Dear Members and Friends of VSI,

VSI volunteers are helping to move research forward. Many VSI members participated in the recent highly-publicized gene study published in the April 21, 2010 issue of the New England Journal of Medicine, confirming for the first time that vitiligo is an autoimmune disease - that the cause of vitiligo lies in our immune system. This same study also challenges the belief that people with vitiligo are more likely to contract melanoma (see the article on this research in this newsletter).

This important groundbreaking work, led by researchers at the University of Colorado School of Medicine, headed by VSI's Medical Advisory Board member Dr. Richard Spritz, and funded by the National Institutes of Health, puts us at the threshold of research that could lead to new therapies specifically designed to control vitiligo. The completed phases of this study have uncovered remarkable findings providing researchers with a greater understanding of the pathways of vitiligo.

I am personally very hopeful about what will come from the current worldwide vitiligo research. New research studies, surveys and clinical trials appear daily, but their outcome is dependent on volunteers. VSI has been a key source of support for research through its patient recruitment efforts. You can help make a difference through your participation as a study volunteer. Please consider joining with us to shape the future.

Much more information is needed to build on these discoveries. More vitiligo patient volunteers, particularly from minority groups, are urgently needed to keep the momentum going. If you have not yet participated in this ongoing study, click here to participate now.

Sincerely,

Jackie Gardner

Dr. Richard Spritz

A major step has been made on the path to understanding vitiligo. Findings from a study of 1,500 vitiligo patients reported in the April 21, 2010 issue of the New England Journal of Medicine confirm for the first time that generalized vitiligo is an autoimmune disease.

So why is this important? We now have a place to begin in our pursuit of the cause, the biology, the treatment, and even the cure of this disease. The greater our understanding of the biology of vitiligo, the more chance we have to design therapies that can maximally control vitiligo. The effectiveness of current vitiligo therapy is variable, as these treatments were not originally developed specifically to treat vitiligo.

In autoimmune disease, the patient's immune system is activated against the body's own proteins. Autoimmune diseases, of which there are many such as Crohn's disease, rheumatoid arthritis, type 1 diabetes, and lupus, are generally treated with immunosuppressive medications to decrease the anti-self immune response. Future vitiligo therapies may be among this same class of immunosuppressive medications.

Specific vitiligo genes are linked to autoimmunity
Richard A. Spritz, M.D., Director of the Human Medical Genetics Program at the University of Colorado School of Medicine, and head of the international team conducting this study told VSI, "Our study provides the first solid proof that vitiligo is an autoimmune disease. Of the 14 genes we discovered linked to vitiligo, at least 13 are directly involved in regulating the immune system or causing autoimmune disease."

Therapeutic clues
What does this autoimmune connection mean for the patient? According to Dr. Spritz, "The immune system's role in vitiligo should now become the focus of future research to control the specific biochemical pathways that are involved in causing the disease. Knowing which pathways are involved in vitiligo should enable scientists to eventually design specific therapies that target those pathways and thereby provide more effective vitiligo control. In fact, the genetic similarities we found between vitiligo and some other autoimmune diseases suggests some of the current drugs out there being developed to treat other autoimmune disease should also be considered for possible treatment of vitiligo."

The largest vitiligo genetics study
Dr. Spritz and an international team of researchers compared the genes of 1,500 people with vitiligo to the genes of 2,800 people without, in the largest genome-wide association study (GWAS) done to date in vitiligo, to see what gene differences or variations might be associated with vitiligo (for more information on the NIH and GWAS research, see accompanying article in blue box below). The hoped-for outcome is that these genetic variations are within or near genes that make proteins that play roles in the pathogenesis of vitiligo. Dr. Spritz noted, "Four of the genes we found in our study may well fit together into one biological pathway that is of particular importance for vitiligo."

Surprises found
A few surprises came out in the research. One was that no genes were found that play roles in any of the non-immune mechanisms that some have suggested might be involved in the pathogenesis of vitiligo. "We had a long list of candidate genes that other scientists had postulated might play a role in vitiligo," Dr. Spritz commented. "None of those genes panned out except those tied to regulating the immune system. That does not mean that those other mechanisms might not play any role in the pathogenesis of generalized vitiligo, but it does make it hard to support roles for supposed mechanisms of disease that don't somehow tie into autoimmunity, at least for typical cases."

Another unanticipated discovery was that some of the identified genes that predispose people to vitiligo at the same time protect from melanoma, raising the speculation that people with vitiligo may face less risk of melanoma than the average person. Dr. Spritz went on to explain, "We found a genetic variation that is more common among vitiligo patients, but that is known to protect against melanoma. The human immune system is always surveilling for tumors - killing most of them off as they are discovered. Vitiligo may be an amplification of this immune surveillance process. Our finding suggests that vitiligo patients might have less risk of melanoma, though we don't really know for sure yet."

Do these findings help us predict who will get vitiligo?
"No," Dr. Spritz responded. "Not yet. Altogether, the genes that we found only account for about 10% of the total risk of developing vitiligo. There's a lot more to the story, and probably there are more genes that we still need to identify. In addition, we still don't know the environmental triggers for vitiligo or, for that matter, any other autoimmune disease. We believe that, for most people, they inherit genes that predispose them to develop vitiligo, but that only happens if they encounter something in the environment that then causes that genetic predisposition to be expressed as vitiligo. We have taken the first big step, identifying some of the most important genes linked to causing vitiligo," but Dr. Spritz cautioned, "There is still a long way to go."

Why do only some family members get vitiligo?
Dr. Spritz noted that susceptibility results from different combinations of susceptibility genes, even in the same family. "Different family members could easily inherit different genetic combinations, just as for height, intelligence, and many other complex traits." Further, he added, "Even among identical twins, both develop vitiligo only one-fourth of the time. Identical twins share all their genes in common, but they don't share their environmental exposures and other life-events. The more we learn about the genetics of vitiligo, the more chance we have of learning about environmental triggers of vitiligo."

What does the future hold?
We asked Dr. Spritz where he will go from here in his research. "We are moving in three directions, all at the same time," he said. "This first study was done in Caucasians because they were the only ethnic group from whom we were able to get enough samples to do a study. For genetic studies of this kind, it is essential that we maintain ethnic homogeneity so that we can see the relatively small genetic effects that are due to vitiligo on the much larger background of genetic differences that are due to ethnicity." According to Dr. Spritz, "We are now adding more Caucasian patients and more controls to that first study, to pick up additional genes we missed on the first pass.

Second, we are studying those genes that we did find in fine detail, to understand exactly what DNA variants in those genes cause risk of vitiligo, and to understand how they raise disease risk. Third, we are now extending our studies to non-Caucasian populations: southeast Asians, Hispanic, African-American, and persons from the Indian subcontinent." However, Dr. Spritz noted, "We are still very short of minority patients and minority 'controls' with whom the genes of the patients must be compared. That is still a big limitation." (Please see accompanying article "An Appeal to Minority Vitiligo Patients.")

Dr. Spritz thanked Vitiligo Support International for being a
major contributor of patient volunteers for this international study.

As many of you know, we are working to discover the genes that cause vitiligo. Understanding these genes will help us understand the basic biology, a key first step towards better treatments or cure. We have now completed the first large genetic studies in Caucasians, and a parallel study has been done in Chinese. The results have given us extraordinary understanding of vitiligo, far better than we have ever had before. The results are also clear that between Caucasians and Chinese Asians, while there are some similarities, there are also very major differences in the causes of vitiligo. Therefore, each ethnic group must be studied individually.

This means that future treatments and even cures may not benefit all patients equally, based on underlying personal and ethnic genetic differences. Thus, certain drugs may work best for certain individuals or for patients from certain ethnic groups. This is already true for some drugs that turn out to only work well in African-Americans, and so are only FDA-approved for use in those patients.

We are in urgent need of patients from the major USA minority groups-African-American and Hispanic-Latino, as well as Indian-Pakistani. To date we have had to rely on Caucasians for our studies as they are the only group that have volunteered to participate in numbers great enough to study.

We need your participation - both minority patients and minority "controls" (non-blood relatives without vitiligo). Your personal information, by law, will be kept private and will not be sold or disclosed. Through your participation, you will help to ensure that future discoveries and treatments will apply to minority groups as well.

Join with us to work for a vitiligo-free future! Click here to participate now.

