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Protecting Against UVA Rays in the Car

VIPOC_Sun_Protection_Vitiligo

People with vitiligo may be concerned about protecting their skin from the sun while driving in a car, as prolonged exposure to UV rays can cause further damage to the skin and potentially worsen the appearance of the white patches.

In most cars, windshields block almost all UVB and approximately 50% of UVA rays. However, side and rear windows are often clear glass, which does not prevent UVA rays from penetrating.

UVA Rays

UVA rays are responsible for aging skin, precancers, and skin cancers

Blocking Harmful Rays

Patients with sun sensitive dermatoses like lupus and all melasma patients are encouraged to tint the side windows of their vehicles to reduce UVA exposures to 15%-30%. Tinting, however, must be in compliance with federally mandated standard of 70% minimum visible light transmittance. Clear tints often work very well.

Missouri Window Tint Laws

Vehicles registered in Missouri are allowed to have the windows to the immediate right and left of the driver tinted to 35%, plus or minus 3% or more light transmittance. The windows behind the driver and the rear glass are not subject to tinting limitations. For Missouri drivers requiring additional protection from the sun, drivers can apply for a window tint permit from the Missouri State Highway Patrol with a physician’s prescription indicating that a serious medical condition exists and a specific tint percentage is needed above the standard allowance.
 It’s important to take steps every day to protect your skin. Adding window tint to your car is one way that you can limit the penetration of dangerous UVA rays.
Image credit: Dr. Mary Noël George

 

 

 

Good news from the Franco-Congolese Vitiligo Association our newest VIPOC member

VIPOC_Vitiligo_FCA1

With a lot of energy and willpower,

 

The President, Huguette Kalenga Fabiola, and the members of the Franco-Congolese Vitiligo Association  have carried out several awareness-raising actions in Kinshasa

 

  • a press conference in the premises of the Ministry of Public Health of Haut-Katanga, in the presence of Dr François Kapamba (Head Director of the Ministry of Public Health), dermatologists, clinicians and many media (TV, radio, press), to provide information on vitiligo and the discrimination suffered by patients.

 

  • the AFCV has officially launched its project to identify people with vitiligo in the Democratic Republic of Congo, so that the disease could be included in the directory of pathologies recognized by the Ministry of Public Health.

 

  • They also focus on the creation of a laboratory specifically dedicated to dermatological examinations.

 

  • They wish to obtain the necessary authorizations for access to the new treatment Ruxolinitib, recently approved by the FDA.

Awareness-raising activities et artistic projects

  • A flashmob in Kinshasa on January 14, 2023, with the participation of several people with vitiligo gathered around the hook “I am vitiliginous, I break the silence”.

 

  • New mascots, video, and Facebook page

https://photos.app.goo.gl/M1hvWfsfFZCpiAG68

https://m.facebook.com/profile.php?id=100080009803272&refid=52&__tn__=C-

 

Vitiligo in Children: A Review of Conventional Treatments

VIPOC.Vitiligo_Vitiligo_in_Children

Introduction

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

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.

Phototherapies

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].

Bath PUVA

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.

Conclusions

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.

Source:

Image credit: Bhanu Vishwanadhula

Assessing Behavioral and Psychological Symptoms in Chinese Vitiligo Patients

VIPOC_vitiligo

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

Introduction

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.

Methods

Ethics

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.

Participants

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.

Measures

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.

Results

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

 

Discussion

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.

Conclusion

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

Disclosure

The authors declare no conflict of interest.

References

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 zhangyanfei723@163.com

Image Credit: Elf Moondance(Pixabay)

The Vitiligo International Symposium 2022

VIS2022_VIPOC_Vitiligo

The Vitiligo International Symposium (VIS) was held from December 9th to 11th in Bangalore (India), organized by the Global Vitiligo Foundation (GVF), with the help of Shweta Organization. It brought together nearly two hundred people, doctors, researchers, dermatologists, the greatest vitiligo experts, laboratories, and patients representatives, from all over the world, around the theme: Unloading the burden of vitiligo

 

“VIPOC was represented by Dr. Maya Tulpule from India, Shweta, Stephen Taylor from the USA, VStrong, Gaone Matewa from South Africa, Beyond Vitiligo and Nicolle Maquignon from the French Vitiligo Association. They had the opportunity to present their different associations, their achievements, and their expectations. They also had the privilege of accessing scientific communications, as well as participating in rich formal and informal exchanges, with the participants during these three days.

VIS2022_VIPOC_Vitiligo_1 

Scientific Presentations

VIS2022_VIPOC_Vitiligo_2

Dr Hamzavi, Dr Parsad, Dr Esmat – GVF

The communications highlighted the complexity of the disease’s pathophysiology, including genetic aspects, autoimmunity, environmental factors, and oxidative stress. (Dr Hamzavi, Parsad, Dr Esmat).

 

Scientific papers have, among others, addressed:

– comorbidities especially with the thyroid (Dr Benzekri- Morocco)

– risk of cancer, lower in people with vitiligo (Dr Singh, India)

– importance of the psychological factors (R Carafello – England)

– correspondence between the distribution at the level of the skin of segmental vitiligo and the subcutaneous course of the superficial arterial vessels (Dr. Gauthier)

– phototherapy (Dr Narayan -Netherlands)

– various tools for measuring disease progression (Vitiligo Diéasse Activity Score – VIDA, Vitiligo Signs Activity Score -VSAS, Vitiligo Extent Scores- VES) (Dr R Mogawer – Egypt)

VIS2022_VIPOC_Vitiligo_

Left to right – Prof Picardo, Dr Gauthier, Dr Raboobee, G Matewa (VIPOC)

Treatments

Numerous presentations highlighted the significant advances in research in the treatment of vitiligo, fulfilling hopes expressed for a long time. This is the case with JAK inhibitors, a very real promise:

  • Recently FDA Approved: Topical – Ruxolitinib (Jak1/Jak2)

To date the only specific treatment for vitiligo: the results of various clinical trials reveal its good effectiveness on all parts of the body, including the feet and hands – often more difficult to repigment. It can be used alone or better, for optimal benefit, associated with phototherapy, recalls Prof Passeron in his presentation.

VIS2022_VIPOC_Vitiligo_4

  • Other treatments under study;

Topicals: Tofacitinib, Cerdulatinib, Cerdulatinib,

Systemic: Ritlecitinib (Pfizer), Baricitinib, Brepocitinib

More specific studies on the feet and hands are in progress, led by Prof Hyun Jeong Ju, (Korea) and Dr Yasmin Tawfik (Egypt).

Other forms of treatment are also possible (laser, grafts, etc.) depending on the specificity of the vitiligo and the patient’s expectation. Total depigmentation is also presented as a solution, which must be very carefully considered and requires that the patient be very well informed of its realization and its long term consequences (D M Abdallah – Egypt).

Alternative medicine and vitamin D intake (Prof Grimes -USA) were also the subject of the presentation.

The BURDEN, central theme of this VIS

 

Dr Pandya

Dr Parsad, Dr Pandya and Dr Hamzavi opened the discussion concerning this burden that vitiligo patients suffer. They also discussed its impact on their own quality of life, loved ones, professional and intimate life. Vitiligo can no longer be neglected and must be treated with  care.

An observation and some figures about these “white spots that affect the soul“, as Dr Hamzavi said.

  • Lack of confidence and lack of awareness/information among both patients and doctors.
  • Great frustration of doctors (nearly 70%) who do not see the proposed treatment succeed, frustration of patients (nearly 50%) who do not follow their treatments (too long, few immediate results)
  • More than 50% of patients hear during their first consultation “There is nothing to do for vitiligo”
  • The economic burden of vitiligo is not sufficiently assessed: hospitalization due to comorbidities, mental health, cost of treatment and constraints (example: phototherapy: travel, duration, etc.)
  • 71% of people are worried about the progression of the disease, 57% express a feeling of shame, 55% are sad and depressed or even suicidal, significant psychiatric comorbidities, 25% show a lack of self-confidence

Epidemiological studies and creation of the “Global Vitiligo Atlas”

Professor Ezzedine recalled the importance of epidemiological studies, which is essential for understanding and evaluating the weight of the burden and its impact on the various populations affected by the disease, considering their geographical location (prevalence, stigmatization in certain countries, rejection etc.).

