corticosteroids used alone [22].

Topical treatments may also be associated to phototherapies. For example, many studies show how nb-UVB combined with different topical drugs (e.g. Corticosteroids, vitamin D analogues, tacrolimus, pimecrolimus, pseudocatalase) could be more efficacy than phototherapy alone [16][17][18][19][20] [21][22][23][24]. In case of a combination, both TCI and vitamin D analogues should be used after UVB, never before to avoid risks such as hyperpigmentation or skin cancer.

Cosmetic camouflage

Due to the deep psychological impact of vitiligo, which risks representing a real stigma for patients, the camouflage of vitiliginous areas is often recommended [25]. Today many products are available. The ideal cosmetic is non – allergenic, colour matching, easy to apply and to remove, water resistant and cost-limited.

Depigmentation therapy

Unresponsive, widespread vitiligo or universal forms may be addressed to a total depigmentation therapy with 20% monobenzyl ether of hydroquinone (MBEH) [26].

Cognitive therapy and psychological support

Among the different type of vitiligo’s treatment, cognitive therapy and psychological support are strictly recommended for children with vitiligo and their parents, especially in the cases where it is clear the impact of the skin disease on their quality of life [27].

Surgical therapies

Surgical therapies are not recommended in childhood vitiligo and must to be limited to patients with stable localised lesions, unresponsive to the more conventional therapies. Surgical techniques in young children have to be also avoided because of their natural body growth in which lesions tend to extends, and they’re difficult to stand still in the post-operative time [4][5][6].

Today, different types of surgical techniques are available (Table 2). Among them, the suction blister epidermal grafting (SBEG) is the best choice for childhood vitiligo.

Table 2

Surgical therapies for childhood vitiligo

Technique Mechanism of actions Side effect
Surgical therapies Mini punch grafts, suction blister epidermal grafts (SBEG), thin Thiersch grafts, transplantation of epidermal cell suspension, cultured melanocyte suspension, and cultured epidermis, combined therapies Correction of the pigmentary disease Cost factor and time consumption; inability to treat large areas; risk of infections; transient hyperpigmentation of recipient or donor site; risk of Koebner phenomenon at the graft site

Among the various surgical techniques, suction blister epidermal grafting (SBEG) has been found to be most convenient and effective for children and adolescents, with an excellent rate of repigmentation (> 75%) in over 80% of patients [28]. Face and lips obtain best results [29].

Other surgical procedures include mini punch grafts; thin Thiersch grafts; transplantation of epidermal cell suspension, cultured melanocyte suspension, and cultured epidermis. Finally, there is the possibility to combine surgical techniques with medical treatments. An excellent example is the microdermabrasion of cutaneous lesions, followed by the topical use of pimecrolimus 1% cream [30].

Apart for the normal problems due to an intervention (e.g. risk of infection), the major problems due to surgical vitiligo therapies are represented by the necessity of expert equipment, the cost and the time consumption. Treatments are not indicated in the case of large vitiliginous areas and/or in the case of active vitiligo. Finally, there are the risks of transient hyperpigmentation of recipient or donor site, and of Koebner phenomenon at the graft site.


Vitiligo’s treatment has two main goals: the first one is to halt the disease progression; the second one is to induce the lesions’ repigmentation, achieving an acceptable cosmetic result. In the last years, several therapeutic options, both medical and surgical, have been proposed for vitiligo. The choice of the best therapy for childhood vitiligo is based on various factors, such as patient’s age, psychological condition and expectation, distribution and extension of skin lesions, type of vitiligo (stable or not), availability and cost of the therapeutic options.


