Vitiligo is an autoimmune skin disease characterized by depigmented macules, which result from progressive melanocyte destruction in the epidermal area [
However, the evaluation of the mental health state in individuals with vitiligo has not been well demonstrated. On the one hand, most dermatologists focus on the treatment of skin lesions and ignore the potential mental symptoms. On the other hand, the majority of vitiligo patients reject the proposal for referral to a psychiatrist due to the stigma associated with psychosis [
Recently, numerous studies in this area have been published. Therefore, an up-to-date meta-analysis is essential to analyze the relationship between anxiety and vitiligo.
This meta-analysis was based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines [
Original articles matched the following inclusion criteria: (1) cross-sectional, case-control, or cohort study design; (2) a sample of patients clinically diagnosed with vitiligo; (3) anxiety was clinically diagnosed or evaluated by specific questionnaires; (4) sufficient raw data were available for analysis; and (5) manuscript in English or Chinese. Exclusion criteria were as follows: (1) reviews, conference abstracts, letters, or case reports and (2) duplicated or overlapping data. The process of article selection was conducted by two researchers (Jiani Liu and Rui Tang) independently. Any discrepancies were resolved by mutual discussion.
Two independent researchers (Jiani Liu and Rui Tang) extracted data from the included studies. The following baseline information were extracted: first author’s name, year of publication, study design, country, race of participants, number of participants, gender information, age, anxiety scales, and quality assessment score. To accurately evaluate the quality of each eligible study, all of studies were evaluated by the Newcastle–Ottawa Scale (NOS) [
All of the data processing and analysis were performed using Stata version 15.0 (StataCorp, College Station, TX, USA). The association between anxiety and vitiligo was estimated by the odds ratio (OR) for dichotomous data and standard mean differences (SMDs) for continuous data, with their corresponding 95% confidence intervals (CIs). The chi-squared test and
A total of 533 publications were identified from the primary online search (MEDLINE 77, Embase 217, the PsycINFO 13, Web of Science 209, and the Cochrane Library 17). Three additional articles were included through reference tracking. Next, 140 duplicates were removed. 337 articles were excluded due to irrelevant topics after screening of the titles and abstracts. After a meticulous full-text review of the remaining articles, 38 articles were excluded. Eventually, 21 studies involving 3259 cases were included for meta-analysis. Details of the online search strategy are presented in Figure
Flow diagram of literature selection strategy.
The main information of the 21 included studies is presented in Table
Characteristics of included studies.
Study | Study design | Country | Participants | Gender (male %) | Age (mean) | Anxiety measurement tools (cut-off) | Anxiety in patients with vitiligo (%) | Quality assessment by NOS (score) |
---|---|---|---|---|---|---|---|---|
Sharma et al. (2001) | Cross-sectional | India | 30 vitiligo and 30 psoriasis | 17 (56.7%) vs. 18 (60.0%) | N/A | DSM-IV | 3.3 | 6 |
Ahmed et al. (2007) | Cross-sectional | Pakistan | 100 vitiligo | 38 (38.0%) | 24.6 | PAS | 10.0 | 5 |
Schmid-Ott et al. (2007) | Cross-sectional | Germany | 363 vitiligo | 79 (21.8%) | 43.5 | ACS-SAA | N/A | 6 |
Saleh et al. (2008) | Cross-sectional | Egypt | 50 vitiligo and 50 psoriasis | 25 (50.0%) vs. 25 (50.0%) | 28.5 vs. 38.2 | TMAS | 14.0 | 6 |
Arýcan et al. (2008) | Cross-sectional | Turkey | 113 vitiligo | 53 (46.9%) | M: 29.2, F: 33.4 | Psychiatrists | 15.9 | 7 |
AlGhamdi (2010) | Cross-sectional | Saudi Arabia | 164 vitiligo | 91 (55.5%) | 27 | IPQ | 57.0 | 6 |