He calls for the development of registries, cohorts, not only in Europe, but worldwide.  Research needs data from patients from all countries/continent.

This could lead to the creation of the “Global Vitiligo Atlas” in order to give official recognition to this “burden” and allow it to be included in a global strategy for the treatment of the disease and the reimbursement of related costs.

VIS2022_VIPOC_Vitiligo_Shweta

Special workshop with Proff Ezzedine, indian patients (some being Shweta members) and VIPOC representatives.

In 2015, the criteria used by researchers to assess the effectiveness of clinical trials focused on three points: repigmentation, adverse effects and the maintenance of this repigmentation. Other criteria (quality of life, progression of the disease, etc.) have since been recommended, but studies show that these have not always been considered.

The questionnaire “What do you expect from your treatment?” What results are truly meaningful to you?” distributed to the participants made it possible to understand the diversity of their expectations.Their responses were not always in agreement with those of the researchers, and but they brought out the existent unanimity about the impact of the vitiligo on their quality of life – in India, the stigmatization is very strong.

Indeed, for the researchers, it is a question not only of obtaining convincing results as to the clinical efficacy of the treatment but also of considering the experience of the patients, their feelings and their expectations, during and following the treatment.

Surveys must be carried out more broadly among patients (children and adults) and their relatives, to obtain a consensus on a standardization of outcome measures (Core outcomes set) and lead to studies that are easily exploitable by all researchers, and essential for health policy makers.

 

 

 

 

 

 

 

 

 

 

 

 

 

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 www.Opzelurahcp.com.

INDICATION

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.

IMPORTANT SAFETY INFORMATION

SERIOUS INFECTIONS

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.

MORTALITY

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

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.

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)

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.

THROMBOSIS

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%).

Pregnancy

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.

Lactation

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.

Source

Photo Credit: Armin Rimoldi

The Genetic Basis of Vitiligo

Vitiligo is a complex disease in which autoimmune destruction of epidermal melanocytes results inpatches of depigmented white skin. Vitiligo has an estimated prevalence of about 0.2e2% in different populations and approximately 0.4% in the European derived white (EUR) population. The fraction of disease risk attributable to genetic variation, termed heritability, is high, with estimates from family studies in EUR of 0.75e0.83 and from SNP based studies estimated at 0.78. About 70% of genetic risk comes from common genetic variants and about 30% from rare genetic variants. Through candidate gene, genomewide linkage, and genomewide association studies, over 50 vitiligo susceptibility loci have been discovered. These have been combined into a vitiligo polygenic risk score, which has allowed various aspects of vitiligo genetic architecture in the EUR population to be better understood. Vitiligo has thus proved to be a particularly tractable model for investigation
of complex disease genetic architecture. Here, we summarize progress to date including dissection of heritability, discovery of vitiligo susceptibility loci through candidate gene, genomewide linkage, and genomewide association studies, relationships to other autoimmune diseases, polygenic architecture of vitiligo risk, vitiligo triggering, and disease onset, and provide suggestions for future directions.

INTRODUCTION

Vitiligo is a common disease in which autoimmune destruction of epidermal melanocytes results in patches of depigmented white skin. Pigment loss is generally progressive, and until very recently, there were no good treatments. Vitiligo is a complex disease, involving both genetic and environmental components. From the genetic standpoint, vitiligo behaves as a typical polygenic condition, each specific genetic factor making a relatively small individual contribution. Nevertheless, vitiligo polygenicity is relatively low and heritability relatively high compared with those of most other complex traits. As a result, the genetic architecture of vitiligo has been easier to discover and understand than that of most other complex traits (Roberts et al., 2020b). Thus, vitiligo provides a particularly tractable model for investigation of complex disease genetic architecture and provides important lessons for predictive, personalized medicine of complex diseases.

Historical Context

Because of its visually dramatic phenotype, vitiligo was recognized relatively early, probably thousands of years ago (Krauss, 2018), with the first known formal medical description in 1765 (Le Cat, 1765). The fundamental pathological defect in vitiligo was defined about a hundred years later when Kaposi (1879) observed a lack of pigmented cells in the involved lesions. Another key observation came with Addison’s (1855) initial description of Addison’s disease, 2 of his 12 cases additionally having vitiligo as well as pernicious (Addisonian) anemia (Figure 1). DeMowbray (1965) suggested that such co-occurring diseases were autoimmune and, furthermore, involved a shared genetic predisposition. The first specific consideration of vitiligo genetics came in 1950 when Stüttgen (1950) and Teindel (1950) simultaneously described multiplex families having multiple relatives affected with vitiligo. Indeed, Stüttgen’s (1950) suggestion that co-occurrence of vitiligo and autoimmune thyroid disease in his family might reflect simultaneous segregation of both dominant and recessive factors constitutes one of the earliest specific hypotheses of complex inheritance.

In the 1960s, efforts began attempting to identify genes that underlie genetic susceptibility to vitiligo (Roberts and Spritz, 2018Spritz and Andersen, 2017). The earliest studies analyzed polymorphic blood proteins, followed subsequently by candidate gene association studies, targeted genetic linkage analyses, genome-wide linkage analyses, and finally GWAS. The GWAS approach has been by far the most successful, thus far defining 50 confirmed loci that are associated with vitiligo susceptibility in the European-derived white (EUR) population and several others in other populations, especially in Han Chinese (CHN). For many of these loci, the corresponding genes have now been identified and, in many cases, also the specific causal DNA sequence variants. This has led to a deep understanding of vitiligo pathobiological pathways and relationship to environmental triggers and has suggested potential new approaches to vitiligo treatment.

Vitiligo Epidemiology and Heritability

Vitiligo has an estimated prevalence of about 0.2–2% in different populations (Zhang et al., 2016), approximately 0.4% in the EUR population. Although about 91% of cases are sporadic (Roberts et al., 2019), the frequency of vitiligo is considerably elevated in probands’ close relatives, about 7% in first-degree relatives (Alkhateeb et al., 2003). Overall, about 8% of patients report at least one affected relative, with a non-Mendelian pattern of recurrence characteristic of complex, polygenic inheritance (Laberge et al., 2005).

The fraction of disease risk attributable to genetic variation is termed heritability (h2), with the remainder attributable to the environment. Heritability sets a ceiling on the importance of genes in disease causation and provides a key benchmark of progress toward the completeness of disease gene discovery. Classical approaches to estimating heritability analyze disease recurrence rates in multiplex families or twins (Tenesa and Haley, 2013); here, we term such family-based heritability h2FAM. The recent availability of very large genetic reference panels from multiple human populations (McCarthy et al., 2016), coupled with techniques for deep imputation of millions of untyped common and rare variants (Das et al., 2018), has enabled the estimation of overall genomic similarity among unrelated, singleton (simplex) cases versus controls (Yang et al., 2011Yang et al., 2015); here, we term such DNA-based estimates of heritability h2SNP.

For vitiligo, estimates of h2FAM and h2SNP are remarkably congruent. Estimates of vitiligo h2FAM from small studies range from about 0.50 to 0.80 in different populations (Arcos-Burgos et al., 2002Das et al., 1985Hafez et al., 1983Zhang et al., 2004) and from a large-scale study in the EUR population was recently estimated as 0.75–0.83, depending on the specific types of relatives studied (Roberts et al., 2020a). These estimates of vitiligo h2FAM are all much higher than those of many other complex diseases, for which h2FAM estimates are typically in the range of 0.3–0.5 (Polderman et al., 2015).

In parallel, vitiligo h2SNP was recently estimated as 0.78 in the EUR population (Roberts et al., 2020a), virtually identical to the estimates of h2FAM in this population. Thus, for vitiligo, essentially all heritability estimated by classical family-based methods can be captured by array-based genotyping and deep imputation of common and rare genomic variation; there is no missing heritability (Manolio et al., 2009). With the progress of imputation and sequencing methods that account for both common genetic variants (risk allele frequency ≥ 0.01), such as those detected by typical GWAS, and rarer genetic variants (risk allele frequency < 0.01), this is also proving to be true for other complex traits (Yang et al., 2015; Wainschtein et al., 20191).

