Senior Clinician Dr. Edward Cowen is Head of the Dermatology Consultation Service at the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the NIH. Dr. Cowen will share his expertise on skin issues as they relate to Graft Versus Host Disease (GVHD).
In this episode Dr. Cowen "covers" it all--dry scaly skin, red rashes, skin fibrosis and fasciitis. His expertise will make patients and caregivers alike feel more confident and knowledgeable about skin GVHD. When should you seek treatment and which doctor should you see? He will address clinical trials, long term prognosis and talks about what is on the horizon for the treatment of skin GVHD.
He mentions topical over the counter treatments like Aquaphor and Sarna, as well as oral antihistamines like Benadryl, Allegra, Zyrtec, and Claritin.
The information in this podcast should not be construed as medical advice. Please consult with your health care provider regarding your medical decisions and treatment. The listed resources are not intended to be endorsements.
Resources:
Dr. Cowen's ruxolitinib trial: https://clinicaltrials.gov/ct2/show/NCT03395340
National Institute of Arthritis and Musculoskeletal and Skin Diseases: https://www.niams.nih.gov/
NIH Clinical Trials Website: https://clinicaltrials.gov/
National Bone Marrow Transplant Link - (800) LINK-BMT, or (800) 546-5268.
nbmtLINK Website: https://www.nbmtlink.org/
nbmtLINK Facebook Page: https://www.facebook.com/nbmtLINK
https://www.niams.nih.gov/about/directory/edward-w-cowen-md-mhsc
Thank you to this season's sponsors:
Incyte Corporation: https://www.incyte.com/
Kadmon: https://kadmon.com/
Note: Transcripts are auto-generated by AI and may not be 100% accurate.
Peggy: Welcome everyone. This series focuses on all things GVHD. We will peel back some layers today. We're going to talk to experts and patients alike about their struggles, victories, their best tips, and so much more. So get ready to be inspired, educated, and updated on this tricky disease. GVHD might be a part of your life post-transplant but we want you to know, and to be encouraged that it most likely is temporary.
We're going to learn from healthcare professionals and survivors in the season who want to share with you so that you can beat GVHD and thrive, despite it you'll appreciate their grit, honesty, and determination to help you live your best life with their guidance and experiences. So today we welcome Dr.
Edward Cowan. Dr. Cowan is head of the dermatology consultation service at the national Institute of arthritis and musculoskeletal and skin diseases at the NIH. Wow. That was a mouthful. Dr. Cohen will share his expertise on skin issues as they relate to GVHD. Welcome Dr. Cowan, it is certainly a pleasure to have you with us today.
We have so many survivors and even caregivers who share their frustration with skin GVHD. So let's just jump right in and offer some relief.
Ed: Well, thank you, Peggy. I'm happy to talk to you today about skin GVHD issue.
Peggy: So Dr. Cowan, what are the signs of chronic skin GVHD and how does one know if their skin has actually developed GVHD?
Ed: Sure. So you think that that would be a pretty straightforward question, but actually there are really. A whole variety of different manifestations for how chronic skin GVHD can present itself. And this is really tricky because patients often aren't necessarily going back to their transplant doctor as often.
So trying to differentiate a allergic reaction from a area of eczema or from GVHD can be really a challenge. The two sort of easiest ways to think about skin GVHD are sort of red rashes and sort of scaly dry sort of eruptions on the skin. And then a rupture ones that involve the skins deeper tissues.
And you may have heard a variety of terms for this there's terms called fibrosis and skin sclerosis. Some people use the term scleroderma like. To try to sort of relate it to the auto-immune disease of scleroderma, but all of these sort of sclerotic manifestations are different ways of saying that the skin is thickening and an abnormal way, and this may not have any visible overlying skin rash.
It may not even be red. There may be pigmentation overlying that, but sometimes what you just notice is that you can't move as well as you used to. So the skin will be thicker. It'll be less pliable, or you just don't have the normal range of motion of your joints that you used to have. And there's lots of reasons that joints could be limited when you've had chronic GVHD, including just being cooped up in bed or de-conditioned for a long time.
