Dear Members and Friends of VSI,

Finding the cause of vitiligo is like solving a mystery. Our body’s pigment cells are the “victim,” but who is the perpetrator of the crime? Or is there more than one perpetrator? The scientists engaged in this hunt are looking for the clues that will lead them to the answer. In recent months, we have obtained more clues that further implicate the immune system and its processes as the source of the “crime.”

One such clue is linked to our eye color. Richard Spritz, M.D. and a team of geneticists at the University of Colorado School of Medicine recently found that vitiligo patients of non-Hispanic European ancestry have a much lower prevalence of gray or blue eye color, and a higher prevalence of tan or brown eye color than in the normal population for those of this ancestry.

As genes strongly associated with gray or blue eye color are also associated with an elevated risk of melanoma, these same researchers felt this strengthened the theory that people with vitiligo are less likely to develop malignant melanomas than the general population. They went on to say that although there are probably additional unidentified genes, those already identified provide insights into the optimal use of existing therapies and even new approaches to treatment.

In this issue, we feature another international group’s work on symptoms that provide more clues as to what may trigger or relate to this “over-activity.” Their work is especially fascinating because it focuses on lesser-known symptoms such as itch and premature hair graying in a family. Their work provides new information not only for the researcher, but also the patient. 

Gene research and patient experience together are not only informative, but are also critical to finding the triggers and cause of vitiligo. Your support of this research through your personal participation as a volunteer helps us to understand more of the vitiligo process. Consider participating in one of the several studies looking for volunteers that are listed in the "Research and Clinical Trials" section of this newsletter. Join with us to solve the mystery of vitiligo!

Sincerely,

Jackie Gardner
Executive Director

We know that vitiligo is a relatively common skin disease that causes pigment loss in about ½ to 1% of the population. Genetic research in the past 5 years has uncovered a great many new clues about this mysterious disease. However, there is still much to learn with regard to why some people experience symptoms that others do not, or why some respond better to one type of treatment than others. Finding these and other answers will likely come from asking more questions. Who's to say which questions or answers are right or wrong, or which patient's story should be documented or dismissed? The research studies we focus on in this article seem to validate the importance of not only listening to the patient, but also carefully documenting the details they present or question.

Dr. Khaled Ezzedine, a French dermatology researcher, and a research group at the Department of Dermatology in Bordeaux, France, recently reported their results from a 4.5 year vitiligo study that confirms, in significant numbers, the association of several vitiligo symptoms that have historically been dismissed by many in the scientific and medical communities. VSI had the opportunity to sit down and talk with Dr. Ezzedine at this year's American Academy of Dermatology meeting. He explained that one idea deserving further exploration is the possibility that within the major classifications of vitiligo, there may exist additional unknown "sub-types." Identifying the sub-types of vitiligo and learning the distinctions of each may explain why symptoms, triggers, and treatment response often vary from person to person.

Vitiligo has traditionally been classified into two major types, Segmental Vitiligo (SV), and Non-Segmental Vitiligo (NSV), and a more recent addition known as "Mixed Vitiligo" (MV).  Although a few sub-types have been identified, such as focal vitiligo and acrofacial vitiligo, very little else is known regarding their clinical characteristics.

Dr. Ezzedine mentioned other clues, such as the specific
location and/or shape of the vitiligo, that could point
toward a specific sub-type.

For instance:

Do you have a V-shaped area of depigmentation on the inside of the wrist?
Do you have pigment loss on the knees?

While the above occurrences may seem common to you, they tend to occur in certain groups of individuals, but not others. What are the common similarities of those who do, or do not experience the above symptoms?  

• Did your vitiligo itch before depigmenting?


• Did you experience a particularly emotional stressful event in the months prior to developing or the spreading of vitiligo?


• Did you, or anyone else in your family, experience premature hair graying?
  

These are less well-known symptoms that many doctors have in the past dismissed as unrelated to vitiligo. If you answer yes to any of the above questions, you may have a select sub-type of vitiligo.

The factors listed to the right are deemed significant to identifying which sub-type of vitiligo may be involved. It is therefore important that the clinician document any of the applicable details for each vitiligo patient.

