The Mental Health Associations With Vitiligo: a Population-based Cohort Study in the UK
Conditions: Vitiligo, Depressive Episode, Recurrent Depressive Disorder, Anxiety Disorders, Social Phobia, Adjustment Disorders, Substance Abuse, Self-Harm, Deliberate, Overdose, Suicide, Attempted, Parasuicide
Sponsor: Momentum Data

 
 
The mental health associations with vitiligo: a population-
based cohort study in the UK [Study protocol] 
 
Version 
2.6 
Date 
18 June 2021 
NCT number 
NCT04953338 
 
 

 
 
Background 
Vitiligo is an acquired skin disorder characterised by depigmented patches of skin that may 
appear in a localised or generalised distribution. Vitiligo is estimated to affect 0.5-2% of the 
global population with an equal incidence between genders, age or racial/ethnic groups [1]. The 
exact cause of the loss of functioning melanocytes in vitiligo remains unknown but is likely to be 
resulted from the complex interplay of genetics, oxidative stress, and autoimmunity [2]. 
 
Although vitiligo is typically asymptomatic, it may substantially affect the psychological 
wellbeing of people living with the condition [3]. This could be due to the unpredictable 
prognosis, the current lack of cure or the perception and emotional burden associated with the 
visibility of vitiligo. A recent systematic review has shown that people with vitiligo are 
significantly more likely to suffer from depression and anxiety compared to the healthy controls 
[4]. However, there is a lack of knowledge of the other types of psychological 
symptoms/disorders that people with vitiligo experience [5]. 
 
Human society places a profound significance on appearance, aesthetics and pigmentation [6]. 
Vitiligo is visible on all skin types, and is particularly noticeable on dark skin tones because of 
the strong contrast. Given the visible difference in appearance of affected and unaffected areas 
of the skin the condition has been construed as being disfiguring. Some studies have suggested 
in those with darker skin vitiligo is correlated with a worse quality of life (QoL) [7, 8]. However, 
these studies have small sample sizes and psychiatric comorbidities and psychological wellbeing 
were not evaluated in the analyses. Further, there are other studies that indicate that people 
with lighter skin tones may also experience distress [9]. 
 
In addition to skin colour, the location of vitiligo lesions may also influence the overall well-being 
and stigmatisation experience of patients. However, inconsistent findings have been reported. A 
few studies showed that patients had a more significant QoL impairment when lesions were 
located on visible sites (e.g. face, neck and hand) [10, 11] whilst other studies did not find any 
relationship [12, 13]. By contrast, some studies report vitiligo lesions on more central body parts 
(e.g. chest, arms and trunks) are more likely to have an adverse impact on emotional wellbeing 
of people with the condition, perhaps because there remains anxiety as to how they might be 
judged by others if the condition were to be revealed [7, 14]. Indeed, the nature of reactions 
received from others is also likely to play an integral role in adjustment and the extent to which 
stigmatisation is experienced [15, 16]. Additional data from mixed method studies is needed to 
further understand this topic and how this may affect the possible comorbid burden of mental 
health conditions. 
 
There is currently a lack of large population-based studies providing reliable estimates of the 
risks of psychological comorbidities associated with vitiligo in the UK. A recent observational 
study using the UK-THIN database [17] highlighted the burden of depression in vitiligo patients 
and found a bidirectional relationship between the two conditions. However, the study did not 
explore the associations with other forms of psychological distress and did not use a validated 
definition for depression. An analysis of the depression risk on the populations of different 
ethnicity and location of the vitiligo lesions, which can be potential sources of heterogeneity, 
were also not conducted.  
 

 
 
Objectives 
To the best of our knowledge, there has only been one large population-based study assessing 
psychosocial comorbidities in vitiligo compared to those without the condition.[17] This study 
was limited only to exploring major depressive disorder (MDD, also termed recurrent 
depressive disorder) and used an unvalidated case definition for MDD. There have been no large-
scale population studies looking at the association between vitiligo and depressive episodes (not 
meeting the criteria for MDD), anxiety, social phobias and other potential psychological 
complications of vitiligo. No current study explores the relationship with ethnicity and 
psychological outcomes or the associations between vitiligo location and a broader range of 
psychological outcomes beyond MDD. The aim of this study is therefore to fill this evidence gap. 
 