Image credit: Bhanu Vishwanadhula

Assessing Behavioral and Psychological Symptoms in Chinese Vitiligo Patients


Background: Vitiligo is a common, acquired depigmenting disorder. The pathogenesis is not clear, neuropsychological factors may be involved. Vitiligo will affect the individual’s physical and psychological health, leading to different levels of psychological behavior problems. However, there are few research on psychological symptoms in patients with vitiligo in China.
Methods: Adult patients with vitiligo were selected in convenient sampling method from March 2019 to November 2019 from the dermatology clinic. They were evaluated by the DLQI (Dermatology Life Quality Index), SCL-90 (Symptom Checklist-90), SADS (Social Avoidance and Distress Scale) and MCMQ (Medical Coping Modes Questionnaire).
Results: The DLQI score was 7.56 ± 6.11, which was in the third level. The SCL-90 score of patients with vitiligo was 136.44 ± 39.19, significantly higher than the Chinese norms (P < 0.05), and it mainly manifested as interpersonal sensitivity, depression, anxiety and phobia, which may be affected by the patient’s gender, marital status, severity of disease, stage and location of skin lesions. The total score of SADS in patients was 10.30 ± 6.38. The total score and scores in all dimensions of SADS were significantly higher than the Chinese norms (all P < 0.05), which were related with the patient’s gender, educational attainment, severity, type and stage of skin lesions. For MCMQ, the facing score was significantly lower than the Chinese norms (P < 0.05), and the avoiding and yielding scores were significantly higher than the Chinese norms (all P < 0.05).
Conclusion: In China, vitiligo affects the patient’s quality of life to varying degrees, resulting in a series of psychological and behavioral problems. We should actively concern and improve the psychological health status and behavior of patients, and multidisciplinary treatment strategies and education about vitiligo should be given to the patients.

Keywords: vitiligo, quality of life, psychological health status, behavioral and psychological symptoms


Vitiligo is a common depigmentation skin disease due to the loss of melanocytes.1 The clinical manifestations are depigmentation spots of different sizes in skin and mucosa, which can be involved in any part of the body and hair. The incidence of vitiligo in the whole world is about 0.5–1% and the incidence varies from race to region and population.2,3 Skin lesions range from very limited to generalized. It also is a disfigurement disease. In addition to affecting individual mental and physical health, it also increases the economic burden of patients and their families, and affects the quality of life of patients.4

The etiology and pathogenesis of vitiligo are very complex. It is generally believed that individuals with genetic tendency show abnormalities in autoimmunity, oxidative stress, endocrine metabolism, neuropsychiatric and other aspects under the stimulation of a variety of inflammatory factors, resulting in melanin synthesis disorder or melanocyte destruction, and finally lead to depigmentation.1 Vitiligo is often misunderstood as a cosmetic disease.5 A large number of clinical practices have shown that patients with vitiligo often have stress events such as overwork, tension, anxiety and mental trauma before the onset of vitiligo.6,7 Psychosocial conditions affect the immune system and play a role in the disease process. More and more attention has been paid to the role of psychosocial factors in the occurrence and development of psychosomatic diseases. Research on the psychosocial factors in vitiligo has been reported.7–9 Therefore, vitiligo is a skin psychological disease that will not directly lead to physical damage but will lead to serious psychological problems in daily life.10

In general, clarifying the psychological and behavioral characteristics of patients with vitiligo, understanding their potential psychological and behavioral symptoms (such as anxiety, depression and social disorder), can help optimize the management of vitiligo, improve the treatment effect, improve the quality of life and promote their physical and mental health development.11

However, there are few researches on psychological symptoms in patients with vitiligo in China. This study aim to investigate the psychological and behavioral status in patients with vitiligo in China through psychological and behavioral related questionnaires, analyze the influencing factors of psychological and behavioral problems, and provide theoretical basis for comprehensive treatment and clinical intervention of vitiligo.



The study and protocols were approved by the Institutional Review Board of the Xi’an Jiaotong University, and performed according to guidelines governing ethics care in China. This study was performed in accordance with the rules laid down in the Declaration of Helsinki. Informed consent has been obtained from all patients for study participation, data collection and publication.


The convenient sampling method was used to select adult patients with vitiligo who came to the dermatology clinic of the Second Affiliated Hospital of Xi’an Jiaotong University from March 2019 to November 2019 as the research object. The inclusion criteria were: 1. All patients were over 18 years old. 2. The diagnosis of vitiligo was made by two dermatologists and wood lamp. 3. All patients had no previous history of mental illness. 4. All patients had no cognitive orientation disorder, had primary school education or above, and could understand the meaning of the questionnaires. 5. All patients voluntarily participated, and expressed their willingness to cooperate to complete the questionnaires carefully. Exclusion criteria were: 1. Patients were under 18 years old. 2. Patients with other skin diseases or major physical or neurological diseases (tumors, heart problems, liver and kidney dysfunction, epilepsy, etc.) that may impair their quality of life or psycho-behavioral status.