Furthermore, the vitiligo h2SNP estimate can be partitioned into the fraction attributable to common genetic variants versus rarer genetic variants (Roberts et al., 2020a). As shown in Figure 2, in the EUR population, common genetic variants account for about 70% of vitiligo h2SNP, whereas rarer genetic variants in the aggregate account for about 30%. Specific identification of such rare vitiligo susceptibility alleles will likely require family studies or GWAS with very large sample sizes that may be difficult to attain for vitiligo.

Figure 2Partitioning of vitiligo risk. Heritability studies (Roberts et al., 2020a) enable total vitiligo risk to be partitioned into an environmental component (∼20%) and a genetic component (∼80%). Moreover, total vitiligo genetic risk can be further partitioned in a ∼70% fraction attributable to common genetic variants (MAF ≥ 0.01), such as those detected by GWAS, and a ∼30% fraction that represents rare genetic variants (MAF < 0.01). MAF, minor allele frequency.

Together, these findings show that vitiligo heritability is quite high; about 80% of vitiligo risk is genetically based, with the remaining 20% attributable to environmental factors (Figure 2). Furthermore, of the genetic risk component, about 70% (56% of total risk) comes from common genetic variants and about 30% (24% of total risk) comes from rare variants, with no remaining missing heritability. Similar patterns have recently been observed for other complex human traits (Hartman et al., 20192).

Identification of Vitiligo Susceptibility Genes

Candidate gene studies

The first attempts to identify specific genes that underlie vitiligo susceptibility were candidate gene association studies. Unfortunately, this study design has proven highly prone to false-positive results because of population stratification artifacts, incomplete correction for multiple testing, and publication bias of positive results (Hirschhorn et al., 2002). Accordingly, candidate gene studies are no longer generally accepted as appropriate for de novo identification of susceptibility genes for complex traits. Nevertheless, this approach successfully provided the first indications of involvement in vitiligo susceptibility of two immune-related candidate genes, CTLA4 (Blomhoff et al., 2005Kemp et al., 1999) and PTPN22 (Cantón et al., 2005), both subsequently confirmed by GWAS results.

Genome-wide linkage studies

Genome-wide mapping methods, including both genome-wide linkage studies and GWAS, are not subject to the problems inherent in candidate gene studies. Genome-wide linkage studies search for genomic regions that cosegregate along with the occurrence of disease among affected relatives in multiplex families. Genetic linkage studies are difficult to accomplish, have relatively modest statistical power and low genetic resolution, and are best suited to detecting uncommon causal variants that exert relatively large effects on disease risk. A total of seven putative vitiligo susceptibility loci were detected by genome-wide linkage analysis (Table 1). Of these, five have been associated with a proposed underlying causal gene: FOXD3 (Alkhateeb et al., 2005), NLRP1 (Jin et al., 2007), PDGFRA (Xu et al., 2010), HLA (Yang et al., 2018), and XBP1 (Ren et al., 2009).

Table 1. Vitiligo Susceptibility Loci Detected by Genome-wide Linkage Studies

Chromosome LOD Score Proposed Gene Population References
1p31.3-p32.2 5.59 FOXD3 EUR Alkhateeb et al., 2005Spritz et al., 2004
4q12-q21 4.01 PDGFRA CHN Chen et al., 2005Xu et al., 2010
6p21-p22 3.73 HLA CHN Liang et al., 2007Yang et al., 2018
7q21.11 3.73 Unknown EUR Spritz et al., (2004)
8p12 3.36 Unknown EUR Spritz et al., (2004)
17p13.3 3.07 NLRP1 EUR Jin et al., 2007Nath et al., 2001Spritz et al., 2004
22q12 3.26 XBP1 CHN Liang et al., 2007Ren et al., 2009

Abbreviations: EUR, European-derived white population; CHN, Han Chinese population; LOD, logarithm of the odds.

GWAS

GWASs typically search for differential genetic associations in singleton cases versus unrelated controls, interrogating hundreds of thousands or millions of DNA polymorphisms across the genome (Altshuler et al., 2008). Furthermore, the genotypes of millions of additional polymorphisms can be imputed using various genome-wide reference panels (Yang et al., 2011Yang et al., 2015). Unlike candidate gene association studies, GWAS can adequately control for population stratification artifacts, apply appropriate multiple-testing correction, and further require independent replication; thus, GWAS results have been largely reproducible across multiple studies. Over the past decade, GWASs have become the gold standard for the primary discovery of genes involved in complex traits, providing deep insights into the corresponding underlying biology (Visscher et al., 2017). At least five GWASs have been reported for vitiligo; three in the EUR population (Jin et al., 2016Jin et al., 2012Jin et al., 2010a), one in CHN (Quan et al., 2010Tang et al., 2013), a small GWAS in Japanese (Jin et al., 2015), as well as a small partial GWAS in subjects from the Indian subcontinent (Birlea et al., 2013) based on the Immunochip (Cortes and Brown, 2011). For reasons that are unclear, the greatest yield has come from the GWAS of vitiligo in EUR, in which 50 loci have thus far been identified that contribute to vitiligo risk (Table 2). Several additional loci have been discovered in CHN (Table 2). A number of vitiligo susceptibility loci appear to be shared across populations, although others may not be, suggesting that the general pathobiology of vitiligo is likely similar across different populations and efficacy of vitiligo treatments might thus transcend ethnic populations.

Table 2. Vitiligo Susceptibility Loci Detected by GWAS

Chromosome Proposed Gene Population OR References
1p36.23 RERE EUR 1.21 Jin et al., (2010a)
1p13.2 PTPN22 EUR, IND, AR 1.38 Jin et al., (2010a)
1q24.3 FASLG EUR, CHN 1.32 Jin et al., (2016)
1q31.3-q32.1 PTPRC EUR 0.83 Jin et al., (2016)
2p16.1 PPP4R3B EUR 1.51 Jin et al., (2016)
2q13 BCL2L11 EUR 1.15 Jin et al., (2016)
2q24.2 IFIH1 EUR 0.77 Jin et al., (2012)
2q33.2 CTLA4 EUR 1.18 Jin et al., (2016)
2q37.3 FARP2 – STK25 EUR 0.80 Jin et al., (2016)
3p24.3 UBE2E2 EUR 0.87 Jin et al., (2016)
3p13 FOXP1 EUR 0.80 Jin et al., (2010b)
3q13.33 CD80 EUR 1.31 Jin et al., (2012)
3q28 LPP EUR 1.32 Jin et al., (2010a)
3q29 FBXO45 – NRROS EUR, CHN 0.87 Jin et al., (2016)
4q24 PPP3CA EUR 0.87 Jin et al., (2016)
6p25.3 IRF4 EUR 0.75 Jin et al., (2016)
6p25.2 SERPINB9 EUR 0.79 Jin et al., (2016)
6p22.1 MHC class I
HLA-A1 EUR, JPN, CHN 1.53 Hayashi et al., 2016Jin et al., 2015Jin et al., 2010a
HLA-A/HLA- B/HLA-C CHN 1.90 Quan et al., (2010)
MHC class II
HLA-DRB1- HLA-DQA12 EUR 1.77 Cavalli et al., 2016Jin et al., 2016Jin et al., 2010a
HLA-DQA1 – HLADQB13 EUR 8.1 Jin et al., (2019)
HLA-DQB14 CHN 1.79 Yang et al., (2018)
BTNL2 – HLA-DRA IND 1.67 Birlea et al., (2013)
6q15 BACH2 EUR 1.27 Jin et al., (2012)
6q27 RNASET2 – FGFR1OP – CCR6 EUR, CHN 0.79 Jin et al., 2010bQuan et al., 2010
7p14.3 CPVL EUR 1.84 Jin et al., (2010b)
8q24.21 PVT1 EUR 1.17 Ben et al., (2018)
8q24.22 SLA EUR 1.19 Jin et al., (2012)
9q33.3 NEK6 EUR 1.15 Jin et al., (2016)
10p15.1 IL2RA EUR 0.77 Jin et al., (2010a)
10q21.2 ARID5B EUR 1.18 Jin et al., (2016)
10q22.1 SLC29A3 – CDH23 CHN 0.88 Tang et al., (2013)
10q22.3 ZMIZ1 CHN 1.18 Quan et al., 2010Sun et al., 2014
10q25.3 CASP7 EUR 0.82 Jin et al., (2012)
11p13 CD44 EUR 1.23 Jin et al., (2012)
11q13.1 PPP1R14B – PLCB3 – BAD – GPR137 –KCNK4 – TEX40 – ESRRA – TRMT112 – PRDX5 EUR 0.87 Jin et al., (2016)
11q14.3 TYR EUR 0.67 Jin et al., (2010a)
11q21 Gene desert EUR 1.34 Jin et al., (2010a)
11q23.3 DDX6-CXCR5 CHN 1.22 Tang et al., (2013)
12q13.2 IKZF45 EUR, CHN 1.33 Jin et al., 2010bTang et al., 2013
12q24.12 SH2B3 EUR 0.79 Jin et al., (2012)
13q14.11 TNFSF11 EUR 1.17 Jin et al., (2016)
14q12 GZMB EUR, CHN 1.25 Jin et al., (2010a)
15q12-q13.1 OCA2 – HERC2 EUR 1.37 Jin et al., (2012)
16q24.3 MC1R EUR 0.71 Jin et al., (2012)
17q21.2 KAT2A-HSPB9-RAB5C EUR 1.21 Jin et al., (2016)
18q21.33 TNFRSF11A EUR 1.21 Jin et al., (2016)
19p13.3 TICAM1 EUR 1.21 Jin et al., (2016)
19q13.33 SCAF1-IRF3-BCL2L12 EUR 0.84 Jin et al., (2016)
20q11.22 RALY – ASIP EUR 0.61 Jin et al., (2016)
20q13.13 PTPN1 EUR 1.15 Jin et al., (2016)
21q22.3 UBASH3A EUR 1.35 Jin et al., (2010a)
22q12.3 C1QTNF6 EUR 1.32 Jin et al., (2010a)
22q13.2 ZC3H7B – TEF EUR 0.79 Jin et al., (2012)
Xp21.3-p21.2 IL1RAPL1 EUR 1.77 Jin et al., (2016)
Xp11.23 CCDC22-FOXP3-GAGE EUR, CHN, IND 0.86 Jin et al., (2016)

