Amit G. Pandya, MD, FAAD

 In terms of what causes vitiligo, we know that there are 40 or 50 genes associated with vitiligo. Ninety percent of them are immune-associated genes having to do with T cells and dendritic cells, and 10% are melanocyte-specific genes. When you see these gene abnormalities because the body is attacking, the T cells are against the melanocytic antigens. We think that the actual genetic cause is about 30% of the overall cause. We say that because let’s say you have a twin brother who’s genetically identical to you. If that brother develops vitiligo, you have about a 25% chance of getting vitiligo. That tells us that genes aren’t everything, and that 70% or 75% is environmental, and we haven’t discovered that environmental cause. Is it a virus? Is it a food? Is it an allergen that we haven’t discovered that causes the vitiligo? Perhaps it’s an insect bite, which then epitope spreading then leads to vitiligo. We haven’t figured that out in terms of environmental cause. Both are needed.

However, only 30% of patients with vitiligo have a family history of vitiligo. We know it’s not necessarily like everybody must have family members, but they likely have 1 of the genetic causes, 1 of the 50 genes, and then there’s some environmental trigger that then causes the onset of vitiligo. In terms of the trigger, we sometimes see that if a person gets, for example, a scrape in their skin and then develops vitiligo, they get a sunburn and they get vitiligo, they get a chemical burn from hair dye and then they get vitiligo. There are some triggers that have to do with the environment that we can see, but most of the time we can’t identify the exact environmental trigger that caused the onset of the vitiligo.

 It’s a tricky topic, this idea of what caused it or why somebody has it. Patients often want to spend a lot of time around the thing that they believe caused it. How do you approach this conversation with patients who likely have a genetic background, but there’s some other trigger that led to the disease manifesting? How do you explain this to patients?

 I tell patients that we believe that 70% of the cause is environmental and 30% is genetic, but we haven’t discovered the exact environmental cause for vitiligo. Some things can trigger it, like a scrape or a sunburn. But that doesn’t explain everything, so we’re still doing research on that.

 Patients often want to take that trigger and then try to control it as if they could dial back time and erase that the event ever happened. How do you discuss that with them? Do you say, “Well, the horse is out of the barn. It sort of doesn’t matter what led to it happening to begin with”? How do you guide that part of the conversation? Because it’s easy for patients, and understandably, it’s easy for them to get hung up on that point and want to control it.

 What I tell them is that vitiligo is an immune-mediated disease in which the immune system is attacking the skin. The immune system is present in your lymph nodes, your spleen, your bone marrow. At some point in your life, around the time your vitiligo started, your immune system started creating millions of T cells that we call CD8+ T cells, whose goal in life is only 1 thing: to destroy your melanocytes. Those T cells are circulating in your bloodstream, and we haven’t discovered a way to remove them permanently from your bone marrow, from your blood, without knocking out your entire immune system, which wouldn’t be healthy for you. Unfortunately, you now have these T cells, which is why they’re coming out of the skin. These T cells are attacking the melanocytes. Our goal is to remove them from the skin. But I don’t have a way of removing them from your bloodstream, so you’ll have that risk of developing new lesions if you’re not treating the skin.

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Drs Pandya discusses vitiligo pathophysiology, the role of genetic and environmental factors, and how to communicate with patients about it.

Vitiligo Etiology and Patient Communication

 titled “Management Strategies and New Directions] in the Treatment of Vitiligo.” I’m Dr Brett King, an associate professor of dermatology at the Yale School of Medicine in New Haven, Connecticut. Joining me in this discussion are my colleagues Dr Heather Woolery-Lloyd, a board-certified dermatologist and the director of the skin of color division in the department of dermatology at the University of Miami, in Miami, Florida; Dr Amit Pandya, a board-certified dermatologist at the Palo Alto Medical Foundation in Sunnyvale, California; and Dr David Rosmarin, the vice chair of education and research and an associate professor at the Tufts University School of Medicine in Boston, Massachusetts.