And so people may not be aware that they're not as flexible because their skin is actually tighter.
Peggy: Okay, well, that's helpful. Many are probably wondering why did I develop skin GVHD and what other health changes should I be thinking about to help me determine if I actually have developed skin GVHD?
Ed: Right. So this is another really important question again, because you're the one who's seeing your skin every day. And you need to determine when to call your transplant doctor or to see someone. To really determine if you need to have treatment for your skin disease. So I think it's important that we sort of discuss some of the risk factors and things to think about.
The first thing patients always want to ask is why did I develop skin GVHD? And in general, the risk factors are the same as the risk of developing graft versus host disease in general. And so obviously if you're a mismatch in any of your HLA alleles, that increases your risk. And the type of immunosuppression and those things also play an important role, but only a small percent of patients we estimate maybe 10% or so develop the skin thickening problem, which is some of the toughest manifestations to treat.
So we've been really interested in trying to understand what puts people at risk for developing that. And we think that if people have received. Total body irradiation as part of their conditioning regimen at the time of their transplant, that probably confers a risk later. And in some cases, years later to developing skin fibrosis.
So one of the risk factors that we now think is relevant is actually the type of transplant conditioning that you received. And our data at the NIH has been confirmed in other places as well. Now, this doesn't mean that you shouldn't get that type of treatment because obviously different regimens are done for different reasons.
And if you don't get a radiation, you may be getting stronger chemotherapy and there's pros and cons to every treatment. But beyond that, we really haven't determined if someone has a pre-existing risk factor before transplant, that makes them at risk for developing skin thickening. It doesn't seem to be people who have a history of more auto-immune disease or whose donor have had autoimmune disease.
And we don't even see that the same antibodies that we find with autoimmune diseases like scleroderma are present in our patients with GVHD, with skin fibrosis. So there's a lot, we still don't really understand. And when it comes to actually thinking about whether a new skin change is possibly due to GVHD, I think there are a number of, sort of things to think about before you talk to your transplant doctor.
So. Skin GVHD is very common in association with other manifestations. It doesn't have to be in certainly you can have only skin involvement, but if you have new eye irritation or mouth sores or mouth dryness, any other sort of new symptoms that suggest other GVHD involvement at the same time, you're developing a new skin rash or a new skin tightness.
That should be a red flag right away to call your doctor because you may be having a flare in multiple organ systems at once. So the skin is actually a very important signal and some of the other benefit stations in terms of liver involvement and other things may not be detectable. And so it is really valuable to pay attention to your skin, people who have been doing well.
And your immunosuppression has been tapered because you're doing so well. That's great news, but that is also a time when you're at now increased risk of possibly getting GVHD because that immune system is now released. And if there's a proclivity there to develop GVHD, that's often when it will happen.
And then sometimes we see flares of skin GVHD when people have had other illnesses and this doesn't necessarily have to be a skin problem, but if they've had, um, a flu or pneumonia or some other underlying infection, or even a drug rash, Often that'll seem to be sort of a trigger to rev up your immune response and sometimes lead to a GVHD flare.
Peggy: That is so interesting. So is a lot of the times skin, one of the first red flags that someone will have post-transplant
Ed: absolutely. And we're talking mostly about chronic graft versus host disease today, but. Acute skin GVHD is a very important signal because obviously acute GVHD can in some patients be very dangerous if it's not adequately treated and controlled because it's associated with potential severe liver injury and diarrhea as well.
And so if those organ systems sort of, uh, get out of control, that can be very dangerous. Fortunately, acute skin GVHD. Is usually controllable. Um, it's very rare for people to have very severe skin GVHD because we have good prophylactic treatment to help prevent people from getting GVHD. But we're called to see these patients very promptly and we biopsy them very soon because if we show that there's acute skin GVHD, that's an important clue that they need to be followed very closely for these internal organs that might also develop.