Abbreviations: AR, Arab; CHN, Han Chinese; EUR, European-derived white; IND, Indian subcontinent; JPN, Japanese population; MHC, major histocompatibility complex.

For associations observed in multiple populations, the first-listed was determined by GWAS and the others by non-GWAS methods.

1

All three populations have major vitiligo association with HLA-A∗02:01.

2

Intergenic SNP rs9271597-rs9271600-rs9271601 haplotype associated with vitiligo susceptibility.

3

Intergenic SNP rs145954018 associated with early-onset vitiligo.

4

Principal association is with HLA-DQB1∗02:02.

5

Tang et al. (2013) interpreted this association as possibly representing PMEL.

As shown in Figure 3, the majority of the loci that have been associated with vitiligo encode genes involved in immunoregulation, apoptosis, and melanocyte biology. For a number of these genes, the causal genetic variants have been discovered, providing important insights into biological mechanisms that underlie vitiligo risk attributable to these genes, Furthermore, together, the corresponding proteins define a functional network that suggests a general pathobiological pathway of melanocyte damage, antigen processing and presentation, immune cell activation, and melanocyte targeting and apoptosis (Spritz and Andersen, 2017).

Figure 3Functional interaction network of proteins encoded by candidate genes associated with vitiligo susceptibility. Unsupervised functional interaction network analysis was performed using STRING, version 11.0 (Szklarczyk et al., 2019) with default settings. Primary nodes were proteins encoded by all the confirmed vitiligo susceptibility loci (Tables 1 and 2). Nodes that shared no edges with any other nodes were then excluded. Edge colors are from STRING: teal, interactions from curated databases; purple, experimentally determined interactions; dark green, gene neighborhood; red, gene fusions; dark blue, gene co-occurrence; light green, text mining; black, coexpression; lavender, protein homology.

Relationship to Other Autoimmune Diseases

Epidemiological studies have shown that the frequencies of several other autoimmune diseases are elevated in patients with vitiligo. In the EUR population, these principally include autoimmune thyroid disease (principally Hashimoto thyroiditis), rheumatoid arthritis, adult-onset type 1 diabetespernicious anemia, Addison’s disease, and systemic lupus erythematosus (Alkhateeb et al., 2003Cunliffe et al., 1968Laberge et al., 2005). Epidemiological studies of autoimmune diseases in vitiligo cases from other populations have shown generally similar associations, although with perhaps some differences (Alissa et al., 2011Ayanlowo et al., 2009Chen et al., 2015Gopal et al., 2007Liu et al., 2005Narita et al., 2011Silva de Castro et al., 2012Zhang et al., 2009) Likewise, these same autoimmune diseases occur at an elevated frequency in vitiligo probands’ first-degree relatives, suggesting that these autoimmune disease associations likely reflect at least partially shared genetic underpinnings (Alkhateeb et al., 2003).

This hypothesis has been completely borne out by genetic studies of vitiligo-associated genes and loci in other autoimmune diseases. Genetic associations of various major histocompatibility complex (MHC) genes and HLA alleles are of course well-established with many different autoimmune diseases. Of the 47 non-MHC loci that have been associated with vitiligo in the EUR population, six appear to involve genes that are specifically relevant to melanocytes and, thus, would not be expected to play roles in autoimmune diseases other than vitiligo. Of the remainder, at least 19 have also been genetically associated with at least one of the other autoimmune diseases that are epidemiologically associated with vitiligo (Figure 4). Many of these shared genetic associations appear to involve the same associated marker alleles and, thus, may potentially represent the same underlying causal variant. Thus, the hypothesis that shared epidemiological associations among various autoimmune diseases to some extent reflect shared underlying genetic predisposition has been fully confirmed.

Figure 4Shared genetic associations among vitiligo-associated autoimmune diseases. In addition to various HLA alleles, at least 19 of the 47 non-MHC loci that have been associated with vitiligo in the EUR population have also been associated with at least one of the autoimmune diseases that are epidemiologically associated with vitiligo (autoimmune thyroid disease, adult-onset type 1 diabetes mellitusrheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease), in many cases involving the same associated marker alleles. Red, immune-related; blue, apoptosis-related; white, function unknown. Note that not all diseases have been studied to similar extents, and so for some diseases, relatively few genetic associations are yet known. EUR, European-derived white population; MHC, major histocompatibility complex.

Polygenic Architecture of Vitiligo Risk

As noted above, about 8% of vitiligo cases report at least one affected relative, with a pattern suggestive of non-Mendelian, complex inheritance (Laberge et al., 2005). Alkhateeb et al. (2003) found that the frequency of vitiligo in probands’ first-degree relatives was about 5–7%, depending on the ethnic population studied.

Roberts et al. (2019) combined data for the most significant SNPs from the 48 autosomal vitiligo GWAS loci—all relatively common—to create a vitiligo polygenic risk score, which they then used as a tool to probe various aspects of vitiligo genetic architecture in the EUR population. Comparing the top 1% of the cases with the rest, this risk score yielded an OR of 8.79—far higher than the risk scores for most other complex diseases (Khera et al., 2018)—owing at least in part to higher ORs of the vitiligo-associated variants than those of most complex diseases. Roberts et al. (2019) found that the positive predictive value of that vitiligo risk score was 71%, again better than polygenic risk scores for most other complex diseases (Wald and Old, 2019). Together, these results indicate that vitiligo is polygenic, although less so than many other complex diseases, and, as noted above, common genetic variants account for a high fraction (about 70%) of vitiligo heritability (Roberts et al., 2020a).

Roberts et al. (2019) also showed a major role for polygenicity in families with multiple affected relatives. They found that the vitiligo risk score in cases from such multiplex families was higher than that in singleton cases, with the risk score generally proportional to the number of affected relatives, and that this high polygenic risk was disproportionately transmitted to those affected relatives. Even in a family with a known high-risk rare variant (in FOXD3), the polygenic risk from common vitiligo variants was exceedingly high. Thus, whereas rare, high-penetrance variants undoubtedly play a role in some multiplex vitiligo families, even in such families, much of the genetic risk comes from over-representation of the same common risk variants involved in singleton vitiligo cases. This suggests that the application of a polygenic risk score might prove clinically useful for risk prediction in such families. Furthermore, the same genetic risk variants and corresponding biological pathways are involved in both simplex and multiplex vitiligo cases, suggesting that the same treatments will generally be applicable to both types of cases.

