Noted improvement of vitiligo to a facial VASI of 0.72 and drastic improvement of repigmentation at 3-month follow-up

Depigmented macules with erythema on the scalp and back of neck with islands of pigmentation

Case authors Mavra Masood, MD, Jennifer Creasor, BSN, and Iltefat Hamzavi, MD, present a case of a 74-year-old female with persistent generalized vitiligo on the face and body. 

Correct answer: A. In a phase 2, randomized, dose- ranging study evaluating ruxolitinib cream for vitiligo, a subpopulation of 19 patients were offered add-on NB-UVB for >12 weeks during the open-label treatment period following the initial 52-week double-blind period, F-VASI and T-VASI scores improved in 15 of 19 patients (78.9%) and 18 of 19 patients (94.7%), respectively.1

A Case of Nonsegmental Vitiligo on the Face and Hands Treated With Combination  Topical JAK Inhibitor and Phototherapy

Significant repigmentation on the forehead, bilateral upper and lower eyelids and periorbital area, and lateral cheeks after treatment with ruxolitinib 1.5% cream over 6 months

Depigmented macules on the forehead, bilateral upper and lower eyelids and periorbital area, and lateral cheeks

Case author Stephen W. Lewellis, MD, PhD, FAAD, presents a case of a 38-year-old female with loss of pigmentation on her forehead, cheeks, and eyelids who did not respond to prior treatment with a topical corticosteroid or calcineurin inhibitor.

Successful Treatment of Nonsegmental Periorbital Vitiligo

April Armstrong, MD, MPH
Chief, Division of Dermatology
David Geffen School of Medicine at UCLA
Los Angeles, CA

Describe the role of emerging therapies for the treatment and management of vitiligo.

Describe strategies to individualize care when using emerging therapies for vitiligo.

Identify techniques for incorporating emerging vitiligo therapies into everyday practice.

Therapeutic Options in Vitiligo Treatment: An Evolving Landscape: An Online Activity

Recall the clinical trial data on JAK inhibitors for the management of vitiligo

Describe strategies to manage AE associated with JAK inhibitors

Discuss how to utilize JAK inhibitors in clinical practice for the management of vitiligo

Open Up to New Treatments for Vitiligo: Online CME Activity

I'm now delighted to bring up simaldesign, Susan Taylor. You know, I must say, the introduction of ruxolitinib cream, the first approved topical therapy for Vitiligo, has changed the way I practice and really helped our patients a lot. So with that, let me turn over the podium to Simal and Susan. Thanks very much, Mark. And this is the lecture that I alluded to earlier in the meeting on Saturday, that we were really going to dive deep into Vitiligo therapy today, along with my dear friend and colleague, Dr. Susan Taylor. Today we're going to focus specifically on pathophysiology of Vitiligo. And this is the session where we're going to really talk about how we approach treatment for patients with various different morphologies. I'm going to go over a little bit of background just to recap. Dr. Taylor is going to go through some data, and then we're going to do cases. So we actually have cases and really talking about what we do in our clinic. Remember, this is a CME talk. Now a few quick reminders. Vitiligo should not be considered a rare disease. And when we first started talking about Vitiligo at all of these meetings many years ago, this was really a small section of a larger talk. Now, fast forward to 2023. We are dedicating time to this really, really challenging condition, both psychologically and for both the patient and family unit. This is a male female equal disease, and over 50% of the cases can actually be diagnosed before the age of 20. There is now data that shows the earlier and faster you treat the depigmentation, the better your chances of repigmentation. So let's say you have someone who comes in and they say, oh, this doesn't really bother me. It's getting lighter, it's getting whiter. I'm not too worried about it. That's fine. But make sure you tell that patient, should you ever decide to treat this, the sooner we treat it, the better. And I think it's very important to say that I have lots of people who come in, we're doing full body skin exams. They didn't even know they had Vitiligo. You've probably seen that same thing, especially in fair skin individuals. I mention it, I tell them what it is, I explain the physiology of it, and I explain what's going to happen. Then ultimately, it's up to them. Now, Susan and I divided these therapies today into various different categories, because the purpose of this talk is to really do an update on therapy and how you combine it with clinical cases. Now typically we think of vitiligo as non segmental, which is the vast majority of cases. You see acrofacial disease, diffuse vitiligo universalis, et cetera, and then a small subset of patients are segmental. Vitiligo, rapid onset dermatomal, unilateral, doesn't spread to other parts of the body. So a patient comes in with segmental. Dr. Taylor and I will tell that patient, guess what? Yes, this is distressing. Yes, this is challenging. But the good news is it's likely not going to spread into non segmental which are the vast majority of cases. Now here you see therapies, everything listed from topical steroids to calcionerin inhibitors, which is what we used all along. We still use those therapies, but remember all along that topical steroids and calcium inhibitors have always been FDA off label for vitiligo. They have never been FDA approved. Now, for the first time ever, we finally have the first ever FDA approved treatment to repigment this disease with topical ruxalitinib. And we're going to get to that in just a minute with the jack inhibitor data. Some of you have asked, well how do you combine surgical modalities for many of these patients? Surgical therapies really are restricted to patients with stable vitiligo, which I define as no new patches of hypo or depigmentation in a twelve month period, or patients with segmental disease. A quick clinical pearl. You have a vitiligo patient who comes in that's got distal fingertip involvement of all ten fingers and toes. They've got distal digit depigmentation. No matter what that patient tells you, they are not stable. Fingertip vitiligo is a sign of instability. Never treat those patients with surgical modality. Those patients need these jack inhibitors and they need additional options. So speaking of jack inhibitors, if you want to read a few. Okay, so you've heard a ton about jack inhibitors at this meeting. We keep talking about it, we're going to keep hammering it. It's great, great data. But if you want to read just maybe one or two papers that go over the science, this paper that's in the blue journal from a few years ago I think is great. You can take a picture, pull up that reference. It's just a nice overview of the science if you ever want to recap. Now, I love showing this schematic. Most of you have seen it. I'll show it to you again in about 30 minutes. I love showing this schematic because it just reminds us that the jack proteins are always coupled as individual pairs. Remember, I always refer to them as the dysfunctional husband and wife. They're in that clingy relationship and they just can't break apart. No matter how much therapy they pay for, they're always stuck together. The drugs bind to them, they try to inhibit it, and then they stop the signaling. Now, how is that relevant in vitiligo? Okay, now, I will tell you, I am not an immunology expert, but I became involved in these jack inhibitor drugs because the diseases that they treat are immunologic based diseases like vitiligo. Now, how convenient that in vitiligo, the key cytokine that causes depigmentation is interferon gamma mediated CD eight t cell activity. The fuel for that CD eight t cell to kill that melanocyte is interferon gamma. And how convenient that interferon gamma predominantly signals through Jack one and two, and therefore topical ruxolitinib or some of these oral jack inhibitors, which are still not yet on label, actually block that jack one two signaling pathway. We're going to come back to that in just a minute and how we actually use these topical jack inhibitors in our therapeutic armamentarium. But with that, I'm going to turn it over to Dr. Taylor to walk us through some of the pivotal trial data. Thank you. Thank you very much. So we're going to start with the pivotal trial data. This data was published in the New England Journal of Medicine this year. Here's the study design. So, 674 subjects, ages twelve or over, were enrolled. Each subject had to have non segmental vitiligo. They were then randomized in a two to one fashion to receive ruxalidinib 1.5% cream twice a day, or placebo. The endpoint was 24 weeks. After 24 weeks, all individuals, those in the placebo group as well as those in the rucks group, continued for another 28 weeks, and then they were evaluated within 30 days. So what was the primary endpoint? The primary endpoint was the proportion of patients who achieved a 75% improvement from baseline in their facial Vassi score at week 24. Now, there were four other key secondary endpoints. Those endpoints included the proportion of patients achieving either 50% or those who achieved 90% improvement from baseline in their facial vase score at 24 weeks. Also, they looked at the proportion of patients achieving 50% improvement from baseline in their total Vassi score. And the total Vassi score includes evaluation of six different body sites again at 24 weeks. Next, we looked at the proportion of patients achieving noticeability score of a lot less noticeable or no longer noticeable at 24 weeks, and the percentage change from baseline in the body surface area at 24 weeks. Of course, safety and tolerability were also assessed. So here is the data from 24 weeks. So there were two pivotal trials. There was true v one and true v two. If you look, the results are similar. So here we see in the middle, in the green, the results of the facial Vassi 75. And we can see almost 30% of individuals after 24 weeks, reached a vassi of almost 30%. Now, take a look at those who received a Vassi of 50. Well, that's almost 50% of the subjects. And then there were about 15% who received or achieved a Vassi of 90. That's pretty spectacular. And those results were similar in both true one as well as true two. So here's the proof is in the pudding. So here is really remarkable, remarkable improvement. Now, remember, this is monotherapy. We will discuss all of the different modalities we use to treat our vitiligo patients. But this is single modality, ruxalitinib, 1.5%. Cream twice a day. So here we see this gentleman at baseline, then week twelve. Please notice that he's probably having a combination of repigmentation from the follicles, perifolicular as well as marginal, moving in from the exterior of the lesions. And then, at 24 weeks, this is an individual who received fassi of 90. Here's a young woman we can see baseline, week twelve, and week four rucks cream twice a day, and she achieved a vassi of 75. In terms of total vassi at 24 weeks, about 20%. And 26% of individuals in the true v one and true v two achieved a significantly greater proportion of repigmentation with the Rux cream as compared to vehicle. I tell my patients who come in, if you have acro involvement, especially hands and feet, those are the areas that are incredibly difficult to repigment. So here we see this very nice result. Baseline, week twelve and week four on an area, the dorsum of the hands. That's really quite a challenge. Again, this is with monotherapy. Here's a leg baseline, week twelve, week four. Here you can see in week four, a perfect example of repigmentation from the follicles in terms of safety and efficacy. The major potential side effects were application, site, acne as well as paritis. If you take a look, very few patients discontinued because of treatment. Emergent adverse events. Only one in each of the group who received the Rux cream. I want to point out that application of the ruxalitinib cream was limited to 10% of the body surface area. And a lot of people say, well, is there significant systemic absorption? And there appears to be very little systemic absorption. They looked at the steady state concentration in both the v one and the v two, and they found that it was well below the IC 50 for jack mediated changes in bone marrow. So I think we can pretty confidently tell our patients that this is indeed safe with very minimal systemic absorption. There's a very nice paper that we all saw where phototherapy was added to tafacitinib, and there were very good results. And I show this slide because I want to emphasize the fact that that data I just showed you was monotherapy. Now, do you get improvement in the response of the jack topical jack inhibitors with phototherapy? Sure. But I just want you to know it's not absolutely necessary. So at this point, we're going to go to our cases, I'm going to join. Perfect. So this is our first case. This is a patient of mine. She's a 62 year old female. She presented with the chief complaint of white patches on her face and her legs. They had been present for twelve months. She had been using a topical student steroid, a super potent topical steroid, as well as calcineurin inhibitors, for four to six months. At that point, I referred her to phototherapy three times a week. But here's what I found out. It took her about 20 minutes to make her first derm appointment. She works in the service industry, so she lost time at work and tips. She made an appointment. She had to take the bus to our medical center. Her partner had to accompany her, her partner translated for her, and the partner took care of a grandchild, so they had to hire a babysitter. Then, of course, there's the costs associated with seeing dermatologists. There's a cost for her phototherapy treatments. Of course, I gave her potent steroid, and there's a cost associated for her skincare products. So, actually, to see a dermatologist and initiate phototherapy, that could be $1,000, and that's $1,000 that this person doesn't have. So when we think about selection of patients, we have to think about, especially for this patient, how ruxalitinib cream would work very well for her and her lifestyle. Well, Susan, I think that's a really important case because the economic impact of phototherapy is abundant. Now, I do lots of phototherapy. So does Dr. Taylor, and it works, and it's certainly an important part. But this case that she presented, I think, is a beautiful example where this patient almost had scattered lesions, she had stable disease. She had been using topicals. This would be a great candidate who can't do phototherapy for just monotherapy. Ruxalitnib cream. Because, remember, Dr. Taylor said 10% BSA, and when you kind of put it on small little lesions, she had facial involvement, and then she had extremities, and that was it. This is a perfect example where you stay within the BSA requirements. You do bid rucks cream, and you continue that without the patient having to feel pressured to do phototherapy. Because, as Susan mentioned, that study showed, yes, phototherapy and jax work better together, but Jax do not need phototherapy to work. You can use rucks monotherapy, and we do that all the time. Okay. Second case, this was my case. This was an indian male. Obviously, I see lots of patients of color in my practice, as does Dr. Taylor. These patients obviously come in with a disproportionate psychological burden, because this is something that culturally, in many cultures, it's extremely ostracizing and stigmatizing. Even today, in January of 2023, tears, family disownment, abandonment, marriage proposals, lifestyle choices, all of these things are real, and they happen. This patient comes in within about two minutes. I know exactly what I'm going to do while the patient's even talking and we're getting our report going down. The reason being, Dr. Taylor, would you comment on sort of what this sort of stands out? So when I look at this case, I see a couple of things. First, I see some confetti vitiligo, and I also see trichomechrome vitiligo. So this means this patient's disease is active. So what I want to do is stop that activity. What I would do is prescribe dexamethasone, four milligrams. I like to dose it on the weekends, Saturday and Sunday. I'd also give this patient a super potent topical corticosteroid and probably a calci neuron inhibitor. That's what I would start with to try to slow it down. Now, maybe you can talk a little bit about antioxidants and vitamins for this patient. So, unstable patient. How do you combine the topical jack? How do you combine the systemics? Completely agree with Dr. Taylor. This patient's getting the oral mini pulse steroid, the dexamethasone, four milligrams, Saturday and Sunday. Quantity twelve no refills. Doing it for six weekends. This patient, if they're open to it, is also going to be told, I need to get you in a light box. Narrowband uvB. I'm also giving this patient polypodium leukotomis twice a day. I'm also giving this patient alpha lipoic acid with vitamin C and vitamin e. This will be in the handout. And this is a great patient where I will say, use your ruxolitinib on your face and your extremities where we know you can get color back. Because remember, the face is fabulous. The face repigments better than other areas. And hands and feet are tough. And then, like Dr. Taylor said, use your topical steroid calcionern inhibitor combo on the trunkle areas. Okay, let's move into our last case and then we'll close. This is an example of a patient who came in the only patch of vitiligo on the entire body. Now, I've shown you this similar image in other talks, the only patch of vitiligo on the entire body. And this was present per the patient for two years. Now what am I going to do with this patient? Dr. Taylor already alluded to the fact that this patient has even. There you go. Active vitiligo because they're trichrome. Everyone can see that, right? You can see the three colors. Doesn't trichrome and activity and confetti doesn't mean you have to have it all over. You can have one area and that be unstable. So this patient is a great patient where you can also give the topical jack monotherapy or you can do narrowband or eczema laser. Eczema laser. Laser. This would be an example of eczema laser. And then combining the antioxidants. Now, in the last couple of minutes, as we bring this home, there's new therapies on the horizon. Ritlicitinib is a study we're currently enrolling in. There are sites available throughout the country. If you have patients who want to be in a clinical trial, go to clinicaltrial Gov. This is an oral therapy that's being investigated for Vitiligo. And then there's several ongoing studies as well. There's one with upatacitinib and one also with other forms of ruxolitinibin phototherapy. But in conclusion, you can tell that this is an exciting time. Ruxolitinib truly is a game changer. I use it now. First line for all of my vitiligo patients, even if it's monotherapy, and I'll turn it over to Dr. Taylor for her concluding remarks. My conclusion is know treatment for Vitiligo is really bright. We had very little in the past, but now we have so many more tools in our toolbox. It's incredibly exciting, and it's so impactful for our patients. So thank you. Thank.

Overview of the pathophysiology of vitiligo

Report on the key data for JAK inhibitors for the management of vitiligo

Explain tactics to prevent and manage AE with JAK inhibitors

Recognize strategies to optimize care for patients with vitiligo

Not Just Skin Deep: Revealing New Strategies to Manage Vitiligo: Online CME Activity

Dr. Pearl Grimes and myself are excited to talk to you about strategies for managing Vitiligo in this CME program. I'm going to start off, then I'm going to tee it up for Dr. Grimes. We're going to talk a little bit at the end about case based examples in treating Vitiligo. Dr. Pearl Grimes really needs no introduction except to say that she is by far one of my favorite people in dermatology and a close, close friend. She's the director of the Vitiligo and Pigmentation Institute of Southern California and, in my opinion, really the guru of pigmentary diseases, and I've learned so much from her over the years. She's also clinical professor in the division of Dermatology at UCLA. Most of you already know me. I'm practicing private practice in Dallas, Texas, and on the faculty at UT Southwestern. Our objectives for the next few minutes, we're going to give you an update on the pathophysiology of Vitiligo, what's new, what's hot, and also talk a little bit more in detail about the Janus Kinase inhibitor drugs for Vitiligo therapy. Finally, Pearl is going to actually give us an overview of all of the things in our therapeutic armamentarium, and we're going to close with some clinical cases. I just want to set the stage for the next 15 minutes of discussion by reminding everyone in the audience and those of you tuning in virtually that Vitiligo is not a rare disease. And when I was in training and working with Pearl early on and many stalwarts in Vitiligo, like Jim Nordland and others, Vitiligo was thought to be an orphan disease. And it's amazing that now in 2022, we have so much emphasis being put on this devastating condition that affects males and females equally, that oftentimes in more than 50% of the cases, shows up before the age of 20. And the disease that's highly linked to psychological burden, including major depressive disease and oftentimes bipolar disorder. With that, I'm going to give you one or two more sound bites and then move into Pearl's portion. A couple of important things I always like to share with vitiligo patients when they present to the practice. The first and foremost thing is I try to find a silver lining. Pearl can attest to this, that these patients come to see us hoping that we have the magic solution as the experts, and we don't. Vitiligo is not curable. It is controllable. It is manageable, but what are some of the positive nuances of this disease? So I always tell my patient, well, yes, you may have vitiligo. I understand that that's extremely difficult for you, your family, for everyone involved, but you have a much less likely chance of developing melanoma. In fact, there is a threefold less risk for vitiligo patients in general to develop malignant melanoma compared to the general population. That's actually one positive piece of information you can provide to these individuals. I also, you've heard me say that the face is fabulous. And these know, they fly into Dallas, they come into the practice to see me, and they know I waited six weeks to come see this guy and flew in, and he's telling me, it's great. I have facial vitiligo. And the message there is that it's fabulous, because 70% to 80% of facial lesions, and in many cases now with newer therapies, even higher percentages can achieve complete repigmentation in a span of anywhere between six months, up to two years if you do aggressive therapy. And I'm going to talk to you about how you can accomplish that. So if you have facial, head and neck vitiligo, those are the patients that we can actually make better. Anytime I'm at an airport or at a grocery store, on a plane, and I see someone with disfiguring head and neck vitiligo, I want to ask them, who's your dermatologist? Have them call me. We'll work it out, because those are areas that can improve. Finally, we're teeing up some treatment options for you that Pearl's going to go over. But remember that vitiligo is a multi therapy disease. This is a disease that is not a monotherapy condition. And even with the advent of the newer jack inhibitors, this is still a multimodal therapeutic approach. Topical steroids, calcium inhibitors, systemic treatment, phototherapy, phototherapy, phototherapy, and finally, psychological treatment for those patients who need it. Pearl, I'm so honored to share the podium with Dr. Desai, one of my dear friends. So what I want to do in the next five or six minutes is review the standard therapies for vitiligo, because I think that as we move forward to optimize therapeutic outcomes for patients with this devastating disorder, I think we will move forward in combining standard and new therapies. So we have amazing new data regarding the burden of disease, where we've conducted a global study in over 1000 patients with vitiligo from around the world. And even if we compare the new data with our older data. The burden of disease for vitiligo is enormous. The overwhelming majority of patients have a reduced quality of life. They experience low self esteem, self worth. It interferes with personal relationships. And recent studies document depressive disorders as well as anxiety conditions in patients with vitiligo. So if we look at treatment strategies, we're at a key place in being able to optimize our treatment strategies based on what we currently know about vitiligo. It is a CD eight interferon gamma jackstat chemokine pathway that is driving the destruction of melanocytes. So how do we approach the disease? The tenets of treatment are stabilization, repigmentation, being able to maintain it long term, how do we do that? We decrease oxidative stress, we decrease the aberrant immune response, and then we must upregulate melanocyte regrowth and pigmentation. Stabilization is 100% key for those patients who have progressive disease. How do we achieve it? We have a number of tools in our toolbox that allow us to effectively achieve stabilization. Probably the two most popular are oral mini pulse dosing with dexamethasone. Intramuscular triumphsinolone has always been popular at my practice. Other modalities are methotrexate, menacycline. Recent studies on mycophenylate, mophatol, and narrowband is great for stabilization and repigmentation. Now, as we begin the therapeutic journey, I think for all of us in the room, it is so important to be cognizant of the factors that play a major role in stabilization. As samal mentioned earlier, anatomic sight. Regardless of the study you're quoting, face neck always provides the best therapeutic outcome. Age of the patient. Children universally probably respond better than adults. Duration of treatment is essential. Vitiligo is a marathon, not a sprint. And it's important to emphasize that to patients early on. If you have leukotrechia, lesional white hairs, that suggests you've destroyed or you've lost those stem cells, melanoblasts in the outer root sheet of the hair follicle, those patients do not do as well. Confetti lesions punctate white areas. Trichrome vitiligo lesions do not do well. And we must bury the myth of duration of disease that you only can optimize outcomes if you get that patient early, because we clearly know in our recent studies that we had significant efficacy in patients who had long term disease. So what are our therapeutic interventions? Certainly localized vitiligo we use the most popular of our topical corticosteroids, the calcinarin inhibitors and targeted phototherapy for limited involvement in those patients who have more severe disease. Phototherapy is essential for patients who have recalcitrant, stable areas of greater than a year. You can utilize autologous grafting procedures. And when the disease is severe, unresponsive, greater than 40%, you can depigment those patients. So I just quickly want to run through these. Certainly, if we look at our number one topical agents, the topical corticosteroids and the calcium inhibitors, they're first line for limited disease. All the data suggests that they're equal in efficacy. Best results face and neck. However, there are some differences. We have to rotate treatment if you're using a mid to high potency steroid for patients, because we want to avoid atrophy and steroid related side effects. In contrast, we don't have to deal with steroid related side effects for the calcinarin inhibitors. So these agents are really key in being able to historically manage long term use and maintenance therapy. I'll just share this quick data on phototherapy. This is a large metaanalysis moderate. In this series of over 35 studies, moderate responses were in 37% of patients at six months. By twelve months, it was 57%. Marked responses literally double from six months to twelve months. And again, if you look at the data for phototherapy, is similar for everything else. Again, best responses, face and neck trunk areas intermediate. And we continue to struggle with the hands and the feet. Eczema laser, excellent for localized lesions. You get even better responses if you combine it with the calcinarin inhibitors. Frequency of treatment essential. And again, that face neck story continues. I think all of you in the room by now who treat vitiligo patients, you probably realize that many patients cannot come into your office for treatment. So we've been doing home phototherapy now for over 20 years. Multiple studies now documenting the efficacy of home phototherapy for patients with vitiligo. The efficacy safety profile is enormous. And again, when you have a patient where they've done well and they have these stubborn, residual stable areas, please consider autologous grafting. We have a number of grafting procedures, punch grafts, suction, blister grafts. But if you choose wisely, the outcomes are amazing, as you see in the slides that I show you here. So with that, now we're going to talk about a new paradigm for vitiligo treatment. And that new paradigm is utilizing ruxalitnib samal. Well, Pearl as always, that was a tour de force and a great overview of so many of the old but good treatment options. And I think you said it best that vitiligo is a disease that's undergoing a renaissance. But we don't replace what we already know works. We augment and make it better. Now, before I get into jacks, I just wanted to point out for those of you in the room who oftentimes ask, well, topical jacks do great for Vitiligo, but why don't they work for alopecia? The reason they don't work well long term for alopecia is because of the depth of that CD eight t cell mediated inflammation. Remember that in Alopecita, most of the immunologic phenomenon is happening at the hair bulb, whereas in vitiligo, remember, most of the immunologic phenomenon is happening at the dermo epidermal junction. So penetration and durability of that response with the jack is why topical jacks for alopecia, frankly, are variable and not that great. And I first really got interested in jack inhibitors based on the initial work done from the Yale group that actually showed that oral tofacitinib, five milligrams every other day, off label, actually fully repigmented almost 85% of a man's hands and feet. And never before, like Dr. Grimes mentioned, have we had therapeutic options for acrovitiligo. So you've heard about Jack's galore at this meeting. Let me just remind you that think of the jaxtat pathway as a critical signaling pathway from outside cell to inside cell. And what I tell my patients is the jacks are like a gatekeeper. So I'm prescribing you a medicine that's going to block that gate so no other inflammatory signals can go through that passageway, making it to its destination. So we're blocking the travel of those cytokines. And that's exactly what this schematic shows. You block the cytokine, it doesn't get where it needs to go, it's on a canceled flight and never reaches its destination, so it never causes further gene transcription. Now, that's a simplistic way, but when I explain it to patients that way, they understand. By the way, someone asked me yesterday, so I added this slide. Is there a good review of every study out there for Janus kinase inhibitor drugs in vitiligo? And there is. Melinda Gooderham published a great consensus paper, if you're interested. This will be in the handout. Or feel free to take a picture if you just want one reference that reviews it all. Now, in the last few minutes before we get to these really incredible cases, because you're here to learn about cases and how Pearl and I approach the disease every day. In our practice, jack inhibitors work, because, again, they block the signal. But more importantly, the jack one two inhibition that we see with topical ruxalitinib is an interferon gamma mediated blockade. So, topical ruxalitinib is blocking interferon gamma signaling, melanocyte destruction. And that's how it works. By the way, this was the data that Pearl and I were a part of that was first published at the EADV last fall. Just two days ago, Pearl. Actually, I just told Pearl, she didn't even know because it's so hot off the press. It just got published in the New England journal. So, for the first time, we have incredible vanilligo options that we've been able to share with the broader healthcare community. I'll just briefly review how FDA approval for this therapy actually came about. This was a 1.5% ruxalitnib, double blinded, placebo controlled vehicle trial for 24 weeks. Patients were studied and then put in the long term extension, and then subsequently followed up. And at the end of the day, what made the FDA say, you know what? This will be the first therapy we ever approve for this disease. What made the FDA say, okay, this truly works? It was the 75% improvement in the patient's facial vasi score, or the f vasi, and that's how we actually determine treatment success. And you don't need to know the numbers here. You just need to notice the statistical significance compared to vehicle. Now, you've seen these images because I've shown them to you. I've been showing you these images probably for the past three or four meetings, because they're just incredible pictures. This man was in the study. He had a 90% improvement. This is an fvazi 90 response at the end of 24 weeks with no phototherapy, no calcium inhibitor, no topical steroid, no antioxidant. Now, in the real world, as Pearl said, I augment my response of my topical jacks with a lot of those things to even make it more robust. But this data is very, very pure and clean because it was monotherapy alone. A young girl. Imagine this young girl in middle school getting bullied, teased on the psychological impact for these young kids. It's profound and it's important, and this is critically important work. My last comment on the data not only does facial vitiligo improve with topical ruxalitinib. So does trunkle vitiligo. So does acrovitiligo. Yes. Hands and feet are still the hardest because they have the least amount of hair follicles, but it doesn't mean it won't work. And it does, and we still use it, I. E. This patient who has dorsal hand vitiligo. And I think Pearl and I would agree that this is a really nice response. We were involved, of course, in this clinical trial. This is a nice example of perifolicular repigmentation. Remember yesterday I reminded you all about marginal repigmentation and perifolicular, two different kind of morphologies. This happens to represent perifolicular. Finally, what's the big fuss about safety with topical jack? So do I use topical ruxolitinib in combination with other therapies? And in my practice, I do, just like Dr. Grimes. However, I do tell my patients usually to use this in less than 10% body surface area. I do not perform lab monitoring. The data from the clinical trial actually shows that the serum concentration of ruxolitinib was still well below any jack two mediated bone marrow changes. So you don't really have to worry about that. In my opinion, if you do have someone who has a history of hematologic issues or thromboembolic phenomenon, we do avoid it. Now, I'm going to turn it back over to pearl in just a minute for the cases, and then we'll close. But remember that phototherapy can. Just like she showed that example with the calcium inhibitors, it can actually augment the response of your jack inhibitors. It does not mean you must have phototherapy for these to work, but phototherapy makes it work better. Pearl, do you want to come on up and let's do the cases? We got time. So samal and I are going to do these cases together. So we have a 24 year old female who presents with progressive white patches of the hands. Very rapid progression over three months. There were no comorbid autoimmune illnesses. When we did the full exam, there were depigmented patches on the face, the neck, and the hands. The patient did have a positive thyroid peroxidase antibody. So recent onset vitiligo. So, Simone, how would you manage this patient? Okay, so this person comes in progressive white patches, by the way. I love that Pearl put the thyroid peroxidase antibody. The number of hashimoto's patients that we pick up by doing that is incredible. I actually learned that from her. Okay, if this patient has progressive disease. This is a patient who needs oral antioxidants, who needs phototherapy, who probably needs systemic steroid stabilization based on how much the disease is spreading. And I would incorporate topical ruxalitinib. So one point to make. Now, we talked about standard therapies versus the new paradigm. So for everyone in the audience, you could go either way. I don't think anyone would criticize you. Would you not agree if you chose to do standard therapy? Absolutely. And then if in three months, if that patient did not respond to traditional, you know that you can place them on ruxalitinib, which will significantly increase the likelihood of having a significant response given the involvement on the face and the neck, I don't think you need to jump in right now and start phototherapy. But keep in mind, phototherapy is amazing for stabilization as well. I think there's one other key point to mention on this patient, given the fact that she has a positive thyroid antibody. If you monitor patients with vitiligo who have normal thyroid function with a thyroid peroxidase antibody, clearly those people are at an increased risk of getting thyroid disease if you follow them long enough. Totally, totally agree. Well, Pearl, let's do this last case and let's wrap up. 48 year old male, progressive areas of depigmentation. Despite calcinor inhibitors and steroids. Look at the body's surface area involvement. Comorbid alopecia riata. BSA is less than 10%, but it's patchy. It's depigment on face, trunk, lower extremities. Lab studies negative. Pearl, you walk in the room, give me your treatment plan. You need phototherapy, you need roxalitnip, maybe some steroids for stabilization, and we need to be aggressive. I agree. Last comment, Pearl, if you will, just remind the audience how you like to do your topical steroid and topical calcium inhibitor. Two weeks of one, two weeks of the other, Monday through Friday. What is your preference? Well, if I'm using steroids and a calci neuron inhibitor in a new patient, what I have done for so often, I'll use the steroid in the morning and the calcineurin inhibitor at night to jumpstart things, and then I transition to a calci neuron. But you can also, I typically rotate one month on, one month off if I feel that I continue to need both. Thank you very much for your attention and for having us both.

Vitiligo

WEDNESDAY, March 13, 2024 -- In a consensus statement published online March 13 in JAMA Dermatology, evidence-based recommendations are presented for the diagnosis and treatment of vitiligo in young patients.Yael Renert-Yuval, M.D., from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues developed evidence- and consensus-based expert recommendations on the diagnosis and treatment of vitiligo in young patients. A total of 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, two on pseudocatalase, and two on microdermabrasion met the inclusion criteria.The authors made 42 recommendations on diagnosis of vitiligo and optimal topical therapeutics; 33 of the recommendations obtained a 70 percent or higher composite agreement and strong agreement. Evidence-based first-line therapies in the management of pediatric and adolescent patients included topical calcineurin inhibitors twice daily, topical corticosteroids with time limitation due to atrophy risk, and topical ruxolitinib (1.5 percent) cream -- used off-label for patients younger than 12 years and limited to nonsegmental vitiligo. Specific guidance was provided using age-based data, a minimum therapeutic trial of six months or longer, prolonged therapy to prevent recurrence, and the positive benefit of coordinated use of ultraviolet therapeutic sources."Suggested next steps include development of a long-term vitiligo registry and head-to-head short- and long-term comparisons of all three major classes of topical therapy," the authors write. "Future studies of vitiligo should aim to identify the role of early intervention as a means of controlling long-term disease activity and preventing T-memory cell accumulation."Several authors disclosed ties to pharmaceutical companies, including Incyte Pharmaceuticals, which funded the study.

33 of 42 recommendations obtained 70 percent or higher composite agreement and strong agreement