Peggy: Wow. That is so important. I'm so glad we're talking about this. So Dr. Cowan, when someone's suffering and they need to talk to their doctor about their skin GVHD, what type of doctor should
Ed: they call? Yeah. Great question for this. I would say it probably varies where you live and how close you are to your transplant center.
And the really are practice differences depending on where you have your post-transplant care. I'm on the east coast where there's a lot of dermatologists and there's a lot of transplant medical centers. Certainly in the middle of the country and on the west coast, you know, practices are different. Um, I know for instance, in Seattle, in that area, the transplant teams were often do their own skin biopsies and don't necessarily involve dermatology.
We're sort of at the opposite end of the spectrum here at the NIH, because our dermatology clinic is located right here in the hospital. They know I have a very specific interest in GVHD. And so I see almost all of these patients pretty soon after they develop symptoms. But I think really the most important thing is as a patient, you want to take ownership early and try to learn as much about your skin symptoms as you can so that when you call your transplant doctor, or if you're going to call a dermatologist, you can tell them exactly what's going on.
And, you know, certainly for dermatology, there can be delays in getting in. And so it may help to talk to your transplant doctor first, say, Hey. Because of these symptoms. I think I might have skin GVHD. Should I come to see you? Is there a dermatologist that you recommend who has experience with GVHD that can help me with that diagnosis?
And as part of that, I think it's really important then to think about the different manifestations so that you can pick it up early. And so I alluded to this earlier with the sort of skin rashes versus the skin thickening. Any red skin rash after transplant. The default is always to think, well, this is skin GVHD, and it certainly is common, but that's not always the case.
So you want to think, have I started any new medications? Are there any other things different, any topical creams or things that I've put on that I'm reacting to? Because of red rashes are not always going to be GVHD. For instance, we see patients that are on treatment with a anti-fungal medicine called voriconazole, and that makes people very sensitive to the sun.
And so we have patients who actually are not having GVHD, but are photo-sensitivity, but they get red rashes and that's sometimes missed attributed as GVHD. The skin thickening part is very critical for the patient to really. Try to detect early and pay close attention to. And, um, as a patient, you may even go to your doctor office, be it a dermatologist or your transplant doctor.
And they may not be able to detect the skin changes because they're subtle. They may not have the time to do a full skin examination. They're dealing with other GVHD problems and your blood work and other things, and you really have to feel the skin and appreciate that. There's a difference in order to detect that.
And so you're the best person. Who's equipped to make that diagnosis. So is your range of motion diminished? Are you not as flexible as you used to be? Do you notice subtle sort of rippling skin changes that can almost just look like cellulite? You know, obviously we think of cellulite and the thighs, but that sort of same subtle rippling can be seen in the abdomen.
It can be seen in the inner aspect of the arms and it might look like cellulite, but if you feel it, it just feels a little bit firmer. And so if you have new changes like that, that's actually a sign of skin thickening that's happening deeper down in the skin. And just as important as it is to detect sort of new skin rashes, the skin thickening features are really critical as a patient for you to be able to detect yourself.
And that's because these changes may be very subtle. And even if you have easy, close access to a transplant doctor or a dermatologist, Those providers might miss it as well, because they may not be examining your entire body. For instance, your transplant doctor is dealing with your oral solar's or other manifestations are focusing on problems with your blood work.
And they're not doing a full skin examination, or they may not be able to lay hands on all of these areas of the body that might have subtle thickening. So for instance, with skin thickening, Sometimes it happens in the creases where your waistband or your Brazil band line is. And you say, well, that's just a mark from where my waistband sits, but if you actually feel the skin, it may feel firmer.
It may have a yellowish color as the skin thickens. And you may notice that these changes are new and you don't want to just fall asleep, attribute that to, you know, a color change because that's where the band of your clothes lies. And so this early change. Is important to diagnose because then if you start treatment early, it's much easier to control that skin thickening versus after you've already had significant range of motion loss, and you're not able to do as many things functionally that you'd like in terms of driving the car and physical activities.
Okay. In the same vein, when you have very deep seated involvement, this can look like cellulite and we all think of cellulite is occurring as a sort of lumpy bumpy appearance on the thighs. But if you get these skin changes on the inner aspect of the arms, or you notice them in other places, this can be skin thickening, the taxi happening in the deeper tissues.
And there may not be a color change. There may not be a rash overlying that area of skin thickening. It just feels like a different texture. Sometimes there'll be a DEMA there, which is swelling. And so if you have new fluid, that's accumulating in your hands or feet. And there's no other explanation.
Certainly you want to get that checked out to make sure there's nothing going on with your heart or other reasons to have a DEMA. But if these things are eliminated and it's potentially skin thickening, again, getting that treatment early on, when you're in that phase. We'll make it much easier to limit the amount of damage that's done by skin fibrosis down the road.
Wow.
Peggy: That's a lot to take in, but I'm sure it's going to be so helpful to so many people. So how does one know if their skin is improving or getting worse? What are the non-prescription things that people can do to help with skin itching, pain, or even tightness?
Ed: Sure. So for the sort of red rash is associated with the superficial form of graft versus host disease.
Usually it's going to be pretty obvious if things are heading the right direction or not, the itching will improve. The dryness and discomfort will improve. Um, some people have sensitivity even when they shower because the skin is so raw and sensitive. And so these things should improve. If your skin is heading in the right direction, it's much trickier to tell whether or not skin thickening is improving.
You can definitely tell it's heading the wrong direction. If you have new areas where you're. Joints aren't quite as flexible or your skin feels tighter than before, but when it's improving, it improves slowly and it improves by softening. So the skin thickening doesn't go away overnight, or even over a few weeks, it takes several months and where the skin felt very hard.
It starts to slowly soften, but you can still feel there's some abnormality there. If you start to get hair growth back, particularly on the legs for both men and women, if you lose hair, that's a sign that the skin fibrosis is sort of hurting the hair follicles. And so, um, by the same token, if you start to have hair regrowing and you have to start shaving your legs, if you're a woman or you notice you're getting hair back in areas, that's a good sign.
And obviously if you have increased flexibility, it's important to stay active for a lot of reasons. But, um, one of the best reasons to stay active is that it helps you monitor your flexibility. And so if you feel like things are getting looser, then that's a good sign, but if they're not getting looser and you're trying to do the same activities, that's also very important because then you can say to your doctor, you know, I've been doing this same exercise regularly.
It's getting much harder to do it. I don't have the flexibility and that will give them strong evidence, even if they can't see. All of these subtle changes that things may need to be changed in terms of your treatment regimen. And
Peggy: are there any non-prescription things that they could be accessing to help with the
Ed: itch?
So, itching is a huge problem with patients who have the more superficial form of sort of the rash of graft versus host disease. We typically will use prescription topical steroids or something called calcineurin inhibitor. You may have heard the term Protopic or Ella Del. And these are prescription things that are anti-inflammatory, but there's lots of other things that you can do to at least try to improve some of that discomfort until you can get to a dermatologist or to a transplant doctor, and they make those adjustments in your medicines.
The first thing you always want to do is make sure that you're not contributing in any way to skin dryness or discomfort. So you want to be using. Moisturizing soaps like dove soap. You don't want to do deodorant soaps or anything that can dry out your skin. And then as soon as you get out of the shower or bath, you want to put on a good moisturizer.
Now the best moisturizers are ointment based because they last the longest, but they're also the greasiest. So some people are willing to do ointment based moisturizers like Aqua for at night. Or at least on areas of their skin that are particularly dry and bothersome. And then you can try either using a lotion or a cream during the day, which is gonna give you some relief, but isn't gonna quite last as long, there are agents that give you some temporary improvement in itch.
One of them is called Sarna and this has menthol and camp four. And these are medicines that are very safe and are over the counter and they give a soothing effect. They're not shutting down the inflammation that's happened with GVHD, but you know, they're safe to use as many times a day as you want.