Vitiligo Triggering and Disease Onset

For autoimmune diseases such as vitiligo, case versus control genetic studies identify inherited risk factors that together increase the likelihood of loss of tolerance in response to an environmental trigger. Whereas no vitiligo environmental triggers are known with certainty, the Köbner phenomenon (Köbner, 1877) is particularly frequent in vitiligo (van Geel et al., 2011), suggesting a major role for skin damage in disease triggering.

Spritz et al. (2004) have studied the vitiligo age of onset in the EUR population as an indirect proxy for disease triggering. Jin et al. (2011) initially showed that vitiligo age of onset is genetically associated with the MHC class II region. These investigators (Jin et al., 2019) later showed that the distribution of vitiligo age of onset is bimodal and that early-onset vitiligo is genetically associated with a specific extreme-risk MHC class II haplotype (OR = 8.1) containing an enhancer variant that upregulates the expression of HLA-DQB1 mRNA and HLA-DQ protein on peripheral blood monocytes and dendritic cells. Elevated HLA class II protein expression on such professional antigen-presenting cells might thus enhance the response to triggering antigens, facilitating loss of tolerance by autoreactive T cells.

In addition to a genetic component underlying vitiligo triggering and onset, Jin et al. (2020) also searched for evidence for an environmental component by analyzing the long-term trends in vitiligo age of onset. Studying EUR vitiligo cases from North America and Europe, these investigators observed a dramatic shift over the period 1970–2004 from the mean onset of about 15 years of age in 1970 to over 30 years of age in 2004 (Figure 5). This change was unrelated to the extreme-risk MHC class II haplotype. Moreover, the pattern of change appeared generally similar among EUR vitiligo cases from both North America and Europe. Together, these findings suggest that exposure to one or more important vitiligo environmental triggers became reduced or delayed over this period in these populations. Whereas the cause of this seemingly beneficial change is not known, important clues might be gleaned by comparison with analogous data from other world populations.

Figure 5Mean age at vitiligo onset in 4,406 EUR cases from North America and Europe by calendar year of onset, 1951–2013. Circles denote means, and vertical bars delimit 95% CIs. Black segments show regression lines for time periods of 1951–1969, 1970–2004, and 2005–2013. Reprinted from Jin et al. (2020) with permission. CI confidence interval; EUR, European-derived white population.

Perspectives and Future Directions

The past two decades have seen extraordinary progress in deciphering the genetic basis of vitiligo risk, both in general terms and in the identification of specific genes and genetic variants that underlie risk. This progress has provided a profound understanding of the pathobiology of vitiligo and its relationship to other autoimmune diseases. Vitiligo behaves as a complex polygenic disease. For the average vitiligo case, about 20% of risk comes from the environment, about 56% from various common genetic variants, and about 24% from a large diversity of rare variants. The common genetic variants associated with vitiligo risk, principally involved in immunoregulation, apoptosis, and melanocyte biology, can be combined in a vitiligo polygenic genetic risk score that has impressive positive predictive value compared with those for other complex diseases.

Nevertheless, many important questions remain. It is clear that the fundamental genetic architecture of vitiligo risk is generally polygenic and that vitiligo polygenic risk is generally additive at the macro level. However, it is not yet known whether polygenic vitiligo involves just one basic pathobiological process or there are multiple vitiligo biological endotypes, defined by different genes and pathways, with risk additive within each endotype. This is an important distinction, because the former would suggest that effective vitiligo treatments would be biologically generic, whereas the latter would suggest that different treatments might be needed for different vitiligo biological endotypes.

A related question is whether the general genetic architecture and pathobiology of vitiligo are similar in different world populations. Many vitiligo susceptibility loci and perhaps some corresponding causal genetic variants appear to be shared in patients from the EUR, CHN, and perhaps other populations. That would suggest that vitiligo in these populations involves shared pathobiological pathways. Nevertheless, other vitiligo susceptibility loci appear to be population-specific. That would suggest the possibility that some cases of vitiligo in one or another population might involve some aspects of differing underlying biology.

At least in the EUR population, about 70% of vitiligo genetic risk derives from common genetic variants. The remaining 30% of vitiligo genetic risk derives from a large diversity of rare genetic variants. As of now, only a single rare, highly penetrant vitiligo susceptibility variant, in FOXD3, has been identified, although it is likely that rare and uncommon variants in MC1R and IFIH1 also play roles. To identify additional specific rare vitiligo risk variants will likely require either association studies with much larger sample sizes or family-based studies to track the cosegregation of rare genomic variants along with genetic risk.

As of now, no large-scale genetic studies have yet addressed segmental vitiligo. The prevalence of associated autoimmune disorders does not appear to be elevated in segmental vitiligo (Iacovelli et al., 2005), suggesting that segmental vitiligo might not represent a fundamentally autoimmune process. Nevertheless, at least some susceptibility genes might be shared between segmental and nonsegmental vitiligo. Taïeb et al. (2008) speculated that segmental vitiligo might reflect some form of cutaneous somatic mosaicism. Might evidence of that be observed by single-cell DNA sequencing or other modern omics approaches?

Perhaps most important, all genetic studies of vitiligo to date have compared the genetic basis of case status with that of noncase status, either in large patient populations or within families. Fundamentally, such studies address the underlying biological determinants of disease occurrence; in the case of vitiligo, autoimmune triggering. Whereas that topic is of key importance, these biological determinants may not be the same as those that influence vitiligo clinical course once autoimmune triggering has occurred, which of course might have the greatest relevance to vitiligo treatment.

Finally, whereas there has thus been great progress toward discovering the genetic components of vitiligo susceptibility, as of now, no common environmental triggers for vitiligo have been identified with certainty. Such knowledge would provide an even deeper understanding of vitiligo pathobiology and furthermore, might provide opportunities to ameliorate vitiligo risk. Unfortunately, whereas we have a rigorous global systematic scientific method to identify genetic risk factors for disease, we have yet to develop an analogous global systematic approach to identify specific environmental risk factors.

Conflict of Interest

The authors state no conflict of interest.

Acknowledgement

We thank the thousands of patients with vitiligo, their family members, and normal control individuals around the world who participated in our studies of vitiligo genetics, as well as our many medical and scientific collaborators.

Richard A. Spritz1,2 and Stephanie A. Santorico

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What to know about laser treatments for vitiligo

Vitiligo can cause the skin to lose its natural color. Laser therapy can help repigment the skin, but this can also cause side effects, such as hyperpigmentation and skin lesions, in some people.

picture showing vitiligo on a person's hand
Eva Szombat/Getty Images

Vitiligo is a skin condition that causes pale patches to develop on the skin. This happens when the body stops producing melanocytes, the cells responsible for the skin pigment melanin. Vitiligo can affect any area, but it mostly occurs on the face, neck, hands, and where there are creases.

There is no cure  for vitiligo, but treatment can help even out a person’s skin tone. Dermatologists can offer a person many treatment options for vitiligo if they would like to treat it.

Laser treatment is one such option; it uses light to restore the lost color of skin. A person should consider all the pros and cons with their dermatologist before commencing treatment.

Keep reading to learn more about vitiligo laser treatments, including the effectiveness of excimer or other lasers in treating vitiligo.

Excimer lasers

Excimer lasers are a popular choice of laser treatment. Excimer laser, or XTRAC, is a type of treatment that uses an ultraviolet light form called UVB to treat vitiligo. The laser uses UVB at a 308 nanometers (nm) wavelength.

This laser can treat localized vitiligo and may be a good option for people who have not responded well to other treatments, such as topical creams or lotions.

Scientists do not fully understand the exact mechanism of action for excimer lasers. They believe that UVB light can enhance the immune response and stimulate the production of more melanocytes, cells that produce a pigment called melanin.

Dermatologists use a wand-like device to apply the light directly to the affected skin areas. This treatment can help restore color to the pale areas.

