Comparing quality of life, anxiety, depression, sleep disturbance, and associated factors in vitiligo and alopecia areata patients

Vitiligo and alopecia areata (AA) are two autoimmune skin diseases that affect patients' quality of life (QoL) and give rise to psychosocial complications, such as depression, negative self‐image, less joyful social engagements, and low self‐esteem. These two disorders have common and uncommon characteristics. Therefore, in this study, we tried to evaluate the similarities and differences in the psychological parameters including quality of life, sleep disturbance, anxiety, and depression levels between, vitiligo and AA patients.


| INTRODUC TI ON
Skin is an exterior barrier, providing communication with the external environment and protection from harmful factors. 1 Additionally, as the most visible part of the body, the skin plays an important role in attraction and attention.Therefore, the presence of any abnormality may lead to psychological, physical, social, and occupational problems in patients with skin diseases. 2tiligo and AA are two skin disorders that share some similarities but also have distinct differences.Both conditions are classified as autoimmune diseases and are characterized by similar pathophysiologies, specifically involving the innate and adaptive immune system. 3Moreover, both diseases lead to a disruption of the aesthetic self-image of affected patients.The visibility and disfigurement of the lesions, combined with the chronic nature of these disorders, as well as the limited available treatment options, negatively impact the mental health of these patients and have placed them among psychosomatic skin disorders. 4,5Vitiligo targets melanocytes, leading to skin depigmentation. 6It is the most common pigmentation disorder with a prevalence range of 0.5%-2.0%. 7AA targets the hair follicle and results in hair loss, which affects approximately 0.63% of the population. 8The course of both diseases is usually almost unpredictable with no complete cure available so far. 9 vitiligo, low self-esteem may have a negative impact on patients' personal and social lives. 10Furthermore, it has been reported that 30% of patients experience psychological problems after disease initiation. 11Social pressure and cosmetic problems may cause severe psychological issues, such as suicidal ideas, anxiety, embarrassment, impairment of sexual function, and difficulty in finding jobs which all result in decreased quality of life (QoL) in vitiligo subjects.Vitiligo can cause distress and feelings of being stigmatized, and in addition, it may lead to depression. 12search has shown that AA has detrimental effects on healthrelated quality of life comparable to those with long-term skin conditions like psoriasis. 13Sense of vitality, mental health, and emotional well-being appear to be the most affected domains in AA patients.
Anxiety and desperation lead to disturbance of sexual relationships, lower sleep quality, and unhealthy coping mechanisms in AA patients, 14,15 Over time, the cumulative disability intensifies and manifests as low self-esteem, social isolation, and decreased ability to reach one's full potential in life. 16udying the social and mental health effects of vitiligo and AA on patients is of utmost importance due to the significant psychological impacts and social burden associated with both conditions.In addition, providing psychological support for patients based on specific impairments not only enhances the patients' well-being but also reduces the burden on their families and society. 17,18Considering the similarities and differences between these two disorders, as well as the lack of research comparing their comprehensive psychological aspects, we tried to perform a study to compare the quality of life, anxiety, depression, and sleep disturbance among patients with AA or vitiligo using different standardized questionnaires and scoring systems to obtain more accurate results.

| Patients population
In this study, patients with a diagnosis of either vitiligo or AA have been recruited from the outpatient dermatologic clinic from November 2017 to December 2020.Our exclusion criteria included patients younger than 14 years of age, lack of enough evidence for precise diagnosis, and disagreement for contribution to this study.
Patients were asked to fill out three questionnaires, including the dermatology life quality index (DLQI), hospital anxiety and depression scale (HADS), and Pittsburgh sleep quality index (PSQI), after obtaining written informed consent.Data including age, sex, marital status, drug history, associated diseases, and education were collected from all participants.To avoid any misunderstanding regarding the questions, a research assistant was available to the patients while filling out the questionnaire.All the study protocols were approved by the local ethical committee.All data were used anonymously.

| Questionnaire
A Persian version of the DLQI questionnaire, developed by Aghaei et al., was used as a validated measurement of QOL with Cronbach's alpha coefficient of 0.77. 19The DLQI consists of 10 questions with four-point scale answers.Questions are categorized into 6 groups: questions 1 and 2, symptoms and feelings; 3 and 4, daily activities;

| Statistical analysis
The data were analyzed with SPSS software version 24.The results were statistically described as mean ± SD in continuous variables.Also, the frequency and percentage of categorical variables were reported.The normality of continuous variables was checked using the Shapiro-Wilks test.Non-parametric statistics were applied for data analysis.Chi-square and Fisher's exact test were used to evaluate the association between categorical variables.The Mann-Whitney U-test was used to compare the acral and non-acral groups.Moreover, the Spearman correlation coefficient was used to measure the variables' association.The level of significance for statistical tests was 0.05.