And it's much better to be applying that multiple times a day than scratching at your skin or harming your skin with the discomfort associated with GVHD. The last thing that's obviously a go-to for many people with itching are anti-histamines and these are used very frequently for allergies. So I think most of us are familiar with medicines like Benadryl.
And then the so-called non-sedating antihistamines and these are medicines like Zyrtec and Alegra and Claritin. So these can help itching as well. The one thing to keep in mind is one of the side effect of anti-histamines is it can make you feel dryer. And so if you already are struggling with dry eye or dry mouth, you do want to be careful, particularly with the higher doses of antihistamines, because it can make those symptoms, um, more problematic.
Well,
Peggy: very good. And we will include a bunch of this in the show notes that will help people find these products. So thank you. I'm sure that people appreciate that. Okay. I think we covered some of the medications that are prescription. So I'm going to jump right in and ask you about clinical trials. We love clinical trials and we love making sure people know about them.
What about clinical trials that are related to skin GVHD? When should one get to that point to look for one? I'd just love to hear what you think about that. Are there lots of them available?
Ed: Let me preface this by saying that GVHD clinical trials are always a challenge because. Uh, there's so many organ systems that could be studied.
And it's very rare that the skin is the only Oregon system that's studied. And so when trying to figure out, okay, what is the best medicine for someone who has skin fibrosis? It can be very difficult from the literature to determine that because even the studies that seem to work for GVHD, They don't always do a good job of telling you which patients had skin fibrosis and which of those had sort of the red rash of GVHD, the latter of which typically responds much quicker than skin fibrosis.
And so sorting through it in evidence-based manner. What's best is really tricky. My particular interest is very much in trying to find skin specific types of treatments so that we can improve. Either the red rash or skin fibrosis in patients who have bad skin disease without necessarily causing them more immunosuppression or more side effects from systemic medicines.
And so this is called skin directed therapy. And so this could be topical medicines. This could be ultraviolet light, or it could be a type of therapy that you ingest, but we think works just on the skin. For instance in anti-fibrotic medicine, one that wouldn't necessarily affect your immune system, but would help to reverse the skin.
Thickening is the holy grail for patients who would have skin thickening, but otherwise are doing well. I will mention, I have a. Specific skin trial right now where we're using an oral JAK inhibitor JAK inhibitors. Uh, as you may know, are one of the more popular new systemic medications that are being used for both acute and chronic graft versus host disease.
And these medicines have been fantastic, but there are potential side effects when you take an oral JAK inhibitor, because it is affecting your immune system in a global manner. So one of the trials we have is for patients who have sort of an active red rash, and we're using a topical form of ruxolitinib a JAK inhibitor, and we're putting that in one part of the body where they have the active rash, and then they get a placebo cream on the other half.
And this is to try to be as scientific as we can be about determining whether or not the topical application will be beneficial to patients who need a skin directed treatment for their GVHD.
Peggy: And where are you with that trial now? Is it going on or is it opening?
Ed: It is going on and we are actively recruiting.
I am sure we'll be able to put in the show notes, the link for clinical trials.gov and possibly even specifically for the trial. In general, there's a similar trial in New York. Obviously we're located in Washington DC, but the NIH is a great place to do clinical trials because in general, we can help with travel costs once people do enroll.
And so we are open to enrollment for patients across the country. So we are actively enrolling we're open again in the post COVID or at least recovering COVID era. And so I would love to have more patients to try to get the trial done and see if this topical approach will be beneficial for patients who don't necessarily need to have systemic treatment for their GVHD.
Peggy: So glad we had a chance to talk about that because the resources available through the NIH, we just know how important that is. And I'm thrilled that you talked about this particular clinical for topical. So thank you so much. My next question is what is the long-term prognosis for skin GVHD?
Ed: Yeah, another really important question, but it's a very challenging question for patients who haven't responded great to their first line therapy, which is, you know, conventional immunosuppressive therapy.