People should not feel pain, and the procedure takes less than half an hour. Dermatologists may recommendattending laser treatment sessions twice weekly for 4-6 months, but this can vary between people.

There are many advantages of using the excimer laser:

  • The laser only treats the affected areas and does not expose the surrounding areas to the radiation.
  • Dermatologists can use it in areas that can be difficult to treat with other therapies, such as phototherapy. These can include the ears and genital areas.
  • Dermatologists can use different templates depending on the areas they are treating.
  • It is safe to use on children.

Side effects

If the dermatologist uses a high dose, the excimer laser can cause blisters on the skin. Other side effects may include:

  • painful erythema or reddening of the skin
  • hyperpigmentation or darkening of the skin
  • skin lesions, if there is a burn

Different lasers for treating vitiligo have their benefits, side effects, and risks. Lasers include:

  • fractional ablative lasers
  • helium-neon lasers
  • Ti: sapphire lasers
  • UVA1 lasers
  • Q-switched nanosecond lasers for depigmentation therapies

Most of these emerging laser types have only been proved effective in a small number of studies.

A study from 2019 looking into the effects of Ti: Sapphire lasers in 21 people found that it can be as effective as excimer lasers and is a useful alternative in some cases.

A 2022 study found that conventional ablative lasers, such as CO2 and Erbium: YAG, can help promote repigmentation when dermatologists combine them with narrowband UVB light. People opting for this combination therapy may experience very few side effects.

Each laser type works differently. For example, fractional ablative lasers work by creating microscopic wounds as they pass over the affected area and ultimately produce an immune response and stimulation of melanocyte cells.

Also, fractional CO2 lasers can cause tissue to contract the area it passes over — an action that can temporarily reduce the vitiligo lesion size. Further research into the effectiveness of fractional ablative lasers for treating vitiligo alone would be beneficial.

Dermatologists may choose candidates carefully, considering the disease’s specific characteristics. These factors may include location, the extent of disease, activity, and type of vitiligo.

Effectiveness of excimer lasers for vitiligo

About 70% of people who opt for excimer laser treatment see results. However, the results may disappear in those who stop treatment within one year.

An older study found that an excimer laser can effectively treat vitiligo. Individuals who opt for this treatment may start experiencing results within a few months.

However, the researchers claim that there is limited research that determines whether people may respond better to the laser treatment depending on their skin type and hair follicle characteristics.

Suitable candidates for laser treatment

Phototherapy and laser treatments are suitable for individuals of any age group and can work on all skin tones. Some lasers might not be suitable for children; however, doctors may use narrowband UVB for children with extensive vitiligo.

A person should check with their dermatologist if they are suitable for the different types of lasers.

Laser vs. other treatment options

Laser treatments may require frequent visits to a dermatologist’s clinic. Also, side effects, such as skin lesions, hyperpigmentation, and blisters, can occur in people having laser treatment.

Other treatment options that dermatologists may recommend for people with vitiligo may include:

  • Surgery: This may be a good option when medications and light therapy do not produce the desired result. It is not safe for children, but it is suitable for adults with stable vitiligo, meaning their condition has remained the same for the past 6 months. During the session, the surgeon removes the skin cells with natural color and transfers the cells to the areas requiring repigmentation.
  • No treatment. People might opt for using cosmetics, such as makeup and skin dyes, to cover the lighter patches of skin. This might be a safer option for children as serious side effects are less likely to occur. However, it can be time-consuming as individuals may have to apply the product frequently.
  • Topical medications: Individuals may opt for medications, such as corticosteroids, that they apply to the skin to add color. Doctors may prescribe topicals for people with smaller affected areas, and corticosteroids can work best on the face. People using products that contain corticosteroids for a long time are more prone to developing skin dryness and fragility.
  • PUVA light therapy: This therapy typically involves using UVA light with another drug called psoralen to treat widespread vitiligo. It is about 50-75% effective in restoring pigment to certain areas of the body, including the face.
  • Depigmentation: This involves removing the remaining pigment on the skin. It can take up to 4 years to complete the process.

Phototherapy

This treatment uses UV light but only certain wavelengths that aim to re-pigment the skin.

Phototherapy helps produce more melanocytes in the skin so that it does not form new lighter patches.

Some people may opt for a full-body phototherapy session, but the duration can vary and might depend on the severity of their condition. For example, those with moderate to severe vitiligo may have to attend more than two sessions every week.

Cost

The cost of vitiligo laser treatment can vary. It can depend on:

  • the areas being treated
  • the number of sessions that person may have to attend
  • the prices set by the clinic

However, as an estimate, clinics might charge $150 or more per session depending on the size of the depigmented area. Also, people may require between 20 to 30 sessions.

Is it safe to use the excimer laser?

A 2018 study states that the excimer laser is safe and effective in treating localized vitiligo. Combining this laser with topical agents, such as tacrolimus or tacalcitol, may provide better repigmentation results.

Research  has also shown the 308nm excimer laser does not increase the risk of skin cancer and premalignant skin lesions in people with vitiligo.

What to expect after laser treatment?

According to the American Academy of Dermatology Association (AAD), people that have dark skin pigment may notice that some of their skin areas are darker in color after the treatment sessions. This, however, should resolve within a few months.

People can return to work after excimer laser sessions, and they can continue with their daily routine.

How many sessions do people require?

This depends on the laser that a person opts for and the severity of their skin condition.

People should expect to attend their clinic frequently if their vitiligo is severe. The treatment course can last months to years.

Summary

Laser therapy can be a good treatment option for people with vitiligo.

Doctors might try a few laser treatments, and the treatment course can depend on the individual’s condition and skin type. Dermatologists may also discuss the treatment duration and decide on the number of sessions a person may need.

However, those who cannot get treated with a laser may opt for other treatment options. These may include topical medications or surgical procedures.

Source:

VITILIGO: A REVIEW OF SOME FACTS LESSER KNOWN ABOUT DEPIGMENTATION

James J Nordlund

Abstract

Vitiligo is a disorder that causes the destruction of melanocytes. It has three important factors underlying this destruction. The depigmented skin has many aberrant functions such as a muted response to contact allergens, a phenomenon also seen in mice that depigment. The white skin of those with vitiligo does not form non-melanoma skin cancers although the white skin of albinos, which has a similar color as vitiligo, is highly susceptible to skin cancer.

Introduction

Vitiligo is a common and easily recognized disorder for all dermatologists, many physicians and some observant members of the general public. It is a disorder that is characterized by white spots typically first noted on the fingers, knuckles, around the eyes and mouth, and on the feet and genitalia. There are two basic mechanisms whereby the skin can become white. Melanin is synthesized by melanocytes within melanosomes that are transferred into the surrounding keratinocytes. The keratinocytes transport the melanin and melanosomes from the basal layer of the epidermis to the stratum corneum where they are desquamated into the environment. Some disorders inhibit or retard the production of melanin formation and the skin develops hypopigmentation. Such disorders include, among many others, oculocutaneous albinism, pityriasis alba, tinea versicolor and nevus depigmentosus. In these disorders, melanocytes are present in normal numbers in the epidermis but produce less than normal amounts of melanin. Typically, the skin exhibits mild to marked hypopigmentation.

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Depigmentation around the eyes (partially blocked), the nares and mouth, all classical and early manifestations of bilateral vitiligo

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Depigmentation of the feet, typical early manifestation of vitiligo

In contrast, other types of leukoderma are characterized by the absence of melanocytes and therefore, complete absence of melanin. Such disorders include piebaldism, the leukoderma of lupus erythematosus and other scarring disorders, and vitiligo. These types of leukoderma typically are totally depigmented. Vitiligo and lupus cause a destruction of melanocytes during postnatal life. Piebaldism affects the migration of melanocytes during embryogenesis and the infant is born with depigmentation of the hair and skin.