Recommendations Developed for Managing Vitiligo in Young Patients

Phototherapy is used to treat vitiligo using both its immunosuppressive effects and its ability to stimulate melanocyte activity.1 It’s effective for active disease by promoting T-cell apoptosis, suppressing inflammatory cytokines, stimulating interleukin-10, and decreasing the number of epidermal Langerhans cells serving as antigen-presenting cells. It is also effective for patients with stable disease as it supports melanocyte proliferation and migration from the hair follicles to the epidermis.1&nbsp;The different types of phototherapy include psoralen ultraviolet-A (PUVA) radiation, ultraviolet-B (narrow-band [NB-UVB][310-315 nm wavelength], and excimer laser [EL][308 nm wavelength], lamp) radiation. PUVA and NB-UVB serve as the main forms of treatment for generalized vitiligo, while EL is commonly used to treat localized vitiligo and is popular among pediatric patients.2&nbsp;NB-UVB and PUVA&nbsp;NB-UVB is currently considered the standard of care and preferred over PUVA because it lessens oxidative stress-induced damage and has fewer limitations and side effects. While PUVA carries the risk of phototoxic effects, nausea, skin cancer, and cannot be used on children and pregnant women, NB-UVB does not require a photosensitizer, can be administered with a lower cumulative dose, has demonstrated superior overall treatment response, and has adverse effects that are well tolerated and disappear hours after treatment (erythema, itching, mild burning or pain).2, 3 Under special conditions–such as patients with refractory vitiligo or higher Fitzpatrick skin phototypes–PUVA phototherapy still remains an option.4&nbsp;NB-UVA efficacy&nbsp;The efficacy of NB-UVB for vitiligo, especially nonsegmental vitiligo, is highly supported; for instance, a retrospective review found that repigmentation persisted in 80% of patients one year after discontinuation of NB-UVB.5 A longer treatment duration has been found to improve treatment outcomes, with at least 6 months required to determine any responsiveness to NB-UVB phototherapy and at least one year required to obtain maximal results.2 The face and neck were the most responsive to NB-UVB, followed by the trunk, extremities, and hands and feet. Barriers to repigmentation include disease activity, autoimmune state, large targeted body surface area, and concurrence of poliosis.2&nbsp;Excimer laser&nbsp;EL is just as6 or more effective7 in treating vitiligo, does not expose normal skin to radiation, and can target areas such as the ears and genitals. A 2022 study found that during a follow-up of 3.38 years after EL treatment, repigmentation persisted in 80% of facial, 40% of body, and 20% of extremity lesions.8 EL is most effective when used early in the clinical process for segmental vitiligo.9 Recent studies have also shown that EL treatment should be combined with topical interventions such as tacrolimus, pimecrolimus, or halometasone.10 Repigmentation is fastest with 3 sessions per week with a minimum of 20 treatments recommended.11, 12 Common adverse effects of EL include erythema, pruritus, blistering, and perilesional hyperpigmentation.13&nbsp;Current evidence suggests that while no vitamin D analogs were found to enhance the efficacy of PUVA or EL for vitiligo, the combination of topical calcipotriol or tacalcitol with NB-UVB increases the rate of response to treatment; the effect of tacalcitol was found to be greater than that of calcipotriol.14&nbsp;As the therapeutic options for vitiligo expand, phototherapy remains a versatile and effective treatment, leveraging both immunosuppressive effects and the stimulation of melanocyte activity. With various modalities available, dermatologists can tailor their approach based on the patient's condition and specific requirements.&nbsp;<ol><li>Zubair R, Hamzavi IH. Phototherapy for Vitiligo. Dermatol Clin. 2020;38(1):55-62. doi:10.1016/j.det.2019.08.005&nbsp;</li><li>Bae JM, Jung HM, Hong BY, et al. Phototherapy for Vitiligo: A Systematic Review and Meta-analysis. JAMA Dermatol. 2017;153(7):666-674. doi:10.1001/jamadermatol.2017.0002&nbsp;</li><li>Pacifico A, Leone G. Photo(chemo)therapy for vitiligo. Photodermatol Photoimmunol Photomed. 2011;27(5):261-277. doi:10.1111/j.1600-0781.2011.00606.x&nbsp;</li><li>Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE; Vitiligo Working Group. Current and emerging treatments for vitiligo. J Am Acad Dermatol. 2017;77(1):17-29. doi:10.1016/j.jaad.2016.11.010&nbsp;</li><li>Silpa-Archa N, Weerasubpong P, Junsuwan N, Yothachai P, Supapueng O, Wongpraparut C. Treatment outcome and persistence of repigmentation from narrow-band ultraviolet B phototherapy in vitiligo. J Dermatolog Treat. 2019;30(7):691-696. doi:10.1080/09546634.2018.1544409&nbsp;</li><li>Linthorst Homan MW, Spuls PI, Nieuweboer-Krobotova L, et al. A randomized comparison of excimer laser versus narrow-band ultraviolet B phototherapy after punch grafting in stable vitiligo patients. J Eur Acad Dermatol Venereol. 2012;26(6):690-695. doi:10.1111/j.1468-3083.2011.04147.x&nbsp;</li><li>Poolsuwan P, Churee C, Pattamadilok B. Comparative efficacy between localized 308-nm excimer light and targeted 311-nm narrowband ultraviolet B phototherapy in vitiligo: A randomized, single-blind comparison study. Photodermatol Photoimmunol Photomed. 2021;37(2):123-130. doi:10.1111/phpp.12619&nbsp;</li><li>Sethi S, Silverberg N. Short and Long-Term Outcomes of 308-nm Laser for Pediatric Vitiligo. J Drugs Dermatol. 2022;21(7):773-775. doi:10.36849/JDD.6895&nbsp;</li><li>Majid I, Imran S. Excimer light therapy in childhood segmental vitiligo: Early treatment gives better results. Dermatol Ther. 2020;33(3):e13408. doi:10.1111/dth.13408&nbsp;</li><li>Li L, Liang Y, Hong J, Lan L, Xiao H, Xie Z. The effectiveness of topical therapy combined with 308-nm excimer laser on vitiligo compared to excimer laser monotherapy in pediatric patients. Pediatr Dermatol. 2019;36(1):e53-e55. doi:10.1111/pde.13726&nbsp;</li><li>Hofer A, Hassan AS, Legat FJ, Kerl H, Wolf P. Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients. Br J Dermatol. 2005;152(5):981-985. doi:10.1111/j.1365-2133.2004.06321.x&nbsp;</li><li>Hui-Lan Y, Xiao-Yan H, Jian-Yong F, Zong-Rong L. Combination of 308-nm excimer laser with topical pimecrolimus for the treatment of childhood vitiligo. Pediatr Dermatol. 2009;26(3):354-356. doi:10.1111/j.1525-1470.2009.00914.x&nbsp;</li><li>Speeckaert R, van Geel N. Vitiligo: An Update on Pathophysiology and Treatment Options. Am J Clin Dermatol. 2017;18(6):733-744. doi:10.1007/s40257-017-0298-5&nbsp;</li><li>Liu X, Yao Z, Wang Y, Chai L, Zhou X. Vitamin D analogs combined with different types of phototherapy in the treatment of vitiligo: A systematic review of randomized trials and within-patient studies. Int Immunopharmacol. 2022;109:108789. doi:10.1016/j.intimp.2022.108789</li></ol>

With an expanding array of therapeutic options emerging for vitiligo, phototherapy remains a safe and effective option

Phototherapy for Vitiligo: An Overview of the Essentials

FRIDAY, Feb. 9, 2024 (HealthDay News) -- Patients with vitiligo have significantly higher health care costs and health care resource utilization (HCRU), according to a study recently published in the Journal of Investigative Dermatology.Khaled Ezzedine, M.D., from Henri Mondor University Hospital in Créteil, France, and colleagues conducted a retrospective cohort analysis to examine health care costs and HCRU among U.S. patients with vitiligo, focusing on direct costs. Between January 2007 and December 2021, patients with vitiligo were matched to controls in a 1:2 ratio (49,512 and 99,024 individuals, respectively).The researchers found that compared with controls, patients with vitiligo had significantly higher all-cause ($15,551 versus $7,735) and vitiligo-related ($3,490 versus $54) costs. Patients with vitiligo also had significantly higher all-cause and mental health-related HCRU. Patients on treatments with systemic effects/mental health diagnoses also had significantly higher differences in all-cause and vitiligo-related health care costs compared with controls."The economic burden was markedly higher for patients receiving a treatment with systemic effects or with new mental health diagnoses than for the total vitiligo population," the authors write. "These findings reveal an unmet need for cost-effective treatments and highlight the importance of fully identifying the drivers of economic burden for patients with vitiligo."Several authors disclosed ties to pharmaceutical companies, including AbbVie, which funded the study.<a target="_blank" rel="noopener noreferrer" href="https://www.jidonline.org/article/S0022-202X(23)02593-9/fulltext">Abstract/Full Text</a>

Differences in all-cause, vitiligo-related health care costs remained higher for those on treatments with systemic effects/mental health diagnoses

Health Care Costs, Resource Utilization Increased for Vitiligo Patients

WEDNESDAY, Jan. 17, 2024 -- For patients with vitiligo, dermoscopy combined with reflectance confocal microscopy (RCM) has higher sensitivity and specificity for measuring disease activity and treatment response, according to a study published online Dec. 18 in Clinical, Cosmetic and Investigational Dermatology.Hui-Fen Wang, from the First Affiliated Hospital of Army Medical University in Chongqing, China, and colleagues assessed disease activity by Vitiligo Disease Activity score, dermoscopy, RCM, and dermoscopy combined with RCM among 279 patients with vitiligo.The researchers found that the sensitivity and specificity of dermoscopy combined with RCM were higher than RCM or dermoscopy alone. At baseline, leukotrichia, pigment network absent, and perilesional hyperpigmentation under dermoscopy in the repigmentation process suggested a poor treatment response; a good treatment response was indicated by incompletely disappearing pigment rings under RCM and perifollicular hyperpigmentation under dermoscopy. By dermoscopy, the proportion of patients with telangiectasia and increased pigment at the lesions and around the hair follicles was significantly higher in the good versus the poor treatment response group; by RCM, the proportion of patients with both increased pigment granules and dendritic melanocytes was higher in the good versus the poor treatment response group."Our study identified that both dermoscopy and RCM can be used to evaluate vitiligo disease activity and monitor treatment response, which is helpful to make optimal treatment regimens," the authors write. "The combination of dermoscopy and RCM can make up for the technical deficiency of each alone and present more objective evaluation than the traditional assessment method."

Sensitivity and specificity of dermoscopy combined with RCM was higher than RCM or dermoscopy alone

Is Dermoscopy, Reflectance Confocal Microscopy Combo Best for Assessing Vitiligo?

THURSDAY, Dec. 21, 2023 (HealthDay News) -- Transplant recipients, especially those receiving hematopoietic stem cell transplant (HSCT), have an increased risk for vitiligo, according to a brief report published online Dec. 13 in JAMA Dermatology.Chul Hwan Bang, M.D., Ph.D., from the Catholic University of Korea in Seoul, and colleagues conducted a population-based cohort study including data from the National Health Insurance Service database of Korea for patients aged 20 years or older who had received a transplant (solid organ transplant [SOT] or HSCT) between January 2010 and December 2017. Patients were compared to age- and sex-matched (1:5) controls who did not receive a transplant. Data were included for 23,829 patients who underwent SOT or HSCT and 119,145 controls.The researchers found that the risk for vitiligo was significantly higher for patients who had undergone transplant than controls (adjusted hazard ratio, 1.73). Kidney and liver transplant recipients also had a slightly higher risk for vitiligo compared with controls, but risk was highest in HSCT recipients (adjusted hazard ratio, 12.69). Compared with controls, those who received allogeneic grafts, those who received autologous grafts, those with comorbid graft-versus-host disease (GVHD), and those without GVHD had a higher risk for vitiligo."The findings suggest that early detection and management of vitiligo lesions can be improved by estimating the likelihood of its development in transplant recipients and implementing a multidisciplinary approach for monitoring," the authors write.<a target="_blank" rel="noopener noreferrer" href="https://jamanetwork.com/journals/jamadermatology/article-abstract/2812441">Abstract/Full Text (subscription or payment may be required)</a>

Increased risk seen for those receiving allogeneic grafts and autologous grafts, as well as those with and without comorbid GVHD

Risk for Vitiligo Increased for Transplant Recipients

TUESDAY, Oct. 17, 2023 (HealthDay News) -- A high proportion of patients with newly diagnosed vitiligo do not receive any treatment, according to a study recently published in Dermatology and Therapy.David Rosmarin, M.D., from the Indiana University School of Medicine in Indianapolis, and colleagues retrospectively analyzed claims data from the Merative MarketScan Research Databases. The analysis included data from 19,335 patients aged 12 years and older with newly diagnosed vitiligo.The researchers found that 49.9 percent of patients did not receive any treatment in the 12-month follow-up. Among those initiating treatment, switching was minimal, with the most frequent first-line treatments being high-potency topical corticosteroids (25.4 percent), oral corticosteroids (23.1 percent), and topical calcineurin inhibitors (TCIs; 14.7percent). Among adolescents initiating treatment, TCI was the most frequently received first-line therapy (30.9 percent). During follow-up, patients with moderate-to-severe vitiligo were very likely to receive treatment, with only 1.5 percent not receiving treatment. Time to first medication claim ranged from 51.9 days for TCI to 178.6 days for systemic immunosuppressants. The mean total days supplied ranged from 14.4 days for oral corticosteroids to 121.0 for immunosuppressants."To help better understand the needs of patients with vitiligo, future studies need to examine which demographic and clinical characteristics are associated with not receiving treatments for vitiligo," the authors write.Rosmarin disclosed ties to pharmaceutical companies, including AbbVie, which funded the study.

Proportion receiving treatment within 12 months higher with more severe disease

Half of Patients With Newly Diagnosed Vitiligo Do Not Receive Treatment

WEDNESDAY, Oct. 11, 2023 &nbsp;-- For stable segmental vitiligo, autologous cell transplant is a new and reliable treatment, with cultivated cells producing better results, according to a review published online Sept. 15 in the International Journal of Dermatology.Ariela A. Souroujon, B.M., B.S., from the Universidad Anahauc México in Huixquilucan, and colleagues examined the efficacy of autologous cell transplant as a therapeutic approach for stable segmental vitiligo in a systematic review. Six of 60 articles met the acceptance criteria for analysis.The researchers found that for many body parts, autologous cell transplant achieved excellent pigmentation rates. Better results were achieved for cultivated cells than noncultivated cells. Autologous cell transplant with cultured and noncultured cells could pigment 80 percent or more where needed."This systematic review highlights that autologous cell transplantation in stable segmental vitiligo holds tremendous promise as a viable alternative for addressing this complex dermatological disorder," the authors write. "It is crucial to explore further and thoroughly investigate the potential of cell transplantation and its associated techniques to establish comprehensive guidelines for standardizing transplantation procedures. It is imperative to address the current limitations that hinder the accessibility of this therapy."

Cultivated cells have better results than noncultivated ones; both types pigment 80 percent or more where needed

Is Autologous Cell Transplant Reliable for Stable Segmental Vitiligo?

Vitiligo is associated with a host of comorbid autoimmune, ocular and auditory, and dermatologic disorders.1 Thyroid disease is the most prevalent of all autoimmune disorders among patients with vitiligo.2 Age, sex, and race affect the presence of other autoimmune comorbidities including alopecia areata, diabetes mellitus, pernicious anemia, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Addison’s disease, inflammatory bowel disease (IBD), Sjögren’s syndrome, multiple sclerosis, and idiopathic thrombocytopenic purpura.1, 3&nbsp;<h6>Autoimmune disorders&nbsp;</h6>A 10-year retrospective study found that 23% of patients with vitiligo had one or more of the following autoimmune disorders: thyroid disease, RA, alopecia areata, IBD, SLE, diabetes mellitus, and psoriasis.4 Sex and age influence the prevalence of comorbidities, with Grave’s disease, Hashimoto’s thyroiditis, atopic dermatitis, RA, SLE, and Sjögren’s syndrome more likely in female patients with vitiligo and psoriasis more likely in male patients. SLE and Sjögren’s syndrome are more common among elderly patients with vitiligo and myasthenia gravis is more common among younger patients.5 Race also affects the types of autoimmune comorbidities present. White patients demonstrated the highest rates of comorbidities, with hypothyroidism most frequently found in White and Hispanic/Latino patients. In contrast, psoriasis was most frequent in Asian patients, and SLE and RA were most frequent in Black patients.4&nbsp;<h6>Thyroid disease&nbsp;</h6>Of all autoimmune disorders, the connection between thyroid disease (especially hypothyroidism and Grave’s disease)6, 7 and vitiligo is most established. Autoimmune thyroid disease (AITD) occurs in a range between 1.61% to 37% of patients with vitiligo compared to only 1% in the general population,8 and patients with vitiligo have a 2.5-times higher risk of developing AITD than those without vitiligo.9 In fact, AITD may have an increased prevalence (6-15%) even among first-degree relatives of patients with vitiligo.10 Vitiligo duration positively correlates with the risk of AITD and larger (&gt;9%) body surface area involvement.11&nbsp;<h6>Ocular and audiological abnormalities&nbsp;</h6>Vitiligo relates to ocular abnormalities as there are melanocytes located in the uveal tract and retinal pigment epithelium (RPE).12 In a study of 150 patients with vitiligo, 16% have ocular abnormalities in the uvea and RPE compared to 5% of controls.1 18.4% of patients with vitiligo demonstrated signs of normal tension glaucoma, compared with 0% of controls. Similar to the relationship between vitiligo and ocular abnormalities, audiological abnormalities are also being investigated as there are melanocytes located in the inner ear (scala vestibuli).13 68.8% of patients with vitiligo had sensorineural hearing loss (SNHL) compared to 6.3% of controls in a study with 16 patients with vitiligo and 16 healthy controls.14&nbsp;<h6>Psoriasis and atopic dermatitis&nbsp;</h6>Furthermore, psoriasis and atopic dermatitis are dermatologic disorders associated with vitiligo, with the latter showing significantly higher prevalence among pediatric patients and patients with early-onset vitiligo.15 There is a strong link between atopic dermatitis and vitiligo, with a systematic review of 16 studies illustrating a much higher frequency of atopic dermatitis among patients with vitiligo in contrast to controls.15&nbsp;<h6>The future of vitiligo comorbidities research&nbsp;</h6>It is critical that care providers remain conscious of these comorbidities in vitiligo, especially autoimmune thyroid disorders. To improve quality of life for patients with vitiligo, future studies should focus on further elucidating the significance of these associations.&nbsp;<h6>References&nbsp;</h6><ol><li>Dahir AM, Thomsen SF. Comorbidities in vitiligo: comprehensive review. Int J Dermatol. 2018;57(10):1157-1164. doi:10.1111/ijd.14055&nbsp;</li><li>Gill L, Zarbo A, Isedeh P, Jacobsen G, Lim HW, Hamzavi I. Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study. J Am Acad Dermatol. 2016;74(2):295-302. doi:10.1016/j.jaad.2015.08.063&nbsp;</li><li>Hadi A, Wang JF, Uppal P, Penn LA, Elbuluk N. Comorbid diseases of vitiligo: A 10-year cross-sectional retrospective study of an urban US population. J Am Acad Dermatol. 2020;82(3):628-633. doi:10.1016/j.jaad.2019.07.036&nbsp;</li><li>Sheth VM, Guo Y, Qureshi AA. Comorbidities associated with vitiligo: a ten-year retrospective study. Dermatology. 2013;227(4):311-315. doi:10.1159/000354607&nbsp;</li><li>Chen YT, Chen YJ, Hwang CY, et al. Comorbidity profiles in association with vitiligo: a nationwide population-based study in Taiwan. J Eur Acad Dermatol Venereol. 2015;29(7):1362-1369. doi:10.1111/jdv.12870&nbsp;</li><li>Sawicki J, Siddha S, Rosen C. Vitiligo and associated autoimmune disease: retrospective review of 300 patients. J Cutan Med Surg. 2012;16(4):261-266. doi:10.1177/120347541201600408&nbsp;</li><li>Bae JM, Lee JH, Yun JS, Han B, Han TY. Vitiligo and overt thyroid diseases: A nationwide population-based study in Korea. J Am Acad Dermatol. 2017;76(5):871-878. doi:10.1016/j.jaad.2016.12.034&nbsp;</li><li>Lotti T, D'Erme AM. Vitiligo as a systemic disease. Clin Dermatol. 2014;32(3):430-434. doi:10.1016/j.clindermatol.2013.11.011&nbsp;</li><li>Vrijman C, Kroon MW, Limpens J, et al. The prevalence of thyroid disease in patients with vitiligo: a systematic review. Br J Dermatol. 2012;167(6):1224-1235. doi:10.1111/j.1365-2133.2012.11198.x&nbsp;</li><li>Spritz RA. Shared genetic relationships underlying generalized vitiligo and autoimmune thyroid disease. Thyroid. 2010;20(7):745-754. doi:10.1089/thy.2010.1643&nbsp;</li><li>Gey A, Diallo A, Seneschal J, et al. Autoimmune thyroid disease in vitiligo: multivariate analysis indicates intricate pathomechanisms. Br J Dermatol. 2013;168(4):756-761. doi:10.1111/bjd.12166&nbsp;</li><li>Biswas G, Barbhuiya JN, Biswas MC, Islam MN, Dutta S. Clinical pattern of ocular manifestations in vitiligo. J Indian Med Assoc. 2003;101(8):478-480.&nbsp;</li><li>Anbar TS, El-Badry MM, McGrath JA, Abdel-Azim ES. Most individuals with either segmental or non-segmental vitiligo display evidence of bilateral cochlear dysfunction. Br J Dermatol. 2015;172(2):406-411. doi:10.1111/bjd.13276&nbsp;</li><li>Fleissig E, Gross M, Ophir I, Elidan J, Bdolah-Abram T, Ingber A. Risk of sensorineural hearing loss in patients with vitiligo. Audiol Neurootol. 2013;18(4):240-246. doi:10.1159/000350337&nbsp;</li><li>Mohan GC, Silverberg JI. Association of vitiligo and alopecia areata with atopic dermatitis: a systematic review and meta-analysis. JAMA Dermatol. 2015;151(5):522-528. doi:10.1001/jamadermatol.2014.3324</li></ol>

The pigmentary disorder is linked to a host of autoimmune disorders, ocular and auditory abnormalities, and dermatologic conditions

Vitiligo and Associated Comorbidities: A Review  

TUESDAY, Sept. 26, 2023 (HealthDay News) -- Patients with vitiligo may have a reduced risk for mortality, according to a study published online Sept. 14 in the Journal of Investigative Dermatology.Hyun Jeong Ju, M.D., Ph.D., from the St. Vincent's Hospital College of Medicine at The Catholic University of Korea in Seoul, and colleagues examined mortality in patients with vitiligo in a population-based cohort study. Patients with incident vitiligo and sociodemographic factor-matched controls were included in a 1:5 ratio, with a total of 107,424 patients with incident vitiligo and 537,120 matched controls. Participant data were pulled from the National Health Insurance Service of Korea database and linked to the National Death Registry.The researchers found that for patients and controls, mortality rates were 34.8 and 45.3 per 10,000 person-years, respectively. A significantly lower risk for mortality was seen for patients with vitiligo (adjusted hazard ratio, 0.75). Patients with vitiligo had significantly lower cause-specific mortality from infectious diseases, oncologic diseases, hematologic diseases, endocrine diseases, neurologic diseases, cardiovascular diseases, respiratory diseases, and renal/urogenital disease."Our findings are significant because they suggest that the autoimmune nature of vitiligo may confer certain protective effects against various causes of mortality, and they offer new avenues for research into the mechanisms underlying this protective effect," Ju said in a statement. "Moreover, understanding the mortality risk in patients with vitiligo will lead to improved patient counseling, health monitoring, and overall management strategies for patients."

