Nanette Silverberg, MD: Taking an Aggressive Treatment Approach to Progressive Vitiligo

Nanette Silverberg, MD, is the chief of pediatric dermatology for Mount Sinai Health Systems and clinical professor of pediatrics and dermatology at the Icahn School of Medicine at Mount Sinai in New York City.

At the 2024 Society for Pediatric Dermatology (SPD) Annual Meeting in Toronto, Ontario, Canada, Silverberg presented a session alongside Leslie Castelo-Soccio, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, titled, "Approach to Progressive Vitiligo." The session was a part of the overarching "To Do or Not To Do? That is the Question - Great Debates in Peds Derm" session.

Silverberg spoke with Dermatology Times to discuss the highlights of her session, milder versus more aggressive and liberal interventions, and the vibrant future of pediatric vitiligo care.

"We're going to have a completely new paradigm in 10 years for kids and for adults, and it's going to be a really exciting time for vitiligo patients," Silverberg said.

Transcript

Nanette Silverberg, MD: Hello, I'm Dr Nanette Silverberg. I am the chief of pediatric dermatology for Mount Sinai Health Systems and clinical professor of pediatrics and dermatology at the Icahn School of Medicine at Mount Sinai in New York City.

I think one of the first things that we have to think about in vitiligo is taking a holistic approach to the patient. One of the first things I'll present is a model of social determinants of health as it relates to vitiligo and why that is important to us as we treat our patients, because we think about offering patients treatment, but there are a lot of barriers to treatment. It's not just barriers to treatment, but there is an interplay of many different factors that enter into a patient's care, which range from genetic predispositions to comorbidities that are either genetically associated or statistically associated.

Of course, then, we have the 2 main barriers, which are late or delayed recognition of disease in many patients, which means that a lot of the patients that we see are already far into the course of their illness. Ideally, if we could, the best is to treat kids before the 6-month mark, and once we hit that 2-year mark of disease, we really start to have a little bit of a drop off of not just of efficacy, but more that the condition has spread a little bit. It's harder if we're just getting a little bit of color per month, the more loss there is, the slower the process.

Finally, we have FDA-approved products, but there's so many issues with our products, and the first is access to care. We have no FDA-approved products for children under the age of 12. We are so fortunate that we have now an FDA-approved product for 12 and up. Of course, we have products for 18 and up. There's a surgical product now. We have the topical agent, topical ruxolitinib, for 12 and over. But most of the products that we use are off label, or we're sharing them on this kind of broad anti inflammatory label. All the years we use topical steroids saying that it's an inflammatory disorder, and then we fight with insurance, because they'd like to say it's a cosmetic disorder, which I don't think they'd say if they had it themselves.

There are so many different issues that relate to vitiligo. This particular session is a controversy session, so the conversation is around sparring with a partner who's going to talk about milder interventions versus, I'll be talking about entering the intervention space faster and more liberally. They are both valid approaches, and there are parents who will choose one or the other. I think probably my, my major take home point to to any audience would be that people change their mind. The disease changes. A child becomes more knowledgeable about their condition, or more they may notice it more.

Years ago, I published a study looking at how emotionally bothered kids were with vitiligo, and we had about half of kids noticing disease in the youngest age groups. But as you hit puberty and that 15 to 17 year age mark, it was like, 96% of kids, were significantly bothered by their illness. That's even though these quality of life studies like the Dermatology Life Quality Index and the CDLQI for children, aren't necessarily vitiligo specific, but it is noticeable on the standard quality of life scores that older kids are bothered by it, so we always leave the door open, is always going to be my major point.

There may be a point where people do feel so bothered by it that they change their mind, and that's an option. There'll be new therapeutics, and people will enter the space. We want people to know that that's always an option. You can always come back and visit us. We'll always give you the new information. I think that if we don't offer hope and therapy to our patients, they don't have to accept it, but if we don't offer them proper information and the options, nobody else will. We're dermatologists. We're pediatric dermatologists. We are the leading experts in children on their vitiligo and their general skin health, and we are best positioned to explain the options, even if the patient doesn't take it.

It is important, I think, for a parent-patient relationship, to know that your parent pursued all the information and looked into it. I think that kids appreciate that. That's part of feeling that you're feeling well cared for. I think we help those interactions, as well. I think that one of the things we know over time is, if you leave people, their disease expands. I had a grandmother with vitiligo, and she started at about age 11, and I have photos of her as a young bride, her 19, getting married, and she had a little bit of vitiligo. Then we have pictures of her with me as an adult, and she had no color, and there was something in between. There were pictures in between showing geographic extension of disease over time. But we know that this is the case. Not everybody goes to 100% loss, but it does spread particularly for certain areas, like hands and feet, certain areas of the face, around the lips and around the eyes, you'll see it just gradually spread outwards. We want to get and contain the conditions, so we're minimizing extension over time, at the very least, and hopefully bringing about color and repigmentation, as well.

I just published some some data on adults looking at vitiligo and localization, but we have some data that's going to published shortly on pediatric vitiligo that we presented at a poster at ReV, which looks at the extent of disease, and there's just a steady extension over time, from under 6 to 6 to 12. Twelve to 17, we just see a gradual increase in surface area. Then it's important for patients to know that this could happen if you're not treating. We do have to make people know. Some people don't care if they're very, very light; it's just never going to show. Then we have our patients of color, where they can't hide it unless they're wearing cosmetics. That's also an intervention that's maybe a less aggressive intervention, but it's am important intervention, as well. Some of the things topics will cover is stigmatization, which has recently been published in Dr Paller's big study on stigma, which I was very fortunate to participate as a site.

