"Speaking of Vitiligo..."

Chemicals can cause vitiligo and also make it worse

Posted On: Tuesday, November 11, 2014 Posted By: John E. Harris

Kanebo cream induces vitiligoMany times patients with vitiligo ask me why they have the disease. As I discussed in a previous post here, patients often mean different things by this question. Probably the most literal interpretation is “what causes vitiligo”? While the answer to this question can be complicated, the simple answer is, “multiple things”. For example, we know that genes inherited from your parents strongly influence the risk of developing vitiligo. This is because it’s more common in people who have others in their family with vitiligo or related autoimmune diseases. I’ll talk more in detail about this in another blog post, because what we have learned recently about the genetics of vitiligo is a fascinating topic.

However while genes clearly influence the risk of vitiligo, they’re not the entire answer. We know this because identical twins, who for the most part have the exact same DNA, don’t always both get vitiligo. If one twin has vitiligo, it’s more likely that the other will get it as well, but this only happens about 23% of the time, while most of the time only 1 twin gets it. If genes didn’t play any role in getting vitiligo, then the risk that an identical twin of an affected patient would get it would be the same as anyone else getting it, about 0.5-1%. So 23% is really high, revealing that genes have a strong influence. However if they were the only influence, then the risk in an identical twin would be 100%, much higher than 23%. But because the risk is less than 100% in the twins of people with vitiligo, we conclude that genes are important, but not the whole story.

If genes aren’t the whole story, what else is there? This has been asked for other autoimmune diseases as well, and typically the response is “environmental factors”. But what are these factors? Most clinicians and scientists assume that these factors are viruses, which we are frequently exposed to and activate the immune system, so they are good candidates. However we have never been able to confirm a virus as an environmental factor, at least for vitiligo, and so we either haven’t found it yet, or we must look for other things.

In fact, one very interesting environmental factor was identified in a large proportion of factory workers who developed vitiligo back in 1939. These factory workers made leather, and wore rubber gloves to protect their hands from the chemicals used in the process. But it turned out that it was the gloves themselves that contained a chemical that induced their vitiligo. The chemical is called monobenzyl ether of hydroquinone, or monobenzone. In fact, it worked so well that we use it now to remove the remaining pigment from the skin of those with widespread vitiligo, in order to make it even. It is prescribed by dermatologists as Benoquin cream. 

This incident strongly implicated chemicals as potential environmental agents that could induce vitiligo. It also raised the question of whether there are other chemicals that can do this and, if so, what products might contain them. The answer is yes, as other chemicals that have been implicated as vitiligo-inducers include 4-tertiary-butyl phenol (4-TBP, found in adhesives) and 4-tertiary-butyl catechol (4-TBC, found in rubber and other products). For the chemists out there reading this, all of these chemicals are phenols, which means they contain a benzene ring with a hydroxyl group attached. This is significant because they appear to mimic the amino acid tyrosine, which is also a phenol, and is the basic building block used by melanocytes to make the pigment melanin. So, melanocytes take up these chemicals as if they were the amino acid tyrosine, which injures them and results in inflammation and autoimmunity. This either induces vitiligo or makes it worse.

A recent fascinating example of this occurred in the summer of 2013 in Japan, when the cosmetics company Kanebo developed a highly effective skin-lightening cream and sold it to hundreds of thousands of consumers. Unfortunately, over 18,000 users developed vitiligo after using it, leading to recall of the product (read about that here). It appears that rhododenol, an active ingredient in the product that is also a phenol that resembles tyrosine, is responsible for inducing vitiligo in those that used the product. Ongoing studies, including those in our lab, are aimed at understanding how this process works. One major concern is that skin lightening is a major industry that attracts new products that may be dangerous for patients. Read about the expected future availability of “skin-whitening candy” here.

So all of this begs the question: “Am I coming into contact with chemicals in the environment that have caused my vitiligo or might worsen vitiligo?” There is some evidence that when people avoid contact with an offending chemical, their response to treatment is much better, and they may eliminate their vitiligo completely. So how can we identify these chemicals? Beyond the ones that have already been identified (monobenzone, 4-TBP, 4-TBC, and rhododenol, listed above), we can’t know for sure. We are actively working on this in the lab as we speak, and we hope to know for sure soon. If we could screen chemicals for their ability to induce vitiligo, we may be able to prevent outbreaks like the rhododenol-induced vitiligo that happened in Japan.

Until we are finished with our studies on this, there are a number of commercial products that have been reported to induce vitiligo, and most of them contain phenols. Here is a link to the study performed by a group in India, and below is a list of suspicious products that they identified, which includes permanent hair dyes, some detergents, and other ornamental dyes sometimes used on the skin. The problem is, exactly which products do this, and what chemicals are directly responsible, is not yet clear, and it is impossible to avoid all suspicious products. Also, it is unlikely that every chemical has this effect on every patient with vitiligo, so some products may be harmful for some patients but not others. That is why the research we, and others, are doing on this topic is so important. When we have some definitive results, we will certainly share them. Stay tuned!

Consumer products (% of patients reporting exposure)

Hair dye (27%)

Deodorant/perfume (22%)

Detergent/cleanser (15%)

Adhesive “bindi” (12%)

Rubber sandal (9%)

Black socks/shoes (9%)

Eyeliner (8%)

Lip liner (5%)

Rubber condom (4%)

Lipstick (3%)

Fur toys (3%)

Toothpaste (2%)

Insecticide (2%)

Alta (decorative color on feet) (1%)

Amulet string (1%)

Multiple chemicals (68%)

 

Products related to work

Rubber gloves (12%)

Lubricating and motor oils (7%)

Detergents (5%)

Printing inks (4%)

Laboratory chemicals (2%)

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