The initial sample consisted of 120 participants, after eliminating the questionnaires invalidated by their incorrect completion, the final sample was 117 (97.5%) in this study. The researcher gave explanation and guidance when necessary. All questionnaires were filled in on site and completed by the patients themselves. All patients who met the inclusion criteria were evaluated by general information questionnaire, dermatology quality of life index (DLQI), symptom checklist 90 (SCL-90), social avoidance and distress scale (SADS) and medical coping style scale (MCMQ). All questionnaires were in Chinese and the validated forms were used.

DLQI is currently the most widely used dermatological life quality questionnaire. It includes 10 questions related to symptoms and feelings, daily activities, leisure, work and school, interpersonal relationship and treatment, to evaluate the impact of skin diseases on patients’ quality of life during the previous 1 week.12 According to the total score of DLQI, the score is divided into 5 grades. 0~1 indicates almost no influence, 2~5 indicates small influence, 6~10 indicates moderate influence, 11~20 indicates very large influence, and 21~30 indicates extremely large influence.

The SCL-90 scale is used for self-assessment by people over the age of 16 and is one of the most well-known mental health testing scales in the world. It consists of 90 items, assessed from 10 factors of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobia, paranoid ideation, psychoticism, sleeping and eating state. According to their self-perception of the psychological state, the subjects rate their symptoms using a scale ranging from 1 to 5 on a scale corresponding to “none”, “very light”, “moderate”, “heavy”, and “severe”. The higher the score, the worse the mental health of the subject.13

SADS was compiled by Waston et al in 1969, and the Chinese version was revised by Hong Ma et al, which has been proved to have good reliability and validity.14 The scale consists of 28 items, including two dimensions of social avoidance and social distress, with 14 questions for each dimension and the score range from 0 to 28 points. The higher the score, the more severe the degree of social avoidance and distress.

MCMQ was formed into a formal Chinese version of the questionnaire by Qianjin Jiang et al, combined with the original Chinese translation version and revised several times.15 Twenty items are assigned to three coping styles: facing (8 items), avoiding (7 items) and yielding (5 items). Using a four-point scoring method (1–4 points), the total score is 20 to 80 points, and the higher the subscale score, the more obvious the coping style.

Statistical Analyses

The collected data were entered into excel and checked by two investigators, and the data were statistically analyzed by SPSS 18.0 statistical software. The mean ± standard deviation was used to describe the measurement data. Single sample t-test, one way analysis of variance (ANOVA) and two independent sample t-test were used to compare the differences. Spearman two-variable correlation analysis was used to analyze the correlation. P < 0.05 was statistically significant.


Basic Demographic Data

As shown in Table 1, a total of 117 patients completed the questionnaires, including 49 males (41.9%) and 68 females (58.1%). The ratio of men to women was 1:1.39. Most patients (67.5%) were younger than 40 years old and had no positive family history (76.9%). For severity of disease, 65.8% patients were mild. More than half of the patients (58.1%) were in progressive stage and 12.0% in rapid progress stage.

Table 1 Demographic Data of Patients with Vitiligo


DLQI Scores of Patients with Vitiligo

The DLQI scores of 117 patients with vitiligo in this survey ranged from 0 to 26 points, and the mean score was 7.56 ± 6.11. 15 of 117 patients (12.8%) had a score of 0–1, indicating that vitiligo had almost no impact on their quality of life, and 39 patients scored 2–5, up to 33.3%, 31 patients (26.5%) had a score of 6–10, meaning that vitiligo had a moderate impact on them. There were 25 (21.4%) patients with 11–20 points. 7 (6.0%) scored more than 20, which impacted of the quality of life greatly, see Figure 1.

Figure 1 The distribution of DLQI (dermatology quality of life index) scores of patients with vitiligo.