Vitiligo, certainly in children, is associated with stigma. We have a lot more hand involvement in these younger kids who have early onset. We have cosmetic difficulties start early, and they lead to psychological and social difficulties. Of course, the comorbidities that are associated, which include vitamin D deficiency, which is a little more common over the age of 3. In my core cohort, we didn't really see vitamin D deficiency under 3. There's a new cohort out of Asia looking at kids below 3 and over 3, 3 to 12, and the 3 to 12 have low, low levels, and the kids under 3, not so much. We certainly have to think about kids at different stages. That's important as well.

But from my perspective, educating parents includes explaining the 3 different levels. I call that my ice cream sundae approach, which, I think everybody likes ice cream, unless you're allergic. But you can find some good substitutes nowadays. The bottom level, that nice ice cream scoop, is your anti inflammatory agents, whether that's topical or oral agents. Of course, we think about oral agents. They are off label, but we think about them more when disease is rapidly spreading. That could be pulse steroids. That could be the new JAK inhibitors that are being developed and are in clinical trials, will certainly become important in that paradigm as they as they become FDA-approved. Certainly, in some of the teenagers, off label, as we did originally with the alopecia areata kids.

Then we have agents that have the chocolate that you put on top on to build your sundae, and those are the things that remit disease and control spread. It's not enough to just stop inflammation. You don't always get your pigment cells jacked up. We need to promote our activity of pigment cells. Some of the way we do that is narrow band UVB does it, all the ultraviolet light treatments, whether it's just walking outside in the sun and playing as a kid, oral steroids for these more aggressive cases, there is some case series on uses of minocycline, which is a lower grade intervention. We have to be mindful of adverse events with minocycline. We certainly, as dermatologists, know about that, and we talked about the JAK inhibitors, so those are the remit and control agents that we're going to be using for the long term. Narrow band UVB is sometimes preferred in those settings because it doesn't have the internal side effects, but the access is very, very limited nowadays. Some of the ways we get around that are doing intermittent 308 nanometer laser, and there is some availability of units for home care, and that's also an option in those settings.

Finally, the last is, after you've worked so hard to get your color in, the cherry on the top is keeping it. That's the cherry on the top where you really want to keep that color there. Some of the ways we do that is maintaining general health, like vitamin D levels and chronic topical care, and that's been described either as twice daily ruxolitinib for people who have repigmented with that, or we can think about tacrolimus twice a week. These agents do, at least, give you at least 50% reduction in recurrence, and they do control disease, even if there is some recurrence. We do have some nice maintenance regimens. I think over time, we're going to have a lot more described, but that's my triple layer ice cream sundae.

Of course, we focus a little bit in the discussion on optimizing topical care by using the pediatric, adolescent, and young adult vitiligo guidelines that I recently put together with some colleagues, which looked at best practices in topical care. Stay tuned for some further segments on general health and screening and systemic agents. Ultimately, I think that we have so many options for care now for patients with vitiligo, and we will get more and more over time, and as those agents come into play, we need to think about, "Why would we use them earlier? Why would you use an oral therapy earlier in disease?" I think we've always thought about most inflammatory skin disease, just as we did with atopic dermatitis and psoriasis, as reactive care: "I see a rash. I will give a cream. It will work, and then if it doesn't work, I'll add in some phototherapy, maybe a little methotrexate." And, of course, methotrexate helps remit,, but, ultimately we waited. We waited long, and now we don't. We have people starting these products earlier and having much more quality of life. I think that we will have this option with vitiligo in the future, and some of the reasons why we think about doing more aggressive care, and even standard interventions of putting somebody in narrow band UVB in this regimen, where we've had our conversation between using just limited topicals, narrow band UVB is considered a little more aggressive, but it's not really an aggressive treatment. It's really quite a mild treatment. We know a lot about it as dermatologists. It's been our friend for many years, and it is very, very helpful. We certainly have that option of offering these treatments.

One of the real reasons that I think that children benefit from kind of putting in treatments faster earlier, is really medication fatigue. It's really a very difficult particularly as you hit adolescence, to be a child with a chronic illness and having to chronically put on topical care and manage over time. If we can get people to a state of remission, which we try to maintain over time with our cherries, we can offer kids topical therapy, free time, more time to be a kid. I think that's ultimately a really nice goal for for pediatric vitiligo.

I think in the next 10 years, maybe the next 15 years, is going to be super exciting in vitiligo. We've already participated in a trial of melanocyte grafting, which is approved for 18 and over, but I look forward to some pediatric studies. I think that we're going to just be able to offer a lot more to our patients, whether they were treated early or they weren't treated early. We're going to be able to offer people much more active intervention. We have so many treatments in development, the JAKs and the the oral JAK and the interleukin 15 blockers, and perhaps interleukin 2 blockade. We're really going to see some really interesting interventions. We're going to have a completely new paradigm in 10 years for kids and for adults, and it's going to be a really exciting time for vitiligo patients.

[Transcript has been edited for clarity.]