Lower all-cause and cause-specific mortality seen, including from infectious diseases, oncologic diseases, endocrine diseases

Reduced Mortality Risk Seen for Patients With Vitiligo

WEDNESDAY, Sept. 20, 2023 -- For generalized-type vitiligo, narrowband ultraviolet B (NB-UVB) treatment combined with tacrolimus 0.1 percent or calcipotriol/betamethasone dipropionate is efficacious, with no significant difference in efficacy at three and six months of follow-up, according to a study published online Aug. 30 in the Journal of Dermatological Treatment.Diala Alshiyab, M.D., from the Jordan University of Science and Technology in Irbid, and colleagues recruited 41 adults with generalized-type vitiligo receiving NB-UVB to compare the efficacy of topical tacrolimus 0.1 percent to that of calcipotriol/betamethasone dipropionate. The patients were classified into two groups: 20 patients receiving calcipotriol/betamethasone dipropionate cream (D group) and 21 patients receiving tacrolimus 0.1 percent ointment (T group). Follow-up was conducted at three and six months.The researchers found an increase in the repigmentation area in the D and T groups from the third to the sixth month (35.4 to 54.7 percent and 32.2 to 45.6 percent, respectively). The between-group differences were not statistically significant. Different levels of improvement were seen in body sites, ranging from the highest in the face and lowest in the hands and feet. There was a negative correlation observed between the duration since diagnosis and response to D treatment."The combinations of NB-UVB with tacrolimus 0.1 percent ointment or with calcipotriol/betamethasone dipropionate are efficacious in treating general vitiligo in adults," the authors write.

No difference seen in efficacy for NB-UVB treatment combined with tacrolimus 0.1 percent or calcipotriol/betamethasone dipropionate

 Combo Treatments Efficacious for Generalized-Type Vitiligo

WEDNESDAY, Sept. 6, 2023 -- Globally, patients with vitiligo report being substantially affected in terms of their emotional well-being and psychosocial health, according to a study published online Aug. 30 in JAMA Dermatology.Kristen Bibeua, Ph.D., from Incyte Corporation in Wilmington, Delaware, and colleagues assessed quality of life (QOL) and mental health in patients with vitiligo. Overall, 3,541 surveyed adults reported a vitiligo diagnosis and competed the survey. The survey was administered from May 6, 2021, to June 21, 2021, in 17 countries.The researchers found that the mean global short-form Vitiligo Impact Patient scale score was 27.3 overall, with the highest score, indicating the greatest burden, for patients from India (mean, 40.2). According to the scale, the QOL burden was profound for patients with more than 5 percent affected body surface area (BSA), darker skin, and lesions on the face or hands (mean scores, 32.6, 31.2, 30.0, and 29.2, respectively). Globally, more than 40 percent of patients reported that vitiligo frequently affected aspects of their daily lives, including choice of clothes to wear (55.2 percent). Overall, 59.4 percent of patients reported frequently concealing their vitiligo. Diagnosed mental health conditions were reported by 58.7 percent of patients and included anxiety and depression (28.8 and 24.5 percent, respectively). Moderate-to-severe depressive symptoms were identified in 55.0 percent of patients, with the highest rates seen among patients in India, among those with more than 5 percent affected BSA, and in patients with darker skin (89.4, 72.0, and 68.3 percent, respectively)."Findings highlight the need to prioritize reduction in the psychosocial burden of vitiligo and increase efforts to educate patients and health care professionals on vitiligo, particularly in countries where patients experience the highest burden," the authors write.Several authors disclosed ties to the biopharmaceutical industry, including Incyte Corporation, which funded the study.

Vitiligo affects patients' daily lives and well-being; more than half of patients report diagnosed mental health conditions

Vitiligo Has Considerable Impact on Mental Health

Vitiligo is a chronic skin disorder characterized by the loss of pigmentation, resulting in the appearance of white patches on the skin. While it primarily affects physical appearance, vitiligo also has significant psychosocial implications. Individuals living with vitiligo often face emotional distress, social stigmatization, and challenges in maintaining self-esteem and body image. This article aims to explore the psychosocial impact of vitiligo, shedding light on the emotional journey experienced by those affected and the importance of support systems in coping with the condition.&nbsp;<h6>Emotional impact of vitiligo&nbsp;</h6>The emotional impact of vitiligo can be profound. Aesthetic concerns and the fear of social rejection contribute to heightened levels of stress, anxiety, and depression among individuals with vitiligo.1 Many experience feelings of shame, self-consciousness, and low self-esteem due to the visible nature of the condition. Coping with the emotional toll of vitiligo requires resilience and psychological support to navigate these challenges.2&nbsp;<h6>Effects on body image and self-esteem&nbsp;</h6>Vitiligo can significantly affect body image and self-esteem. The loss of pigmentation in visible areas such as the face, neck, and hands can lead to a negative perception of one's appearance.2 Studies have shown that individuals with vitiligo may develop distorted body image and exhibit avoidance behaviors, such as wearing concealing clothing or avoiding social situations.1-3 The impact on self-esteem can be particularly severe, as the condition may interfere with personal relationships, career aspirations, and overall quality of life.&nbsp;<h6>Stigmatization and misconceptions&nbsp;</h6>Stigmatization and discrimination are common experiences for individuals with vitiligo. Societal misconceptions and ignorance surrounding the condition can result in social exclusion, teasing, and bullying. The public's lack of awareness about vitiligo often leads to misunderstandings, further exacerbating the challenges faced by those affected. Such experiences can contribute to feelings of isolation and can significantly impact mental well-being.&nbsp;<h6>Techniques for coping with the psychosocial impact of vitiligo&nbsp;</h6>Coping with the psychosocial impact of vitiligo requires a multifaceted approach. Psychosocial interventions, such as cognitive-behavioral therapy (CBT), have been effective in reducing distress and improving self-esteem among individuals with vitiligo.4 CBT helps individuals reframe negative thoughts and develop adaptive coping mechanisms. Additionally, support groups and online communities provide platforms for individuals to share experiences, receive emotional support, and promote self-acceptance.5&nbsp;<h6>The patient journey towards well-being&nbsp;</h6>The psychosocial impact of vitiligo is far-reaching, affecting individuals emotionally, socially, and psychologically. Recognizing and addressing these challenges is vital for the well-being of those living with the condition. Psychosocial interventions, support networks, and increased awareness can empower individuals with vitiligo to navigate their emotional journey and cultivate a positive self-image.&nbsp;<h6>References&nbsp;</h6><ol><li>Kent G, M al-Abadie. Factors affecting responses on Dermatology Life Quality Index items among vitiligo sufferers. Clin Exp Dermatol. 1996;21(5):330-333.&nbsp;</li><li>Kostopoulou P, Jouary T, Quintard B, et al. Objective vs. subjective factors in the psychological impact of vitiligo: the experience from a French referral centre. Br J Dermatol. 2009;161(1): 128-033. doi:10.1111/j.1365-2133.2009.09077.x&nbsp;</li><li>Salzes C, Abadie S, Seneschal J, et al. The Vitiligo Impact Patient Scale (VIPs): development and validation of a vitiligo burden assessment tool. J Invest Dermatol. 2016;136(1):52-58. doi:10.1038/JID.2015.398&nbsp;</li><li>Ongenae K, Beelaert L, van Geel N, Naeyaert JM. Psychosocial effects of vitiligo. J Eur Acad Dermatol Venereol. 2006;20(1):1-8. doi:10.1111/j.1468-3083.2005.01369.x&nbsp;</li><li>Geisler A, O'Connell KA, Pandya R, et al. Importance of and instruction for starting a vitiligo patient support group. Dermatol Online J. 2022;28(6):10.5070/D328659723. doi:10.5070/D328659723</li></ol>

Navigating the emotional and social challenges and enhancing support strategies for patients with vitiligo

Psychosocial Impact of Vitiligo

Historically, areas of trauma prompt an autoimmune reaction against melanocytes. Many of the factors, including metabolic abnormalities, oxidative stress, inflammation, and autoimmunity, unsurprisingly contribute toward melanocyte loss.1 The more recently described convergence theory combines all the existing theories into a comprehensive one, where several different mechanisms all reduce the viability of melanocytes. These primary pathogenic mechanisms include genetics, autoimmunity, oxidative stress, and neural hypothesis. However, vitiligo’s relationship with the environment, psychological stress, comorbidities, and individual genetic factors are difficult to integrate in terms of its pathogenesis.2&nbsp;<h6>Genetics&nbsp;</h6>A few genome-wide association studies have been performed in European subjects and have found 23 new loci and 7 possible loci which may provide a framework for vitiligo’s genetic architecture and pathobiology.3 Many of these genes encode immune and apoptotic regulators, autoimmune diseases, and melanocyte regulators. Another study found that TYR, TYRP1, DCT, and LARP7 were all related biomarkers of vitiligo while the immune cells CD4 T cell, CD8 T cell, Tregs, NK cells, dendritic cells, and macrophages are related to vitiligo occurrence.4&nbsp;<h6>Autoimmunity&nbsp;</h6>Autoimmunity is closely related to genetics, with around 85% of the vitiligo susceptibility genes related to innate and adaptive immunity and apoptosis.1,2 In addition, vitiligo is often associated with other autoimmune disorders and other immune modulating drugs. Melanocytes use exosomes, miRNAs, melanocyte-specific antigens, and damage-associated molecular patterns to communicate stress to the innate immune system and dendritic cells to function as antigen-presenting cells. CD8+ T cells produce interferon-γ (IFN-γ), which after binding causes the recruitment of Janus kinase-1 to transcribe IFN-γ genes. Also, many patients with vitiligo have an impairment of T regulatory cells that help suppress the proliferation of activation of CD8+ autoreactive effectors. In addition to the CD8+ cells, a case study found that unstable vitiligo may be associated with autoimmune thyroiditis due to elevated thyroglobulin antibodies (TgAb) levels despite normal thyroid stimulating hormone and free thyroxine. Thyroid abnormalities and elevated TgAb may provide a useful and more widely available biomarker for vitiligo.5&nbsp;<h6>Oxidative stress&nbsp;</h6>After exposure to UV radiation and other chemicals, cutaneous melanocytes are more susceptible to excessive reactive oxygen species (ROS) production. These ROS are both endogenously and exogenously triggered through melanogenesis, the activation of the unfolded protein response, environmental factors, medications, and other internal disorders. During oxidative stress, ROS induces autophagy through the Nrf2 antioxidant pathway. However, excessive activation of Nrf2 antioxidant pathway actually inactivates autophagy.6 The Koebner phenomenon also implicates ROS because chronic friction increases inflammation and further increases the ROS. Oxidative stress also contributes to the loss of melanocyte dendrites.&nbsp;<h6>Neural hypothesis&nbsp;</h6>The neural or stress hypothesis asserts the neurochemical mediators secreted by cutaneous nerves are responsible for the cytotoxicity towards melanocytes.7 This hypothesis is supported by severe emotional stress or trauma, which may trigger or exacerbate vitiligo. A 2018 examination found some neural and endocrine markers that play a pivotal role in pathogenesis and/or consequences of vitiligo, including decreased free triiodothyronine and free thyroxine serum levels, an increase in cortisol serum levels, and a decrease in ACTH serum levels.8&nbsp;<h6>References</h6><ol><li>Diotallevi F, Gioacchini H, De Simoni E, et al. Vitiligo, from pathogenesis to therapeutic advances: state of the art. Int J Mol Sci. 2023;24(5):4910. doi:10.3390/ijms24054910&nbsp;</li><li>Marchioro HZ, Silva de Castro CC, Fava VM, Sakiyama PH, Dellatorre G, Miot HA. Update on the pathogenesis of vitiligo. An Bras Dermatol. 2022;97(4):478-490. doi:10.1016/j.abd.2021.09.008&nbsp;</li><li>Jin Y, Andersen G, Yorgov D, et al. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016;48(11):1418-1424. doi:10.1038/ng.3680&nbsp;</li><li>Zhang J, Yu R, Guo X, et al. Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. Bioengineered. 2021;12(1):2214-2227. doi:10.1080/21655979.2021.1933743&nbsp;</li><li>Moore AY, Cepica T, Maberry S. Amelioration of unstable vitiligo and normalization of thryroglobulin antibodies with oral tofacitinib. JAAD Case Rep. 2022;23:64-66. doi:10.1016/j.jdcr.2022.02.025&nbsp;</li><li>Xuan Y, Yang Y, Xiang L, Zhang C. The role of oxidative stress in the pathogenesis of vitiligo: a culprit for melanocyte death. Oxid Med Cell Longev. 2022;2022:8498472. doi:10.1155/2022/8498472&nbsp;</li><li>Mohammed GF, Gomaa AH, Al-Dhubaibi MS. Highlights in pathogenesis of vitiligo. World J Clin Cases WJCC. 2015;3(3):221-230. doi:10.12998/wjcc.v3.i3.221&nbsp;</li><li>Kotb El-Sayed MI, Abd El-Ghany AA, Mohamed RR. Neural and Endocrinal Pathobiochemistry of Vitiligo: Comparative Study for a Hypothesized Mechanism. Front Endocrinol. 2018;9:197. doi:10.3389/fendo.2018.00197</li></ol>

Analyzing vitiligo’s complex pathways and exploring the convergence theory

Update on Pathogenesis of Vitiligo

For clinicians, staying up to date on advancements and updates in vitiligo is crucial for providing the best care to patients. With recent research and new data on prevalence, pathogenesis, and treatment options, there is compelling information emerging to advance vitiligo research.&nbsp;<h6>Updates on prevalence&nbsp;</h6>New data collected on the prevalence of vitiligo reveal that between 0.76% and 1.11% of adults in the United States have vitiligo (diagnosed and undiagnosed). Approximately 40% of adults with vitiligo may be undiagnosed; among this population, there was a higher proportion who were non-White or of Hispanic, Latino, or Spanish origin and demonstrated unilateral presentation.1&nbsp;<h6>Insights on pathogenesis&nbsp;</h6>The pathogenesis of vitiligo is most clearly summarized in the convergence theory which combines the genetics, autoimmunity, oxidative stress, and neurological system dysfunction mechanisms whereby each decreases overall melanocyte survival.2, 3 In addition, environmental factors, psychological stress, comorbidities, and other common susceptibilities are also challenging to integrate into its pathogenesis. Recent articles explore and summarize the role of oxidative stress, HMGB1, chemokines,3, 4, 5 immunopathogenesis,5 and genetics6, 7 in vitiligo. Lipopolysaccharide may reduce melanocyte synthesis by regulating autophagy,8 and unstable vitiligo may be associated with autoimmune thyroiditis due to elevated thyroglobulin antibodies levels despite normal thyroid stimulating hormone and free thyroxine.9&nbsp;<h6>An overview of therapeutic options&nbsp;</h6>Narrow-band ultraviolet B (NB-UVB) phototherapy is currently the primary therapeutic choice for generalized vitiligo, and psoralen and ultraviolet A phototherapy are considered for spreading vitiligo.10&nbsp;The effectiveness of various surgical methods has also been studied. Data from a recent systematic review and meta-analysis found that the technique that resulted in the highest repigmentation degree of &gt;90% among the largest number of treated patients was thin skin grafting, followed by suction blister grafting, cultured epidermal cell suspension, noncultured epidermal cell suspension, punch grafting, and noncultured follicular cell suspension.11 The matching of the surgical method to the patient, type of vitiligo, and lesion location was deemed most important.12&nbsp;Various Janus kinase (JAK) inhibitors have shown potential in the management of vitiligo. Rapid skin pigmentation resulted from male patients with vitiligo consuming oral ruxolitinib, and patients treated with topical ruxolitinib demonstrated substantial repigmentation after 52 weeks of treatment. The safety and efficacy of tofacitinib and baricitinib and each inhibitor’s combination with phototherapy in vitiligo treatment are currently being investigated.13&nbsp;Topical corticosteroids may be most effective on recent and facial lesions and in combination with NB-UVB phototherapy. An immunomodulator such as topical tacrolimus increases the proliferation of melanocytes and does not come with the adverse effects associated with corticosteroids.14&nbsp;Finally, afamelanotide–a synthetic analog of the key melanogenesis molecule α-MSH– stimulates melanogenesis–promotes the transfer of eumelanin into melanosomes and acts on the altered inflammatory microenvironment of vitiligo lesions. Afamelanotide is administered as a subcutaneous, biodegradable, controlled-release implant. Combination therapy of afamelanotide and NB-UVB phototherapy has been shown to induce repigmentation with few, well-tolerated side effects.2&nbsp;To provide the best care for patients with vitiligo, it is important for clinicians to note these recent publications’ updates on vitiligo prevalence, pathogenesis, and treatments.<h6>References</h6><ol><li>Gandhi K, Ezzedine K, Anastassopoulos KP, et al. Prevalence of vitiligo among adults in the United States. JAMA Dermatol. 2022;158(1):43-50. doi:10.1001/jamadermatol.2021.4724&nbsp;</li><li>Diotallevi F, Gioacchini H, De Simoni E, et al. Vitiligo, from pathogenesis to therapeutic advances: state of the art. Int J Mol Sci. 2023;24(5):4910. 2023;24(5):4910. doi:10.3390/ijms24054910&nbsp;</li><li>Marchioro HZ, Silva de Castro CC, Fava VM, Sakiyama PH, Dellatorre G, Miot HA. Update on the pathogenesis of vitiligo. An Bras Dermatol. 2022;97(4):478-490. doi:10.1016/j.abd.2021.09.008&nbsp;</li><li>Wei G, Pan Y, Wang J, Xiong X, He Y, Xu J. Role of HMGB1 in vitiligo: current perceptions and future perspectives. Clin Cosmet Investig Dermatol. 2022;15:2177-2186. doi:10.2147/CCID.S381432&nbsp;</li><li>Hlača N, Žagar T, Kaštelan M, Brajac I, Prpić-Massari L. Current concepts of vitiligo immunopathogenesis. Biomedicines. 2022;10(7):1639. doi:10.3390/biomedicines10071639&nbsp;</li><li>Spritz RA, Santorico SA. The genetic basis of vitiligo. J Invest Dermatol. 2021;141(2):265-273. doi:10.1016/j.jid.2020.06.004&nbsp;</li><li>Jin Y, Andersen G, Yorgov D, et al. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016;48(11):1418-1424. doi:10.1038/ng.3680&nbsp;</li><li>Sun L, Sun J, Huo X, et al. Lipopolysaccharide reduces melanin synthesis in vitiligo melanocytes by regulating autophagy. Exp Dermatol. 2022;31(10):1579-1585. doi:10.1111/exd.14629&nbsp;</li><li>Moore AY, Cepica T, Maberry S. Amelioration of unstable vitiligo and normalization of thryroglobulin antibodies with oral tofacitinib. JAAD Case Rep. 2022;23:64-66. Published 2022 Mar 10. doi:10.1016/j.jdcr.2022.02.025&nbsp;</li><li>Nimkar P, Wanjari A. Vitiligo and the role of newer therapeutic modalities. Cureus. 2022;14(11):e31022. doi:10.7759/cureus.31022&nbsp;</li><li>Ju HJ, Bae JM, Lee RW, et al. Surgical interventions for patients with vitiligo: a systematic review and meta-analysis. JAMA Dermatol. 2021;157(3):307-316. doi:10.1001/jamadermatol.2020.5756&nbsp;</li><li>Frączek A, Kasprowicz-Furmańczyk M, Placek W, Owczarczyk-Saczonek A. Surgical treatment of vitiligo. Int J Environ Res Public Health. 2022;19(8):4812. doi:10.3390/ijerph19084812&nbsp;</li><li>Qi F, Liu F, Gao L. Janus kinase inhibitors in the treatment of vitiligo: a review. Front Immunol. 2021;12:790125. doi:10.3389/fimmu.2021.790125&nbsp;</li><li>Vinardell MP, Maddaleno AS, Mitjans M. Melanogenesis and hypopigmentation: the case of vitiligo. Indian J Dermatol. 2022;67(5):524-530. doi:10.4103/ijd.ijd_1067_21</li></ol>

Navigate the latest insights in vitiligo with a comprehensive update on prevalence, pathogenesis, and treatments.

Highlighting and Reviewing Recent Publications on Vitiligo

Vitiligo is a common, acquired, autoimmune disorder seen in clinic characterized by the progressive loss of melanocytes leading to depigmented macules and patches.1 Estimated prevalence rates range from 0.1 to 2% of the global population, and it has been shown to have significant impact on psychosocial function as well as quality-of-life metrics.2 Vitiligo can affect any skin surface and is generally classified into 2 subcategories: segmental (occurring in a dermatomal or quasi-dermatomal pattern) and nonsegmental (which may be generalized, universal, acrofacial, or mucosal). Phototherapy has emerged as a safe and effective treatment modality for patients with vitiligo due to its proven efficacy and favorable side effect profile. While several options exist, the best studied, most successful forms of phototherapy for vitiligo include narrowband UVB (NB-UVB) and excimer light/laser. This article provides a high-level overview of these modalities as well as an up-to-date reference of their efficacy, dosing, mechanism, adverse effect profile (Table).&nbsp;<h6>NARROW BAND UVB (NB-UVB) PHOTOTHERAPY&nbsp;</h6>NB-UVB phototherapy is characterized by targeted exposure to polychromatic light with a peak emission wavelength between 311 nm3 and 313 nm3. Numerous clinical studies have demonstrated the effectiveness of NB-UVB in repigmenting vitiligo lesions, with success rates ranging from 48% to 64%.3-5 Common side effects include pruritus, erythema, burning/blisters, xerosis, and darkening/thickening of normal skin.3 While the carcinogenic risk of patients with vitiligo receiving NB-UVB treatment remains incompletely defined, studies have identified no increased risk of skin cancer in patients receiving NB-UVB for psoriasis.3,6 Also, interestingly, despite the absence of melanin, the development of skin cancers in vitiligo lesions is rare.3 In 2017, the Vitiligo Working Group generated recommendations for NB-UVB use in patients with vitiligo that include optimal frequency of administration (3 times per week), initial dosing (200 mj/cm2), dose adjustments based on degree of erythema and missed doses, special site instructions, complication management, and pre- and post-treatment recommendations.4&nbsp;<h6>EXCIMER&nbsp;</h6>Excimer is a newer targeted form of phototherapy characterized by a wavelength of 308nm (UVB) that may be administered using a laser or lamp medium.3 Excimer laser emits a monochromatic wavelength at high irradiance with spot sizes ranging from 15 to 30 mm.5 Smaller spot sizes allow selective treatment of vitiligo lesions, reducing risk of perilesional hyperpigmentation. However, small spot size also makes this modality time-consuming and unsuitable for patients with vitiligo involving large body surface areas (&gt;15% TBSA).3 The monochromatic excimer lamp also emits light with a 308-nm wavelength and has been shown to have equivalent efficacy to laser with larger area effect, shorter treatment times, and lower cost.5 Several studies have compared the therapeutic efficacy of excimer and NB-UVB in vitiligo and have shown similar overall effectiveness, with excimer demonstrating a more rapid and greater degree of specific lesion repigmentation.7 Excimer has also been shown to excel in the treatment of segmental vitiligo when compared with NB-UVB, with studies showing that only 7.7% of patients with segmental vitiligo respond with NB-UVB compared with 42.4% of patients treated with excimer.8 Dosing regimens are relatively similar to NB-UVB.9&nbsp;<h6>COMBINATION THERAPY&nbsp;</h6>Notably, both NB-UVB and excimer phototherapy have improved repigmentation when combined with other modalities–particularly corticosteroids (oral and topical), topical calcineurin inhibitors, oral antioxidants, dermabrasion with Erbium laser, fractional CO2, and subcutaneous afamelanotide.3&nbsp;In all, as the therapeutic armamentarium for vitiligo expands, phototherapy continues to serve as a safe and effective cornerstone for its management that dermatologists should understand and be able to implement.<h6>Comparison of Efficacy, Side Effects, and Ideal Clinical Scenarios for the Most Common Forms of Phototherapy for Vitiligo</h6><img src="https://d18uhdhjoz8by6.cloudfront.net/Table_5785a0d0e1.jpg" alt="Table.jpg" srcset="https://d18uhdhjoz8by6.cloudfront.net/thumbnail_Table_5785a0d0e1.jpg 231w,https://d18uhdhjoz8by6.cloudfront.net/small_Table_5785a0d0e1.jpg 500w,https://d18uhdhjoz8by6.cloudfront.net/medium_Table_5785a0d0e1.jpg 750w," sizes="100vw" width="750px">&nbsp;Of note, while other phototherapy modalities have shown a degree of efficacy for vitiligo, including visible light and low-level light therapy (for segmental vitiligo in children with periorbital / perioral lesions) as well as broad-band UVB and broadband UVA, the supportive evidence for these modalities is limited, and safety data largely supports adjunct use in lieu of NB-UVB and excimer.<h6>REFERENCES&nbsp;</h6><ol><li>Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;386(9988):74-84. doi:10.1016/S0140-6736(14)60763-7&nbsp;</li><li>Silverberg JI, Silverberg NB. Quality of life impairment in children and adolescents with vitiligo. Pediatr Dermatol. 2014;31(3):309-318. doi:10.1111/pde.12226&nbsp;</li><li>Esmat S, Hegazy RA, Shalaby S, Hu SC, Lan CE. Phototherapy and combination therapies for vitiligo. Dermatol Clin. 2017;35(2):171-192. doi:10.1016/j.det.2016.11.008&nbsp;</li><li>Mohammad TF, Al-Jamal M, Hamzavi IH, et al. The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo. J Am Acad Dermatol. 2017;76(5):879-888. doi:10.1016/j.jaad.2016.12.041&nbsp;</li><li>Leone G, Iacovelli P, Paro Vidolin A, Picardo M. Monochromatic excimer light 308 nm in the treatment of vitiligo: a pilot study. J Eur Acad Dermatol Venereol. 2003;17(5):531-537. doi:10.1046/j.1468-3083.2003.00818.x&nbsp;</li><li>Weischer M, Blum A, Eberhard F, Röcken M, Berneburg M. No evidence for increased skin cancer risk in psoriasis patients treated with broadband or narrowband UVB phototherapy: a first retrospective study. Acta Derm Venereol. 2004;84(5):370-374. doi:10.1080/00015550410026948&nbsp;</li><li>Lopes C, Trevisani VF, Melnik T. Efficacy and Safety of 308-nm monochromatic excimer lamp versus other phototherapy devices for vitiligo: a systematic review with meta-analysis. Am J Clin Dermatol. 2016;17(1):23-32. doi:10.1007/s40257-015-0164-2&nbsp;</li><li>Do JE, Shin JY, Kim DY, Hann SK, Oh SH. The effect of 308nm excimer laser on segmental vitiligo: a retrospective study of 80 patients with segmental vitiligo. Photodermatol Photoimmunol Photomed. 2011;27(3):147-151. doi:10.1111/j.1600-0781.2011.00587.x&nbsp;</li><li>Zhang XY, He YL, Dong J, Xu JZ, Wang J. Clinical efficacy of a 308 nm excimer laser in the treatment of vitiligo. Photodermatol Photoimmunol Photomed. 2010;26(3):138-142. doi:10.1111/j.1600-0781.2010.00509.x&nbsp;</li><li>Bae JM, Jung HM, Hong BY, et al. Phototherapy for vitiligo: a systematic review and meta-analysis. JAMA Dermatol. 2017;153(7):666-674. doi:10.1001/jamadermatol.2017.0002&nbsp;</li><li>Casacci M, Thomas P, Pacifico A, Bonnevalle A, Paro Vidolin A, Leone G. Comparison between 308-nm monochromatic excimer light and narrowband UVB phototherapy (311-313 nm) in the treatment of vitiligo--a multicentre controlled study. J Eur Acad Dermatol Venereol. 2007;21(7):956-963. doi:10.1111/j.1468-3083.2007.02151.x&nbsp;</li><li>Sethi S, Silverberg N. Short and long-term outcomes of 308-nm laser for pediatric vitiligo. J Drugs Dermatol. 2022;21(7):773-775. doi:10.36849/JDD.6895&nbsp;</li><li>Sahin S, Hindioğlu U, Karaduman A. PUVA treatment of vitiligo: a retrospective study of Turkish patients. Int J Dermatol. 1999;38(7):542-545. doi:10.1046/j.1365-4362.1999.00654.x&nbsp;</li><li>PE, Minus HR, Chakrabarti SG, et al. Determination of optimal topical photochemotherapy for vitiligo. J Am Acad Dermatol. 1982;7(6):771-778. doi:10.1016/s0190-9622(82)70159-8</li></ol>

Phototherapy for the Treatment of Vitiligo – What Every Dermatologist Should Know

Illuminating the Path to Skin Repigmentation

MONDAY, July 24, 2023 (HealthDay News) -- Vitiligo diagnosis is more common in older adults and in Hispanic/Latino and Asian American patients, according to a study published online July 19 in JAMA Dermatology.Nicole Mastacouris, from the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in New Hyde Park, New York, and colleagues estimated the incidence and prevalence of diagnosed vitiligo across age, sex, and racial and ethnic subgroups in a cohort study and cross-sectional study including electronic health records for children, adolescents, and adults across four U.S. census regions.The incidence analysis included 2,980,778 patients with vitiligo, and the prevalence analysis included 1,057,534 patients. The researchers found that the overall incidence rate of diagnosed vitiligo was 22.6 per 100,000 person-years (PY) after adjustment for age and sex, and prevalence was 0.16 percent. Patients aged 60 to 69 years had the highest sex-adjusted overall incidence rate (22.6 per 100,000 PY), and prevalence was highest among those aged 70 years or older (0.21 percent). Asian American, Hispanic/Latino, those reporting other or multiple races, Black, and White patients had age-adjusted incidence rates of 41.2, 37.3, 31.1, 29.6, and 18.7 per 100,000 PY, respectively. Age-adjusted prevalence was highest among Hispanic/Latino patients followed by Asian American, those reporting other or multiple races, Black, and White patients (0.29, 0.27, 0.24, 0.22, and 0.13 percent, respectively)."These observations may support improving awareness of vitiligo disease burden in medical and public sectors, informing research agendas, improving enrollment of racial and ethnic minority populations in trials, and developing health policies," the authors write.One author disclosed ties to the pharmaceutical industry and is co-copyright holder of the HS-IGA and HiSQOL instruments.

Vitiligo most commonly diagnosed in older adults and in Hispanic/Latino and Asian American patients

Incidence Rate of Diagnosed Vitiligo 22.6 per 100,000 Person-Years

Vitiligo is a skin disease characterized by loss of melanocytes resulting in depigmentation of skin, hair, or mucous membranes. Several theories exist to discern the pathogenesis of melanocyte loss, or loss of function.1 The strong association of vitiligo with other comorbid autoimmune conditions suggests that vitiligo should be categorized as an autoimmune disease. The vast array of autoimmune conditions associated with vitiligo, together with other comorbid conditions, are highlighted below.&nbsp;<h6>Autoimmune diseases&nbsp;</h6>Autoimmune diseases are closely correlated with vitiligo. In the United States, an estimated 10% to 15% of patients with vitiligo have one or more comorbid autoimmune disorders as opposed to 3% in the general population.2,3 Thyroid disease is among the most commonly associated autoimmune diseases, however, vitiligo is associated with a multitude of other autoimmune diseases as listed below.4,5 It is important to note that associations with comorbid diseases vary widely based on the study population and geographical locations of patient populations.&nbsp;Autoimmune comorbidities with a higher prevalence among patients with vitiligo4,5:&nbsp;<ul style="list-style-type:disc;"><li>Alopecia areata&nbsp;</li><li>Diabetes mellitus Type 1&nbsp;</li><li>Discoid lupus erythematosus&nbsp;</li><li>Guillain-Barre syndrome • Inflammatory bowel disease&nbsp;</li><li>Linear morphea&nbsp;</li><li>Myasthenia gravis&nbsp;</li><li>Pernicious anemia</li><li>Rheumatoid arthritis&nbsp;</li><li>Sjögren syndrome&nbsp;</li><li>Systemic lupus erythematosus&nbsp;</li><li>Systemic sclerosis&nbsp;</li><li>Thyroid disease&nbsp;</li></ul><h6>Thyroid disease&nbsp;</h6>Of the long list of autoimmune conditions associated with vitiligo, thyroid disease is one of the most well-studied. Patients with vitiligo have shown a higher prevalence of autoimmune thyroiditis, hypothyroidism, hyperthyroidism, Graves’ disease, Hashimoto thyroiditis, and thyroid cancer.5 The prevalence of thyroid disease in patients with vitiligo varies widely, with estimates ranging from 1.61% to 37% compared to 1% of the general population.4&nbsp;<h6>Psychiatric comorbidities&nbsp;</h6>Patients with vitiligo also have a higher prevalence of some psychiatric diseases, including body dysmorphic disorder, adjustment disorders, impulse control disorders, developmental disorders, risk of suicide or self-inflicted injury, attention deficit hyperactivity disorder, disruptive behavioral disorders, and obsessive-compulsive disorder.5 Interestingly, some studies have shown patients with vitiligo may have lower odds of developing an anxiety disorder, depression and mood disorders, schizophrenia, and substance abuse disorders.5&nbsp;<h6>Other comorbidities&nbsp;</h6>Melanocytes are present in the eye (uveal tract and retinal pigment epithelium) and ear (membranous labyrinth of the inner ear),4 and ocular abnormalities including hypopigmented spots of the iris and retinal pigment epithelium have been identified. Patients with vitiligo may have decreased visual acuity, increased risk of dry eye syndrome, and normal tension glaucoma. Sensorineural hearing loss is found in patients with vitiligo in higher proportion than in the general population.4&nbsp;Vitiligo is linked to a higher proportion of chronic skin diseases such as atopic dermatitis, psoriasis, lichen planus, and chronic urticaria in various studies.4,5 Patients with vitiligo have also been found to have higher prevalence of asthma, allergic rhinitis, and metabolic diseases such as metabolic syndrome and diabetes mellitus.5&nbsp;<h6>Conclusion&nbsp;</h6>Vitiligo is a disease that results in skin depigmentation. However, the comorbid conditions associated with vitiligo go beyond the skin as the disease is associated with several comorbid conditions that providers should be aware of. Patients with vitiligo should be appropriately assessed for comorbid autoimmune diseases, ocular, and audiology deficits when indicated. Providers should also be cognizant of the psychosocial impact that vitiligo may have on patients.&nbsp;Vitiligo is a disease that results in skin depigmentation, but the comorbid conditions associated with it go beyond just the skin. Patients with vitiligo should be appropriately assessed for autoimmune diseases, ocular, and audiology deficits when indicated. Providers should also be cognizant of the psychosocial impact that vitiligo may have on patients.&nbsp;With many comorbidities associated with this disease, it’s vital that clinicians explore these conditions to ensure comprehensive care for their patients with vitiligo.&nbsp;<h6>References:&nbsp;</h6><ol><li>.Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin. 2017;35(2):257-265. doi:10.1016/j.det.2016.11.014&nbsp;</li><li>Gill L, Zarbo A, Isedeh P, Jacobsen G, Lim HW, Hamzavi I. Comorbid autoimmune diseases in patients with vitiligo: a cross-sectional study. J Am Acad Dermatol. 2016;74(2):295-302. doi:10.1016/j.jaad.2015.08.063&nbsp;</li><li>Cooper GS, Stroehla BC. The epidemiology of autoimmune diseases. Autoimmun Rev. 2003;2(3):119-125. doi:10.1016/s1568-9972(03)00006-5&nbsp;</li><li>Dahir AM, Thomsen SF. Comorbidities in vitiligo: comprehensive review. Int J Dermatol. 2018;57(10):1157-1164. doi:10.1111/ijd.14055&nbsp;</li><li>Lee JH, Ju HJ, Seo JM, et al. Comorbidities in patients with vitiligo: a systematic review and meta-analysis. J Invest Dermatol. 2023;143(5):777-789.e6. doi:10.1016/j.jid.2022.10.021</li></ol>