Mental Health Status and Univariate Analysis of Patients with Vitiligo

The mental health status of 117 patients with vitiligo was evaluated by SCL-90 questionnaire. As shown in Table 2, the mean score was 136.44 ± 39.19, which was significantly higher than the Chinese norm of SCL-90 (129.19 ± 40.25)13 (P < 0.05). Among the 10 factors, the scores of depression, anxiety, interpersonal sensitivity and phobia were significantly higher than the Chinese norms13 (all P < 0.05).

Table 2 Comparison Between SCL-90 Score in Patients with Vitiligo and Chinese Norms (mean±SD)


For Single factor analysis, as shown in Table 3, in terms of the total score of SCL-90 and the scores of interpersonal sensitivity, depression, anxiety and phobia, it was found that female patients were significantly higher than those of men (P < 0.05), the married group were lower than those in the unmarried group (P < 0.05), the patients in rapid progression stage were significantly higher than those in progressive and stable stage (P < 0.05), and patients with skin lesions on the exposed site also scored significantly higher compared with those without exposed lesions (P < 0.05). In addition, it was found that there were significant differences in interpersonal sensitivity and depression scores among patients with different diseases severity (both P < 0.05).

Table 3 Univariate Analysis of Patients with Vitiligo in the Score of Total SCL-90 and Interpersonal Sensitivity, Depression, Anxiety and Phobia (Mean ± SD)


Social Status and Univariate Analysis of Patients with Vitiligo

The scores of SADS in 117 patients with vitiligo in this survey ranged from 0 to 26, the mean score was 10.30 ± 6.38, and the mean score of social avoidance was 5.13 ± 3.38 and social distress was 5.17 ± 3.67. Compared with the Chinese norm,14 it was found that the differences were statistically significant (P < 0.05), see Table 4.

Table 4 Comparison Between SADS Score in Patients with Vitiligo and Chinese Norms (mean±SD)


For single factor analysis of social status of patients with vitiligo, the score of social avoidance in women was higher than that in men (5.69 ± 3.39 vs 4.35 ± 3.24, t = 2.156, P = 0.033). The total scores of SADS and social distress in the junior middle school group were significantly higher than those in the other three groups (all P < 0.05). For severity of disease, the total SADS and social avoidance scores in mild group were significantly lower than that of severe group (all P < 0.05). The total score of SADS, social avoidance and social distress score of patients in rapid progressive stage were significantly higher than those in the other two groups (P < 0.05), see Table 5.

Table 5 Univariate Analysis of Patients with Vitiligo in the Score of Total SADS, Social Avoidance and Social Distress (mean±SD)


Medical Coping Mode in Patients with Vitiligo

The score of face coping was lower than the Chinese norm,15 and the scores of yield coping and avoidance coping were higher than the Chinese norm (P < 0.05), see Table 6.

Table 6 Comparison Between MCMQ Score in Patients with Vitiligo and Chinese Norms (mean±SD)


Impact of Medical Coping Style on Patients’ Mental Health

As shown in Table 7, yield coping and avoidance coping were positively correlated with the scores of interpersonal sensitivity, depression, anxiety and phobia (all P < 0.05). Face coping was negatively correlated with social avoidance and distress (P < 0.05), and yield coping and avoidance coping were positively correlated with social avoidance and distress (all P < 0.05), see Table 8.

Table 7 Impact of Medical Coping on Patients’ Mental Health

Table 8 Impact of Medical Coping on Patients’ Social Status



Vitiligo is a common acquired depigmentation skin and mucous membrane disease, which can involve hair follicles. This disease is easy to diagnose, but difficult to treat. Repeated recurrence, and the change of appearance will damage the physical and mental health of patients to varying degrees.