| Study population
In this research, 188 patients (83 males (44.14%) and 105 females (55.85%)), were recruited.Moreover, 94 (50%) patients had AA, and 94 (50%) had vitiligo.The mean ± SD age of AA and vitiligo patients was 32.35 ± 7.563 and 37.56 ± 14.404 years, respectively.There were no significant differences in gender distribution, marital status, and disease duration between the two groups.However, we detected a higher mean age range in our vitiligo patients (pvalue < 0.001), while a higher employment rate was seen in AA patients (p-value = 0.044).Furthermore, a higher number of AA patients had a history of other diseases.Patients' baseline characteristics are summarized in Table 1.

| Quality of life
The QoL median score was 9.28 ± 7.85 and 5.66 ± 5.02 in AA and vitiligo subjects, respectively, interpreted as moderate impairment in both groups.A significant difference between the two groups has been found (p-value: 0.002), which shows lower QoL in AA subjects compared to vitiligo patients.This study showed that employed patients had better QoL in both groups (p-value < 0.001), and patients with higher education levels had better QoL, but this difference was only significant in the vitiligo group (p-value: 0.020).
The relation between age and DLQI was determined by Spearman's rho correlation coefficient, which showed a negative correlation between age and DLQI, but it was not significant (p-value: 0.633 for AA, p-value: 0.190 for vitiligo).Besides, QoL was not affected by gender, marital status, duration of the disease, and history of other diseases.The results of DLQI and associated factors are summarized in Tables 2 and 4.

| Anxiety and depression
This study showed that the mean depression scores were 8.24 ± 5.20 in AA patients and 5.37 ± 4.49 in vitiligo patients, and this difference was statistically significant (p-value < 0.001).
Besides, the anxiety mean score was 10.88 ± 5.22 and 6.55 ± 4.48 in AA and vitiligo subjects, respectively.There has been a significant difference in anxiety mean scores between groups (p-value<0.001).Depression and anxiety scores were higher in  2 and 4.

| Sleep disturbance
Sleep disturbance was observed in 64.9% (61 cases) of AA patients, while it was observed in 59.3% (35 cases) of vitiligo patients.
However, there was no statistical difference between the two groups (p-value = 0.488).No association was found between age, gender, marital status, employment status, disease duration, education and history of other diseases, and sleep disturbance.Results are shown in Tables 3 and 4.

| DISCUSS ION
In this study, we compared QoL, depression/anxiety, and sleep disturbance using DLQI, HADS, and PSQI scores between vitiligo and AA patients.According to our knowledge, this is the first study that compares all these three factors in AA and vitiligo patients.Our data revealed that AA patients not only had a lower QoL but also were at a higher risk of anxiety and depression compared to vitiligo patients.

| Quality of life and associated factors
The mean DLQI score for vitiligo and AA in our study was 5.66 ± 5.02 and 9.28 ± 7.85, respectively.In a study by Temel et al. 22 comparing QoL in vitiligo and AA, higher DLQI scores were reported in AA patients, consistent with our findings.
Additionally, a systematic review and meta-analysis conducted by van Dalen et al. 23 on AA and a study performed by Al-Shammari et al. 24 on vitiligo reported a moderate impact on quality of life, which was in accordance with our research.Furthermore, a study evaluating vitiligo's impact on QoL in different countries found that worldwide DLQI scores ranged from 1.82 to 15. 25 This wide range could be attributed to variations in awareness about vitiligo within different communities.Generally, Middle Eastern countries tend to have higher DLQI scores compared to European countries, which may be influenced by factors like skin color, disease education, and cultural stigma. 26Moreover, a study examining the effect of vitiligo treatment on DLQI scores demonstrated a statistically significant improvement in scores between pre and posttreatment. 27nder is among the factors that may affect patients' QoL.
Despite the fact that previous studies have suggested that women with vitiligo or AA experience lower QoL than men, 28,29 we did not find any gender-related differences in QoL in either vitiligo or AA subjects.Notably, our finding is compatible with the results of van Dalen et al. 23 research on AA and Al-Shammari et al. 24 study on vitiligo patients.This outcome might be explained by the use of hijab by females to cover both hair and skin in Islamic countries. 30nsidering the impact of age and marital status on QoL in vitiligo and AA patients, conflicting results have been found in different studies.It has been reported that both vitiligo and AA cause poorer total QoL in young patients. 23,31While Aghaei et al. 19  Regarding the effect of educational level, Gupta V et al. 33 found that vitiligo patients with less education had lower QoL, but Yang et al. 31 in the aforementioned study obtained a significantly poorer QoL among highly educated subjects aligns with our findings.
Considering the effect of occupational status on QoL, our research showed that employed patients had better QoL in both vitiligo and AA subjects.However, results from other studies are inconsistent with our investigation.For example, Wong et al. 34 showed that employed vitiligo patients had a lower QoL because they were more embarrassed to attend work.As described by Mishra et al. 35 about QoL in vitiligo, we also found that employment leads to a better socioeconomic status and more opportunities; therefore, employed patients may appreciate a better QoL.
The effect of disease duration on QoL has been a matter of debate in different studies.Hedayat et al. 36 reported that patients who had vitiligo for less than 5 years had a better quality of life.In contrast, regarding AA duration, Bilgic et al. 37 suggested that a longer duration of AA improves QoL.However, we did not find any significant association between disease duration and QoL in either AA or vitiligo subjects, which agrees with Jankovic et al. 38 study.