Comorbidities associated with vitiligo go beyond just the skin, making it vital that clinicians consider these associated conditions to ensure comprehensive care for their patients

Exploring the Comorbidities Associated with Vitiligo 

While no definitive cure exists for vitiligo, treatments are available. Treatments for stabilizing rapidly progressive vitiligo include low-dose oral glucocorticoids and phototherapy. Therapeutic alternatives for managing stable, segmental vitiligo include topical therapies like topical corticosteroids and calcineurin inhibitors, targeted phototherapy, and surgical therapy such as tissue and cellular grafts.1 Recently, many promising therapeutics have emerged, particularly small-molecule inhibitors that target intracellular signaling molecules and biologics that target cytokines.2<h6>JAK inhibitors for vitiligo management</h6>Two of the most prominent treatments target Janus-activated kinase (JAK) signaling.3 Tofacitinib, an FDA-cleared JAK1/3 inhibitor, is safest in its 2% topical form and has demonstrated a mean improvement of 70% in facial vitiligo area scoring index (VASI) when implemented alongside narrow-band ultraviolet B (NB-UVB) therapy.4Ruxolitinib, a JAK1/2 inhibitor, became the first FDA-approved at-home treatment for nonsegmental vitiligo after its 1.5% cream demonstrated safety and effectiveness through 2 clinical trials—after 24 weeks, 30% of patients showcased 75% improvement in facial VASI with the main side effect being application-site acne, which disappeared after discontinuation of treatment.5<h6>Stimulation of Wnt/β-catenin signaling as adjuvant therapy</h6>The stimulation of Wnt/β-catenin signaling—which impacts the proliferation, migration, and differentiation of melanocytes—is being considered as an adjuvant therapy for vitiligo treatment.2 Both microinjury6 and some phenanthridine-derived Wnt-specific agonists binding with the Axin protein7 have been shown to activate the Wnt/β-catenin signaling pathway and induce vitiligo repigmentation.<h6>Targets for vitiligo therapy</h6>Since studies suggest that microRNAs (miRNAs) affect gene expression in melanocytes and are associated with genetic polymorphism, immune response, oxidative stress, and melanocyte functions,8 miRNAs are targets for vitiligo therapy. Anti-miRNAs, locked-nucleic acids, or antagomiRs have the potential to neutralize the overactivation of miRNA. miRNA replacements that involve the reintroduction of a gene-suppressor miRNA mimic or adeno-associated virus-mediated miRNA gain-of-function can regulate gene expression.9Regulatory T cells (Tregs), which can suppress self-reactive T cell activation and expansion, are another target because a clear lack of Tregs was observed in vitiligo skin.10 Increasing the number of Tregs through infusing purified populations of Tregs delays depigmentation in mice.11 In addition, 0.1% topical rapamycin increases the abundance of Tregs and is currently being investigated in a phase 2 clinical trial.12Monoclonal antibodies that target cytokines (IFN-γ, CXCL10, CXCR3, HSP70i, IL-15, IL-17/23, TNF) are now part of vitiligo treatment.2 Inhibiting IFN-γ especially—the cytokine that impedes melanogenesis, induces melanocyte apoptosis, and recruits T cells to the skin—has been effective. Mice with vitiligo treated with an IFN-γ-neutralizing antibody (XMG-6) at a dose of 100 to 500 μg twice a week demonstrated significant improvements in depigmentation.13 Furthermore, 4 patients exhibited repigmentation of the treated area and boundary retreat after receiving intradermal perilesional XMG-6 injections.14<h6>Looking ahead</h6>With numerous clinical studies underway testing new JAK inhibitors and cytokine-targeted therapies such as IL-15 blockers, there is much to anticipate with emerging treatments to manage vitiligo.<h6>References</h6><ol><li>Böhm M, Schunter JA, Fritz K, et al. S1 Guideline: Diagnosis and therapy of vitiligo. J Dtsch Dermatol Ges. 2022;20(3):365-378. doi:10.1111/ddg.14713</li><li>Feng Y, Lu Y. Advances in vitiligo: update on therapeutic targets. Front Immunol. 2022;13:986918. doi:10.3389/fimmu.2022.986918</li><li>Birlea SA, Costin GE, Roop DR, Norris DA. Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization. Med Res Rev. 2017;37(4):907-935. doi:10.1002/med.21426</li><li>Mobasher P, Guerra R, Li SJ, Frangos J, Ganesan AK, Huang V. Open-label pilot study of tofacitinib 2% for the treatment of refractory vitiligo. Br J Dermatol. 2020;182(4):1047-1049. doi:10.1111/bjd.18606</li><li>Rosmarin D, Passeron T, Pandya AG, et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo. N Engl J Med. 2022;387(16):1445-1455. doi:10.1056/NEJMoa2118828</li><li>Han X, Chang L, Qiu Z, et al. Micro-injury induces hair regeneration and vitiligo repigmentation through Wnt/β-catenin pathway. Stem Cells Dev. 2022;31(5-6):111-118. doi:10.1089/scd.2021.0276</li><li>Yang BJ, Fan SR, Zhang XF, et al. Design, synthesis and structure-activity relationship optimization of phenanthridine derivatives as new anti-vitiligo compounds. Bioorg Chem. 2022;119:105582. doi:10.1016/j.bioorg.2021.105582</li><li>Li L. The role of microRNAs in vitiligo: regulators and therapeutic targets. Ann Dermatol. 2020;32(6):441-451. doi:10.5021/ad.2020.32.6.441</li><li>Kwekkeboom RF, Lei Z, Doevendans PA, Musters RJ, Sluijter JP. Targeted delivery of miRNA therapeutics for cardiovascular diseases: opportunities and challenges. Clin Sci (Lond). 2014;127(6):351-365. doi:10.1042/CS20140005</li><li>Klarquist J, Denman CJ, Hernandez C, et al. Reduced skin homing by functional Treg in vitiligo [published correction appears in Pigment Cell Melanoma Res. 2010 Jun;23(3):477. Wainwright, Derek J [corrected to Wainwright, Derek A]]. Pigment Cell Melanoma Res. 2010;23(2):276-286. doi:10.1111/j.1755-148X.2010.00688.x</li><li>Mukhatayev Z, Dellacecca ER, Cosgrove C, et al. Antigen Specificity Enhances Disease Control by Tregs in Vitiligo. Front Immunol. 2020;11:581433. doi:10.3389/fimmu.2020.581433</li><li>Daily topical rapamycin for vitiligo. ClinicalTrials.gov identifier: NCT05342519. clinicaltrials.gov/ct2/show/NCT05342519. Updated August 4, 2022. Accessed June 21, 2023.</li><li>Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin. J Invest Dermatol. 2012;132(7):1869-1876. doi:10.1038/jid.2011.463</li><li>Skurkovich S, Skurkovich B, Kelly J. Anticytokine therapy, particularly anti-IFN-gamma, in Th1-mediated autoimmune diseases. Expert Rev Clin Immunol. 2005;1(1):11-25. doi:10.1586/1744666X.1.1.11</li></ol>

An overview of new and emerging treatments and research in vitiligo

Advancements in Treating Vitiligo

<h6>Use of camouflage in vitiligo: a cross-sectional survey&nbsp;</h6>Published in Journal of Cosmetic Dermatology | June 23, 2023&nbsp;In a cross-sectional survey, the authors examined the statistics of camouflage use among patients with vitiligo. Results showed that younger patients, female patients, and patients with skin of color were most likely to use camouflage.&nbsp;Overall, 45.6% of participants reported using some method of camouflage. One-fourth of nonusers or irregular users cited limited knowledge of products as a barrier to use, and only 21.6% of those under dermatologic care reported that their dermatologist discussed camouflage with them. The authors suggest dermatologists may consider increasing patient education on camouflage, particularly for the demographic groups who are most likely to use it.&nbsp;<h6>The underestimated role of mitochondria in vitiligo: from oxidative stress to inflammation and cell death&nbsp;</h6>Published in Experimental Dermatology | June 20, 2023&nbsp;In this review article, the authors explore the association between mitochondrial dysfunction and its role in the pathogenesis of vitiligo. They discuss the critical role that nuclear factor erythroid 2-related factor 2 (Nrf2) plays in mitochondrial homeostasis, the possible correlation between downregulation of Nrf2 in vitiligo and mitochondria damage, and why both mitochondria and Nrf2 may be promising targets in vitiligo treatment.&nbsp;<h6>Vulvar lichen sclerosus and vitiligo: overlap and clinical features&nbsp;</h6>Published ahead of print in Journal of the American Academy of Dermatology | June 14, 2023&nbsp;In this research letter, the authors performed a retrospective case series and systematic review to examine co-occurring cases of vulvar lichen sclerosus (VLS) and vulvar vitiligo (VV). Based on their findings, the authors recommend evaluating patients with VV for key clinical features that may suggest concomitant VLS.&nbsp;<h6>Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility&nbsp;</h6>Published ahead of print in American Journal of Human Genetics | June 13, 2023&nbsp;In this study, the authors investigated whether predisposing class I major histocompatibility complex (MHC-I) alleles for vitiligo and psoriasis could protect against melanoma. The authors found that autoimmune-allele carriers exhibit a significantly later age of melanoma diagnosis in the Cancer Genome Atlas and a decreased risk of developing melanoma among individuals in the Million Veteran Program.

Everything you need to know this month to stay up to date on the latest research in vitiligo

Research Roundup: Vitiligo

Vitiligo is one of the most common conditions treated by dermatologists, and one that has a significant psychosocial impact on patients. The treatment of vitiligo can be challenging, and treatment results are often disappointing. However, there are several new treatments that offer hope to patients who suffer from this chronic, and often stigmatizing, condition.&nbsp;<h6>JAK inhibitor ruxolitinib approved as topical treatment&nbsp;</h6>In July 2022, the FDA approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients 12 and older. Topical ruxolitinib is the first FDA-approved treatment for repigmentation in patients with vitiligo.2 It is a JAK inhibitor that functions by inhibiting JAK1 and JAK2 protein kinases, leading to a decrease in proinflammatory cytokines and chemokines.3&nbsp;In two phase 3 randomized clinical trials, twice daily application of ruxolitinib cream for 24 weeks resulted in greater repigmentation of facial skin in patients with vitiligo compared to a vehicle cream. The most common side effects were application-site acne and pruritus.4 Unlike topical steroids, which have historically been one of the mainstays of vitiligo treatment, topical ruxolitinib does not cause striae or atrophy. Stinging or burning at the application site, an oft-reported side effect with topical calcineurin inhibitors, was infrequent with ruxolitinib cream.4&nbsp;While long-term safety data for topical JAK inhibitors is lacking, trial results found that the mean plasma concentrations of ruxolitinib were well below 281 nM, a proxy for evaluating JAK-related myelosuppression in bone marrow.4&nbsp;<h6>Clinical trials underway investigating more JAK inhibitors for vitiligo&nbsp;</h6>Clinical trials are ongoing to evaluate the efficacy and safety of other JAK inhibitors for vitiligo, including studies on oral JAK inhibitors, and several case reports have shown efficacy of oral tofacitinib and oral ruxolitinib in vitiligo.5 A recent phase 2B study of ritlecitinib, an oral JAK3/TEC inhibitor, found it to be well-tolerated and efficacious in the treatment of patients with active nonsegmental vitiligo over the course of 48 weeks.6&nbsp;Promising developments in alpha-melanocyte-stimulating hormone analogues Alpha-melanocyte-stimulating hormone analogues are another promising area of drug development in vitiligo. Afamelanotide is a synthetic analogue of alpha-melanocyte-stimulating hormone that stimulates melanogenesis. In a double-blinded, multicenter study, patients treated with NB-UVB plus afamelanotide achieved repigmentation rates higher than those seen with NB-UVB alone.7 Studies are currently underway to evaluate afamelanotide as monotherapy for vitiligo.8&nbsp;<h6>The future of vitiligo treatment&nbsp;</h6>While there is still no cure for vitiligo, there are a number of emerging new treatment options for patients. Dermatologists should be aware of the advances in treatment within the field so they can offer patients access to the full complement of available therapeutic options.&nbsp;<h6>References</h6><ol><li>Narayan VS, Uitentuis SE, Luiten RM, Bekkenk MW, Wolkerstorfer A. Patients' perspective on current treatments and demand for novel treatments in vitiligo. J Eur Acad Dermatol Venereol. 202;35(3):744-748. doi:10.1111/jdv.16927&nbsp;</li><li>Sheikh A, Rafique W, Owais R, Malik F, Ali E. FDA approves ruxolitinib (Opzelura) for vitiligo therapy: A breakthrough in the field of dermatology. Ann Med Surg (Lond). 2022;81:104499. doi:10.1016/j.amsu.2022.104499&nbsp;</li><li>Haq M, Adnan G. Ruxolitinib. In: StatPearls [Internet]. StatPearls Publishing; 2023. Updated Sept 27, 2022. Accessed June 29, 2023. <a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/books/NBK570600/">https://www.ncbi.nlm.nih.gov/books/NBK570600/</a>&nbsp;</li><li>Rosmarin D, Passeron T, Pandya AG, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387(16):1445-1455. doi:10.1056/NEJMoa2118828&nbsp;</li><li>Harris JE, Rashighi M, Nguyen N, et al. Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol. 2016;74(2):370-1. doi:10.1016/j.jaad.2015.09.073&nbsp;</li><li>Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88(2):395-403. doi:10.1016/j.jaad.2022.11.005&nbsp;</li><li>Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE; Vitiligo Working Group. New discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol. 2017;77(1):1-13. doi:10.1016/j.jaad.2016.10.048&nbsp;</li><li>Clinuvel. First vitiligo patient enrolled in afamelanotide monotherapy study. Clinuvel. Published October 20, 2022. Accessed June 29, 2023. https://www.clinuvel.com/first-vitiligo-patient-enrolled-in-afamelanotide-monotherapy-study-20221020/</li></ol>

Treatment of vitiligo can be challenging, but with promising new treatments emerging, the therapeutic options for patients are increasing 

What’s New and Hot in Vitiligo

For patients with active nonsegmental vitiligo (NSV), oral ritlecitinib is effective and well tolerated over 48 weeks, according to a study published online Nov. 9 in the
 
 Journal of the American Academy of Dermatology
 
 .




 Khaled Ezzedine, M.D., Ph.D., from the Hôpital Henri Mondor and Université Paris-Est Créteil, and colleagues examined the efficacy and safety of ritlecitinib in patients with active NSV in a phase 2b trial. A total of 364 patients were randomly assigned to once-daily oral ritlecitinib ± a four-week loading dose (200/50 mg, 100/50 mg), oral ritlecitinib without a loading dose (50 mg, 30 mg, or 10 mg), or placebo for 24 weeks in the dose-ranging period. In a 24-week extension period, 187 patients received ritlecitinib 200/50 mg daily.




 The researchers found that the percentage change from baseline in the Facial-Vitiligo Area Scoring Index differed significantly from placebo for the ritlecitinib 50 mg group with or without a loading dose (–21.2 and –18.5, respectively, versus 2.1) and the ritlecitinib 30 mg group (–14.6 versus 2.1). In the extension period, accelerated improvement was seen after treatment with ritlecitinib 200/50 mg. Across the 48-week treatment, there were no dose-dependent trends observed in treatment-emergent or serious adverse events.




 "This phase 2 trial suggests ritlecitinib is an effective and well tolerated treatment for patients with active NSV," the authors write. "As indicated by data during the extension period, longer treatment duration may be required for optimal repigmentation."




 Several authors disclosed financial ties to pharmaceutical companies, including Pfizer, which manufactures ritlecitinib and funded the study.




 <a class="rm-stats-tracked" href="https://www.jaad.org/article/S0190-9622(22)02989-9/fulltext" target="_blank">
 Abstract/Full Text (subscription or payment may be required)
 </a>

Significant differences seen from placebo in percentage change from baseline in the Facial-Vitiligo Area Scoring Index for 50, 30 mg ritlecitinib

Is Ritlecitinib Effective, Tolerated for Active Nonsegmental Vitiligo?