• You will begin by doing your own research on current vitiligo treatments in order to decide which treatment/s you are comfortable with and best fit your lifestyle and budget.
  
  
• You want to locate a vitiligo specialist or doctor willing to prescribe current treatments and be encouraging and supportive.
  
  
• You can begin with the telephone. If you are looking for a doctor or have been given the name of a doctor who is not a recognized vitiligo specialist, it will be a good idea to call the office and find out if they are treating other vitiligo patients.
  
  
• If they are not treating other vitiligo patients, you may want to call another doctor's office.
  
  
• If they say yes, you should ask what types of treatments the doctor prescribes for vitiligo patients. It will be important to know if they are prescribing the treatments you are interested in.
  
  
• If the patient is a child, you'll want to know if they have experience treating children with vitiligo and what treatments are offered for children. Some doctors won't use all available treatments for children, depending on the age of the child.
  
  
• VSI has its own Doctor Search of patient recommended doctors.

Prepare for your visit.

• Be prepared to provide basic information to the physician such as
• When did you first notice pigment loss?
• Were there precipitating factors, such as sunburn or illness?
• Did the vitiligo begin slowly with a single depigmented area?
• Did you notice many small areas over the entire body?
• Did it begin rapidly and spread quickly?
  
  
• If you have been on treatment, be prepared to describe your experience including:
• How long ago did you see the prescribing doctor?
• Are you currently using any type of treatment? If so, what?
• Which treatment/s have you tried?
• How did you use the treatment? For example, if it was a topical treatment, how many times a day did you apply it? How long did you leave it on? How many days a week did you apply it?
• How long did you use the treatment? (days, weeks, months)
• Did you see results?
• Did you experience side effects? If so, what were they?
  
  
• You may be asked to provide background information on your family such as have you or anyone in your family experienced any of the following:
• Early graying/white hair
• Alopecia areata
• Thyroid disease (either hypo or hyperthyroid)
• Psoriasis
• Insulin-dependent diabetes
• Pernicious anemia
• Addison's disease
• Celiac disease
• Other medical, surgical, environmental, social or emotional issues

Do your own research on vitiligo in order to be in the best position to discuss which treatments are best for you. The specific treatments a physician may recommend will depend on the type of vitiligo and the age and health of the patient. You can find detailed information on the full range of vitiligo treatments and factors affecting choice of treatment at Treatments

Having a friend or family member along and/or taking a tape recorder on
this first visit may be useful in recalling instructions or information later.

Know what to expect from your visit.

Diagnosis and evaluation procedures:

Each doctor's protocol will differ, but the following are common procedures to expect.

• a total body skin examination
• observation with a Wood's lamp (similar to a black light)
• photographs of representative areas in order to track progress on follow-up exams

The doctor will also order laboratory tests to assist his/her evaluation of the vitiligo. Typical lab tests for vitiligo include all or part of the following:

• Antinuclear Antibody (ANA) - This test helps determine if the patient has other autoimmune diseases.
• Thyroid peroxidase antibody (TPOAb) - Thyroid antibody testing is primarily ordered to help diagnose an autoimmune thyroid disease and to separate it from other forms of thyroiditis.
• Complete Blood County (CBC) with differential,
• comprehensive metabolic panel,
• thyroid panel, including Free T3, Free T4 and TSH
• 25-Hydroxy-Vitamin D
• folate/B12

Some doctors will prescribe vitamins or supplements to help stabilize the immune system. These are not so much a treatment but an adjunct therapy. Listed below are some of the more typical supplements recommended, as frequently vitiligo patients have decreased levels of these vitamins:

• Multi Vitamin
• Vitamin B12
• Folic acid
• Vitamin D

While these supplements are generally considered safe, age and health may affect the dosage and appropriateness of some or all of these supplements for certain individuals.

If your doctor recommends a treatment, important questions to ask that can help you decide whether you want to go forward with the treatment are:

• How does this treatment work to help vitiligo?
• What are its possible side effects?
• How is it used and how often?
• If topical, can it be washed off? If so, after how long?
• If you want to apply sunscreen and the topical medication, which would you apply first?
• What type of results might you expect to see?
• How long will it take for me to see results?
• How long will you use this treatment?
• Does insurance normally cover the treatment? If not, can the doctor help to secure coverage?
• How much will the treatment cost?