Ajose et al. (2014) | Cross-sectional | Nigeria | 102 vitiligo and 87 albinos | 51 (50.0%) vs. 53 (60.9%) | 35.94 vs. 30.05 | HADS-A (>10) | 18.6 | 9 |
AlShahwan (2015) | Cross-sectional | Saudi Arabia | 64 vitiligo and 811a | N/A | N/A | HADS-A (>10) | 26.6 | 6 |
Morales-Sanchez et al. (2017) | Cross-sectional | Mexico | 150 vitiligo | 47 (31.3%) | N/A | BAI (>15) | 60.0 | 8 |
Raikhy et al. (2017) | Cross-sectional | India | 53 vitiligo and 947a | N/A | N/A | ICD-10 | 11.3 | 7 |
Sorour et al. (2017) | Cross-sectional | Egypt | 108 vitiligo and 934a | 48 (44.4%) vs. N/A | N/A | DSM-V | 31.5 | 9 |
Sawant et al. (2019) | Cross-sectional | India | 100 vitiligo | 56 (56.0%) | M: 35.8, F: 36.9 | ASC-SAA | N/A | 8 |
Dabas et al. (2020) | Cross-sectional | India | 95 vitiligo and 86 melasma | 34 (35.8%) vs. N/A | N/A | GAD-7 (>8) | 21.1 | 9 |
Chen et al. (2020) | Cohort | China | 1432 vitiligo and 5728b | 559 (39.0%) vs. 2239 (39.1%) | 47.08 vs. 46.09 | ICD-9-CM | 12.2 | 8 |
Balaban et al. (2011) | Case control | Turkey | 42 vitiligo and 33 HCs | 19 (45.2%) vs. 14 (42%) | 39.70 vs. 35.12 | DSM-IV, LSAS | 4.8 | 8 |
Zang and Ji (2012) | Case control | China | 80 vitiligo and 40 HCs | 33 (41.3%) vs. 16 (40.4%) | 29.1 vs. 29 | SAS (>50) | 47.5 | 8 |
Karelson et al. (2013) | Case control | Estonia | 54 vitiligo and 57 HCs | 22 (40.7%) vs. 23 (40.4%) | 36.6 vs. 39.7 | ES-Q (>12) | 22.0 | 7 |
Wei et al. (2013) | Case control | China | 55 vitiligo and 118 HCs | 29 (52.7%) vs. 60 (50.8%) | 40.98 vs. 40.56 | HAMA (>14) | 10.9 | 5 |
Mufaddel and Abdelgani (2014) | Case control | Sudan | 24 vitiligo and 105 HCs | N/A | N/A | HADS-A (>8) | 62.5 | 7 |
Karia et al. (2015) | Case control | India | 50 vitiligo and 50 HCs | 22 (44.0%) vs. N/A | 33.6 vs. N/A | DSM-IV | 8.0 | 7 |
Ucuz et al. (2020) | Case control | Turkey | 30 vitiligo and 30 HCs | 18 (60%) vs. 18 (60%) | 12.3 vs. 13.3 | K-SADS-PL | 10.0 | 6 |
Abbreviations: N/A: not applicable; HCs: healthy controls; M: males; F: females; NOS: Newcastle–Ottawa Scale; AHRQ-11: 11 Agency for Healthcare Research and Quality; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; PAS: Psychiatric Assessment Schedule; ACS-SAA: Adjustment to Chronic Skin Diseases Questionnaire-Social Anxiety/Avoidance; TMAS: Taylor Manifest Anxiety Scale; IPQ: Illness Perception Questionnaire; LSAS: Liebowitz Social Anxiety Scale; SAS: Self-Rating Anxiety Scale; ES-Q: Emotional State Questionnaire; HAMA: Hamilton Anxiety Scale; HADS-A: Hospital Anxiety and Depression Scale-Anxiety; BAI: Beck’s Anxiety Inventory; ICD-10: International Classification of Diseases, 10th Edition; DSM-V: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; ICD-9-CM: International Classification of Diseases, 9th Revision, Clinical Modification; GAD-7: General Anxiety Disorder-7; K-SADS-PL: Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version. aNonvitiligo patients with skin diagnosis; bpatients without vitiligo.
Six case-control studies reported data about the prevalence of anxiety in both vitiligo patients and healthy controls [
The strength of association between anxiety and vitiligo: (a) Forest blot; (b) Begg’s funnel plot.
The prevalence of anxiety in male and female patients with vitiligo was separately provided in four studies [
Female predominance of anxiety in patients with vitiligo: (a, c) Forest plot; (b, d) Begg’s funnel plot.
Nineteen studies [
The pooled prevalence of anxiety in patients with vitiligo: (a) Forest plot; (b) Begg’s funnel plot.
Sensitivity analysis was conducted to confirm the stability of all of the analyses with respect to the comorbidity of vitiligo and anxiety. The pooled results of all of the analyses were not significantly changed after the removal of any specific studies (Figure
Sensitivity analysis: (a) for the strength of association between anxiety and vitiligo; (b) for the female predominance (OR) of anxiety in patients with vitiligo; (c) for the female predominance (SMD) of anxiety in patients with vitiligo; (d) for the pooled prevalence of anxiety in patients with vitiligo.