Vitiligo will not bring serious health problems to patients, but lead to serious cosmetic problems. Many studies have shown that vitiligo lesions have a certain impact on the quality of life of patients.16,17 Consistent with the DLQI score in the world,17 the overall average score was 8.2, which was in the third level. The DLQI score of the 117 patients investigated in our study was (7.56 ± 6.11), in the third-level effect, indicating that vitiligo had a moderate impact on the quality of life of patients. DLQI scores are concentrated in 2–20 points, which is in the second to fourth level of influence. It is worth noting that 32 (27.4%) patients had DLQI scores higher than 10 in our research, indicating that the disease had a great impact on their quality of life. The change of appearance will affect the personality characteristics and social relations of patients to a certain extent. Studies have shown that the quality of life of patients with vitiligo is significantly related to their psychological distress and mental health.18 Importantly, the quality of life of vitiligo may be largely affected by psychosocial comorbidity.19

Skin plays an essential role in our interaction with the world, and skin color is important in perceiving someone’s health.20 The results of our study showed that the total score of SCL-90 was 136.44, which is significantly higher than the Chinese norm. The mental health problems of patients with vitiligo in China are mainly manifested as interpersonal sensitivity, depression, anxiety, and phobic anxiety. In this study, the total scores and all dimensions of SADS in vitiligo patients were significantly higher than the Chinese norms, indicating that compared with the general population, vitiligo patients had obvious social distress and social avoidance.

Many studies have shown that vitiligo has a greater impact on women’s mental health, and women are more prone to have mental symptoms and social disorders. Vitiligo sufferers experience limited participation in social interactions, job opportunities, religious activities, making friends, etc., showing significant social anxiety and avoidance.21 Compared with men, women experienced severe social distress, anxiety, and avoidance. In the study of Sawant,22 it was found that the degree of helplessness, depression and anxiety, social anxiety/avoidance and participation restriction of women were significantly higher than that of men. In our study, the scores of interpersonal sensitivity, depression, anxiety, phobia and social avoidance in women were significantly higher than men. Men and women have different psychosocial reactions to vitiligo. Women may pay more attention to their self-image, have more sensitive thoughts, and are more likely to feel embarrassed and ashamed of the reactions of people around them. Adverse emotional reactions make them become more helpless and negative when face to diseases. They take the initiative to avoid some social activities and avoid going out to contact with people. Moreover, men and women have different understanding and value to the relationship between marriage and love. Female patients are more worried about the impact of vitiligo on their mate selection and marital status, and the social acceptance of women suffering from vitiligo is low, which makes them more vulnerable.

Studies have shown that vitiligo has a negative impact on patients’ life and marital status. Patients with vitiligo feel troubled and ashamed when they start sexual relations and emotional experience.10 Our study showed that unmarried patients have more negative symptoms of interpersonal sensitivity, depression, anxiety and phobia than married patients. The score of social avoidance and distress were slightly higher than that of married people, but the difference is not significant, indicating that both unmarried people and married people all suffer from social distress and avoidance. Education level is an important demographic characteristic of an individual, which affects person’s cognitive behavior to a great extent. A study showed that the higher the level of education, the more the patients can rationally understand the disease and reduce the burden caused by the disease.23 Consistent with the results of our study, the scores of interpersonal sensitivity, depression, anxiety, phobia, social avoidance and distress of patients with junior high school education are higher than those with senior high school, junior college, undergraduate, graduate and above education. With the increase of disease severity, the scores of vitiligo patients in interpersonal sensitivity, depression, anxiety, phobia, social avoidance and distress showed an upward trend. Patients with severe pigmented diseases have an increased frequency of mental illness.24 The scores of interpersonal sensitivity, depression, anxiety, phobia, social avoidance and distress in skin lesions with rapid progression were significantly higher than those in progressive and stable stage. The scores of interpersonal sensitivity, depression, anxiety, phobia, social distress and avoidance of patients with skin lesions at the exposed site were higher than those without skin lesions at the exposed site, but only significant difference in the level of mental health, indicating that the mental health status of patients with the exposed lesions was worse than that of patients without lesions at the exposed site.23

In this study, the face coping score of patients with vitiligo was significantly lower than the Chinese norm, and the yield and avoidance coping scores were significantly higher than the Chinese norms. And face coping was negatively correlated with patients’ social avoidance and distress, and yield and avoidance coping were positively correlated with patients’ interpersonal sensitivity, depression, anxiety, phobia, social avoidance and distress. Scholars believe that the psychological intervention treatment of vitiligo should start with the treatment education of patients. Through the education of disease and standardized treatment, we can improve patients’ cognitive level of disease, significantly reduce the anxiety and fear, and increase their belief in actively facing disease.11

Participants with a good understanding of vitiligo were more likely to show a positive attitude toward vitiligo patients than those with insufficient knowledge of the disease.25 In addition to psychotherapy and/or counseling for patients, general education on vitiligo for unaffected people may help to reduce the stigma associated with vitiligo and improve the psychosocial health of patients and their caregivers.

