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"Speaking of Vitiligo..."

IN HIS WORDS – Dr. Amit Pandya

martes, abril 06, 2021
By:  Amit Pandya

Vitiligo’s crystal ball

One of the frustrating aspects of vitiligo is its unpredictability. It’s hard to know when it will become active and when it will be stable. Individuals with vitiligo tell me they often worry about waking up and finding a new spot on their skin. They worry about the future and wonder if their vitiligo will get worse. But what if there was a crystal ball that could tell you what was in your future? 

Dr. Amit PandyaIt would be great if we had a blood test to predict the activity of vitiligo. This is called a biomarker and although we don’t have one available yet, several labs around the world are working on it. So, is it possible to determine if vitiligo is active? Most individuals with vitiligo know when their vitiligo is worsening. They either see new spots or worsening of existing spots. But sometimes it’s hard to know for sure. When you look at your own vitiligo spots every day, it may be hard to determine if they are changing. Also, it may be difficult to know if a spot on the skin is new or if it has been there for a while. This is where photography can help. Taking a photograph of vitiligo spots every 1 to 3 months greatly helps in monitoring them. By comparing a spot to a photograph taken earlier, you can easily detect worsening, improvement or stability of the spot. You can also see if a new spot has developed close to an old spot. This form of serial photography has helped me tremendously over the years. I will often see a patient who complains of new spots developing on their skin but when we look at the pictures of their spots from the last visit together, it’s clear the spot was already present back then. Conversely, the previous images often help confirm new spots in patients who believe they are stable. A smartphone is very helpful in documenting vitiligo spots this way and performing serial photography over time.

So, other than photography, are there any other ways to tell if your vitiligo is active? How about looking for signs in the skin that can predict future worsening? Fortunately, several clinical signs of activity have been discovered over the years. These signs include the Koebner phenomenon, trichrome vitiligo and confetti-like depigmentation and make up what I call vitiligo’s crystal ball. When these signs appear, you can reliably predict that your vitiligo will worsen over the next few weeks or months unless it is treated.

The Koebner phenomenon was discovered by Joseph Koebner in 1942. He noticed that some skin conditions developed in areas that were scratched or traumatized. The rash would appear in the exact area where the scratch occurred and took on the shape of the scratch or scrape. This phenomenon can be seen in several conditions, including psoriasis, warts and vitiligo. The appearance of the Koebner phenomenon is a sign of activity and most individuals who have this sign will worsen over the next few months. I see this in several scenarios. A man might notice that his vitiligo appears in the areas of his face where he shaves every day. A woman notices her vitiligo appears under the straps of her brassiere. A teenager who plays center on the football team notices his vitiligo appears on his elbows and knees due to trauma during games and practices and under the chinstrap of his helmet. An individual gains weight and notices vitiligo appearing under the belt due to excessive friction from the tight belt. Any repetitive trauma can cause the Koebner phenomenon and I always look for it when examining my patients.

Trichrome vitiligo, also called hypochromic vitiligo in Europe and other parts of the world, is another sign of vitiligo activity. This form of vitiligo presents as 3 colors: white in the middle of the vitiligo spot, light brown adjacent to the white skin, and normal skin color surrounding the light brown area. Usually, the white color is in the center with light brown skin surrounding the white area like a ring. This is a common and important sign of activity. The light brown areas represent newly affected skin that is in the process of becoming white. Even if you start treatment, these areas have already lost their melanocytes and are destined to turn white before they improve. This is often the reason why some of my patients believe they are worsening when they start treatment, especially with phototherapy. This often occurs at their 3-month visit after starting treatment. I explain the worsening they perceive is simply due to the former light brown areas turning white, as expected. Once this happens, new pigment fills in the white areas and improvement occurs. Again, serial photography can help monitor areas of trichrome vitiligo as it disappears with treatment and new areas of pigmentation appear.

The final sign of activity is called confetti-like depigmentation. My research team first described this sign in a group of patients in 2016. We noticed that some patients came into the clinic with many small white dots that varied in size from pinpoint white spots to spots about the size of a pencil eraser. They were in groups and appeared around existing vitiligo spots or new areas altogether. Sometimes hundreds of these small dots were visible on the skin. The appearance of the spots was like white confetti thrown onto the skin, so we coined it confetti-like depigmentation. If the patient did not follow through with treatment, the areas of confetti-like spots were inevitably worse at the next visit, at which time we noticed the small spots of confetti had enlarged, and many had coalesced into larger white spots. We saw this happening in numerous patients and suspected this was a sign of activity. After documenting this in a group of patients, we published our finding in the Journal of the American Academy of Dermatology. Since then, many investigators have confirmed our finding and confetti-like depigmentation is now established as an important sign of vitiligo activity.