When will you see the Doctor again?

Depending on the prescribed treatment, most doctors will want to see the patient again in around 3 months to assess progress.

A nationwide shortage of the generic prescription drug Methoxsalen is threatening the ability of vitiligo patients using PUVA to continue therapy. Belonging to the group of medicines called psoralens, Methoxsalen increases the skin's sensitivity to UV light and is used to improve the effectiveness of UV light therapy. A psoralen (such as Methoxsalen) plus UVA light is known as PUVA therapy.

The unprecedented shortage began last fall when the U.S. product manufacturer, Valeant Pharmaceuticals, lost their supplier of the active ingredient. Popularly known by the brand name "Oxsoralen" or "Oxsoralen Ultra," the medication was primarily obtained from Valeant as a gel capsule to be taken orally, or as a lotion to be applied topically. Some doctors contacted by VSI have reported they still have access to the topical version of the drug, but are concerned that their current supplies will be eventually exhausted. One doctor reports trying to switch a PUVA patient over to narrowband UVB (NB-UVB) therapy before their current supply of the Methoxsalen drug runs out.

VSI has found that Methoxsalen powder is available at some compounding pharmacies and can be used to create the psoralen lotion used for topical PUVA treatment, as well as for a compounded Methoxsalen capsule. This substitute capsule is not exactly the same as Oxsoralen. It is absorbed less and more slowly than the original drug. The required dose is, therefore, slightly higher and should be administered 2 hours prior to UVA exposure.

• To find a compounding pharmacy in your area or nearby, search the Professional Compounding Centers of America website or call 1.800.331.2498. You may also contact VSI at [email protected].
• Contact your insurance company to find out if the compounded drug will be covered by your policy.
• Check with the compounding pharmacy as to its policies regarding insurance. Some compounding pharmacies may not accept insurance, or may mail a reimbursement form with the medication for patients to submit to their own insurance providers. If you cannot find one in your area, search in other states. You may be able to receive the medication through the mail.

You can stay informed on this situation with updates at the American Academy of Dermatology Association website.

VSI will continue to track this issue and keep our members informed.

If you are Caucasian (white) or non-Caucasian (non-white) with vitiligo your participation as a research volunteer is vitally needed to help identify the genes linked to vitiligo. Scientists with the international VitGene Consortium project spanning 18 countries are working to understand the biology of vitiligo in order that more effective vitiligo treatments can be designed. Patient volunteers of Chinese/Taiwanese, Japanese, and Korean descent, as well as USA Hispanic/Latino, African-Americans, Middle-Eastern Arabs, and Indian/Pakistanis of subcontinent origin are especially needed.

You can participate in this important research by completing a questionnaire without leaving your home. Click here to participate.

You must save this to your computer to fill out, and return via mail to the address provided on the questionnaire - or email to [email protected]. Just one questionnaire per family, please. Be sure to provide complete contact information, including name, email, mailing address, and telephone number to ensure that the scientists can reach you.

You can learn more about this important research by reading the article on the initial findings of the international VitGene Consortium project in this newsletter issue. We hope you will participate in this very important research. It is easy and yet so important to the future of all in the vitiligo community.

Individuals with vitiligo develop milk-white patches of skin due to loss of the skin pigment cells (melanocytes) in these areas. Skin transplantation can be an effective treatment option for vitiligo patients for a specific group of patients. One particular skin transplantation technique, the melanocyte-keratinocyte transplantation procedure (MKTP) has been used successfully in Sweden, India and Saudi Arabia for more than 13 years.

In the MKTP, melanocytes are taken from a person's normal skin and then transferred to the vitiligo patches. The hope is that melanocytes will grow in this new location and the skin color may be restored. This procedure can be performed on an outpatient basis and patients can resume most normal activities immediately after the procedure.

We are performing this procedure in the Henry Ford Hospital (HFH) Dermatology Clinic in a clinical trial in order to see if we can achieve the same success that has been experienced in other parts of the world using this technique. This procedure is only appropriate for patients whose vitiligo has not worsened in the past six months. People who develop vitiligo or thick scars (keloids) on parts of the skin which are scratched or cut should not undergo this procedure. Study participants would have to be able to come to the HFH dermatology clinic in Detroit, Michigan 7 times in 12 months. Further study requirements can be discussed by contacting the study doctors.