This study also has some limitations: 1. This study only conducted a sampling survey in one hospital. 2. The sample size is limited, resulting in a small number of cases collected in some age, diseases severity and stage. Multicenter and large sample research should be done in the future. 3. We not used VitiQoL tool to analyze the quality of life of patients with vitiligo.26 4. There is no research on the effect of psychotherapy in patients with vitiligo.


In China, vitiligo affects the quality of life of patients to varying degrees, resulting in a series of psychological and behavioral problems, including interpersonal sensitivity, depression, anxiety, phobia, social avoidance and distress, which are mainly affected by the patients’ social demographic situation (gender, marital status, educational level), disease-related situation (stage, severity, whether there are skin lesions at the exposed site) and coping style. At the same time of routine treatment, clinicians should also actively pay attention to and improve the mental health and behavior of patients with vitiligo.

Other Reads : Factors Affecting Quality Of Life In Patients With Vitiligo Part 1


The authors declare no conflict of interest.


1. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;386(9988):74–84. doi:10.1016/S0140-6736(14)60763-7

2. Talsania N, Lamb B, Bewley A. Vitiligo is more than skin deep: a survey of members of the Vitiligo Society. Clin Exp Dermatol. 2010;35(7):736–739. doi:10.1111/j.1365-2230.2009.03765.x

3. Kruger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206–1212. doi:10.1111/j.1365-4632.2011.05377.x

4. Morrison B, Burden-Teh E, Batchelor JM, Mead E, Grindlay D, Ratib S. Quality of life in people with vitiligo: a systematic review and meta-analysis. Br J Dermatol. 2017;177(6):e338–e339. doi:10.1111/bjd.15933

5. Ezzedine K, Sheth V, Rodrigues M, et al. Vitiligo is not a cosmetic disease. J Am Acad Dermatol. 2015;73(5):883–885. doi:10.1016/j.jaad.2015.07.039

6. Picardi A, Pasquini P, Cattaruzza MS, et al. Stressful life events, social support, attachment security and alexithymia in vitiligo. A case-control study. Psychother Psychosom. 2003;72(3):150–158. doi:10.1159/000069731

7. Lai YC, Yew YW, Kennedy C, Schwartz RA. Vitiligo and depression: a systematic review and meta-analysis of observational studies. Br J Dermatol. 2017;177(3):708–718. doi:10.1111/bjd.15199

8. Osinubi O, Grainge MJ, Hong L, et al. The prevalence of psychological comorbidity in people with vitiligo: a systematic review and meta-analysis. Br J Dermatol. 2018;178(4):863–878. doi:10.1111/bjd.16049

9. Wang G, Qiu D, Yang H, Liu W. The prevalence and odds of depression in patients with vitiligo: a meta-analysis. J Eur Acad Dermatol Venereol. 2018;32(8):1343–1351. doi:10.1111/jdv.14739

10. Bidaki R, Majidi N, Moghadam Ahmadi A, et al. Vitiligo and social acceptance. Clin Cosmet Investig Dermatol. 2018;11:383–386. doi:10.2147/CCID.S151114

11. Taïeb A, Meurant JM. Should we prioritize psychological interventions in the management of vitiligo? J Eur Acad Dermatol Venereol. 2018;32(12):2053–2054. doi:10.1111/jdv.15297

12. Patel KR, Singam V, Vakharia PP, et al. Measurement properties of three assessments of burden used in atopic dermatitis in adults. Br J Dermatol. 2019;180(5):1083–1089. doi:10.1111/bjd.17243

13. Liu YY, Wu SJ, Li YQ, Shao F, Su JK, Liu XF. A survey of mental symptoms of Chinese population based on SCL-90. Chin Ment Health J. 2018;32(5):437–441.