In today’s discussion, we’re going to discuss vitiligo and its management. This is an exciting time to be a dermatologist because translational medicine is leading to new targeted therapies for many dermatologic diseases, and vitiligo is 1 of them. New insights into pathogenesis have led to drug development in vitiligo, and it’s more important than ever that we understand this disease. Today’s 

® roundtable will facilitate that. With that, let’s get started.

In segment 1, we’re going to cover a clinical overview and burden of disease. Leading off will be Amit, who’s going to describe vitiligo, its prevalence, potential contributors to vitiligo etiology, and other things. Amit, take it away.

Vitiligo is an autoimmune disease in which the immune system comes into this skin and destroys melanocytes, which are the cells that give us color in the skin. When it comes to prevalence, it’s around 1% of the world’s population, but this is hard to pin down. That’s because there are a lot of undiagnosed individuals. A recent study showed that 30% or 40% of people have vitiligo, but they haven’t seen a doctor and are living with it. There are more data coming out, but we think it’s somewhere between 0.8% and 1.4% of the population.

When it comes to age, we know that the highest peak of onset of vitiligo is somewhere between ages 20 and 30. It tends to occur in younger individuals, but I routinely see patients who have vitiligo for the first time when they’re 60 or 65 years old, so it’s a bell-shaped curve. Some people have it younger, and some people have it older. When it comes to race, some studies seem to show that it’s higher in certain populations, but those are very small studies. Right now, we don’t have good evidence that it’s much higher than 1%—for example, in India or other countries. Also, there doesn’t seem to be a difference when it comes to gender. It seems to be equal in men and women when it comes to the etiology.

You said melanocyte destruction. If they’re destroyed, can we get them back, or is it that they’re put to sleep? How do you think about that?

What happens is that CD8-positive T cells come out of the bloodstream. They crawl into the epidermis in the super-basal layer. They find the melanocytes and produce granzyme and perforin, which are potent enzymes, which punch holes into the melanocyte and cause the death apoptosis. Those melanocytes are completely destroyed, and they are then removed by macrophages and just at the apoptotic pathway. When it’s done, there are 0 melanocytes in the skin, unlike pityriasis alba, unlike nevus depigmentosus, and unlike idiopathic guttate hypomelanosis, which still has melanocytes in the epidermis. But they’re just not producing melanin for the keratinocytes in that area.

 Another question. Do you think about vitiligo differently? You said that it more commonly has onset in younger populations, but that you can have new vitiligo onset in a 60-year-old. Do you have different concerns about vitiligo when it appears in a 60-year-old vs a 20-year-old?

 If I see a 60-year-old patient, especially a White patient with new-onset vitiligo, I’m going to be looking for nevi or new lesions that look like melanoma because there’s the leukoderma associated with melanoma that occurs in older individuals. I have seen only 2 cases in my career, but it’s incumbent on me to do that examination. In 99% of patients who develop deep pigmentation—that is in the right distribution, etc—it’s going to be vitiligo.

A vitiligo expert, Dr Amit Pandya, provides an overview of vitiligo. 

Vitiligo Overview

 The most important messages I would give to health care providers who are seeing patients with vitiligo is, No. 1, to listen to the patient. Find out what they want to achieve with the treatment of their vitiligo, and express to them that it takes a while to see that improvement. I ask the patient to commit to about 9 months of treatment to see a difference. I highly suggest taking baseline photographs, and then seeing the patient every 2 to 3 months and taking photographs at every visit, so that you can see the 10% or 20% improvement in the lesions. If you don’t do that, it’ll be difficult for you to determine if there’s been 10% or 20% improvement, and certainly for the patient to determine that, which often causes pessimism and then abandoning treatment. When you see that improvement in the photographs, you will be motivated with future patients and will understand how vitiligo can be repigmented if you have patience and the right outlook in terms of expectations for treatment.

I also recommend that health care providers look for signs of activity such as confetti-like lesions, trichrome lesions, and the Koebner phenomenon, because patients who have those lesions must be treated aggressively. Perhaps they need oral mini-pulse dexamethasone, phototherapy, and topicals, all combined to stop it from spreading, because those patients are in danger of rapidly worsening vitiligo. Finally, I recommend that health care providers give support to patients and talk to them about the psychological effects of vitiligo. If you find that the patient appears to be depressed or having significant psychological issues, perhaps recommend counseling, or referring them to a psychiatrist to help them deal with this condition while they’re undergoing treatment.