Compared with the relevant study by Osinubi et al. [
Plenty of clinical studies have reported the viewpoint that patients with vitiligo are susceptible to anxiety disorders. We first conducted a quantitative assessment of the susceptibility of anxiety in vitiligo patients. Several hypotheses may explain the increased prevalence of anxiety disorders among individuals with vitiligo. In some regions, skin depigmentation may be regarded as a sign of low social status, and patients with skin depigmentation suffer from more discrimination in daily life [
Subgroup analysis was conducted to evaluate the influence of different cultures on the prevalence of anxiety among participants with vitiligo. Although the results did not achieve statistical significance, an interesting appearance was that the pooled prevalence of anxiety increased from 15% for studies conducted in Asians to 23% for that in the Middle East. This diversity might be related to different levels of vitiligo acceptance between different cultures [
Most viewpoints assumed that vitiligo patients with dark skin (Fitzpatrick skin phototypes IV-VI) are more susceptible to anxiety, depression, and other psychological diseases because of greater notable depigmented patches and the stigma [
This association between vitiligo and anxiety can partly be explained by molecular biological mechanisms. Both the skin and the brain originate from the ectoderm during embryogenesis and are regulated by many of the same hormones and neurotransmitters [
As far as we know, this study is the first meta-analysis to clarify the female predominance of anxiety in vitiligo patients. According to our data, females have a higher risk of anxiety and develop more severe social anxiety, which may be related to greater cosmetic awareness and lower self-confidence [
We have observed notable heterogeneity between studies with respect to the pooled prevalence of anxiety, which may be due to the fact that different anxiety-specific scales and clinical diagnostic criteria were utilized in different studies. Six clinical diagnostic criteria (such as DSM-V, ICD-10, and K-SADS-PL) and 10 different validated screening scales were separately applied in the included studies, of which two scales (ACS-SAA and LSAS) were aimed at evaluating social anxiety. Therefore, we conducted a subgroup analysis to identify whether the difference in outcome assessment tools would be a potential heterogeneity source. Our results indicate that the prevalence identified by clinical criteria was significantly lower than that identified by screening scales. This can be explained by the fact that the purpose of screening scales is to identify as many anxiety symptoms or subclinical anxiety emotions as possible and to rate these manifestations; however, the purpose of clinical criteria is to accurately diagnose clinical anxiety disorders and to conduct medical interventions in a timely manner. In the subgroup analysis, the heterogeneity between studies was slightly lower. Differences in measurement standards among various screening scales were among the confounding factors that cannot be avoided. An interesting problem is that thresholds applied to screening scales to define anxiety symptoms also differed between studies. Even if the same scale was used, like HADS-A, the measurement thresholds to define outcomes differed between studies [
Additionally, depression, phobia, adjustment disorder, and somatoform disorder also occur in patients with vitiligo [
The limitations of our article are worth discussing. For example, the case-control studies comparing the prevalence of anxiety in vitiligo patients and healthy controls are limited. Only a small number of studies reported the prevalence of anxiety in female and male patients separately. Although no heterogeneity has been observed in these analyses, more related studies with more candidates are required to support our conclusion. Moreover, the high heterogeneity in the analysis of the prevalence of anxiety in vitiligo patients cannot be ignored. Besides the measurement tools, other factors might be taken into consideration for the heterogeneity, such as the study design and age of participants. Therefore, more results based on those confounding factors would be helpful to our further research.
In conclusion, comorbidity of anxiety and vitiligo is common in the clinic. Patients with vitiligo have an enormous burden due to anxiety, with female predominance. Dermatologists and psychiatrists should be vigilant to the presence of anxiety, apply appropriate interventions to reduce the psychological impacts in a timely manner, and thus promote recovery in vitiligo patients. A better designed case-control study and larger sample sizes are warranted for future studies. Moreover, in the field of psychodermatology, a uniform scale to measure anxiety in vitiligo patients is urgently needed.
The data supporting this meta-analysis are from previously reported studies and datasets, which have been cited. The processed data are available from the corresponding author upon request.
The authors declare that there is no conflict of interest regarding the publication of this paper.
Study design was handled by JL and RT. Data collection and analysis were handled by JL, RT, YX, and ML. Manuscript preparation was handled by JL, YS, QD, HZ, ZZ, and ZP. Manuscript revision was handled by YX, ML, and RX. All coauthors approve the manuscript for publication.
This work was supported by the National Natural Science Foundation of China (No. 81773333 and No. 81703134), Development and Reform Commission of Hunan Province Innovation Project (2019412), and Hunan Natural Science Foundation (Nos. 2019JJ50853 and 2018JJ3772).
We thank LetPub (
Figure S1: subgroup analysis of the influence of different regions on the pooled prevalence of anxiety among patients with vitiligo. The result is shown in the Forest plot.