14. Wang XD, Wang XL, Ma H. Manual of mental health assessment scale. Beijing. 1999;13:213–214.

15. Shen XH, Jiang QJ. Report on application of Chinese version of MCMQ in 701 patients. Chin J Behav Med Sci. 2000;9(1):18–20.

16. Gupta V, Sreenivas V, Mehta M, et al. What do vitiligo impact scale-22 scores mean? Studying the clinical interpretation of scores using an anchor-based approach. Br J Dermatol. 2019;180(3):580–585. doi:10.1111/bjd.17040

17. Amer AAA, Gao XH. Quality of life in patients with vitiligo: an analysis of the dermatology life quality index outcome over the past two decades. Int J Dermatol. 2016;55(6):608–614. doi:10.1111/ijd.13198

18. Bonotis K, Pantelis K, Karaoulanis S, et al. Investigation of factors associated with health-related quality of life and psychological distress in vitiligo. J Dtsch Dermatol Ges. 2016;14(1):45–49. doi:10.1111/ddg.12729

19. Ezzedine K, Eleftheriadou V, Jones H, et al. Psychosocial effects of vitiligo: a systematic literature review. Am J Clin Dermatol. 2021;22(6):757–774. doi:10.1007/s40257-021-00631-6

20. Silverberg JI, Silverberg NB. Association between vitiligo extent and distribution and quality-of-life impairment. JAMA Dermatol. 2013;149(2):159–164. doi:10.1001/jamadermatol.2013.927

21. Salman A, Kurt E, Topçuoglu V, et al. Social anxiety and quality of life in vitiligo and acne patients with facial involvement: a cross-sectional controlled study. Am J Clin Dermatol. 2016;17(3):305–311. doi:10.1007/s40257-016-0172-x

22. Sawant NS, Vanjari NA, Khopkar U. Gender differences in depression, coping, stigma, and quality of life in patients of vitiligo. Dermatol Res Pract. 2019;2019:6879412. doi:10.1155/2019/6879412

23. Mishra N, Rastogi MK, Gahalaut P, et al. Dermatology specific quality of life in vitiligo patients and its relation with various variables: a hospital based cross-sectional study. J Clin Diagn Res. 2014;8(6):YC01–YC03. doi:10.7860/JCDR/2014/8248.4508

24. Dabas G, Vinay K, Parsad D, et al. Psychological disturbances in patients with pigmentary disorders: a cross-sectional study. J Eur Acad Dermatol Venereol. 2019;34(2):392–399. doi:10.1111/jdv.15987

25. Tsadik AG, Teklemedhin MZ, Mehari Atey T, Gidey MT, Desta DM. Public knowledge and attitudes towards vitiligo: a survey in Mekelle City, Northern Ethiopia. Dermatol Res Pract. 2020;2020:3495165. doi:10.1155/2020/3495165

26. Lilly E, Lu PD, Borovicka JH, et al. Development and validation of a vitiligo-specific quality-of-life instrument (VitiQoL). J Am Acad Dermatol. 2013;69(1):e11–e18. doi:10.1016/j.jaad.2012.01.038

By Xiaoying Ning, Yanfei Zhang, Wei Wang, Huling Yan, Yumin Xia

Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China

Correspondence: Yanfei Zhang, Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email

Image Credit: Elf Moondance(Pixabay)

Approaching Nonsegmental Vitiligo with a Focus on the Immune-Mediated Aspects of the Disease and a New Treatment Option to Consider

Managing vitiligo has been a challenging journey. There have been limited options available for dermatologists to offer to help treat the chronic, inflammatory, autoimmune skin condition affecting approximately 2-3 million people1, including more than 1.5 million diagnosed, in the United States2. Vitiligo involves more than simply cosmetic issues, reinforcing the need for further research and management options for these patients and the dermatologists who care for them.

Progress in Research Around Vitiligo Management

In recent years, researchers have made important progress in understanding the underlying pathology of vitiligo. Based on preclinical data, the JAK/STAT pathway has been shown to mediate the production of IFNγ. IFNγ producing cytotoxic T lymphocytes have been shown to mediate melanocyte destruction in human vitiligo3. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

As JAK inhibition is linked to reduced skin inflammation and T-cell-mediated melanocyte destruction, a logical approach is to diminish local inflammation and facilitate endogenous repigmentation in patients with vitiligo. Proof of concept of JAK inhibition was demonstrated in small studies4, leading to Phase 3 trials and the recent U.S. Food and Drug Administration (FDA) approval of the first topical JAK inhibitor for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older.