In their study, the French researchers followed 213 children; 142 with NSV, 59 with SV and 12 with mixed vitiligo. While carefully documenting the many symptoms and characteristics reported and observed, the French team made an interesting discovery. They found many of these lesser-known symptoms in a significant number of the study patients.

Itching, for example, a symptom not widely accepted as typical of vitiligo, seemed to be part of the depigmentation process, at least for many in the study. They found that a little over 20% of the NSV participants experienced itching prior to depigmentation. This was more than twice the nearly 9% of SV patients who reported itching before depigmentation. In both types, the itching at the onset of flares of depigmentation improved when depigmentation ceased.

This finding correlates with an earlier similar finding reported in 2009 by Dutch investigators, who also found that 20% of 245 adult patients with generalized vitiligo had vitiligo-associated itching. They recommended itching should be further investigated given that the traditional opinion has been that vitiligo only rarely involves itching, which is an inflammatory process.

Another somewhat controversial symptom, family history of premature graying of the hair (more than 50% white hair before the age of 40) was reported by 44% of the NSV patients; this reflected a much higher incidence than the 19% seen in those with SV. A family history of premature hair graying has been reported and discussed in the past, but was most often dismissed as insignificant to vitiligo.

A third controversial factor reported was the role emotional stress plays in triggering vitiligo. The French group found that 31% of the NSV, and 14% of the SV patients, reported emotional stress as preceding their onset of vitiligo.

Greek researchers in 2011 similarly found emotional stress to play a role in triggering vitiligo.  Of the 133 vitiligo patients they studied, 24% with childhood-onset and 37% with late-onset vitiligo recalled a stressful event just before the onset of vitiligo. Though emotional stress preceding a flare of depigmentation has long been reported by many patients, its connection to vitiligo remains controversial and has for the most part been disregarded and under-reported by the medical field.

A 2008 Serbian medical report found that a high proportion, up to 80%, of autoimmune disease patients  reported uncommon emotional stress before disease onset. The theory is that psychological stress triggers certain (neuroendocrine) hormones that disrupt the immune system, which contributes to the onset of autoimmune disease. According to the Serbian report, this type of stress triggers a vicious cycle, as the disease itself also causes significant stress in the patients. They recommend that the physician and patient discuss potential physical and emotional stresses to avoid, and that treatment for autoimmune diseases should include stress management and behavioral counseling to minimize or prevent stress on the immune system.

Other findings included the association of halo nevi, which were present more frequently in NSV than in SV by a significant margin. Halo nevi are common benign skin lesions that are the result of an immune response against melanocytes. They appear as uniformly colored moles, tan, pink or brown in color, that are surrounded by hypopigmentation (pigment loss).

The chart below from the French study shows the percentage that each symptom occurred either in the SV or NSV patients. They're ranked with the symptoms most commonly found in both SV and NSV at the top, progressing to those primarily found in NSV toward the bottom. You'll see that symptoms such as pruritus, (itching) and halo nevi occur in significant numbers among the NSV patients, but in negligible percentages of the SV group.

The researchers advised that SV patients who exhibit signs of inflammation and/or autoimmunity, such as itching and/or halo nevi, should be carefully followed up because of a possible increased risk for MV.

Though the devastating emotional and psychological impact of vitiligo diminishes self-confidence, initially leading many to many social exclusion, it has long been considered a harmless, cosmetic skin disorder undeserving of aggressive treatment. Learning more about the sub-types of vitiligo will help identify which treatments are more (or less) likely to work for each patient. However, the scientific and medical community must carefully listen to and document the information shared by the vitiligo patient. We have data on the major types of vitiligo, but, says Dr. Ezzedine, if we are to further clarify possible sub-types, we will need to dig deeper, learning more about the physical health, family history, and physical experiences of the vitiligo patient. Larger, more in-depth studies are needed to understand the complete range of symptoms and triggers, and to gain insight into what drives the vitiligo disease process.

What's On Your Mind?