There seem to be three major factors involved in the destruction of melanocytes in patients with vitiligo.The first is that vitiligo patients inherit a set of three “vitiligo” genes which predisposes them to destruction of melanocytes. There probably are many different sets of three genes that can cause vitiligo so that not every individual would necessarily inherit the same three. The second abnormality relates to the melanocytes themselves. Melanocytes from patients with vitiligo differ from those obtained from a person without vitiligo. For example, vitiligo melanocytes require different and more fastidious culture conditions than those from normal individuals.Also, vitiligo melanocytes are much more sensitive to phenolic chemicals than normal melanocytes and readily undergo apoptosis when exposed to such agents.The third factor is an environmental agent(s) that activates (or inhibits) the genes involved, thereby setting in motion the process of destruction of the susceptible melanocytes. The vitiligo genes activated (inhibited) by the environmental agents seem to cause an excessive immune reaction that induces melanocytes to undergo apoptosis, and depigmentation of the skin results.

Vitiligo principally affects melanocytes. However, keratinocytes also manifest some damage, mostly a granular degeneration. It is not widely recognized that Merkel cells also are absent from depigmented skin. The significance of this absence and the impact it has on the function of the epidermis are not known. The cells of the epidermis, i.e., keratinocytes, Langerhans cells, melanocytes and Merkel cells, work closely together. It should be expected that loss of one or the other cells from the epidermis would alter its function. It is thought the Merkel cell functions as a neurosensory cell. It has been shown that sweating and bleeding times are altered in the depigmented skin of a patient with vitiligo.Alterations in cholinergic activity and morphology of sweat glands which are innervated by cholinergic sympathetic nerves have been observed by some investigators although not by all observers. The functional changes observed in depigmented skin might be related to the collateral damage to keratinocytes and/or Merkel cells. There are other functional abnormalities in vitiliginous skin which will be discussed later.

There are two main types of vitiligo, unilateral (often called segmental) and bilateral (usually termed generalized). Segmental vitiligo will be discussed later. However, the word “segmental” is often confused with the term “dermatomal”, the latter meaning the pattern of sensory innervation of the skin. Segmental is rarely, if ever, dermatomal, so unilateral is a better term to avoid confusion.

Bilateral or generalized vitiligo can begin at any age and tends to progress intermittently over the life of the patient. It produces depigmentation that is remarkably symmetrical in distributionA patch on the right side of the body is matched by a patch in a similar location on the left side. The entire body can depigment although it rarely does so. The classical presentation of the depigmentation is a remarkably symmetrical distribution of depigmentation beginning on the fingers, feet, wrists, elbows, axillae and around the mouth and eyes. There is no explanation for this symmetry. Yet, it is so typical and common that symmetrical depigmentation is one criterion for the diagnosis of vitiligo. (Depigmented patches can be randomly scattered. This has been labeled atypical vitiligo.) Dr. RB Goudie, a Scottish pathologist, was intrigued by the symmetry that characterized vitiligo. He noted that the distribution of some autoimmune endocrine disorders such as thyrotoxicosis resembled in some ways the distribution of vitiligo. He also noted that malignant lymphomas often appeared as tumors symmetrically involving both sides of the body. He hypothesized that benign lymphocytes honed to specific sites in the skin where they might be responsible for the symmetry of vitiligo.Although his ideas are no longer popular, they are based on the known propensity of cutaneous lymphocytes to migrate to specific sites in the skin and the role of lymphocytes in causing depigmentation. His ideas are worthy of reconsideration.

Extensive depigmentation of a woman which illustrates the symmetrical distribution of classical bilateral vitiligo

Unilateral (segmental) vitiligo differs from generalized vitiligo in many important aspects. It more commonly begins in children and young adults and progresses for a limited period, usually 1–2 years, and then remains static for the life of the individual.It affects just one side of the body. In contrast to bilateral vitiligo, the distribution is asymmetrical on the skin. However, the patterns also are not random. The various sites affected by the depigmentation are repetitious. The patterns on the face have been classified.There are patterns affecting the neck and trunk which resemble each other in location and shape.It is important to note that a nevus depigmentosus and a cafι-au-lait spot can have a similar shape, pattern and location as segmental vitiligo. These similarities of patterns and distribution for unilateral vitiligo and nevus depigmentosus suggest that unilateral vitiligo corresponds to embryological developmental patterns for melanocytes in their migration from the neural crest to the epidermis.

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Unilateral (segmental) vitiligo affecting one side of the face of a young boy. Note that the depigmentation does not correspond to a dermatome

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Unilateral depigmentation (segmental vitiligo) affecting the neck of a woman. Note the very similar distribution of depigmentation in the two men pictured below

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Unilateral depigmentation (segmental vitiligo) on the neck of a man with a distribution similar to the pictures below

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Nevus depigmentosus on the neck of a boy. The pigmentary abnormality was present at birth in the patient

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Nevus depigmentosus on the neck of a man. The pigmentary abnormality was present at birth in the patient

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Unilateral depigmentation (segmental vitiligo) of the neck of a man which is similar to the depigmentation seen  in previous photos

Typically, bilateral vitiligo progresses over the life of the individual so that the person has partially normal and partially depigmented skin. This probably is the worst outcome. Of course, it is best to be one’s own color but it is the worst condition for most people to have two colors at least on visible skin such as the hands, face, neck and arms. To avoid this, for some patients, the treatment of choice is depigmentation of the normal skin by applications of monobenzone by which they achieve a single color. This is what Michael Jackson did to achieve a single white color. Occasionally, nature achieves the same end. A very small number of patients will develop over a period of a few months a very rapid depigmentation of the entire integument and also the hair. Dr. Aaron Lerner called it “veloce vitiligo” or rapid vitiligo. These individuals go from having dark skin to having totally depigmented skin and hair in a period of months. It can occur spontaneously but in my personal experience has followed in a few individuals generalized erythematous drug eruptions. How or why this happens is not known.

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An Indian woman with veloce vitiligo. She lost almost all of her pigmentation on the skin and hair over a period of some months

The three cells of the epidermis, keratinocytes, Langerhans cells and melanocytes, form a troika so to speak and work together. As noted above, it should not be surprising that depigmented skin has some altered functions if one part of the troika is missing. Several Japanese workers noted that depigmented skin of vitiligo patients did not react to sensitization with dinitrofluoro benzene (DNFB) to produce contact dermatitis. In their experiments, DNFB was applied to normal skin to induce contact allergy. A challenge was applied to both normal and white skin. The white skin did not respond. In other experiments, the sensitizing dose of DNFB was applied to white skin and the challenge to both white and pigmented skin. The pigmented but not the white skin responded.These findings suggest that the afferent limb of the immune response is intact in the white skin, but the efferent limb is not so. In the same studies, Candida antigen was injected into the dermis of both white and pigmented skin and the dermal response was normal in both.The discrepancy between epidermal and dermal immune responses might be attributed to loss of the melanocytes which could have immune/inflammatory functions.

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The epidermis is composed of three main cell types that work together like a troika

Others have noted that depigmented skin does not respond to contact allergens. Monobenzone as noted above is used to depigment skin for those with depigmentation too widespread to repigment. Some individuals applying monobenzone develop a contact allergy to the medication. However, the allergic dermatitis is manifested only in the pigmented skin.In separate studies, investigators observed that the inflammatory response to irritants was abnormal in white skin compared to pigmented skin. It seems especially fascinating that graft versus host skin disease in one individual with piebaldism affected preferentially the white skin, emphasizing again that the three cells of the epidermis work together and that melanocytes likely play a role in inflammation.

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A woman treated with monobenzone, who developed a contact allergy. The dermatitis is exclusively confined to the pigmented skin

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A man treated with monobenzone, who developed a contact allergy. The dermatitis is exclusively confined to the pigmented skin

A muted response to contact allergens is not unique to humans. There is a species of mice that has an acquired form of depigmentation resembling vitiligo, called the mi/mivit/vit mouse. The skin and follicles of the mouse have normal numbers of Langerhans cells in both the pigmented and depigmented stages.However, the response of the mouse to potent contact allergens is highly muted after the skin and pelage have lost their melanocytes. This aberrant response might be due to inability of depigmented skin to express intercellular adhesion molecule 1 (ICAM-1). Humans with vitiligo show altered expression of ICAM-1 in the epidermis. ICAM-1 is critical to a normal immune response.