We will conduct a large population-based study in the UK to determine the risks of comorbid 
mental health conditions (including depression, anxiety and other potential psychological 
complications of vitiligo) in people with vitiligo compared to control and to evaluate whether 
the relative risks may vary by different ethnicity. Reliable population-based estimates of the 
psychological burden associated with vitiligo are important to gain a better understanding of the 
condition and to ensure patients of different characteristics are provided with appropriate 
psychological support following diagnosis. 
 
Primary objectives 
• Briefly describe the epidemiology of vitiligo in the dataset: vitiligo incidence of vitiligo 
over time and by age, sex, ethnicity and sociodemographic factors and lifetime 
prevalence by age and sex. 
• Describe the prevalence of common mental health conditions (depressive episodes, 
recurrent depressive disorder and anxiety disorder), overall and stratified by 
sociodemographic factors and location of lesion, in adult patients diagnosed with 
vitiligo in a contemporary real-world population compared with matched controls 
without vitiligo 
• Describe the incidence of common mental health conditions (depressive episodes, 
recurrent depressive disorder and anxiety disorders), overall and stratified by 
sociodemographic factors and lesion location, in adult patients diagnosed with vitiligo 
in a contemporary real-world population compared with matched controls in the first 
two years after vitiligo diagnosis. 
• Describe current primary care service utilisation (primary care visits) and management 
patterns (secondary care referrals) in people vitiligo with and without mental health 
conditions. 
Secondary objectives 
• Describe the baseline prevalence and post diagnosis incidence of other potential 
psychological or work-related complications of vitiligo. These will comprise; time of 
work for illness, unemployment, social phobia, adjustment disorder, substance abuse, 
self-harm, overdose, and parasuicide or suicide attempts. 

 
 
Methods 
Data source 
This study will use routinely collected and collated data from the Optimum Patient Care 
Research Database (OPCRD). This database incorporates pseudonymised primary care records 
from up to 700 GP practices distributed across England, Wales, Scotland and Northern Ireland. 
The current OPCRD cohort size is over 5 million actively registered people, and historic records 
available for 10.1 million people. The cohort dataset can be enhanced through direct-to-patient 
and direct-to-care provider questionnaires.  
 
Study design 
The study will use the retrospectively collected data of all eligible patients within OPCRD at the 
date of data extraction. Within this primary care cohort, all patients with vitiligo will be 
identified using Read diagnostic codes. A diagnostic algorithm will be used to facilitate robust 
case identification vitiligo. This will comprise the identification of anyone with a vitiligo specific 
diagnosis code followed by exclusion of anyone with a diagnosis code for an alternative 
depigmenting disorder coded within a one-year period (six months before or after their first 
vitiligo diagnosis code). The list of alternative depigmenting disorders is shown in table 1. 
 
 

 
 
 
Condition group 
Conditions/causes included 
Congenital and genetic hypomelanoses 
Piebaldism 
Tuberous sclerosis 
Hypomelanosis of Ito 
Waardenburg syndrome 
Hermanski-Pudlak syndrome 
Griscelli syndrome 
Menkes syndrome 
Post-inflammatory hypomelanoses 
Post-inflammatory leukoderma including after Atopic 
eczema or Psoriasis 
Lichen planus 
Pityriasis alba 
Lichen sclerosus 
Post traumatic leukoderma 
Post traumatic leukoderma 
Para-malignant hypomelanoses 
Cutaneous T-cell lymphoma (mycosis fungoides) 
Melanoma associated depigmentation 
Occupational/drug induced hypomelanoses 
Occupational vitiligo 
Other induced hypomelanoses  
Para-infectious hypopigmentation 
Pityriasis versicolor (or tinea versicolor) 
Leprosy* 
Leishmaniasis* 
Others 
Melasma 
Morphoea 
Idiopathic guttate hypomelanosis  
Xeroderma pigmentosum 
Progressive macular hypomelanosis  
Nevus depigmentosus 
Cutaneous sarcoidosis 
Table 1. Potential differential diagnoses for vitiligo which will be used as exclusion criteria if 
they appear as diagnoses in the medical record within six months of the initial diagnosis of 
vitiligo (six months before or after the vitiligo diagnosis). *As these conditions are extremely 
uncommon in the UK they will not be used in the exclusion process 
 