| Depression and anxiety and associated factors
0][41] Our study revealed that there are a higher anxiety and depression levels among AA patients compared to vitiligo.[44] Regarding associated factors, we did not find any significant correlation between age or gender and anxiety or depression in vitiligo and AA subjects.However, previous studies have found that female patients with vitiligo or AA are at a higher risk of developing depression and anxiety. 12,45,46Furthermore, we found that employed AA patients had significantly higher depression and anxiety scores, which opposes the findings in Yildiz et al.'s research. 44We hypothesized that employment may cause embarrassment for patients when attending work and having to interact with more people.

| Sleep disturbance and associated factors
Sleep disturbance is associated with autoimmune diseases such as vitiligo and AA. 47Moreover, patients with sleep disorders are at a greater risk for AA and vitiligo. 47We found no significant differences in sleep disturbance between the two groups; however, the prevalence of sleep disturbance was significantly high in both groups (59.3% and 64.9% for vitiligo and AA, respectively).In a study by Sharma et al., 48 the prevalence of sleep disturbance using DSM-IV criteria in vitiligo patients was reported 20%, which is contrary to the results of the current study, where we used the PSQI-P questionnaire to screen sleep disturbance.The higher prevalence of sleep disorders in our study might be attributed to the difference in diagnostic methods between the two studies.Regarding sleep disturbance in AA patients, more than threequarters (77.3%) of the patients had poor quality of sleep based on the PSQI score of 5 or higher, which was in line with the current study. 49 did not find any correlation between sleep disturbance and demographic or disease-related factors in patients with vitiligo and AA, which is consistent with Öztekin et al. 50study findings.
Our study had some limitations.We did not divide the patients into groups based on the severity and duration of the disease or age range.More research with the age range and severity classification will result in more accurate findings.

5 and 6 ,
leisure time; 7 work/school; 8 and 9; personal relationships; and question 10, treatment.The total score varies from 0 to 30 and was calculated by summing the scores.The higher score showed worse QoL.The HADS questionnaire was designed by Zigmond and Snaith in 1983 and is commonly used to evaluate the level of anxiety and depression.HADS consists of 14 items, 7 questions are related to depression, and 7 questions are related to anxiety.Each question score is 0 to 3, and the total score ranges from 0 to 21 for each subscale.We obtained the final scores by summing all items.A global score of less than 7 was considered normal, 8-10 as mild disease, 11-14 as moderate, and 15-21 as severe anxiety or depression.The Persian version of HADS was developed with Cronbach's alpha of 0.78 for the HADS anxiety sub-scale and 0.86 for the HADS depression sub-scale. 20PSQI-P is a self-report, 19-question questionnaire that evaluates seven components: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.Each question scores from 0 to 3, and the total score ranges from 0 to 21.Higher scores show worse sleep quality.A score of more than 5 was considered as having a sleep disorder.Cronbach's alpha was calculated at 0.77 for the Persian version of PSQI. 21

5 |
CON CLUS IONAccording to our current knowledge, this is the first study comparing QoL, depression/anxiety, sleep disturbance, and associated factors in AA and vitiligo patients.This study revealed a higher QoL and a lower level of anxiety and depression in vitiligo patients in comparison to AA patients.No association was found in terms of age, gender, marital status, and QoL in the two groups.While sleep disturbance was common in both groups, the prevalence was almost equal in vitiligo and AA patients.There were some limitations in our study.We did not classify the patients according to the severity of the disease or age range.Further studies with the classification of age range and disease severity will lead to more precise results.We suggest additional studies with larger sample sizes and closer age range.

Alopecia areata N (%) Vitiligo N (%) p-Value
a Unemployed present unemployed, housewife, and retired patients.bSingleconsists of single and widow patients.TA B L E 1 Comparison of patients' characteristics between two groups.employedpatients,but this difference was only significant in AA subjects (p-value: 0.027 for depression and 0.031 for anxiety).This study revealed no statistically significant correlation between age, gender, marital status, history of other diseases and disease duration, and depression/anxiety scores.Results are presented in Tables Spearman's rho correlation coefficient for the association between age and DLQI, anxiety, and depression scores.Mean age ± SD in AA and vitiligo patients and its correlation with sleep disturbance.The P-value is calculated with Independent-Samples Mann-Whitney U Test. PSQI>5 is considered as having sleep disturbance.
TA B L E 2 TA B L E 4 Dermatologic quality of life (DLQI), depression score, anxiety, score, and sleep disturbance and its correlation with demographic characteristics of patients with alopecia areata and vitiligo.