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Studies Show Combination Therapy Best for Vitiligo

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If you suffer from white patches on the skin, otherwise known as vitiligo, there are several treatment options available. Choosing the right treatment can be difficult. However, new studies show vitiligo responds best to multiple forms of treatment- making the decision much easier. Learn more about the best treatment methods below.

Vitiligo is a condition of the skin in which pigmentation slowly fades and leads to small to large patches of completely white skin in its place. Vitiligo was long thought to be untreatable, but recent medical research has shown that several treatment options can be effective- both natural and medical.

Studies examining the increase in vitiligo cases have uncovered a wide range of possible triggers for the development of the disease. However, a new study from 2014 has also found that combination therapy is the most effective when treating the disease. Read more about these two studies and the possible treatment methods for vitiligo below:

How Common is Vitiligo?

Vitiligo is characterized by depigmentation on the skin and often affects the hands, feet, face, and the joints between the torso and limbs. In rare cases, vitiligo can affect the entire body. Although vitiligo was at first thought to be extremely rare, cases seem to be increasing worldwide. An estimation from the Journal of the American Medical Association-Dermatology states that approximately 1 out of every 100 people in the United States suffer from mild to severe vitiligo.

Other studies support the idea that vitiligo cases are increasing. A 1999 study published in the Indian Journal of Dermatology, Venereology, and Leprology found that globally, cases of vitiligo have increased between 4 and 5 percent over previous decades.

The study examined 5000 individuals with vitiligo to try and identify why vitiligo cases may be on the rise.

What Causes Vitiligo?

Vitiligo is thought to be caused by a variety of factors-none of which point to a clear cause for the disease. Commonly, vitiligo is thought to be a genetic, autoimmune, or stress-triggered disease. Other possible causes include neurologic problems or melanocyte self-destruction.

However, the Indian study listed above offers an additional possible explanation- environmental factors. The study found that just over 68 percent of the vitiligo patients in the 5000 patient study had the same precipitating factors. According to the study researchers, 68 percent of patients had dealt with a major illness, severe emotional stress, surgical or physical trauma, or pregnancy.

Other significant factors included consumption of stale preserved foods, water contaminated with industrial waste, and old medicines. There were even some incidences of air contaminated with industrial waste leading to cases of vitiligo. Repeated drug intake also triggered vitiligo in just over 26 percent of cases, including antibiotics.

The study researchers theorized that these precipitating factors worked to disturb the immunological balance in the body, which triggered the autoimmune response to produce symptoms of vitiligo. Upon further research, the study researchers found evidence to support the theory that the entire melanocyte system is defective in patients with vitiligo.

This study, and other similar studies can help identify how to prevent vitiligo, rather than simply treat the symptoms after they occur.

Common Causes of Vitiligo

Although the exact root causes of vitiligo are unknown, studies have shown that vitiligo can be caused by an autoimmune attack on melanocytes, toxic chemicals, oxidative stress, defective melanocytes, genetic defects, and nerve damage.

Autoimmune Attack on Melanocytes: This is usually the cause of vitiligo associated with other autoimmune diseases especially thyroid disorders. When the cells of the immune system go on a rampage, the melanocytes are one of the targets.

Once destroyed, vitiligo quickly sets in. This autoimmune attack on the skin can also cause psoriasis and alopecia areata.

Oxidative Stress: The accumulation of harmful free radicals and hydrogen peroxide in the skin has been shown to increase the rate of death of melanocytes. When this oxidative stress overwhelms the skin, the levels of antioxidant enzymes such as catalase are reduced.

Vitiligo caused by oxidative stress can be clinically distinguished by the yellowish green or blue fluorescence of the skin under a special light.

Defective Melanocytes: Improperly formed melanocytes are more easily destroyed than normal melanocytes. This theory suggests that vitiligo affects people who have these malformed melanocytes. The cellular abnormality can be structural (rough endoplasmic reticulum) or functional (dysregulation of surface receptors).

Nerve Damage: There have been vitiligo cases that arise only after some nerve damage. Therefore, some experts believe that the change in neurochemical mediators released at nerve endings can affect the production of melanin and cause vitiligo.

Genetic Defects: Multiple genetic defects may increase the risk of developing vitiligo in certain people. Genes play a significant role in the formation of melanocytes, synthesis of melanin, protection against oxidative stress and regulation of autoimmune response.

Therefore, a genetic defect in any of these processes can cause vitiligo.

There are 2 types of skin pigmentation changes: hyperpigmentation and hypopigmentation.

Hyperpigmentation

When there is an increased production of melanin in the skin, hyperpigmentation results. It is the unusual darkening of the skin, even the hyperpigmented areas of the skin.

The chief cause of hyperpigmentation is prolonged exposure to intense ultraviolet light especially sunlight. However, hyperpigmentation can also be caused by certain physiological states such as pregnancy; diseases such as Addison’s disease; and drugs including sulfa drugs.

Melasma is a good example of hyperpigmentation of the skin.

Melasma is also called chloasma, chloasma faciei or mask of pregnancy. It can affect both men and women.

Melasma presents as dark or tan discolorations on the skin. Its irregular, hyperpigmented macules are usually found on the face and they expand over time. However, when it affects pregnant women, it usually goes away after pregnancy.

Melasma can be caused by hormonal changes and it is commonly seen in women taking oral contraceptives or undergoing estrogen replacement therapy.

Melasma is only a cosmetic discoloration and not an actual disease. Those who have it are advised to wear strong sunscreens. It can be treated with hydroquinone cream, topical tretinoin, azelaic acid, chemical peels, microdermabrasion, and laser therapy.

Hypopigmentation

Hypopigmentation is the reverse of hyperpigmentation. It is caused by reduced melanin production.

The two most common forms of hypopigmentation are albinism and vitiligo.

Albinism is a genetic disorder with no cure. Albinism is a complete lack of skin pigmentation which is caused by a defect in the genes coding for the enzyme that produces melanin.

Vitiligo is an autoimmune disorder caused by the destruction of the melanocytes in the skin by immune cells. It presents as white patches of depigmented areas of the skin.

Vitiligo has no cure but there are treatments to stop its progression and even regain some skin pigmentation.

Why Skin Color Changes
  • Genes
  • Heat
  • Injury
  • Ultraviolet radiation
  • Heavy metals
  • Drugs
  • Allergy
  • Infections
  • Hormonal changes

The Most Effective Treatment for Vitiligo

Although there are many treatment options for vitiligo, not all of them are effective. In fact, most medical treatments for vitiligo are rather ineffective. However, a new study has discovered a treatment method that may provide the biggest improvement in vitiligo symptoms.

The study was published in September 2014 in JAMA Dermatology. The study found that a combination of phototherapy and implantation of afamelanotide provided more benefit than either of those treatments alone.

The Multicultural Dermatology Center at Henry Ford Hospital in Detroit, Michigan conducted a clinical trial on 55 adult patients with vitiligo. These patients were assigned to receive monotherapy or combination therapy. All patients were suffering from a slow progression of the disease from the three months leading up to the study.

The monotherapy group acted as a control group for the combination group which received afamelanotide combined with ultraviolet B (NB-UV-B) phototherapy. Afamelanotide is a synthetic version of the naturally occurring α-melanocyte-stimulating hormone, which is what stimulates pigment production in the skin. Each patient received afamelanotide injections once a month for four months.

Both groups underwent NB-UV-B phototherapy 2-3 times a week for 6 months. Both groups saw improvement in their symptoms, but the combination group improved the most. The combination group showed a 48 percent improvement versus a 33 percent improvement in the control group. The combination group also saw faster results than the monotherapy group. The greatest improvement was seen on the face and upper extremities. However, since this clinical trial was so small, further studies are necessary to identify the limitations and benefits of combination therapy.

Despite the problems with the study, this research supports the idea that a multi-faceted approach is best for reversing vitiligo symptoms.

Other Medical Treatment Options for Vitiligo

Although none of the medical treatment options for vitiligo are completely effective, many patients do show some recovery and repigmentation after trying medical treatment. The most common medical treatments for vitiligo include:

Topical Corticosteroid Creams

Corticosteroid refers to a class of natural and synthetic compounds including steroid hormones and their analogs. Natural corticosteroids are produced from cholesterol in the adrenal cortex.

Corticosteroids are important to many physiological and biochemical processes in the body. They are involved in inflammation, immune response, electrolyte balance and metabolism.

Glucocorticoids are one class of corticosteroids that control the metabolism of proteins, carbohydrate fat. They also have anti-inflammatory properties. A prime example of glucocorticoids is cortisol.