 
The eligible vitiligo cases will comprise all incident cases of vitiligo over the last 15 years (2004-
2020). Sociodemographic details will be extracted for all these cases and matched controls 
(described below). Sociodemographic data will comprise age group, gender, ethnicity, and 
socioeconomic status. Ethnicity will be categorised as follows to be consistent with the UK 
official census categories: White, Asian, Black African/Caribbean, Mixed, and Other. The index of 
multiple deprivation (IMD) will be used as a measure of socioeconomic status. This is derived 
from postcode at the point of data extraction and is available for nearly all patients contributing 
data. 
 
Each incident case of vitiligo will be matched with an unaffected control (people without vitiligo 
at the date of matching) using propensity score matching (matching on the sociodemographic 

 
 
variables list above and matching within primary care practice where numbers allow). The 
mental health conditions proposed to be examined are listed in table 2.  
 
In addition, we will also explore whether the presence of a mental health condition at vitiligo 
diagnosis is related differences in service utilisation/management. We will describe the 
potential association between the presence of a mental health condition at vitiligo diagnosis and 
whether this is associated with increased primary care visits or an increased chance of a 
secondary care referral to dermatology. We will compare primary care visits and secondary care 
referral rates over the first year after diagnosis in those with a depressive illness of anxiety 
disorder at baseline to those without using Cox proportional hazards models adjusted for 
sociodemographic factors and other potential confounders. We will also report the overall 
primary care visit frequency and secondary care referral rate for comparison. 
 
 
Condition 
Description 
Primary outcomes 
Depression 
Recurrent depressive disorder or treated depressive episode 
Anxiety 
Non-phobia related anxiety episodes or disorder 
Secondary outcomes 
Time off work for 
illness 
Issue of a Med 3 certificate of fitness for work – indicating time 
off work for illness or other coded evidence of time off work 
Unemployment 
Any primary care coded evidence of unemployment 
Social phobia 
Diagnosis of social phobias including agoraphobia 
Adjustment disorder 
Diagnosis of adjustment disorder 
Intentional Overdose 
Any recorded intentional overdose or self-poisoning episode 
Substance abuse 
Record substance abuse including cannabis, alcohol, opioids, 
cocaine, hallucinogens, hypnotic/anxiolytic agents, or other 
substances. 
Self-harm 
Any recorded code indicative of self-harm by any method 
Suicide attempt 
Any recorded attempted suicide or parasuicide episode 
Table 2. The mental health and related conditions to be explored. 
 
Statistical methods 
Standard descriptive statistics (mean, standard deviations, etc) will be used to describe the 
characteristics of the study cohort. The study will report the baseline prevalence (odds ratio) 
and incidence (hazard ratio) for each mental health condition in the vitiligo cases compared with 
controls. These outcomes will be compared between cases and controls in subgroups by gender 
and ethnicity. Within the vitiligo cohort the relationship between disease characteristics and the 
primary outcomes will be examined. Statistical significance for analyses will be reported using 
P values and 95% confidence intervals as appropriate. 
 
Adverse event reporting considerations 
This query/analysis involves the use of retrospectively collected data of all eligible patient data 
that exist as structured data within the OPCRD by the time of query/ analysis start. 

 
 
 
In these data sources, individual patient data are not retrieved or validated, and it is not possible 
to link (i.e., identify a potential association between) a particular product and medical event for 
any individual.  Thus, the minimum criteria for reporting an adverse event (AE) (i.e., identifiable 
patient, identifiable reporter, a suspect product, and event) cannot be met. 
Conclusions 
This study will provide the first population-level analysis of the risk of multiple psychological 
comorbidities in people with vitiligo. The results will provide a measure of the magnitude of any 
associations. These insights will be invaluable for clinicians managing patients with vitiligo; 
highlighting in a much more detailed fashion than is already known the psychological impact of 
vitiligo.  These findings will be facilitative in allowing early interventions to be targeted to those 
most at risk, thus potentially preventing the development of more serious mental health 
problems. 
 
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