Often, patients ask me if they’ll be on phototherapy forever, or if they must be on this pill or these creams forever. I tell them that their vitiligo will improve, but at some point, they will hit a plateau. In other words, they will come in one day and they will not be any better than their last visit. At that point, I move into maintenance therapy. If they’re on phototherapy 3 times a week, I drop them to twice a week for a month, then once a week for a month, and then once every other week for 2 months, and see if the vitiligo returns. If it doesn’t, I stop phototherapy. If it does come back, I put them on a maintenance therapy perhaps once a week, so that the vitiligo can be stable.

This is the same with topical therapy. Once they have reached maximum repigmentation, I drop the topical therapy. For example, topical steroids, especially the strong ones, I typically give them once a day, 5 days per week, Monday through Friday, when I’m trying to repigment. For maintenance therapy, I drop down to twice a week, and that includes topical steroids. For topical immunomodulators, such as tacrolimus and pimecrolimus, I usually use twice a day. But once again, for maintenance therapy, I’ll drop to twice a week in the areas where they have vitiligo, and the areas where they used to have vitiligo, so it doesn’t return. This maintenance therapy is very important.

I also give all my patients information about great web resources where they can get more information, good information, about vitiligo. There are many sites on the web with confusing messages about vitiligo. I send them to good locations such as the Global Vitiligo Foundation website, where they can get accurate, up to date, scientifically based information about vitiligo to guide their treatment.

Amit G. Pandya, MD, FAAD, shares advice for the detection and treatment of vitiligo.

Clinical Pearls for the Management of Vitiligo

This is an exciting time for me and the treatment of vitiligo. In my entire career, I have not seen studies for actual drugs to treat vitiligo that have progressed so far as they have today. We now have multiple topical and oral medications that are being studied for the treatment of vitiligo, and hopefully, ultimately, we’ll get FDA approval for treatment. One of these medications is topical ruxolitinib, which is a topical JAK inhibitor. This has already completed phase 3 studies, and over 50% of the patients who were treated got over 50% of the color back on their face, what we call a F-VASI50 [50% improvement in Facial Vitiligo Area Scoring Index] after 6 months of application. This is the cream, without phototherapy treatment. This is exciting, that a cream applied twice a day for 6 months can get over half the color back on your face with no other treatment. On the body, after 6 months, there was about 25% repigmentation overall with just the cream. I’m sure that with phototherapy, we will see much higher responses. There’s also an oral JAK inhibitor that’s being studied by Incyte Corp that is in phase 2 studies. It will be exciting to see the result of that.

Recently, there have been reports of an oral JAK inhibitor from Pfizer. This one, ritlecitinib, achieved its goals, its primary outcome measure, in that the oral JAK inhibitor was better than placebo at the end of the 6-month study. After 6 months, there was about 25% repigmentation, but after 12 months, it was more like 60% to 70% repigmentation of the face just with this oral JAK. There is also an anti–IL-15 [interleukin-15] antibody study that’s ongoing. We don’t know the results of that, but this is designed to affect the resident memory T cells, which are considered the reason why vitiligo comes back in the exact same spot when it returns. By removing these resident memory T cells, perhaps one can have durable remission. This anti–IL-15 antibody, which is a subcutaneous injection, is an exciting study, and hopefully we’ll see the results of that soon.

Finally, afamelanotide is a melanocyte-stimulating hormone analogue, which was studied several years ago. It was found that when you combine afamelanotide, which is an implant that is applied underneath the skin, with narrowband UV-B [ultraviolet B] therapy, you get faster results when it comes to repigmentation and stimulation of the melanocytes, than using narrowband UV-B alone. There are many studies that are ongoing, several have been completed. I’m looking forward to seeing our new armamentarium for vitiligo in the near future.

Dr Amit G. Pandya discusses novel drugs in the pipeline for the treatment of vitiligo.

Amit G. Pandya, MD, FAAD

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