Mineralocorticoids, on the other hand, are the corticosteroids that control electrolyte balance and water levels in the body. They promote the reabsorption of sodium in the kidney. Aldosterone is an example of mineralocorticoids.

There are other ways of classifying corticosteroids.

Corticosteroids By Chemical Structures
  • Group A or Cortisones – Hydrocortisone, Cortisone, Prednisolone and their salts
  • Group B or Acetonides – Triamcinolone, Budesonide, Halcinonide
  • Group C or Betamathasone-like – Bethamethasone, Dexamethasone and their salts
  • Group D or Esters – Ester salts of the above corticosteroids

Corticosteroids are formulated to be delivered by different routes of administration. The most popular dosage forms in which corticosteroids are presented are oral and topical forms. However, corticosteroids can also be formulated as inhalation, ophthalmic and injectable medications.

Synthetic corticosteroids can have one or both glucocorticoid and mineralocorticoid activities.

For example, dexamethasone is a glucocorticoid, fludrocortisone is a mineralocorticoid while prednisone has both mineralocorticoid and mineralocorticoid activities.

Glucocorticoids are more widely used than mineralocorticoids. Some of the medical conditions treated with glucocorticoids are arthritis, dermatitis, hepatitis, sarcoidosis, inflammatory bowel syndrome and lupus.

Corticosteroids can have very serious side effects and they are rarely recommended for long-term use.

Mineralocorticoids, for example, can cause hypertension, elevated sodium levels and low potassium levels. These side effects are due to the retention of sodium in the kidneys.

Long-term side effects of corticosteroids include insulin resistance, diabetes mellitus, osteoporosis, depression, erectile dysfunction and hypothyroidism.

Topical corticosteroids can cause stretch marks and unsightly lesions as well as shrink and thin the skin.

Corticosteroids can also suppress the immune system and inhibit the process of wound healing. It is also not recommended for pregnant women because of teratogenic side effects.

Why Corticosteroids Work for Vitiligo

The desirable property of corticosteroids in vitiligo therapy is its immunosuppressive effect.

Vitiligo is caused by the progressive destruction of melanocytes. Melanocytes are the specialized skin cells responsible for producing melanin, the pigment that gives the skin its color. It is when these cells are lost that the skin loses its color and white patches appear.

Different causes have been proposed for vitiligo. These include autoimmune attack on melanocytes, intrinsic defects in melanocytes, nerve damage, oxidative stress and genetic factors. However, the most popular of these proposed theories is autoimmune attack on melanocytes.

In a way, vitiligo can be described as an autoimmune disorder. It has been reported to present along with other autoimmune disorders such as thyroid dysfunction, diabetes mellitus and alopecia areata.

When the cells of the immune system see melanocytes as foreign bodies, they attack them.

There are clear evidences that both cellular and humoral immunity are involved in the destruction of melanocytes. For example, specific antibodies and CD8+ T cells are found in high levels in vitiligo patients.

Corticosteroids can prevent this autoimmune attack on the melanocyte by suppressing the immune system. By blocking the cells of the immune system, corticosteroids spare melanocytes and allow the production of melanin to proceed.

Therefore, the immunosuppressive property of corticosteroids can help stop the depigmentation of the skin and even repigment vitiligo patches.

Studies on the Use of Corticosteroid in Vitiligo Treatment

Oral Corticosteroid

In a 2003 study published in the Indian Journal of Dermatology, Venereology and Leprology, the efficacy of low dose oral corticosteroid was tested in 100 vitiligo patients.

Each of the patients were given 0.3 mg/kg of body weight of prednisolone for 2 months. This dose was then halved in the third month and further halved in the fourth month. After 4 months, the patients were then evaluated.

The results showed that depigmentation stopped in 90% of the patients and 76% of the patients experienced repigmentation.

The low dose of oral corticosteroid was used to minimize side effects.

This study showed that low dose, oral corticosteroids can be effective in the treatment of rapidly spreading vitiligo while producing no serious side effects.

Topical Corticosteroids

A 1976 study published in the British Journal of Dermatology recruited 20 vitiligo patients for a trial of 2 topical corticosteroids.

The patients were divided into 2 groups. One group received 0.05% clobetasol propionate and the other group were given 0.1% betamethasone valerate. After 3 months of treatment, the patients were examined.

The results showed that both topical steroids were effective in the treatment of vitiligo in some (and not all) patients. Also, more patients experienced repigmentation with betamethasone valerate than clobetasol propionate.

Combination Corticosteroid Therapy

A 2004 study published in the journal, Pediatric Dermatology, accessed the benefits of combining topical corticosteroid with another vitiligo medication. The result was then compared with treating with only corticosteroids.

In this study, 12 vitiligo patients were advised to use topical corticosteroids in the morning and calcipotriene in the evening.

Calcipotriene is a vitamin D analog that has been proven to improve vitiligo spots especially when combined with ultraviolet irradiation (UVA and UVB).

The results of this study showed that 83% of the patients responded to treatment with the combination of calcipotriene and corticosteroids. In this group are 4 patients who had been unsuccessfully treated with corticosteroids. Of the successful cases, 95% of the patients experienced full body repigmentation.

This study showed that vitiligo cases that did not respond to corticosteroid may be successful treated by combining corticosteroids with other vitiligo treatments.

How to Use Corticosteroid for Vitiligo

While many report that oral corticosteroids produce better results than topical corticosteroids, many prescribers advise against treating vitiligo with oral corticosteroids because of their serious side effects.

Furthermore, it is easier for prescribers and patients to monitor topical corticosteroids and withdraw them at the first signs of side effects.

Generally, oral corticosteroids are reserved for severe vitiligo cases but even those cases can be treated with other safer, topical vitiligo drugs such as tacrolimus and vitamin D analogs like calcipotriene.

Corticosteroids are not recommended for treating vitiligo patches that occupy large areas of the skin. They work best for localized vitiligo. They should also be avoided when vitiligo spots affect highly visible parts of the body such as the face.

Besides topical vitiligo drugs such as calcipotriene, topical corticosteroids can also be combined with ultraviolet light therapy. Different studies have shown that this combination produces better results than each treatment used alone.

Only low strength topical corticosteroids should be used for children.

When some researchers analyzed the body of studies done on the use of corticosteroids in the treatment of vitiligo, it was concluded that class 3 and class 4 topical corticosteroids were the most effective.

Corticosteroids in these classes include betamethasone valerate, hydrocortisone butyrate, methylprednisone, clobetasol propionate and betamethasone dipropionate.

Clinicians recommend that topical corticosteroid therapy should be stopped if no significant improvements are seen after 2 months of treatment.

Where low dose oral corticosteroid therapy is not possible, high dose pulse therapy may be advised. This form of treatment involves short treatment with intravenous corticosteroids.

Mini Grafting

In small cases, vitiligo patients can undergo skin grafting to replace unpigmented skin with pigmented skin from other areas of the body. This treatment is not without risks and is impossible for large sections of vitiligo.

PUVA Photochemotherapy

PUVA is an acronym for the term Psoralen UltraViolet A radiation, which is the solar spectrum between 320 and 400 wavelengths in nanometers. A psoralen is a plant chemical that boosts the absorption of UV light, boosting how much UV light is absorbed by the skin. The chemicals mix with your DNA and inhibit the multiplication of the cells that contribute to skin pigment loss. PUVA is a combination therapy that is used to treat vitiligo that is not responsive to other treatment types.

Currently, UVB treatment is preferred in patients with vitiligo because it has a similar effectiveness rating with fewer side effects, but some patients may still respond better to PUVA therapy.

Types of PUVA Therapy

The standard form of the therapy has patients take an oral supplement of the psoralen (usually 8-methoxy psoralen) and then exposes them to UVA light for several minutes about an hour after the patient takes the supplement. In some cases, a psoralen cream is applied to areas of the skin that lack pigmentation. Patients may also soak in a tub of medicated liquid before undergoing PUVA treatment.

The Benefits of PUVA Therapy for Vitiligo

The biggest advantage to PUVA treatment is that the medication used does not affect anything other than the skin. It also can be used to treat large areas of the skin, which is beneficial in patients who have lost a lot of pigment to vitiligo. The drug is only activated when the skin is exposed to UVA light, further minimizing the risk of drug therapy.

The Disadvantages of PUVA Therapy

Patients cannot administer PUVA therapy on their own. They must visit a medical professional for treatment. In some cases, when PUVA therapy is stopped, vitiligo returns. In these cases, treatment would have to continue indefinitely to maintain proper skin pigmentation. The risks of side effects are high when compared with UVB therapy for vitiligo.