“For patients who want to be repigmented, we had limited options to help,” explains David Rosmarin, M.D., Vice Chair of Research and Education, Department of Dermatology at Tufts Medical Center. “With the first approved pharmacologic treatment for nonsegmental vitiligo repigmentation now available, we now have a new option to offer our patients to help them manage their condition should they choose to treat their disease.”

Opzelura: The First and Only Topical JAK Inhibitor

In July 2022, the FDA approved Opzelura™ (ruxolitinib) cream 1.5% for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older. A nonsteroidal JAK inhibitor, Opzelura is applied topically on up to 10% body surface area (BSA) twice daily5.

The TRuE-V clinical trial program enrolled adults and adolescents 12 years of age and older with nonsegmental vitiligo affecting at least 0.5% facial BSA and 3% nonfacial BSA. Results from the Phase 3 TRuE-V clinical trial program demonstrated that the proportion of subjects achieving a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75) was significantly greater at Week 24 (primary analysis) compared to vehicle, with further improvement in an open-label extension at Week 52.

  • In the randomized Phase 3 TRuE-V1 and TRuE-V2 studies, the primary endpoint of F-VASI75 (the proportion of patients achieving a 75% improvement in the facial Vitiligo Area Scoring Index) at Week 24 was attained by significantly more patients who applied Opzelura versus vehicle in TRuE-V1/TRuE-V2, respectively (approximately 30% vs. approximately 8%/13%, P<0.0001)6. At Week 52, approximately 50% of Opzelura-treated patients achieved a 75% improvement in F-VASI75.
  • Additionally, at Week 24, more than 15% of patients treated with Opzelura achieved ≥90% improvement from baseline in F-VASI (F-VASI90), compared to approximately 2% of patients treated with vehicle. At Week 52, the percentage of Opzelura-treated patients who achieved F-VASI90 doubled to approximately 30%.

In clinical trials, the most common adverse reactions (incidence ≥ 1%) are application site acne, application site pruritus, nasopharyngitis, headache, urinary tract infection, application site erythema, and pyrexia6. The labeling for Opzelura includes a Boxed Warning for serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis. See additional Important Safety Information below.

The Future of Vitiligo Management

While the management of vitiligo was often previously seen as cosmetic, new research and management approaches are increasingly focused on treating vitiligo as an immune-mediated disease.

“The approval of Opzelura for the treatment of nonsegmental vitiligo presents a new option and an opportunity to revisit discussions with appropriate patients who are seeking repigmentation,” adds Dr. Rosmarin. “By working closely with our patients to determine their treatment goals, we can help ensure those looking to treat their vitiligo are aware of what is now available.”

An individualized plan is important to help manage the disease, and novel approaches can offer new options to help some patients successfully achieve their desired goals.

Opzelura may work for some, but not all, patients. To learn more, visit


OPZELURA is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.

Limitations of Use: Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.



Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death. Reported infections include:

  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
  • Invasive fungal infections, including cryptococcosis and pneumocystosis.
  • Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled. Carefully consider the benefits and risks of treatment prior to initiating OPZELURA in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA.

Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib.

No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA. During OPZELURA use, monitor patients for the development of signs and symptoms of TB.

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.

Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C.


In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.


Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

Non-melanoma skin cancers, including basal cell and squamous cell carcinoma, have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.


In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.


Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately.

Thrombocytopenia, Anemia, and Neutropenia

Thrombocytopenia, anemia, and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.

Lipid Elevations

Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.

Adverse Reactions

In nonsegmental vitiligo, the most common adverse reactions (incidence ≥1%) are application site acne (6%), application site pruritus (5%), nasopharyngitis (4%), headache (4%), urinary tract infection (2%), application site erythema (2%), and pyrexia (1%).


There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.


Advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives).

Please see Full Prescribing Information, including Boxed Warning, and Medication Guide for OPZELURA.


Photo Credit: Armin Rimoldi