For more information please contact Dr. Marsha Henderson at 313-916-6964 or [email protected]

Though there are many different treatments available for vitiligo, there are none that are effective in all patients. We are performing a study comparing the genes of patients with vitiligo to those without the disorder in order to uncover targets for new treatments.

We will be collecting blood samples from vitiligo patients and healthy adults without the disease. We will perform testing to evaluate the genes that are different between the 2 groups as well as determining what these genes do. We are seeking 500 volunteers with vitiligo and 500 healthy controls for this important study. Participants would have to come to the Henry Ford Hospital Dermatology Clinic in Detroit, Michigan for a single visit and they will be compensated for their time.

For more information please contact Dr. Marsha Henderson at 313-916-6964 or [email protected]

VSI's presence on the web will take on an entirely new appearance in the coming weeks. Newly designed features, increased practical information and educational content, and an upgraded ability to search for and quickly locate specific information are just a few highlights to look forward to.

As we announced in our Spring newsletter, these website improvements will enable VSI to alert our members to important research and treatment developments, and to better support those with vitiligo. The new technology and tools will enable VSI to overcome the limits of its current site, which is strained to meet the growing demand for information and support.

The donations from you, our Supporting Members, have made this update possible - thank you! We hope that you will enjoy exploring all the new features and abilities.

• " I noticed some hair coloring products advertised as "herbal" contain an ingredient called p-Phenylenediamine. Is this a phenol, and if so, is it one of the phenols that should be avoided if you have vitiligo? (Source: Ray Boissy Ph.D., Professor of Dermatology & Cell Biology and Director of Basic Science Research at the University of Cincinnati College of Medicine)

Yes, p-Phenylenediamine is a phenol, and while it has not actually been documented to cause vitiligo, it has been implicated, and could conceivably induce vitiligo. Though it has not been tested, it is implicated because of its structure as a phenol that can conceivably interact with tyrosinase.

• " Every summer I begin to lose pigment on the back of my hands, then in the autumn they repigment. Can you explain why this happens?

Many people experience what you are describing due to a greater exposure to sunlight during the summer months. Even though sunlight contains the full light spectrum rather than just the therapeutic rays, when NB-UVB light is not available, some doctors will prescribe sunlight exposure for treatment. Typically, if a person is not treating their vitiligo during the winter months, for those with lighter skin tones there is very little contrast on the skin between pigment and no pigment. Each spring and summer as sun exposure increases, so does the contrast, and you begin to notice the pigment you've lost over the winter. However with consistent sun exposure over the summer months, by autumn you begin to see some repigmentation. If you were to continue light treatments throughout the winter months, you would most likely continue to regain pigment and stand a better chance of retaining the new pigment. For more information on sunlight as a treatment, visit VSI's Treatment Page.

• " If I choose to depigment, once I am completely depigmented, will that change the odds of my children getting vitiligo? (Source: Richard A. Spritz, M.D. Professor and Director Human Medical Genetics Program University of Colorado Health Sciences Center)

Under most circumstances, vitiligo is partially genetic in origin (hereditary), meaning the vitiligo genes are part of your DNA. Current vitiligo treatments (or the results) do not alter a person's DNA. So your children would have the same chance of acquiring the vitiligo genes from you regardless of treatment or depigmentation on your part. Genetic studies have shown that only 5% to 7% of children will get vitiligo even if a parent has it.

Amazon.com has all kinds of items in addition to books. As long as shopping is done through this link, Amazon.com, or from the Amazon box on our Community Home Page, Amazon returns a portion of the sale to VSI. The more items members buy, the higher the percentage!

Our Vitiligo Library and Store is also powered by Amazon. It contains books, articles and products for those with vitiligo.

Our other program is iGive.com. The iGive shopping mall has over 700 stores where you can shop and VSI gets a percentage. Let friends and family know about iGive, so they can support VSI, too. You do have to register for iGive. Once you've registered, you can either shop directly through their "mall" on iGive's website or by downloading their toolbar, which makes it even easier. iGive also has a search function powered by Yahoo at isearchigive.com that earns VSI a penny per search. The power of numbers makes this also an effective way to support VSI.