The U.S. Food and Drug Administration has approved Opzelura (ruxolitinib) as the first topical treatment for vitiligo.




 The 1.5 percent cream is approved for continuous topical use twice daily to affected areas of up to 10 percent of body surface area in patients aged 12 years and older. More than 24 weeks of treatment may be needed for satisfactory patient response.




 The approval was based on results from the TRuE-V clinical trials, in which more than 600 patients were randomly assigned to Opzelura or placebo. At week 24, 30 percent of patients treated with Opzelura achieved ≥75 percent improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75) versus 8 to 13 percent of patients treated with placebo. Approximately half of Opzelura-treated patients achieved F-VASI75 at week 52.




 "There have been no FDA-approved therapies available to date and the approval of Opzelura therefore marks a significant milestone," David Rosmarin, M.D., from Tufts Medical Center in Boston, said in a company press release. "I welcome a medical treatment that helps my patients with nonsegmental vitiligo who are interested in potentially reversing the depigmentation caused by their disease."




 Approval was granted to Incyte.




 <a class="rm-stats-tracked" href="https://investor.incyte.com/news-releases/news-release-details/incyte-announces-us-fda-approval-opzeluratm-ruxolitinib-cream-0" target="_blank">
 More Information
 </a>




 <a href="https://consumer.healthday.com/u/physiciansbriefingstaff">
 <img alt="HealthDay" src="https://assets.rbl.ms/23636171/origin.png" style="max-width: 150px;"/>
 </a>

Opzelura can be used twice daily in patients ages 12 years and older

FDA Approves First Topical Treatment for Vitiligo

For patients with nonsegmental vitiligo with depigmentation covering ≤10 percent of total body surface area, ruxolitinib cream yields clinically meaningful facial and total body repigmentation, according to a study presented at the annual meeting of the American Academy of Dermatology, held from March 25 to 29 in Boston.




 David Rosmarin, M.D., from Tufts Medical Center in Boston, and colleagues randomly assigned patients aged 12 years and older diagnosed with nonsegmental vitiligo with depigmentation covering ≤10 percent total body surface area to receive 1.5 percent ruxolitinib cream or vehicle for 24 weeks in a 2:1 ratio, after which all patients could receive ruxolitinib cream for 52 weeks. Data were included from two phase 3 studies with 221 and 229 patients receiving ruxolitinib cream and 109 and 115 patients receiving vehicle.




 The researchers found that for the primary end point of ≥75 percent improvement in facial Vitiligo Area Scoring Index (VASI), ruxolitinib cream was statistically superior to vehicle at week 24 (29.8/30.9 versus 7.4/11.4 percent, respectively); ruxolitinib cream was also statistically superior for all key secondary end points, including ≥50 percent improvement in total VASI. Among patients who applied ruxolitinib from day 1, increases were seen in responses through week 52. Treatment-related adverse events occurred in 18.6/15.4 percent of those who applied ruxolitinib cream through 52 weeks, most frequently application site acne (5.9/5.3 percent) and application site pruritus (5.0/4.4 percent).




 "Ruxolitinib cream demonstrated clinically meaningful facial and total body repigmentation through 52 weeks in phase 3 studies and was generally well tolerated," the authors write.




 The studies were funded by Incyte Corporation, the manufacturer of ruxolitinib.




 <a class="rm-stats-tracked" href="https://www.aad.org/member/meetings-education/am22" target="_blank">
 More Information
 </a>

Clinically meaningful improvement reported in facial and total Vitiligo Area Scoring Index with ruxolitinib cream

AAD: Ruxolitinib Beneficial in Nonsegmental Vitiligo

The Facial Vitiligo Area Scoring Index (F-VASI), which uses the fingertip unit (FTU), is precise and reliable for assessing the extent of facial involvement in patients with vitiligo, according to a study published in the February issue of the
 
 Journal of the American Academy of Dermatology
 
 .




 Jung Min Bae, M.D., Ph.D., from The Catholic University of Korea in Suwona, and colleagues developed and validated a practical instrument for facial vitiligo. The ratio of a hand to an FTU was calculated for 98 healthy volunteers to define the FTU. The sum of all FTUs of each vitiligo lesion on the face was measured as the F-VASI. Six raters evaluated 11 patients with facial vitiligo twice two weeks apart in the validation study.




 One hand was measured at 32.1 ± 1.3 FTU, which was highly consistent across age groups, sexes, and races. The researchers found remarkably high accuracy for the F-VASI (concordance correlation coefficient, 0.946), and intrarater reliability was also high (intraclass correlation coefficient, 0.903; interrater reliability, 0.903).




 "The FTU is a practical and precise measurement unit for assessing the extent of facial involvement in patients with vitiligo (F-VASI)," the authors write. "It not only allows for more precise assessments of small focal lesions on the face or genital area but can also complement VASI measurement of widespread vitiligo through proper conversion."




 Several authors disclosed financial ties to the pharmaceutical and health care industries.




 <a class="rm-stats-tracked" href="https://www.jaad.org/article/S0190-9622(21)02082-X/fulltext" target="_blank">
 Abstract/Full Text (subscription or payment may be required)
 </a>

Facial Vitiligo Area Scoring Index, using the fingertip unit, has high accuracy and intrarater reliability

Facial Vitiligo Area Scoring Index Reliable for Facial Involvement

Who is the ideal patient for ruxolitinib for vitiligo?

How do you set expectations with patients before starting them on ruxolitinib for vitiligo?

How quickly can patients expect to see results with ruxolitinib for vitiligo?

What is the safety profile of ruxolitinib for vitiligo?

Can ruxolitinib for vitiligo be used with other JAK inhibitors?

What are the limitations of use for ruxolitinib for vitiligo?

What follow-up or monitoring do you recommend for patients on ruxolitinib for vitiligo?

How does your treatment approach differ in treating segmental vs nonsegmental vitiligo?

What is the role of the JAK-STAT pathway in vitiligo?

How can dermatologists address challenges and disparities in access to vitiligo care?

Advancements in Vitiligo: 2024 and Beyond

Advancements in Vitiligo: 2024 and BeyondVitiligo has long been a challenging condition to manage effectively. However, recent years have seen significant strides in understanding and treating this condition. In this Topical Conversations segment, Seemal Desai, MD, FAAD, shares his excitement about the evolving landscape of vitiligo treatment.Innovations in management and treatment of vitiligoOver the past several years, there have been notable innovations in the management and treatment of vitiligo. One of the most significant milestones was the introduction of the first FDA-approved therapy for repigmenting vitiligo, topical ruxolitinib 1.5% cream. Topical ruxolitinib 1.5% cream is currently the only FDA-approved treatment for nonsegmental vitiligo repigmentation. &nbsp;In the TRuE-V1 and TRuE-V2 trials of ruxolitinib cream 1.5%, nearly 1 in 3 patients achieved at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) and 24 weeks. Also at 24 weeks, ~15% of patients achieved complete or nearly complete repigmentation in F-VASI (F-VASI90).Emerging research on oral therapeutics for vitiligoLooking ahead to 2024 and beyond, Dr Desai anticipates the emergence of new data on oral JAK inhibitors for vitiligo. While topical treatments have shown promise, oral JAK inhibitors present a new frontier in vitiligo treatment. Among these, oral upadacitinib has shown promising results in recent studies. Additionally, research is underway on oral povorcitinib and other oral therapeutics, offering potential benefits beyond repigmentation.UpadacitinibAt week 24 of a 52-week, Phase 2b multicenter, randomized, double-blind, placebo-controlled study evaluating upadacitinib in adults with nonsegmental vitiligo, upadacitinib met the primary endpoint of percent change from baseline in F-VASI with 11-mg and 22-mg doses versus placebo in adults with nonsegmental vitiligo.At week 52, the percent reduction from baseline in F-VASI was numerically greater than results at week 24 for all upadacitinib doses.The safety profile was consistent with the known safety profile for upadacitinib.PovorcitinibIn a Phase 2b randomized, double-blind, placebo-controlled, dose-ranging clinical trial evaluating the safety and efficacy of povorcitinib, an oral small-molecule JAK1 inhibitor, results showed that treatment for adult patients with extensive nonsegmental vitiligo was associated with substantial total body and facial repigmentation at Week 52.Povorcitinib was well tolerated at all doses and also shows evidence of potential durability of response following treatment discontinuation, with 32 patients who completed the follow-up period through Week 76 maintaining total body and facial repigmentation.Future prospectsThe landscape of vitiligo treatment is rapidly evolving, with exciting developments on the horizon for 2024 and beyond. From the introduction of FDA-approved topical therapies to the emergence of oral JAK inhibitors for vitiligo, dermatology is witnessing unprecedented progress in the management of this challenging condition.

What is the mechanism of action for ruxolitinib for vitiligo?

Why is there a boxed warning for ruxolitinib for vitiligo?

What are the most common adverse reactions seen with ruxolitinib for vitiligo?

What is the recommended dosing regimen for ruxolitinib for vitiligo?

Can ruxolitinib for vitiligo be used on sensitive skin areas?

What are some ways you set expectations with patients before starting them on ruxolitinib for vitiligo?

Are there ways to treat vitiligo surgically? 

What long-term management strategies do you recommend for patients with vitiligo?

How do you counsel patients with vitiligo on the dangers of unregulated skin lightening / bleaching creams?

What is the psychosocial impact of vitiligo? 

Microneedling for patients with vitiligo: a promising option for repigmentation 

In this episode of Topical Conversations, Naiem Issa, MD, PhD, explores the use of microneedling as a promising approach to facilitate repigmentation in patients with vitiligo.&nbsp;Looking beyond topical anti-inflammatory agents in challenging cases&nbsp;After months or years of treatment, vitiligo may reach a stable phase or burn out, rendering topical anti-inflammatory agents, such as ruxolitinib, tacrolimus, and pimecrolimus, and topical and oral corticosteroids, ineffective in promoting repigmentation. Dr Issa emphasizes the need to shift focus towards melanocyte or melasome regeneration in these cases.&nbsp;Identifying melanocyte reservoirs: three key locations&nbsp;In these challenging cases, Dr Issa emphasizes the need to allow for melanocyte or melanosome regeneration and repigmentation.&nbsp;Melanocyte stem cell niches and reservoirs are pivotal for repigmentation, utilizing chemotaxis to enter vitiliginous lesions to begin proliferating and dropping pigment through melanosome generation.&nbsp;Dr Issa highlights 3 primary locations where stem cell niches are found:&nbsp;<ul><li>The hair follicle bulge: in the bulge, stem cells can awaken through a number of inflammatory cytokines, called the cytokine milieu, to grow, divide, and mature into melanocytes and migrate into vitiliginous lesions&nbsp;</li><li>The outer edges of vitiliginous patches: with an active lesion, some melanocytes may persist at the rim&nbsp;</li><li>The dermal papillae: some melanocytes and melanocyte precursors may be present below the epidermis; this is typically found on acral sites such as the hands and feet, which are often more difficult to repigment&nbsp;</li></ul>The role of microneedling: repigmentation stimulation&nbsp;Microneedling, utilizing controlled wounds typically ranging from 1.5 to 2.5 millimeters in depth, serves 2 crucial purposes in vitiligo therapy:&nbsp;<ul><li>Enhanced medication delivery: By creating microchannels, microneedling facilitates the effective delivery of medications, including topical anti-inflammatories and agents promoting regeneration like bimatoprost&nbsp;</li><li>Proinflammatory milieu activation: The process triggers an increase proinflammatory milieu, involving cytokines such as platelet-derived growth factors and TNF beta. These signals jump-start the melanocyte and melanosome reservoirs, fostering an environment conducive to repigmentation&nbsp;</li></ul>Clinical insights: microneedling techniques&nbsp;Dr Issa shares his experience with microneedling using the skin pen, detailing a technique that uses it on the lesion itself and also extends use 1 cm beyond the vitiliginous lesion to maximize melanocyte recruitment and increase the chances of successful repigmentation.&nbsp;As a cost-effective alternative, Dr Issa highlights cases where manual microneedling, using an 18 or 20 gauge needle, has yielded impactful results at low cost.&nbsp;Microneedling as a viable step in vitiligo repigmentation&nbsp;Microneedling has emerged as a promising step in the therapeutic ladder for patients with vitiligo who have exhausted traditional treatments. By harnessing controlled wounds and activating a proinflammatory milieu, microneedling opens new avenues for repigmentation.

The Role of Oxidants and Antioxidants in Vitiligo 

Hello, everyone. This is Dr. Nai Misa. I'm a board certified dermatologist practicing with forefront dermatology over in Vienna, Virginia, which is right outside of Washington, DC. I am also adjunct assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery, as well as clinical instructor at the West Virginia University College of Osteopathic Medicine. And for today's series of vital Ligo, we were going to talk about oxidants and antioxidants and their purpose in the development and resolution of vitiligo. Why do we care about oxidants and antioxidants? Well, the thing is that, as you probably already know, Vitiligo starts with a sort of insult. Why does an insult matter? The insult comes in many forms. Could be from sun damage, could be from major stress, could be for some traumatic incident, it could be from medications, it could be from other autoimmune problems, if you will, that causes an inflammatory destruction. And this kind of stress manifests in a reduction in the immune privilege of the melanocytes in the skin. So, as you probably know, is that melanocytes are typically immune privileged, meaning that the immune system does not recognize the antigens on the melanocytes, hence they do not go and attack them. This is very similar to hair follicle immune privilege, which becomes decomposed in the alopecia areata. So it's a very similar kind of mechanism. So distress causes reduction in the immune privilege of the melanocytes. And then you have your immune system recognizing it. Then you have the production of CD, eight positive t cells that come and attack those causing destruction of the melanocytes and causing vitiligo. And so with oxidants, what happens is that during this destructive stress, you have an increase in oxidants, and these go and cause the formation of reactive oxygen species that affect the cell membrane of the melanocytes, can also affect the organelles within the cell and really just cause an overall oxidative type of destruction. And as part of this destruction, it causes apoptosis and causes the increased expression of antigens by the dying melanocyte that the immune system recognizes. So as a compensatory response, you have antioxidants in general, such as catalase or suproxide dismutase, that try to act. But if that machinery is kind of messed up, if you will, then you have a reduction in the utility of those antioxidants. So there was a paper that was recently described that looked at catalase specifically which is an antioxidant enzyme that tries to mop up these oxidants. What they found is that in vitilignous lesions compared to normal lesions, that there was a reduction in the catalase expression in the serum of these patients, and more so in unstable vitiligo, or very active vitiligo. There was even less catalase than there was in stable vitiligo. So really there's an effect on reducing the amount of antioxidants in the system to allow for compensation. However, there was also superoxide dismutase, which many of you know as probably the antiaging protein. There was a paradoxical increase in the superoxide dismutase in those patients, which could be a compensatory methodology to try to make up for the lack of catalase and for the increase in the oxidative molecules. And so there is this yin and yang, if you will, of oxidation and antioxidants in order to try to prevent the destruction of melanocytes and hence the antigen presentation. And so there's a lot of studies looking into use of antioxidants, such as, like anacetylcysteine, looking at other types of supplements to kind of mop those things up, those oxidants up, and try to prevent not only the formation of vitiligo, but the progression and the data on that, is still premature. And we are learning a lot about this. But what we do know currently, even though we can't make any real recommendations because there's no randomized clinical trials and things like that, but the progression of oxidants leads to destruction, leads to the development of vitiligo, and possibly that we could use antioxidants to prevent this to more to be determined. Thank you. Thank.

In this installment of Topical Conversations, Naiem Issa, MD, PhD, FAAD, discusses oxidants and antioxidants and their role in the development and resolution of vitiligo.&nbsp;<h6>Why do oxidants and antioxidants matter in vitiligo?&nbsp;</h6>Vitiligo starts with an insult that can come in many forms, including sun damage, major stress, traumatic incidents, medications, and other autoimmune disorders that cause inflammatory destruction. This kind of stress manifests in a reduction in the immune privilege of the melanocytes in the skin.&nbsp;Melanocytes are typically immune privileged, meaning that the immune system does not recognize the antigens on the melanocytes and do not attack them.&nbsp;The stress initiates a reduction in the immune privilege of the melanocytes, which triggers production of CD8+ T cells that cause destruction of the melanocytes, leading to vitiligo. This mechanism is similar to that seen in alopecia areata, in which hair follicle immune privilege becomes decomposed.&nbsp;During this destructive stress, there is an increase in oxidants, which causes the formation of reactive oxygen species that affect the cell membrane of melanocytes and the organelles of the cell and cause overall oxidative destruction. This destruction, in turn, causes apoptosis and increased expression of antigens by the dying melanocyte that the immune system recognizes.&nbsp;As a compensatory response, antioxidants such as catalase or superoxide dismutase try to act, but with malfunctioning machinery, there is a reduction in the utility of those antioxidants.&nbsp;<h6>Catalase expression in vitiligo&nbsp;</h6>A paper by Kassab et al published in the Journal of Clinical Medicine looked specifically at the antioxidant enzyme catalase. The study found that in vitiliginous lesions, when compared to normal lesions, there was a reduction in the catalase expression in the serum of these patients and more so in unstable vitiligo, which showed even less catalase than in stable vitiligo. This demonstrates there is an effect on reducing the amount of antioxidants in the system to allow for compensation.&nbsp;However, the study also showed a paradoxical increase in those patients in superoxide dismutase, also known as the anti-aging protein. This could be a compensatory methodology to make up for the lack of catalase and for the increase in the oxidative molecules, representing the interplay present between oxidants and antioxidants to try to prevent the destruction of the melanocyte, thus the antigen presentation.&nbsp;<h6>The future of antioxidants in vitiligo research&nbsp;</h6>While the data in this area is still premature, there are studies currently looking into the use of antioxidants like n-acetylcystein and other types of supplements to mop up oxidants and prevent the formation and progression of vitiligo.&nbsp;Current knowledge does support that the progression of oxidants leads to the development of vitiligo, and future research is warranted to determine if the use of antioxidants can prevent it.