In a 2012 study published in the International Journal of Dermatology, patients who had UVB therapy had side effects in about 7 percent of cases, but patients who had PUVA therapy had side effects in 57 percent of cases. Two of these cases were so severe that the patients discontinued treatment.

Side Effects of PUVA

According to several studies, PUVA has several side effects, the biggest of which is an increased risk for skin cancer. The more UVA treatments are administered, the higher the risk for skin cancer. Skin aging (sometimes known as leathery skin) is also increased with PUVA therapy. In some cases, the treatment can cause skin burns, nausea, and dizziness.

PUVA Effectiveness

According to numerous studies, repigmentation occurs in about 70 to 80 percent of all patients who try PUVA therapy. Complete repigmentation is seen in about 20 percent of cases. After two years, about 75 percent of patients relapse either a small amount or completely. It takes between six and 24 months for full results to be seen with PUVA therapy.

According to studies, darker skin responds best to PUVA treatments. When applied topically, PUVA therapy is even more effective and requires less exposure to UVA light. However, topical PUVA therapy is more likely to result in advanced skin aging, blisters, burns, and hyperpigmentation.

How PUVA Works

In most cases, the patient with vitiligo takes an oral supplement of psoralen about one hour before light therapy. If a topical cream is used, it is applied 30 minutes before sun exposure. The patient is then exposed to UVA lights for a specified length of time depending on the severity of vitiligo. In most cases, a patient is placed inside a box that looks similar to a tanning bed and precise amounts of UVA radiation are targeted onto the areas of the body with pigmentation loss. It takes about 15 treatment sessions before significant pigmentation is seen.

Treatments are usually spread at least 48 hours apart to prevent sunburns. Energy levels are adjusted based on the patient’s acceptance of the UVA radiation. It can take up to two years for full effects of the treatment to take place. Usually, patients decide whether to continue treatment after about 30 sessions. If improvements are not seen within 30 sessions, PUVA therapy is not effective for that patient.

PUVA vs NB-UVB Treatment for Vitiligo

In most cases, medical professionals prefer UVB treatment to PUVA as side effects are generally more mild with UVB treatments. Although the 2012 study comparing the two types of UV therapy for vitiligo showed similar effectiveness in skin pigmentation, recovery time, and relapse rate; patients who completed UVB therapy showed better tolerance for the treatment. Additionally, the patients in the UVB group had a better response group overall, had fewer side effects, and had better color matching than the UVA group.

For this reason, if UVB treatment is available, patients should start with that treatment method first before moving on to PUVA therapy.

Boost the Effectiveness of PUVA Therapy

Some research suggests that the effectiveness of PUVA therapy (and UVB therapy) can be boosted with a variety of lifestyle and diet changes. If you are considering a light therapy for vitiligo, also consider making these lifestyle changes at the same time to boost the effectiveness of your treatment. According to some clinical trials, certain vitamins and nutrient levels are low in patients with vitiligo.

Often, vitiligo patients are low in vitamin B6, B12, and B9, which are used to support the pigmentation of the skin as well as regulate energy and the function of the nervous system. Research suggests that a few other supplements can also boost the effectiveness of light therapy for vitiligo patients.

Picrorhiza is an immune-system booster that can help prevent autoimmune conditions like vitiligo. Some researchers believe that vitiligo is caused by the skin mistakenly attacking skin pigment in an overactive autoimmune response.

Khellin is another common supplement to take in combination with light therapy. According to some studies, when patients take khellin the effectiveness of their treatment increases. Khellin works similarly to psoralen by making the skin more receptive to UV light. For this reason, it is important to make sure you don’t get too much sun exposure outside of targeted light therapy if you are taking khellin or psoralen medication.

Another supplement that has been shown to boost the effectiveness of light therapy in vitiligo patients is L-phenylalanine. L-phenylalanine is an amino acid that helps repigment skin. In one study, a combination of L-phenylalanine, UVA light, and 0.025% clobetasol propionate was able to treat vitiligo on the face without side effects. When combined with khellin, 63 percent of patients had 75-100 repigmentation on the face within 12 months.