Typically, then you're going to go to a second or third line treatment, and there are as a smaller subset of patients that still struggle even with these additional treatments. For those patients getting back to sort of our earlier question. These are ones that absolutely would be great candidates for a clinical trial, but always it's hard to say when their skin is going to finally calm down and become quiescent.
You know, the conventional wisdom is at some period of time, even if all of our great treatments don't necessarily seem to make a big difference, your immune system will sort of a collaborate in and hopefully will calm down and allow your skin to slowly get back to normal. But I always have a lot of difficulty predicting when that's going to be at the NIH.
We tend to see patients who have struggled with different treatments and are coming to see us because they haven't responded great to some of the first and second line treatments. I will say, certainly patients who have skin fibrosis, this is a process that takes many months for that sort of skin to thicken.
And it takes many months for it to reverse. We still don't have a great biomarker where we can check something in the blood. To say, you know, the skin is active or the skin is not active and we just need to wait for the skin to reverse. But I also want to make sure people understand that this is not the same as like burn wounds or burn scars.
I don't use the term scarring when it comes to the skin thickening with GVHD what's happening. Is that the collagen, which is the dermis, which is the normal protective layer underneath your epidermis. Is just making too much collagen. So it's a little bit thicker than it should be. And your body is that always in a dynamic state where we are always laying down new collagen, and then we have proteases in our body that are breaking down collagen.
So patients do improve over time. The skin does soften. The dermis can get thinner, but it's, it's a slow process. Um, frustratingly slow for many patients. And the goal is to try to maintain as much functionality, you know, ability to do all the normal things that you need to do and preserve that range of motion until things soften either with appropriate treatment or on their own.
Peggy: All right. Well, thank you. So, Dr. Cowan, given your experience with GVHD the last, what, 19, 20 years overall, how do you feel patients are dealing with skin issues? Any closing
Ed: thoughts? Yeah. I think what I've learned as every patient's experience is different. And, uh, we're fortunate because we get to see patients from all over the country.
And I'm constantly in awe of patients who on the face of things have an extraordinary burden of skin disease and they may be functionally limited. Um, they may be very high-functioning professionals who are struggling even to, you know, get out of a wheelchair. But they still just have this, you know, dynamic sort of energy and positive outlook.
And then we have patients who, what I would say is, you know, much more limited disease, but are really struggling. In some cases, it may just be the appearance of the disease. We did one study where in patients with skin of color, we asked them how much their skin involvement. Bothered them and the pigmentary change and sort of the marks of the disease were just as bad as the fibrosis.
And so the visibility of the skin is a huge part of this disease that I think has dermatologists. And maybe as transplant doctors, we sometimes overlook, you know, we say, well, we've got to control the fibrosis. We have to control the rash, but then people are left with a lot of. Damage and pigmentary changes, which persists for years, and this can really affect people.
The other thing that I really have come to appreciate is that people want to get better, but the resources available to them are not the same that we have at the NIH everywhere. And this is no more true than when we talk about things. Like photophoresis where we're asking people to take two days out of their life every two weeks or every month and travel to a center that may not be.
In their city or even in their state, for instance, we've had a patient who had to take a train and a bus and a car in rural Canada in order to get close enough to a transplant center that could perform photophoresis for his GVHD. And so in addition to dealing with this burden of disease and all of these medications, I think we need to recognize when we ask patients to do thing, the added burden that that's adding to them.
And try to think in a multidisciplinary way, what's really the best approach to improve quality of life at the same time that we're trying to improve their disease
Peggy: itself. That's very compassionate. And thank you so much, Dr. Cowan, I, I just know this is going to help so many people and it was such a pleasure to talk to you today.
Any closing remarks as we end this very valuable session.
Ed: Well, it's been a pleasure talking with you. If patients have questions, I'm always reachable by email and I'm happy to talk to people about potential trials as well. Thanks once again, for allowing me to speak with you,
Peggy: uh, thank you so much and we'll make sure all of that's included in the show notes.
Thank you.