Patient-centered Care in Vitiligo: Navigating the Patient Conversation and Treatment Goals 

Hi everyone. Today I'm going to be discussing the article perspectives of vitiligo patients voices from the National Vitiligo conferences by O'Connell et al. Published in July of this year. This study looked at surveys of participants who attended the virtual US World Vitiligo Day in both 2000 and 22,021. When polled about acceptance of their disease, 40% reported that they were accepting of their vitiligo on most days. However, the majority of patients, 76% in 2020 and 92% in 2021, also stated that they would like a cure for their vitiligo. I think this is really important for us as clinicians to recognize. Even though a patient may be accepting and comfortable with having the condition and even showing their disease publicly, as 40% of patients reported they still would like to find a treatment that could decrease their disease burden. In fact, the survey also showed that 20% of patients were interested in trying treatments, even if they included moderate side effects. This highlights a necessity to have open discussions with our patients and consider individualized care, considering some patients may be open to attempting more aggressive therapy while others are not interested in treatment or only willing to attempt treatments without side effects. With many new treatments for Vitiligo in the pipeline, this is a really exciting time for our patients and a time for to start these conversations and provide some hope for a disease that has great impacts on quality of life but has long been understudied. Thanks.

In this installment of Topical Conversations, Tina Bhutani, MD, MAS, provides her thoughts on the article, “Perspectives of Vitiligo Patients: Voices from National Vitiligo Conferences,” published in SKIN: The Journal of Cutaneous Medicine by O’Connell et al.<h5>Study background&nbsp;</h5>This study looked at surveys taken by participants who attended the virtual US World Vitiligo Day in 2020 and 2021.&nbsp;<h5>Study results&nbsp;</h5>When polled about acceptance of their disease, 40% responded that they are accepting of their vitiligo on most days.&nbsp;However, most participants (76% in 2020 and 92% in 2021) reported that they would like a cure for vitiligo.&nbsp;<h5>Impact on patient conversations and treatment approach&nbsp;</h5>Dr Bhutani comments on the importance for clinicians to recognize that even though a patient may be accepting of their condition, comfortable with it, and show it publicly (as 40% reported doing), they would still like to find a treatment that would decrease their disease burden.&nbsp;The survey showed that 20% of patients were interested in trying treatments even if they included moderate side effects. Dr Bhutani remarks that this highlights the importance of having open discussions with patients and considering individualized care, since some patients may be open to attempting more aggressive therapy while others are not interested in treatments or only willing to attempt treatments without side effects.&nbsp;<h5>The future of vitiligo treatments&nbsp;</h5>With many new treatments for vitiligo in the pipeline, Dr Bhutani reflects that this is an exciting time for patients and a good time for providers to start these conversations with patients to provide hope for this condition that has a significant impact on quality of life but has long been understudied.&nbsp;Read the full article in <a target="_blank" rel="noopener noreferrer" href="https://jofskin.org/index.php/skin/article/view/1793">SKIN: The Journal of Cutaneous Medicine.&nbsp;</a><h5>Key points&nbsp;</h5><ul><li>“Perspectives of Vitiligo Patients: Voices from National Vitiligo Conferences” was published in SKIN: The Journal of Cutaneous Medicine&nbsp;</li><li>The study examined results of a poll that solicited information from participants regarding their quality of life with vitiligo&nbsp;</li><li>Results showed that a majority of patients would like a cure for vitiligo, even though 40% reported they are accepting of their condition on most days 20% of patients were interested in trying treatments even with moderate side effects&nbsp;</li><li>Clinicians should have open discussions with their patients with vitiligo and consider individualized care</li></ul>

Perspectives on Vitiligo: Insights From the Global VALIANT Study

Hello, this is Iltvat Hamzavi, and I'm here to speak to you about the results of a study that was published recently in the British Journal of Dermatology called the Valiant Study, which was exploring the natural treatment history of vitiligo. And it was focused on looking at what the patient experience is, as well as looking at what the healthcare provider experience is with this very disfiguring condition. As many of you know, Vitiligo is a depigmentary disorder where you lose color at key points in your life in very socially stigmatizing locations, such as the face and the hands. And the valiant study looks at a natural history and management of that condition from the perspective of both the patient and the healthcare practitioner. And valiant stands for Vitiligo and life impact among international communities. So it was a study that was based upon a survey instrument that was distributed across the world, in Africa, Asia, Latin America, North America and Europe. And they targeted around 3500 patients, and then they also targeted around 1200 clinicians. And the patients completed a 25 minutes survey. The primary care physicians or the dermatologists completed a 30 minutes survey. And then we compared the different groups across the different populations, and what we found among the 3541 patients who completed the full analysis or were included in the analysis was the average age was around 38. The preponderance of this population who responded the survey, there is a higher percentage of skin type, one to three, about 59%, and then the mean duration of the disease was about 12.7 years, and it took about 2.4 years to get diagnosed. Most of the time, lesions appeared on the hands in about 40% and on the face, about 38%. As far as the physicians who were involved, most of them had about eight years of experience treating vitiligo. 91% specialized in dermatology, 8% were primary care physicians or other fair care physicians, and about 62% identified themselves as specialists in vitiligo. 44% of patients reported being misdiagnosed, especially when it occurred in more than 5% of their body surface, especially when they had darker skin, especially when they had facial lesions. Misdiagnoses. These were sun damage, fungal infections, or atopic dermatitis. About 17% of primary care physicians and dermatologists, again, healthcare practitioners reported encountering patients who refer to them, who are also misdiagnosed, and there was geographic variation in these findings, but you can find these results throughout the world. In addition, 57% of patients reported being told by their healthcare practitioner that the vitiligo could not be treated and 44% gave up on finding any effective treatment. And the treatments that were reported to be used or suggested by the primary care physicians, the dermatologists, were topical medications, photoprotection, laser therapy, as well as other surgical options. So two thirds of patients reported receiving effective care. And effective care, as defined by the patient, was a reduction in cessation of spread and then repigmentation. But the core element that patients wanted to achieve was a reduction of the psychological burden. The effect of this disagreement condition is well beyond what happens in the skin, and the impact on the psychology of our patient community through stigmatization was well documented and many of the goals that we listed, about 24% wanted to achieve that reduction, 37% wanted to achieve repigmentation, and about 14% wanted to achieve a reduction in psychological burden. So what this idea shows is that there's a profound burden of vitiligo, with nearly half of patients reporting greater than 5% body surface. Average time to diagnosis is 2.4 years, which is a diagnosis that should be made very easily in many situations. And there's definitely differences on skin type and cultural issues that seem to affect the ability to make the diagnosis as well as the psychological burden the patients feel. There's also perception out there that you cannot treat vitiligo, which, as so many of the publications have shown, is not true. But it is widespread and widely held, both among the patient community as well as the healthcare practitioners. And the goals of both the patient and the healthcare practitioners are the same. They want to stop cessation, they want to repigment, and they want to reduce the psychological burden. This is the first global survey to explore the natural history and treatment of vitiligo from the perspectives of both patients and hcps at the same time. And again, with half of patients reporting greater than 5% body surface taking so many years to get diagnosed, there's a significant frustration that's building up that we hope can be addressed with future treatments. Thank you very much.

In this installment of Topical Conversations, Dr. Iltefat Hamzavi sits down to discuss the results of the VALIANT study, which explored the natural treatment history of vitiligo and was published in the British Journal of Dermatology in July 2023.<h5>Vitiligo and the VALIANT study</h5>The VALIANT (Vitiligo and Life Impact Among International Communities) aimed to investigate the natural treatment history of vitiligo, a pigmentary disorder causing color loss in areas of the skin that can be socially stigmatizing for patients. The study focused on understanding the patient and healthcare provider experiences related to this condition.The study was based on a survey distributed globally across Africa, Asia, Latin America, North America, and Europe. Around 3,500 patients participated in a 25-minute survey, and around 1,200 clinicians (primary care physicians and dermatologists) completed a 30-minute survey. Results were then compared across the different populations.<h5>Patient profiles</h5>Among the 3,541 patients who completed the full analysis, the average age was 38, and 59% of participants reported Fitzpatrick skin types I-III. The mean duration of the disease was 12.7 years, taking 2.4 years to receive a diagnosis. In survey participants, lesions appeared on the hands and face in about 40% and 38% of cases, respectively.<h5>Physician profiles</h5>Of the 1203 clinicians who completed the survey, 91% specialize in dermatology and 8% are primary care physicians or other care physicians. Around 60% identified themselves as vitiligo specialists. Clinician respondents had on average 8 years of experience treating vitiligo.&nbsp;<h5>Survey results: misdiagnoses</h5>Of the patients surveyed, 44% reported being misdiagnosed. Patients with vitiligo occurring on more than 5% of their body surface, patients with darker skin, and patients with facial lesions particularly noted difficulty with receiving a diagnosis.Misdiagnoses included sun damage, fungal infections, and atopic dermatitis. About 17% of both primary care physicians and dermatologists reported encountering patients referred to them who were misdiagnosed.&nbsp;While there were geographic variations among these findings, similar results were found globally.<h5>Survey results: treatment</h5>Fifty-seven percent of patients reported being told by their healthcare practitioner that their vitiligo could not be treated, and 44% reported they had given up on finding an effective treatment. Treatments that were reported to be used or suggested by the primary care physician or dermatologist were topical medications, photoprotection, laser therapy, and surgical options.<h5>Survey results: effective care</h5>Two-thirds of patients reported receiving effective care, defined by the patient as a reduction or cessation of spread and repigmentation.A core element that patients sought to achieve was a reduction of the psychological burden of vitiligo, with mental effects of the disease going well beyond just what is happening in the skin.<h5>Implications for dermatology</h5>The results of the VALIANT study show that there is a profound burden associated with vitiligo with nearly half of patients reporting greater than 5% body surface area affected and a time of 2.4 years to diagnosis for a condition that should be easy to identify.The survey results also revealed that there is a common misperception that vitiligo cannot be treated. Although many publications have disproved this, it is nonetheless a widely held belief among both the patient community and healthcare practitioners.With these factors considered, this global survey emphasizes the significant frustration that is mounting among patients and the practitioners who treat them that can hopefully be addressed with future developments and advances in vitiligo education and management.To read the full study published in the British Journal of Dermatology, click <a target="_blank" rel="noopener noreferrer" href="https://watermark.silverchair.com/ljad245.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA2EwggNdBgkqhkiG9w0BBwagggNOMIIDSgIBADCCA0MGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMX5V9-MHsh4UtmQYyAgEQgIIDFGv2S4nMY1oqmdJqAc47hiyKl2BFRZp7HtQoN7ABGUGRybwdmWBOmG86sQh5u1StnaFuElQuzuV8FAlO6hPzuf7JDeqDF1kliJmPdkDq1awxpqAa9mxDuUDdxJs9MDu63G5W1VFZGk3ULW_mR_ByNxXiDq-HMlhH9aESceVPkuHi61qj6PutyptC3NDBNpLRVPgzY_Gf_J_mQasVqVYyMizb_nt37cypxpAN3saqAOOhnLIAI-f4KLNgqGOTU0ifJp1XRBJFwe9fI8ern3fWjxDbS5t3RBe2BNu-U9r1jW6QrbzszivU4gmx1sb5JJk5f2Ce0o1_jy_EjGyj2RZX2_FPfJH91lpLehUcfmXbmoNKNnXo0onaGYG4NVs0tChMTZLRp_3OMBlS6E5V97efZ2NFi1dykQwUUVDRGkZsBc_R6yUlAExRTVXuALp45Lz0U2F7yXDcv4S05iDtjySYixnKffB1D6fNEtsNriG4CYvoGA5Y70z6vIN--HREWAdDI3edtfWX60KjZmhs3xBwTGIpQ2Damkzao3jCALB4zFxiuLV0HpBNr7ytKA8qI24BB2nQtROy9LRzgLYhzS0zllaTjztz1dAj1LQZLYPzSGFLBYsMSRNL9YcrsvOZ4Buq60M0Pg8g6MyGBiyKntz4NXhwocbTHxnC2gAc7ndzHAGyHBfV6_GOkVrOIjNwTjD8qmU1g_VXZQrsvOWNXazM6U_87toGM7wtfwMCQaFxNXJ0QV-QR6eGkd7loYWljWUa_uWQtSxWhndhu6tzWL7-Qg0k8C4YYYnMrPrOibTcQXl9044B1_B3Sxc_GQiTDJ-8NKWQiPGqB42k-nwYDr5Iq7COyB0sEesVfuwrOAet2fvHDEn8ODVk-eONNUI6mCi_ALw7Bh7mw6d3-7nH3oM5zbxeXRlCgNqPO3yK4wdcFYkjOShm9FXH6g6JcrJTS2J3VK8VLxtcogqWOg34plnCbxqyua3d5RN7Ci-dy8xoFAdBoLovqO0g0k87CPhkzHmf5ibMH6HAr9awuSAPtpDs-2Qrg3dp">here</a>.<h5>Key points from the VALIANT study</h5><ul><li>It is the first global survey to explore the natural history and treatment of vitiligo from both a patient and HCP perspective</li><li>3,541 patients and 1,203 were surveyed</li><li>Mean time to diagnosis was 2.4 years</li><li>45.2% of patients had &gt;5% affected BSA</li><li>44.9% of patients reported an initial misdiagnoses</li><li>Reported rates of misdiagnoses were greater among patients with darker skin, &gt;5% affected BSA, and facial lesions</li><li>56.7% of patients reported being told vitiligo could not be treated</li><li>26.3% of HCPs did not believe an effective therapy for vitiligo exists</li><li>44.6% of patients reported giving up on finding an effective therapy</li><li>HCPs most commonly recommended prescription topicals, sun protection, and phototherapy, but comparatively few patients reported using these</li><li>34.4% of patients reported having surgery or other procedures, but only 14% of surveyed HCPS recommended surgery &nbsp;</li></ul>

The pathogenesis of vitiligo is very complex, but it boils down to three broad areas. Number one, we know that there's an immunologic basis for this disease where there is immunologic attack on the melanocyte. We know also that there's the effect of reactive oxid species and oxidative stress leading to destruction of the melanocytes. We also know that it's important in the management to stimulate regeneration of melanocytes. So our approach to managing vitiligo is really based on this pathogenesis. We want to control the abnormal immune system attack on the melanocyte, we want to reduce reactive oxidative species and oxidative us on the melanocyte, and we want to promote regeneration of melanocytes to get repigmentation and.

Vitiligo and Skin of Color Implications

Vitiligo can affect any population of any skin complexion, racial ancestral background. But when vitiligo affects individuals with richly pigmented skin, the contrast between lesional skin and nonlegional skin can be quite striking and therefore more disfiguring for that patient. If you add on top very various cultural factors that can also add to the stigmatization of vitiligo, you can clearly appreciate the burden of vitiligo on patients with skin of color and some of the nuances in terms of the quality of life impact. So the bottom line, as clinicians, we shouldn't underestimate the psychological burden of vitiligo on our patients and provide them with the appropriate treatment to get as much repigmentation as we can for them, particularly in highly visible, sensitive areas like the face and the hands.

Combination Therapy for Vitiligo

When it comes to treating vitiligo, combination approaches tend to be most effective in broad strokes. When we combine therapies that address the autoimmune mediated attack on melanocytes as well as stimulate melanocyte repigmentation and some therapies that might reduce sedative stress damage of the melanocytes. If we take this multipronged approach, we generally get the best outcomes. Now, what does that mean in reality? Well, in cases where there's a larger body surface area, combining topical therapy with phototherapy and supplementing with oral antioxidants would be a comprehensive approach to treating a patient like that. For patients with limited body surface area, topical with or without eczema laser for lesions that might be more stubborn or slow to repigment.

Well, the biggest advance in the treatment of Vitiligo in the past year has been the recent approval of topical ruxalitnib cream, the first ever prescription therapy approved by the FDA for the treatment of vitiligo. And this has really been transformative for our patients. Being able to use an approved cream twice a day, safely and effectively, over an extended period of time, and see repigmentation, whether it's facial vitiligo or vitiligo on the body, has really been transformative. Beyond topical therapy, we are seeing in the pipeline some interesting, exciting research with jack inhibitors that are oral. We're seeing being procedural therapy for vitiligo, a modification of the melanocyte keratinocyte transplantation protocol, which is something that will be hopefully available and approved for use in our offices. So really an exciting time to be treating vitiligo.

Is vitamin supplementation important in treating vitiligo? Are there supplements that you recommend for your vitiligo patients?

Vitamin supplementation in combination with jack inhibitors and tcis. All those questions are critical and important in vitiligo. The short answer is I do use vitamin supplementation for my patients with Vitiligo. I do make sure they've had their vitamin D checked, they're getting their thyroid and iron checked with their pcp supplement as needed for those based on lab work. But I also recommend alpha lipoic acid with vitamin C and vitamin D, typically in a 100 to 150 milligram dosing for the combined capsule. And I recommend polypodium leukotomas twice a day for my patients, which helps to increase their body's own uv protective factor. All.

How effective are home phototherapy/UV units for Vitiligo?

Home phototherapy for vitiligo is something that I do find effective in my practice. I'll tell you. During the COVID pandemic, home phototherapy helped a lot of my patients because they couldn't come to the office. We had restrictions on how many people you could let in. We had patients who didn't want to come in even if they could. And home phototherapy certainly helped many of them continue in their treatment. Do I think in office phototherapy is better? Well, it depends on the, and it depends on your treatment outcome. But yes, home phototherapy has been something very helpful, and it continues to be an important part of my therapeutic armamentarium.

Vitiligo Condition Center

Featured in Vitiligo

Who is the ideal patient for ruxolitinib for vitiligo?

Latest Vitiligo Videos

How do you set expectations with patients before starting them on ruxolitinib for vitiligo?

How quickly can patients expect to see results with ruxolitinib for vitiligo?

Vitiligo Case Study

A Case of Nonsegmental Vitiligo on the Face and Hands Treated With Combination Topical JAK Inhibitor and Phototherapy

Vitiligo News & Research

Educational Courses You Might Like on Vitiligo

Therapeutic Options in Vitiligo Treatment: An Evolving Landscape: An Online Activity

Open Up to New Treatments for Vitiligo: Online CME Activity

Not Just Skin Deep: Revealing New Strategies to Manage Vitiligo: Online CME Activity