Nutrients that Boost Light Therapy Effectiveness
  • Khellin
  • Vitamin B9
  • Vitamin B6
  • Vitamin B12
  • Picrorhiza
  • L-phenylalanine

Bleaching

For patients who do not respond to other treatments, or do not want to do other treatments, some doctors prescribe topical creams to remove pigment from elsewhere on the body. Often, monobenzylether of hydroquinone cream is used to whiten the skin.

Non-Medical Treatment Options

As stated in the studies above, there are a variety of factors that are implicated in the development of vitiligo, and addressing these conditions at the source could help the skin repigment without the need for medical intervention.

Eliminate Toxins

The Indian study found that individuals who lived in toxic environments were more likely to develop vitiligo than individuals living in clean environments. Industrial waste products in drinking water dramatically increased a person’s chances of developing the disease. One of the easiest ways to improve the quality of water is to drink bottled mineral water or to filter water using a high-quality water distiller or carbon block filter. These filters can remove a vast array of chemical contaminants in any water source.

Although residents in the United States are less likely to have severely contaminated water, groundwater is still poisoned by factories daily. For example, in West Virginia and Ohio, Industrial giant DuPont was sued by nearly 3,000 people in 2014 due to the company’s practice of dumping perfluorooctanoic acid (C8) (used in the production of Teflon products) into the Ohio River. The results of a 2005 study conducted on the side effects C8 found that the chemical can cause kidney cancer, testicular cancer, high cholesterol, ulcerative colitis, pregnancy-induced high blood pressure, and thyroid disease.

Just because water comes from a U.S.-based water source does not mean it is not contaminated with waste chemicals.

Repair Stress Damage

Damage from medical procedures, illnesses, and even emotional stress can all contribute to an increased risk of developing vitiligo. Removing stress from the body can help the body recover and improve the immune system. A properly working immune system is less likely to trigger an autoimmune response like the one responsible for the spread and development of vitiligo. Concentrated de-stressing efforts, such as stepping down from stressful roles, spending time each night relaxing, and engaging in de-stressing activities like meditation and massage can help repair stress damage.

Improve the Diet

The foods that you eat can play a role in the progression or development of vitiligo. As the Indian study uncovered, an unhealthy diet full of processed and stale foods led to the further progression and development of the disease. Certain vitamins are known to improve the quality and health of the skin, which may also be helpful in reducing vitiligo symptoms. These nutrients include:

Important Nutrients for Skin Health
  • Vitamin B12
  • Folic Acid
  • Vitamin C
  • Vitamin D
  • Vitamin A
  • Copper, iron, and zinc

One of the richest sources of minerals, B vitamins, and vitamin D in the diet is seafood. Fatty fish like sardines, salmon, and shellfish have large concentrations of these vitamins. Vitamin A can be found in orange foods, as well as red meat products, particularly liver and other organ meats.

Supplement for Immune Health

Since vitiligo is an autoimmune disorder, improving the immune system could help prevent the spread of the disease. According to WebMD, carotenoids, antioxidants, zinc, selenium, vitamin E, vitamin C, and vitamin D are all essential nutrients that support immune system health. Adding foods that contain these nutrients and supplementing with any missing nutrients could help control symptoms of vitiligo.

Reduce Drug Exposure

Another potential trigger for vitiligo is extended drug use. The Indian study even found that widespread antibiotic use was implicated in some cases of vitiligo. According to the researchers, patients with a family history of vitiligo should carefully consider the potential side effects of the medication before starting any treatment in case the development of vitiligo is a side effect. Patients on long-term medication who also have symptoms of vitiligo should discuss the potential link with their doctor. Never cease the use of a medication without the approval of a qualified health professional.

Vitiligo: Multiple Causes, Multiple Treatments

According to the studies outlined above, vitiligo can be caused by a variety of factors and responds best to a variety of treatment options. Individuals suffering from vitiligo should see the best results when combination therapies are used-both medical and non-medical. Depigmentation of the skin is an autoimmune response that likely points to several potential causes in the body’s systems. Addressing these problems from the inside out is likely to produce better long-term results than simply treating the condition from the outside alone.

Sources


http://www.sciencedaily.com/releases/2014/09/140917172741.htm

http://www.ijdvl.com/article.asp?issn=0378-6323;year=1999;volume=65;issue=4;spage=161;epage=167;aulast=Behl

http://www.mayoclinic.org/diseases-conditions/vitiligo/basics/causes/con-20032007

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