Q. Is it safe to use Narrowband UVB (NB-UVB) when planning, or during, pregnancy?

A. While NB-UVB is generally considered safe for pregnant patients, studies have shown that UV radiation can reduce or deplete the body of folic acid. This reaction to UV radiation is more pronounced in lighter-skinned individuals, and less with darker skin. Because insufficient folic acid during prenatal development is known to cause neural tube (brain and spinal cord) defects in the infant, Dr. Jenny Murase, M.D., of the UCSF dermatology department advises folic acid supplementation for female vitiligo patients undergoing phototherapy who are planning to, or may become, pregnant.

To minimize any risk, because critical periods of organ development actually begin before many women realize they are pregnant, Dr. Murase, recommends baseline folic acid testing before, at the beginning of pregnancy, and again toward the end of the first trimester.

Dr. Murase says about 0.5 mg/d of folic acid is recommended in a normal pregnancy. High-risk patients can take as much as 4 to 5 mg/d, but it is necessary to rule out vitamin B12 deficiency when prescribing over 1 mg/d. She said that the folic acid supplementation can be included in a woman's prenatal vitamins and should continue throughout the pregnancy.

Q. Can Coloring My Hair with Hair Dye Cause Pigment Loss?

A. Yes, the small phenolic/catecolic derivatives in hair dye can easily penetrate the epidermis and travel down the hair follicle to the bulge region where melanocyte stem cells reside, eventually causing pigment loss. (Source: Ray Boissy Ph.D.)

• Would the pigment loss be localized, or is it possible for these chemicals to cause systemic pigment loss in areas other than where they are applied?

The initial effect of these compounds would be local and induce vitiligo in the interfollicular epidermis of the scalp and beard areas, and possibly induce hair graying after prolonged use. And yes, ultimately, this process could result in stimulating and/or recruiting a genetically regulated heightened autoimmune response causing systemic pigment loss in other areas of the body for those patients with generalized vitiligo.

• What are some of the hair dye ingredients known to cause pigment loss?
  (Source: Ray Boissy Ph.D.)

P-Phenylenediamine
P-Amonophenol
4-Amino-2-Hydroxytoluene
M-Aminophenol
Benzyl alcohol
P-Aminophenol

Medical News Updates

Highlights of recently-published medical
articles on vitiligo and its treatments

Self-Tanners Found To Promote
Aging of Sun-Exposed Skin

German researchers found that the skin is especially susceptible to free-radical damage or accelerated cell aging from ultraviolet light exposure for 24 hours after self-tanner (containing 20% DHA) is applied. Testing the skin forty minutes after applying the DHA solution, the researchers found that when combined with UV light exposure, the skin formed more than 180 percent additional free radicals (molecules which promote cell aging), essentially doubling that of untreated skin.

Dihydroxyacetone (DHA) is the most frequently used self-tanning agent. It is used for cosmetic applications and though higher strengths can be purchased online, in the United States, the FDA limits concentrations to a maximum of 15%. Most drugstore products range from 3% to 5%, with professional products ranging from 5% to 15%. The percentages correspond with the product coloration levels from light to dark. The higher the self-tanning concentration, the higher the radical induction.  Because DHA-treated skin increases the level of free radicals with UV exposure, the researchers concluded that, in order to avoid an accelerated photoaging process, users would be best advised to avoid or limit sun exposure for 24 hours after applying self-tanning products.

The study also noted that application of a "potent topical antioxidant" prior to, or at the same time as application of the self-tanner, is being studied as a way to neutralize this reaction.

Surface Eye Alterations Found in Vitiligo Patients

Periocular vitiligo (vitiligo around the eye/s) was found by Turkish researchers in a study of 30 vitiligo patients to be associated with ocular (eye) surface and tear function alterations. A control group of 50 people were included in the study. Both groups were subjected to tests measuring tear function and assessing the cells of the conjunctiva.

The researchers found that people with vitiligo around the eye on average had a mild "dry eye" as compared to the control group. A score of over 10 is considered normal, between 5-10 is marginal, and below 5 means low tear function or very dry eyes. Tests of the tears in the eyes of those with vitiligo started drying on average in 9.5 seconds as compared to 13.1 seconds of those in the control group.

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Research & Clinical Trials

New Clinical Trial in Massachusetts!

Major Expansion of Vitiligo Genetics Project

Patients and Controls Invited to
Participate in Online Vitiligo Survey

Volunteers Needed for NB-UVB
and Epidermal Grafting Trial

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