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Mice with mivit/mivit gene. The mouse on the left has a piebald band on the leg but a normal pigmented pelage in early life. The mouse on the right is undergoing depigmentation with loss of melanocytes from the epidermis and hair follicles

One of the most mysterious features of vitiligo is the resistance of skin depigmented by vitiligo to producing skin cancers. It is a common worry for physicians and patients with vitiligo that they might get a melanoma. It is possible for a patient with vitiligo to get a melanoma but only in their normally pigmented skin. The white skin is devoid of melanocytes and thus unable to generate a melanoma. It is baffling that the white skin is also highly resistant to formation of keratinocyte malignancies, i.e., basal and squamous cell carcinomas.

Vitiligo skin is totally depigmented. The color is similar to that of albinism. Albinos are known to have a high incidence of skin cancer, especially in Africa where most albinos have oculocutaneous albinism type 2, a disorder caused by mutations in the p-gene. Most of these are squamous cell carcinomas. Interestingly, few individuals with other forms of oculocutaneous albinism, types I, III and IV, have been reported to have skin cancer. There are many possible explanations for this, the most obvious being that those living in Africa have little access to sufficient sun protection. In contrast, it has been suggested the mutations in the p-gene are related to melanomas  as well as causing oculocutaneous albinism II. Similar studies on the p-gene and skin cancer have not been done for non-melanoma cancers but it is a project which may be worth doing. It must be stated that melanomas are very infrequent in albinos of any type.[

Patients with vitiligo can get skin cancer of any type in their normal skin but there is a paucity of reports of non-melanoma skin cancer in the white skin. This observation is particularly puzzling because the treatments for vitiligo include both ultraviolet B and psoralen-ultraviolet A (PUVA), both carcinogenic forms of light. Of interest is a recent report in which the incidence of skin cancer was studied in a cohort of 477 vitiligo patients. Half of these were Caucasians and the other half were dark skinned (Fitzpatrick skin types IV, V, VI). There with six patients with skin cancers, all with light colored skin (Fitzpatrick types I, II, III). Four of the six occurred in normal skin and only two affected the depigmented skin. Several points are worth noting. No individuals with type IV skin or darker had a skin cancer. Depigmented skin is of the same color in individuals of all ethnic backgrounds, i.e., totally white. One would expect that the cancers affected individuals of all skin color equally. The other point is that the cancers were most common (four of the six) in the normally pigmented skin. One would expect a majority to be in the depigmented skin. This is consistent with the idea that vitiligo skin is resistant to formation of skin cancers.

It is of note that actinic damage also is less visible in white skin than in the pigmented skin of those with vitiligo. Several studies on patients with vitiligo treated with PUVA showed no increase in skin cancer incidence. In contrast, albinos exhibit sun damage from early childhood. Some white skin caused by the absence of melanocytes from other causes seems susceptible to carcinogenesis. Thermal scars or depigmented skin of patients with discoid lupus are susceptible to formation of cancers. Of particular interest are patients with piebaldism caused by defects in the c-kit oncogene. As noted above, piebald skin reacts differently from normally pigmented skin to a graft versus host immune reaction. In my own series of three families with piebaldism, actinic damage is common and seems to have a predilection for the white skin rather than the pigmented normal skin . This seems to be the reverse of our observations for vitiligo skin. That the melanocytes have some role in inflammation, carcinogenesis and other processes seems probable.

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The neck of an African woman who had vitiligo for over 20 years. She was a farmer and worked in the sun daily. Note the elastosis of the neck, but the normal overlying white epidermis

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The hands of the African woman shown  above  who had vitiligo for over 20 years. She was a farmer and worked in the sun daily

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The arms of a woman with piebaldism (c-kit). She has marked sun damage and many actinic keratoses, mostly in the depigmented patches on her arms

There is no doubt that skin color and susceptibility to skin cancer are related. Lighter skin has a high propensity for all forms of skin cancer compared to darker skin. It has been enigmatic to me that my students from Asia, China, Korea and Japan have a skin color not that much darker than mine with a European ancestry (Swedish and Hungarian). Asians are not so pigmented as Africans, Indians or Middle Easterners. Yet, their risk for skin cancers is low. My conclusion is that skin color is just one factor related to skin cancer risk. Other factors related to repair of damage, resistance to mutation and/or other factors play as big or bigger role in defense against skin cancer as skin color. This point is made clear, especially from the data on vitiligo and albino patients and skin cancer and the types of skin cancer identified in albinos, mostly squamous cell carcinomas. Why don′t albinos get more basal cell carcinomas and/or melanomas?

Finally, it is well known among those who are interested in vitiligo that treatment is difficult and frustrating. Some of the areas of depigmentation are especially difficult to repigment, such as the hands and feet. It seems mysterious to many. However, it has been shown that the hair follicle is the reservoir for repigmentation. Nature, for reasons not clear, evolved skin on the fingers, ventral surface of the wrist, the feet and genitalia that is hairless, i.e., glabrous. Such skin or skin with white hairs cannot respond to medical treatment  but only to surgical treatments which are a means to make a reservoir where there was none.

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The leg shows repigmentation from the hair follicles

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The leg has all white hairs and no repigmentation is visible except in one spot (arrows and circle)

Clearly, these are the musings of an old person thinking over the decades about vitiligo. Most of the interest by investigators is focused on an immune basis for melanocyte destruction. These studies are important to understand the cause of vitiligo. Little has been done to study the defects in the melanocytes which make them susceptible to destruction. There is so little interest in the melanocyte as a member of the inflammatory response because the prevalent bias about the melanocyte is that it is exclusively a protection against sun damage, a role it plays as part of a much larger function in the skin. There must be an important message in the fact that skin cancer is unusual in vitiligo skin but common in albino skin, the obvious difference being the presence of dysfunctional melanocytes in the latter patients. It is my hope that a younger student will not only study these phenomena and find the causes of vitiligo but also find the answer to other important questions about the epidermis and pigmentation.

Source 

Photo Credit: Envato Elements

VIPOC Appoints Mrs. Gaone Matewa As New President

                        

NEWS RELEASE

 

FOR IMMEDIATE RELEASE

 

Vitiligo International Patient Organizations Committee (VIPOC)

12/09/2022

VIPOC Appoints Mrs. Gaone Matewa As New President

VIPOC appointed Mrs Gaone Matewa as the New President of the organisation. An experienced leader, Mrs Gaone Matewa will succeed Mr Jean-Marie Meurant and assume the responsibilities.

Gaone Matewa is a dedicated marathon runner, a proud mother of two busy boys, and a published medical author on the topic of vitiligo. She is also the founder of Beyond Vitiligo and Beyond Vitiligo Botswana.

Matewa has always believed in expanding the awareness of vitiligo to other countries and acquiring as well as conducting research on this disease. This inspired her to attend as many skin conferences as possible to do so. She then met Meurant at one of these conferences and she, “grew fond of his passion for the research and solutions around vitiligo.”

“Jean Marie showed great leadership skills and believes in the power of collaboration and unity. He believed that challenges surrounding vitiligo should not be conquered separately and thus, VIPOC was formed. I became a member of the VIPOC family in its early stages in 2017 because I believed in this vision.  The problems faced by vitiligo patients are the same everywhere I believed VIPOC to be the best manner of taking vitiligo support and research across the globe.” Matewa Said

Meurant expressed how proud he is of Matewa regarding the New presidency and stated that she would be a great fit as president.

Gaone has collaborated with some of the top dermatologists, medical researchers, and members of the international skin community. She has also been a part of the Global Skin organisation, a global non-profit devoted to advancing knowledge about and research into the other 41 skin disorders.

Just to name a few, Gaone has been named by Mail & Guardian South Africa as one of the 200 most influential young South Africans. Additionally, True Love South Africa nominated her for the 2019 Women Making a Difference class award.

She received a BBA degree in International Finance & Investment as well as an Honors in Risk Management. She is a qualified accountant with 10 years of experience, and she sits on few boards.

About VIPOC

The Vitiligo International Patient Organizations Conference is an official association based in Paris. Our purpose is to improve the daily life of vitiligo patients, provide them with the support and information they need, promote understanding, recognition, and work on cures and care for vitiligo by the medical community and society.

The community and support organisation for vitiligo patients’ groups, was created in 2018 after multiple patient organisations had discussed the idea of banding together to improve the awareness and the lives of people with vitiligo.