What is the proof that these signs really mean that vitiligo is active and will worsen soon? Confirmation is usually performed by sampling the skin with a skin biopsy and examining it under a microscope. Research performed by many physicians and scientists over the last 10 years has shown that vitiligo is caused by an attack on melanocytes by a part of the immune system called T cells. You have read about this many times in Dr. Harris’s blogs. Melanocytes are the cells in the skin that produce melanin, which gives all of us our natural skin color. There is a unique population of T cells that are specifically being made by the immune system in people with vitiligo. They are in the blood circulation and travel throughout the body. In areas that develop vitiligo, they come out of the blood vessels and crawl into the epidermis, which is the top layer of skin where melanocytes reside. The T cells find the melanocytes, surround them, attack them with special enzymes and kill them. This is now accepted as the predominant cause of vitiligo. Many researchers have observed these T cells attacking melanocytes in biopsies of vitiligo spots that show the Koebner phenomenon, trichrome vitiligo and confetti-like depigmentation. As Dr. Harris has published in his blog and many research papers, the skin of vitiligo produces certain signals, called chemokines, that attract these T cells to the skin. These chemokines can also be detected in higher amounts in spots that have the Koebner phenomenon, trichrome vitiligo and confetti-like depigmentation. This is the proof that signs of activity that we see with our eyes reflect destruction of melanocytes by the immune system precisely in the areas where these signs are located.

How many people have these signs of activity? We studied 200 consecutive new patients that came to our clinic seeking help for their vitiligo.  We were surprised to find that 61% had at least one of the 3 signs of activity described above. Many patients had 2 or 3 signs of activity. We were able to recognize these signs in our patients and initiated appropriate treatment as a result. Admittedly, this is only one study at an advanced care clinic specializing in patients with vitiligo referred to me by other physicians. It’s possible these signs are not as common in other groups of patients. More studies need to be performed to determine the prevalence of these signs. However, enough researchers from around the world have reported these signs in their patients to conclude they occur in a significant number of individuals with vitiligo.

So, what can be done if there are signs of vitiligo activity on the skin? Stopping the T cells that are attacking melanocytes is one of the key steps in stabilizing and improving vitiligo. This can be accomplished with topical medications, such as tacrolimus, pimecrolimus, steroid creams and ointments, and, more recently, topical JAK inhibitors. They can stop the T cells in the skin and inhibit vitiligo activity. Some patients, however, require stronger, oral medications if many signs of activity are present over large areas of the body. I have seen patients with thousands of confetti like spots, often with other signs of activity. These individuals often require oral steroids for a few months to stabilize the skin. While long term oral steroids at high doses may cause side effects, the benefits of short term, low dose treatment usually outweigh the risks in most patients. Oral JAK inhibitors can also stabilize the skin but unfortunately, they are not approved for vitiligo yet, so insurance companies often don’t cover them, and they are much too expensive for the vast majority of patients to afford as an out-of-pocket expense. The above medications stabilize the skin, but to improve the spots, phototherapy is usually required. Narrow band ultraviolet light is the preferred choice of phototherapy for most patients. These are the two main pillars of vitiligo therapy: 1) remove the T cells that are attacking the skin with various medications and 2) use phototherapy to stimulate the good cells (melanocytes) to grow and produce more melanin in order to repigment the skin.

I hope this glimpse into my fascinating world of vitiligo evaluation and treatment was helpful. I find it very interesting to carefully examine my patients with standard lighting and a Woods lamp (black light) using a Sherlock Holmes approach to see what I can discover in my skin exam. I find tremendous satisfaction in counseling and coming up with a treatment plan based on my examination and working together with my patients to stop the progression of vitiligo and try to bring the pigment back. We are not successful in all patients, but we can usually stop progression of the condition and bring back a significant amount of pigment in most individuals. The relief on the faces of my patients makes it all worthwhile. I’m hopeful the many studies that have been initiated recently by pharmaceutical companies will result in breakthroughs that will benefit individuals with vitiligo worldwide. After 30 years of practice, the future to me looks brighter than ever.

About the Author:

Amit G. Pandya, MD
Staff Dermatologist, Palo Alto Medical Foundation
401 Old San Francisco Road, Sunnyvale, CA 94086
Appointments: 650-934-7676 

Clinical Professor, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX