Your Skin and Graft versus Host Disease

Presenters: Milan Anadkat, MD , Washington University School of Medicine in St. Louis: ​Najla El Jurdi, MD, University of Minnesota 

This is a recording of a workshop presented at the 2019 GVHD Summit. 

Presentation is 35 minutes, followed by 21 minutes of Q&A. 

Summary:

The skin is the most common organ affected by graft-versus-host disease (GVHD). Treatment options depend on type of GVHD and symptoms

 Highlights: 

• There are two types of GVHD: acute and chronic. Both can affect the skin, but symptoms are different.
• Skin is the most common organ affected by GVHD. The first sign of skin GVHD is usually a rash.
• Treatments for skin GVHD may increase the risk of skin cancer.

Key Points:

• 07:23  Skin GVHD can look like a rash, sores in mouth or genitals, chronic itching, change in skin color, difficulty tolerating heat due to sweat gland damage and/or tight skin.
• 14:55 Physical therapy, massage and/or stretching may help with tight skin
• 21:10  Topical steroid creams are an important tool in treating skin GVHD 
• 22:18  Vitamin A pills, prescribed by your doctor, may help calm the inflammation caused by skin GVHD
• 23:14  Light therapy treatments such as phototherapy or photopheresis may also be helpful.
• 27:39 Patients who have had a transplant have an increased risk for developing skin cancer. 
• 30:27  You should do a self skin check every one-two months and schedule an annual doctor visit to check for signs of skin cancer.
• 31:23  There is no such thing as a safe tan
• 32:09  Wearing clothing to protect from the sun and applying sunscreen (SPF30) when going outside can reduce the risk of developing skin cancer.

Transcript of Presentation 

00:01  [Moderator] My name is Peter Gordon. I'm an 11-year transplant survivor myself. As a matter of fact, this Halloween night, it'll be exactly my 11-year anniversary and like I'm sure many of you... Oh, thank you. Like I'm sure with many of you, I have had all sorts of effects from GVHD on my skin and also the underlying tissue. So, I'm really looking forward to this session this morning and learning from our experts. One reminder, we're going to leave plenty of time at the last part of this presentation to ask questions, so if you can hold your questions until then that would be great. Let me introduce our experts and our speakers.

00:41 Introduction of Speakers: First of all, we have Dr. Milan Anadkat. He is a Professor of Dermatology and Residency Program Director at Washington University School of Medicine. His clinical focus is in the area of Complex Medical Dermatology with a unique interest in On Code Dermatology. He's a national leader in the field of Dermatologic Therapeutics graft-versus-host Disease, how appropriate, and Chemotherapy-induced Adverse Reactions.

Dr. Najla El Jurdi is an Assistant Professor of Medicine in the division of Hematology, Oncology, and Transplantation at the BMT Clinic at University of Minnesota. Her clinical interests include acute and chronic GVHD, regimen related toxicities as well as very importantly, survivorship care. Love it. Please welcome our presenter, Dr. Anadkat.

01:49 [Anadkat] Okay. Well, good morning everybody and I just have to say it's an absolute pleasure to be here. I'm really looking forward to speaking to you guys about the skin and graft-versus-host disease. So, I have been at Washington University in St. Louis as faculty for 13 years. And the entire time my clinic has been embedded within the Siteman Cancer Center there, and I've just really enjoyed over the years taking care of patients who are undergoing cancer therapy, including hematologic malignancies, and just having that unique position to manage the skin complications that arise during that journey.

So, just walk you through the journey of what I've seen and what I think you guys should understand about dermatologic challenges for patients undergoing that process. So, these are just visuals of the Siteman Cancer Center on the left. And then across from the hospital, a unique way of torture is to place a beautiful park called Forest Park right across from the hospital, so that when we are at work we can see what everyone else is doing. Jogging, and golfing, and running, and I suppose it makes us feel better to know that others are enjoying nature next to us.

03:05 Disclosures: So, I have a lot of disclosures, none of which are relevant for the talk today, but I do always think it's important to discuss. For a long time I worked with a lot of companies to help manage skin toxicities from chemotherapy specifically, and then treatments for cutaneous metastasis that are under development. I think the unique part of this is these are all disclosures for drugs that I never prescribed, but it's really just helping people manage how to deal with them.

03:31 Learning Objectives: So, these are the objectives for our few minutes together this morning. And then as Peter mentioned, we'll leave plenty of time to talk and discuss. Usually one of my favorite parts of every session is the Q&A where we can just chat. So, the objectives for today are

• to explain risk factors for developing skin graft-versus-host disease
• to describe some of the various manifestations. Every dermatologist loves to show pictures. I'm going to show lots of pictures, and so hopefully we have fun with that. Discuss some potential therapies.
• And then last, I do think it's important to talk about skin cancer in the setting of graft-versus-host disease and where I think that plays a role.

04:12 Definition of GVHD:  So, we'll start basic, what is graft-versus-host disease? And as we know, the graft is the donor and the host is you, the recipient. And so, what's happening is we are placing a new immune system in a different body. And as a result, sometimes that new immune system attacks its new tissue environment because it believes that these surrounding tissues, be it the skin or other organs, look unfamiliar.

04:41 Risk Factors for GVHD:  I think I'm up here because skin is a very common look for what happens in graft-versus-host disease. In fact, it's the most common organ that is affected. Other common organs include the liver, the intestines, the lung, and the eyes as dictated by your agenda today.

So, some of the risk factors for developing graft-versus-host disease, it has to do with the degree of mismatch. The more different the grafts and the host are, the more likely graft-versus-host disease will occur. Some of the settings that increase the mismatch likelihood have to do with the age of the recipient. The older the recipient is the more likely graft-versus-host disease is to affect.

If the donor is female, especially female to male as a match, there's more likely to be a mismatch. If the donor is female who has already had children, it further increases the amount of things that female donor's immune system has seen and is then projecting into its new host.

And then also it depends on the source. Sometimes if the source of the stem cells of transplantation come directly from the blood as opposed to umbilical cord or bone marrow, but rather it comes as a peripheral blood donation, it is more likely to see signs of graft-versus-host disease in the skin.

So, as I alluded to earlier, I think dermatologists have a role in this discussion going forward because the skin is the most commonly affected site period, when it comes to graft-versus-host disease. And I've sort of given you some ranges of percentages for the other organs involved, the mouth, the liver, and then a laundry list of other organs that can be affected.

06:32 Skin Rash:  So, specifically, let's talk about skin in terms of what we will see. And I think globally the most common description of what's going to happen with graft-versus-host disease in the skin is a rash. But as you may appreciate, that's a very nonspecific thing I just said. Like what type of rash, what color is it? What does it look like? Where is it on the body?

So, we're going to get into that a little bit because just saying a rash doesn't help anybody. So, we're going to get into some details. I think things to remember when we talk about dermatologic care is it's not just the skin, but it's the hair, it's the nails, it's the genitals, and it's inside the mouth, right? So, all of that falls under the purview of a skin doctor or dermatologist. So, getting sores in the mouth or the genitals are something to keep in mind that is relevant if that happens.

07:23 Itching, whether or not you see a rash, your dermatologist may see the rash, so if you're itching. If you get a change in skin color, and we'll go over some specifics here in a moment.

07:33  GVHD damages sweat glands: And then just dryness, right? The act of conditioning chemotherapy specifically attacks sweat glands. And so, everybody who's been exposed to chemotherapy, which means everybody who's had an allogeneic bone marrow transplant has been exposed to chemotherapy and or radiation that specifically attacks sweat glands, and sometimes that effect never leaves for years, if not decades afterwards.

So, when your sweat glands are affected, your skin becomes dry very readily and sometimes just never moisturizes the same way after the transplant. You also sometimes have a tougher time handling heat because your heat regulation system is not the same, right? Your air conditioner is a little broken.

08:22 Tight Skin:  So, other specific manifestations include tight skin. And so tight skin I think can sometimes be obvious. You can't close your hands as much or you can't move the joints, or we get joint contractures, you can't open your mouth as much. There are other more subtle signs of tightening in the skin where you have this new appearance of cellulite. A lot of times we call it pseudo-cellulite because it's not really cellulite, but you get this rippling in the skin in certain areas where it's not typical to get cellulite. And then when you have tightening, especially over the trunk, it's hard to take those deep breaths because of that tightening on your skin. So, these are all subtle manifestations of tightening of the skin as well.

09:02 What acute GVHD looks like: So, if we're going to talk about different phenotypes or different looks of what the rash of skin graft-versus-host disease is, we should first talk about how there's two main categories. There's acute graft-versus-host disease and then there's chronic. As the name would imply, most people think of acute graft-versus-host disease is happening fairly soon after the transplant, and for the most part that's true. And then chronic rappers host disease or skin changes that happen later after the transplant, and again, for the most part, that's true. There are nuances to that which we'll get to. But it is important to know that these two subcategories look differently to the naked eye.

Acute is more generalized and pink, and I'll show you an example. And chronic tends to have a few different looks. So, this is an example of acute skin graft-versus-host disease. So, in our world, we would call this a morbilliform rash. And what that really means is it's a rash that looks like measles. So, if anyone is old enough to remember what measles looks like, this is what it looks like. It affects the face and the trunk and it is pink and oftentimes scaly, and itchy, and everywhere.

What is unique about graft-versus-host disease as opposed to other rashes, say an allergic reaction to when you take a medicine, is that graft-versus-host disease loves to affect the hands, and it loves to affect the feet, and it loves to affect the face and the scalp, and that is just not where most rashes go. So, when your scalp and face, your hands and feet are affected, that is really suspicious for graft-versus-host disease as opposed to something else because most rashes just don't go there. So, the look itself of the rashes, pink and splotchy and fairly nonspecific but where it goes and when it appears is very suspicious acute skin graft-versus-host disease.

11:09 What chronic GVHD rash looks like:  This is in contrast to the look and I'm really emphasizing the look of chronic graft-versus-host disease. And there's two main looks we're going to talk about.

One look falls under an umbrella called lichenoid. And lichenoid is a microscopic description for what the rash looks like there. But for our purposes today, we need to know that lichenoid eruptions are purple. Purple things don't usually appear on the skin, right? That is an odd color for a rash, but it is really common for lichenoid rashes in chronic graft-versus-host disease. And in fact, we call it lichenoid chronic graft-versus-host disease. And again, it's really weird for rashes to appear on the face, the hands, and the feet, but not for graft-versus-host disease, so this is a common area for lichenoid graft-versus-host disease to effect on the face.

What's also unique about this rash, not only is it purple, but where it affects you in the skin is where all of the color in your skin resides, which means the rash is purple, but when the rash goes away it leaves a considerably dark stain. And that stain takes forever to fade.

Now, depending on the skin color of which I see many in the room, the darker your skin color, the more pigment you have in the skin, the darker stain you're going to get from this rash. So, I have seen people where the stain takes months and sometimes up to a year to go away. That is problematic, right? So, the sooner we catch it and the sooner we extinguish the fire from that inflammation, the less of a stain we get. But that is problematic. And again, this is a rash that likes to affect the face. I've never yet seen a patient who's really happy about that stain that takes up to a year to resolve from their face, but it does happen.

13:12  Chronic GVHD can affect fingernails:  So, other places where lichenoid or this purple rash likes to effect is the nails, and sometimes you can get these long streaks of the nail. Sometimes, you can completely destroy the nail because of the lichenoid inflammation, and it's happening right where the nail starts growing. So, at the base of your nail fold where the cuticles are, that's where the nail factory or nail matrix is. That's where the nail grows. And that's where all the inflammation in graft-versus-host disease likes to go, and it affects the nails.

If the inflammation is intense enough, it doesn't just cause rippling or ridging of the nails, it causes destruction. We need our nails. We need our nails to type, we need our nails to button our shirt. When our nails are destroyed, it kind of affects our daily functioning. So, again, catching this sign of inflammation is important.

14:02: Chronic GVHD can affect the lips and lining of the mouth:  Lichenoid eruptions also like to affect the mucosa, and so I'm showing you pictures of the mouth. The genitals are equally affected. A really common area to be affected would be the lips and the inside of the cheeks, what we call the buccal mucosa. So, the inside of the cheeks and the lips are another common area.

Again, sometimes you just get a rash, but sometimes you get sores and ulcerations. It affects taste, it affects the foods you like to eat. Some foods are just no longer enjoyable if it burns and stings every time you have that meal, so it clearly does affect quality of life.

It also confuses other doctors, right? When you get sores in the mouth, someone else thinks it could be herpes, and it could be. Someone else thinks it could be a skin cancer, and it could be, so it does masquerade as other things. But when you put the whole picture together, this is an important thing to consider as one of the causes of your mouth problem.

14:55 Chronic GVHD can cause tight skin:  The other big category of chronic skin graft-versus-host disease. So, the first is lichenoid, this purple, and then the other is the tight skin category, which we call sclerodermoid, or tight skin graft-versus-host disease. And sometimes the tight skin areas affected are very localized and focal, but sometimes they're all over the place.

So, I'm going to show you different examples. And as you may imagine, the disturbance from this disease is completely related to how much of your skin is affected and where. Okay. So, on the left, you see an example of a gentleman who's got chronic sclerodermoid graft-versus-host disease as a little few circles on the back of his neck and upper back. Little itchy, kind of stands out, not a huge impact on his quality of life. Whereas the lady on the right has sclerotic graft-versus-host disease. Tight skin changes over her ankle, so she can't move her ankle. That's the problem. And if she moves her ankle too much, the skin tears or rips. So, different impact, similar extent of disease.

Other examples. So, these are examples of that pseudo-cellulite look where you see this really commonly on the flanks. If anyone raises their arms in the mirror, sometimes we have a little extra tissue in our arms but it doesn't pull. But when you have sclerotic changes there and what's happening is you're getting tightening specifically not just of the skin but of this layer called the fascia, which is what lines our muscles under our skin. Well, that's supposed to be loose, and forgiving, and elastic. But when it's not and it stays tight, you get this pseudo-cellulite appearance like I'm showing you here in the inner arms or again around the waistband very, very commonly.

So, when you see this look, it is almost always chronic sclerotic graft-versus-host disease of the deeper tissue layers. And so, these are all patients that have walked through my doors and patients that we have taken care of, so I'm just trying to show you some real-life examples.

17:00  How to determine if it is acute or chronic skin GVHD:  A few rules that I think I should point out for what it's worth. The description, like I said earlier of acute versus chronic, is, for the most part, thought to be time-related and I think that's mostly true. But about a decade ago the rules changed a little bit, and for good reason. So, it used to be before 100 days after transplantation is acute, and after 100 days is chronic. And we just took those rules, and we messed them all up and now it really comes down to what does it look like? The 100-day thing doesn't actually matter in terms of describing acute versus chronic, it's rather just what it looks like.

Does it look purple? Is it tight skin? Or is it that generalized measles-like rash? That's it. That's what determines whether it's acute or chronic.

As I told you earlier, there are some really unique sites that are affected with graft-versus-host disease that in the dermatology world in general just don't happen all the time. So, when you get a rash all over, and on the palms and the soles, and or on the face or the scalp, that is unique. There is a handful of rashes that do that rather than hundreds, and graft-versus-host disease is one of them.

The other interesting thing is you don't actually need a biopsy to make a diagnosis of graft-versus-host disease. So, skin biopsies are very commonplace for skin doctors or other doctors and it allows us to look at that inflammation that we see on your skin under the microscope, and it can be informative and it can be helpful, but it is not absolutely necessary.

What's absolutely necessary is to know that we are encountering a patient who has had a bone marrow transplant. The donor was someone other than themself, and they have a rash that looks like graft-versus-host disease. And in the right setting, that's it.

Now, the amount of comfort your doctor may have in making that call without a biopsy, the amount of experience they may have may dictate whether or not they do a biopsy. And that's okay. There's no harm in doing a teeny tiny little skin biopsy, but it's not essential to make the diagnosis. It would not be crazy for me to look at you and say, "That's it. I've seen that before. I'll see it again. And that's what you have and that's it," to make the diagnosis. And this is all based on the NIH consensus. So, the National Institutes of Health had a consensus statement in 2004 stating what I'm saying. So, we are about 15 years out from those recommendations.

19:35 Treatments for skin GVHD: So, let's transition now after showing you a few pictures of what it looks like, talking about how to treat it. I think we not only want to treat the disease, but we want to remember to treat the symptoms, right? The idea that we have graft-versus-host disease, may be bothersome, but so is the itching, and so is the pain, and so is the tightening. And so, we want to actually address the functional problems of skin graft-versus-host disease rather than just the philosophical being of the disease.

So, again, depending on what your circumstances are, it could be itching, it could be joint contractures and a decrease of motion, it could be that the skin is opening up and creating wounds. So, we'll walk through a couple of these things.

20:18  Dermatologists may be able to treat skin GVHD in ways an oncologist might not think of:  So, I do think it's important as a dermatologist to talk to you specifically about what is unique that dermatologists can offer to this discussion. And there are certain skin-specific therapies, but I think dermatologists are uniquely suited to offer as additional therapies in ways that you're very skilled oncologists may not think of. Right?

I think the larger, broader anti-rejection meds that are offered, your oncologist are experts at. And I rarely will see a dermatologist that's going to add to what your oncologist already knows there. But there are some things we can slip in as dermatologists where we add value.

First and foremost, it's with creams, right? We live in a world of creams and skin directed therapies. I think the picture here is about one-tenth of what's available to us to offer to you, and so that makes it very confusing for those that don't do it every day. But in a nutshell, this comes down to steroid creams or certain specific non-steroid creams that are anti-inflammatory that you can put on the skin to calm down inflammation.

21:20 Steroid Creams:  Taking a steroid by mouth requires that it goes through your intestines, through your liver, through your body, and what's left gets to your skin. Taking the steroid and putting it on your skin allows me to put a lot more steroid on your skin without it getting elsewhere in your body.

So, the value of topical steroids are hugely important even if you're on internal steroids. Study after study has shown this, so I wouldn't minimize the hassle of putting a cream on your skin because it really does add value in a way that internal sometimes don't.

There are different strengths of steroids. There are really strong and really mild and something in between. Sometimes, I will show you the example of a hot sauce chart and you can see that there's spectrums of that. It's the same in the world of topical steroids. And I tell you this because you have thick skin areas on your body like your hands and then you have thin skin areas like your face or your genitals. So, not all creams should go everywhere, but your dermatologist knows that, and they can dictate what's safe and appropriate for certain areas.

Other skin directed therapy includes phototherapy where we shine light on your skin or photopheresis, where light is exposed to your blood and I'll show you some visuals of that. 

22:18 Vitamin A pills to treat skin GVHD:  And lastly, there are unique pills that are used in the world of dermatology, but very rarely outside and specifically in this setting, Vitamin A pills, and in my experience it has to Acitretin, which is one of many Vitamin A pills. Others in the audience may have heard of Isotretinoin or Accutane, which is used for teenage acne, which is another Vitamin A pill, does not suppress the immune system, does not further complicate the toxicities associated with a lot of the anti-rejection meds used for graft-versus-host disease, but add value and calming down inflammation to the skin without interfering with the other things your oncology team is doing.

23:14 Phototherapy to treat skin GVHD: Phototherapy. So, let me focus on the two light modalities, phototherapy and photophoresis for a moment. This is a visual of phototherapy, which can be delivered with either ultraviolet A light or ultraviolet B light. The intent of phototherapy, what the ultraviolet light does in controlled doses under doctor supervision - so this is not just a tanning bed - is that it takes away inflammation in the skin. It specifically targets a type of inflammatory cell on the skin and allows that to shut off so it doesn't cause persistent inflammation. So, it helps with itching. It can help with skin tightening and it can physically make the rash disappear on the skin when sometimes creams aren't enough.

Why is this useful? Well, it's one less pill. It's our ability to deliver medicine to your skin and just your skin without taking something internal. So, what's typically done is a patient wears goggles to protect their eyes, usually wears underwear or some covering to protect their genitals, and otherwise is exposed when they walk into the light booth. And we turn the light booth on for most patients, 30 seconds on the first day and the next day, 45 seconds and the next day, 60 so far less than you would get in a tanning bed. You go usually three times a week and usually you go for one to two months, and that is an effective course. So, three times a week for one to two months, it's quite safe. It's quite quick.

24:40 Extracorporeal Photopheresis: The other light-based modality is called Extracorporeal Photopheresis which translates into light delivered to your blood outside of the body. So, it looks in some ways like a dialysis machine, you are connected to an IV, blood is taken out of your body. We shine ultraviolet light on the blood when it's out of your body, and then we return the blood back in. So, we take it out, we shine ultraviolet light, we put it back in. So, it's photo therapy, but just to the blood. And what this does through some still not totally understood but better understood over the last 30 years, is that it changes the immune systems inflammatory signals.

And so it controls and it balances the immune system. It regulates it. So, when it comes back in, it turns off the overactive inflammation signals and it increases the suppressor inflammation signal. So, it creates balance in your immune system.

So, why is this nice? It's also very safe, right? It's not an internal pill. It's quite safe. The issue with this would be that there are select centers that do photopheresis and select centers that do not, although it is throughout the country. It also takes a few hours to do and you're hooked up to an IV. But typically the most frequent cycle for photopheresis would be weekly, but most patients eventually are managed by coming into that hospital every two to four weeks to get their photopheresis.

26:15 Physical Therapy for Skin GVHD:  Other things to consider, especially for those that suffer from tight skin or sclerodermoid graft-versus-host disease would be emphasizing the role of physical therapy, right? It's the use it or lose it. If you have a frozen shoulder, the best thing you could do is to start moving it again. So, if you have a joint contracture, working with a physical therapist who maintain the motion that you have and to stretch the skin will help as would deep tissue massage and stretching. These may or may not sound basic, but they're quite important to remember as part of the cascade more than just prescription therapies.

26:51 Systemic steroids to treat skin GVHD:  And then there's a laundry list of options that your oncologist has available to them to also treat graft-versus-host disease. The mainstay of therapy is Prednisone, but as we know, Prednisone carries a significant side effect profile that we want to be wise for avoiding, and that's why there are many traditional immunosuppressants and other very promising therapies but I will say that this is not unique to dermatologic care. I think many times these therapies are helpful at treating skin graft-versus-host disease, but it's not solely reliant on a dermatologist to do. And so, for the sake of time and really valuing what I think I add to this, I'll simply provide you with a list of a sampling of the most common agencies. But I think for me to go through this in detail is probably not necessary.

27:39 Treatments for skin GVHD slightly increase the risk of skin cancer: I do want to close the canned lecture part, before we get into the questions, talking about skin cancer. Skin cancer can be an issue in patients who have graft-versus-host disease, but I want to emphasize it is not the graft-versus-host disease as much as it is the medicines used to prevent graft-versus-host disease.

So, in the world of dermatology, we see a lot more skin cancer on patients who take medicines that suppress their immune system. We also see a lot more skin cancer in patients whose immune systems are altered. So, by definition, if you had a bone marrow transplant, your immune system has been altered, so it increases your risk a little. If you have a blood cancer, a leukemia or lymphoma, your risk is increased. But if you take medicines that suppress your immune system, your risk is increased significantly more. The only population where I see more skin cancer is in solid organ transplant recipients because they take more medicine.

28:47 Types of Skin Cancer So, there's three main skin cancers we should talk about: basal vell skin cancers, squamous cell skin cancers, and melanoma. Those are the three most common in the world.

Basal cell skin cancers are the most common. They're also not terribly dangerous. They're pink, and they're shiny, and we oftentimes talk about them being pearly, meaning they have the sheen or the shine of a pearl. They look different. They do break down at times, bleed or ulcerate.

Squamous cell carcinomas are a little bit more warty in appearance. They're thicker, they're crustier, they have more scale on top, and they tend to be more painful. This is the cancer, more than any other, that is elevated in patients whose immune systems are suppressed.

So, in the world, basal cells are more common, but in the world of patients on immune-suppressing medications, squamous cell carcinomas are far in a way the most common type of cancer. These do have a low risk of spreading and being aggressive, especially in those on medicines who suppress their immune system.

And then malignant melanomas are probably the most common of the truly deadly skin cancers, right? It's technically not the most, but it's the most common, and the most discussed of the deadly skin cancers. And these are typically in odd dark color, blue, black, gray, brown, and they just look odd and asymmetric. And so, here are some examples of malignant melanoma.

30:27 How to Reduce the Risk of Skin Cancer: So, things that can be done to reduce the risk for skin cancer. Well, understanding that being on immune suppressing medications drive some of that. So, you do what you can within that, but there are other reasons that you're on at that are important.

And then protecting yourself from the sun, which we'll talk about.

And then lastly, just paying attention, right? Pay attention to your own skin. Get undressed and look in the mirror every one to two months or have a significant other look at areas that you can't like your back, like the back of your legs. If anybody in here has seen hair grow, it's a really slow process. Similarly, I would not recommend looking at your skin every day. Change is a really slow process, right? So, I really do mean every one to two months, not every day. You will never appreciate change if you look at the same thing every day, you got to revisit it every month or two. Give it some time to change if it's going to.

31:23 There’s no such thing as a safe tan:  See a dermatologist if you're higher risk, meaning your fair skin and meaning you're on medicines that suppress your immune system. More often, if you are producing skin cancers. There's no such thing as a safe tan.

People tan as a physiologic response, as your body's response to sun damage. You damage the skin with sun, it says, "Oh, no. I should try and be darker, so that the next time I see sun, I'm not as damaged." But the damage has already happened. So, the tanning before we go on vacation, it's a terrible idea, right? Tanning. If you tan, you were sun-damaged. Check.

32:09 Sun-Protective Clothing: Okay. I really think that clothing is the most important thing when it comes to sun protecting. Wide brim hats, clothing, keeping sleeves long, keeping pants long.

If anybody here has ever traveled abroad, the warmest places in the country are filled with locals who wear hats, who wears sleeves, who stay indoors during the middle of the day. The people who have tank tops, and shorts, and sunscreens are tourists. Okay. So, clothing is far and away the most effective way to protect you. Okay. If you put sunscreen on, you have to reapply every 90 minutes. If you put a shirt on, it'll stay on. You don't have to remember to keep the shirt on. 

33:00  Use sunscreen that is at least SPF 30 and reapply every 90 minutes:  If you use sunscreen though, you've got to use a lot, and so there are different labelings and this is the FDA's way of confusing us a little bit, but I will tell you as a bottom line, SPF 30 is good enough. The bigger numbers are fine, but there is a very small incremental benefit when you go from an SPF 30 to an SPF 70. There's a very small benefit, but there is a huge benefit going from something below 30 up to 30, so it is not linear. It's really helpful to get to 30. Once you get above 30 you probably feel better that you're putting a 50 or 70 on, but you still got to reapply after 90 minutes.

You got to put it on every day. Ultraviolet light is able to penetrate through clouds, so even on a rainy day or a cloudy day, you can get sun damage. Sunscreens lasts for 90 minutes, that's as long as they last. So, you put it where you're not covered with clothing.

Sunscreens only lasts for 20 minutes or less if you go on the water. So, they have removed the word waterproof from sunscreen. They now say water resistant or something else, but it's their way of saying it'll work for a little bit. Again, clothing stays on when you go in the water. Sunscreens wash off.

So, I will end. I want to say again, I'm really thankful to my patients. Most importantly, my colleagues who are excellent, the mentors that I've had along the way and my family. This is a picture of my daughters who I'm sadly away from right now. And this is my father who had AML and had an allogeneic transplant and was transplanted at our institution and did very well for short period of time after. Unfortunately passed two years ago submitting to his disease. But this fight that you guys have is very real to me and I and I applaud you guys all for what you're doing.

34:58 Question & Answer Period [Moderator] Now I'd like to take some questions to both of our guests, Dr. Anadkat and Dr. El Jurdi. Wait until you have a microphone please, so you can ask the question and we can all hear it. Yes ma'am. Right here.

35:11 Is special sun-protective clothing worth the cost?  [Audience] Hi, my name is Jennifer and the great presentation. Thank you. I have skin GVHD. My question to you is how do you feel about, you mentioned clothing as a obviously more permanent form of sunscreen than the topicals, but I wear Coolibar and some SPF clothing. It's quite expensive and it's not necessarily my style because it's limited in its look. Is there a benefit to wearing that? Is it really work? I have noticed I wear it, I live in California where it's very sunny, and I still find that I get a little bit of burn sun irritation while I'm wearing it. Like through the car window or just outside. So, is it true, does it work? Does it last? What's your thoughts on that?

[Anadkat] Sure. So, the question of sun-protective clothing, and there are specific brands that are marketed to be sun protective. The technology of those fabrics are beneficial compared to everyday fabrics. It comes down to how tight the fabric is stitched. And so, a loose white tee shirt, if you pull it, you can see through a little bit easier than you could more tightly woven fabric. So, I think they make efforts to be more tightly woven. They also make efforts to have sun protective material within the clothing that doesn't wear down, so there are benefits.

But I will emphasize that clothing period, is more beneficial than sunscreen. I think sun protective clothing has added benefit, but I think that's most important when you're out for hours on the beach, if you're swimming in a pool where sometimes once the clothing gets wet, it's a little bit more porous and able to get through.

I've found not just the marketed brands but a lot of sporting goods stores will sell that, and so instead of these online brands, which are good, but like you said, there's a limitation on fashion and as my wife will tell you, I shouldn't be dictating your fashion. Sporting goods store oftentimes and sporting sections of Target and Walmart even, like stores that aren't necessarily as high priced will have these options of long sleeve sporting shirts that have a UPF, which is how their clothing is labeled, a universal protective factor.

So, do I think it's helpful? Yes. Do I think that's your only option? No. Look, California's more hot than St. Louis. And the sun is more intense than it is in St. Louis. And so, I know that when patients go there they feel it more. And we talked earlier also about the damage that happens to your sweat glands, so you may feel hot because of that, but not so much be getting sun. Right? So, I think those two things aren't necessarily related to the quality of your clothing as much as the fact that that greenhouse effect in your car in California is making you more hot than it may from where you're coming from.

38:01 Are hyperbaric oxygen chambers or laser treatments helpful for skin GVHD: [Audience] One thing... I've got skin GVHD and everybody's got an answer for what I should be doing, that kind of stuff. And you didn't mention anything about and maybe I butcher this a little bit, but the hyperbaric chambers or laser treatments, do you think that those are viable options to consider to help reduce or treat some of the symptoms, or are you finding that they don't really have an effect?

[Jurdi] Laser therapy on top of what we discussed?

[Anadkat] So, I think there's low-level laser therapy, which is oftentimes discussed as a modality to help with sores from graft-versus-host disease, especially in the mouth, it's discussed. And the other discussion that you had was for hyperbaric chambers. I assume you mean hyperbaric oxygen chambers?

[Audience] Yes.

 [Anadkat] They're totally different. So, low-level laser therapy has limited evidence. So, could it work? Maybe. Does it definitely work? Not necessarily. And so, would I recommend it broadly? No. Does that mean it couldn't work for someone? No. But I think the quality and extent of study that's been done for that therapy is quite limited. The publication of marketing has been broad, but the actual study has been limited.

Hyperbaric oxygen I think has a role for wounds, which sometimes does plague people with especially sclerodermoid or tight skin graft-versus-host disease because once it ulcerates... Anytime you have a wound, the way that the wound heals is by attracting the skin around it to come back and close up the wound.

Well, if the skin around the wound is not healthy, it's tight and has graft-versus-host disease, it's much harder to recruit cells from an unhealthy surrounding. So, hyperbaric oxygen, along with a lot of other modalities, not in and of itself, can help sometimes for chronic wounds, but just as much as simple wound care, and compression, and making sure it doesn't get infected.

So, I don't think either of those things are necessarily panaceas where you have to do it and if you're not, you're missing out. Do I think there's a role? Maybe. But I think as you have probably suspected too, when things sound that good, it's hard. Like it's hard to give credit to any one thing.

The world of medical devices are also different than the worlds of prescription, right? The process of getting a medical device approved is a lot less cumbersome than the world of getting a drug approved. So, it's easier to get these things on the market sometimes, which is maybe why they're more broadly used but less well-understood.

[Jurdi] Yeah. And I would add to that, always ask your oncologist and go back to them. You hear a lot of random things over the news and a lot of modalities that are, for example, being used for wounds, not within the GVHD world that are being kind of marketed as possible therapies for GVHD. So, it's important to make that distinction and go back to your oncologist and see if any of these therapies are being used within the clinical trial for GVHD patients and not go to the community to use devices that have not been approved for GVHD specifically yet. So, always within a clinical trial for things that are new, and we don't know how well they work in GVHD specifically.

[Moderator] You have a question over here, sir?

41:34 Recommendations for Outdoor Protection [Audience] Yes, sir. I like to enjoy my sports. I'm a golfer and I have skin GVHD. Now, I'll wear a windbreaker and just my golf hat. Okay. Should I be putting lotion on my back of my neck or anything? I mean, I don't feel it. It doesn't feel like it's bothering me, but I'm out there and I'm playing. Okay. I'm above ground and I'm doing it. So, that's my attitude.

[Anadkat] Right. No, I think that's great. And I also love my sports, and I love being outside and I am a terrible golfer, but I love to do it. And so I get it. And so knowing what I know about golf is that most people like to golf on pretty days. The diehards will golf any day of the year, and I think God bless you if you're doing it on New Year's Eve in St. Louis, but usually, it's a sunny day when you're out there. It on average takes people four to five hours to golf 18 holes. And so at the very least you want to make efforts to, to sun protect or reapply at the term, right at nine holes to reapply. The question of should I put it on my neck or not? I mean the proof's in the pudding. Is your neck darker than your back?

[Audience] No.

[Anadkat] Then, you're probably not getting as much sun. Right? But what type of covering do you have? Do you have a collared shirt? How big is your hat? Right? I mean, so clothing dictates most of it, right? And I think most of your benefit is there. Your body was made to get a little bit of sun. Burns mean you got too much. Tans mean you got more there. And there are many people where they come in, and we take their shirt off and there is a band on their neck where it's dark and the rest of their back is white. Well, we take a picture and I show the patient. I was like, "Why do you think this is? Why do you think your neck is a different color than your back?" And so, that's fine. So, the proof is in the pudding, but I think making efforts is what you want to do. The goal is not to restrict you from living and restricted for being outside, but it's to be smart about it.

[Audience] Well, yeah. I mean I go out with a jacket, wear long sleeves, put a hat on and walk to the mailbox like that.

[Anadkat] I think that's great. I think sleeves and a hat are good. And I've also found that wearing sleeves when I golf offers me one more excuse as to why I'm not very good.

[Moderator] A question right over here.

43:52 Hyperbaric oxygen therapy for sclerotic skin:  [Audience] Hi. A couple of quick questions. With regards to hyperbaric oxygen therapy, is there have been any studies or about treatment in sclerotic, very tight, sclerotic skin without ulceration or is it really just for wounds and ulcerations? Potentially.

[Anadkat] So, if I understand that the question is the hyperbaric oxygen and utility in sclerotic graft-versus-host disease-

[Audience] Without ulceration.

[Anadkat] Is there any study? Not that I'm aware of.

43:02 Compression Treatments for Tight Skin [Audience] No. So, not aware of. And have you ever heard of something called Physio Touch or LymphaTouch? It's some sort of a machine that I think does some sort of a vibrational therapy for the tight skin. I went to a conference a couple of years ago where somebody just swore by it, one patient, but I'm wondering if you've ever heard of it or know anything about it.

[Anadkat] I've heard of devices like this. They’re lymphatic presses.

[Audience] Right. And cupping and that kind of thing.

[Anadkat] Yeah. I think the idea of having some compressive device to help with symptoms, if that helps you, that's fine. I think sometimes when you have sclerotic changes in the skin, it affects the lymphatics, which are the drainage pipes that prevents you from being swollen. So, I think a common scenario where that's done is for the breast cancer patient who's had a lymph node surgery, and then they have a swollen arm. So, those types of things are more broadly used in that setting. So, for sclerotic disease, it's harmless.

 [Audience] Right.

 [Anadkat] Is it essential? Not necessarily for everybody, but I think this is one of those things. Is it equivalent to a deep tissue massage for you? Is that equivalent to stretching out those bands?

Right. Because that's what they are saying that it's just going to try and break down the fibrosis, but again, massage might do the same thing. At best. But I do think it's harmless and I think some of these things, right, you have to follow your gut, you have to follow your oncologist's guidance. But at the very beginning, our goal would be to do no harm.

45:43 UVA and UVB Treatments [Audience] Sure. Absolutely. And with regards to UVA treatments, do you prefer the UVA one or the Narrowband UVB, and you use it with or without psoralen. And what about proof of baths? And what about any risk of increased risk of skin cancer being?

46:00 [Anadkat] These are great questions. So, this goes down to the phototherapy question and I sort of loosely went over that. There's UVA and UVB. The truth is, as you've alluded to, there's different types.

So, there is two types of UVA phototherapy. One is where you take a pill called Psoralen and that makes you sensitive to light, and then you go in the Light Box about 30 minutes later. So, that's P plus UVA, PUVA. And PUVA will increase your risk for skin cancer, period. We don't really use that for graft-versus-host disease anymore.

There is UVA one which is just a portion of UVA light spectrum where it's just half of that spectrum. And the idea with that is because it's a longer wavelength of light, it goes deeper into the tissue, but that is not universally available throughout the country. There are very few centers in the country that have UVA one, and it's a longer treatment.

And then the most common that's available now is Narrowband UVB. And that is my preference for most because it's quick. You are in and you are out in seconds to minutes, whereas the others are longer. And there have been studies that have shown that patients who have had 250 plus treatments of Narrowband don't have an increased risk for skin cancer because of it.

So, my preference is Narrowband as opposed to the UVA because one, UVA is rare and hard to find, and takes a long time. And the other UVA is going to cause skin cancer whereas the UVB one, that's most commonly available in any dermatologist office. Right? So, even with the dermatologist who's not comfortable, it's the most common type of phototherapy across the country is Narrowband UVB.

 [Audience] And should you use-

[Moderator]  Can I just jump in for a moment? We just want to make sure everybody gets a chance to raise questions. So, can I suggest maybe approach the doctor afterwards because I know you have a whole long list, and he's a great guy. I'm sure he'll be happy to answer your questions.

 [Audience] No problem.

[Moderator] Thank you so much. There was another mic. Who has the mic?

 [Audience] I have it.

 [Moderator] Yes ma'am. Go ahead.

48:05 [Audience] Does GVHD cause skin and joint pain? I have a question about joint pain and skin GVHD. Is it related to the GVHD or could be like other underlying causes like arthritis or something?

 [Jurdi] Yeah. Very good question. So, joint and muscle problems and pains are very common in chronic GVHD patients. And they could be related to a skin chronic GVHD because of the skin tightening that restricts the joint movement, and therefore causes deeper joint inflammation and decrease in the range of motion.

But they could be chronic GVHD-related inflammation in the muscles surrounding the joints that eventually causes that joint to be under a lot of pressure, under a lot of inflammation, and therefore decrease in the range of motion.

And it could be within the joint itself. And remember also common things being common, it could be just an arthritis issue.

So, I think certainly it could be multiple reasons causing joint issues in patients with chronic GVHD, either skin, or inflammation in the muscle, or inflammation in the joint or different degrees of just kind of regular arthritis. That would happen with time as well.

49:25 [Audience] Seaweed Baths Hi. I have GVHD of the skin. I had a question in regards if you've ever come across anybody who found relief from seaweed baths. Prior to my diagnosis, I would love to take a seaweed bath. It was the best thing for my skin, for my joints. Do you think there's any adverse effects because now I have the GVHD to still continue doing that? Have you ever heard of it?

[Anadkat] I have heard of seaweed baths. I will be honest in that I don't know as much as I'd want to know about this to answer the question. But my-

[Audience] There's lots of healing properties in seaweed.

 [Anadkat] No, no, no, no, no. I read about that and I appreciate that. So, I think the way I would answer this is I'd want to know about the seaweed bath like components. I'd want to make sure that you're not having any skin irritation secondary to it. I think some of the issues that I run into when people use plant-based therapies, in general, is allergic contact dermatitis or secondary irritation to the skin because your skin is different post-transplant than it was before.

 [Audience] I haven't done that since I've been diagnosed. That's why-

[Anadkat] So, are you more sensitive? Are you more prone to an allergic reaction or an irritant reaction on your skin? So, it'd be the type of thing that I would probably do a test area rather than an immersive bath.

[Audience] A full immersive... Okay.

[Anadkat] And I think that's really the risk. That's the risk but that would be with anything, seaweed, or something independent. Now is it beneficial? That I think is up to you, but I think the harm is going to come in the irritation with some of these plant-based therapies.

 [Audience] So, to do a test area first?

 [Anadkat] Right. So, I always tell people like natural can be good, but poison ivy is natural also.

[Audience] Yeah. I know.

 [Moderator] We have a gentleman over here in the back. Sir.

51:16 Recommended Topical Steroids [Audience] I want to thank you very much for your presentation. I've had a lot of trouble finding a dermatologist who understands anything about GVHD. So, I think you really brought an amazing skill set today. And with that in mind, I just want to ask you what would you recommend as a topical steroid for chronic skin rash GVHD? That it's not any of those sort of sclerotic ones that you put up on the board that I'm glad I don't seem to have right now. But just something that you would say is generally... I've been using Clobetasol. It's the only thing that my oncologist has ever seen fit to recommend, but I've been using eczema cream just because I'm buying it and it seems to make me feel better. But what would be your kind of go-to baseline recommendation for that chronic skin rash, itching GVHD?

 [Anadkat] Okay. So, I have a feeling that there can be more that we talk about after but I will give you my overview answer which is any topical steroid that works is, first of all, a good idea. Clobetasol is one of the category of the strongest topical steroids that are in existence. The overview on topical steroids is, if you put it where you have skin inflammation, when you have skin inflammation, and if you stop it when you no longer have skin inflammation, you're fine.

If you open the package insert it'll say to not use for more than two weeks, but that is written by non-dermatologists. So, any dermatologist is fine if you use it where you have the rash when you do. Clobetasol shouldn't be put on the face or the genitals, but otherwise, it's probably okay. But I can get into some more details maybe on the side because some of these sound like there may be a little bit more specific, but everybody's skin's a little different and everybody's skin issues is different. So, I do think we have to individualize it.

 [Moderator] Okay, folks. We have time for one more question. Sir.

53:29 [Audience] Chronic GVHD I've also heard that the effects of chronic graft-versus-host would fade over time. And so, I was looking at reducing some of the medications and like the photopheresis and stuff. And it seems like, well, I was doing this somewhat okay, I guess. And then after I reduced it ,it like, got way worse, and they kind of tried to be encouraging and say that you can recover from that, but now I'm learning that you don't really recover too much.

So, it seems like, at least for my case, if anything, I probably should have been looking at increasing what I was doing. I haven't been doing photopheresis, and Imbruvica, and those pills that started with an M, so the three of them I had been doing and I cut out the photopheresis and the Imbruvica and then it flared up really bad in my muscles and stuff.

So, what's your experience? Does it really fade over time or is it more a case where you need to be maybe looking at increasing what you're doing to stave off further effects?

[Jurdi] So, we can certainly talk about this a bit more afterwards. There is no doubt that chronic GVHD is called chronic for a reason and it's because it is a disease that we have to deal with and for a long period of time. And as what was presented earlier today is not really a straight path. And that's, unfortunately, the reality for most patients with chronic GVHD if it affects multiple organs. So, the answer to your question really would depend on what are the organs that are affected and to what extent? And that could help answer your question better. 

Thankfully though, with the message that we're trying to give today is that there are a lot of new therapies that are coming up for chronic GVHD, and so there's always hope. Right? And of course, the reason why we're coming up for these therapies is that we want to try them in patients like yourself who've had multiple lines of therapies before to try to control the disease better and then slowly take you off the other therapies that you've been exposed to before. So, it's really not a straight path. And the reason why we have new therapies is that we want to improve on that and decrease the number of therapies whether ECP, photopheresis and multiple different ways we approach chronic GVHD by introducing some novel therapies for that.

 [Audience] Just be careful about moving because I tried going from the Imbruvica to-

56:37 [Moderator] We really have to keep moving because we really need to wrap up our time here because we're going to send you off to grab lunch in the main room over there. And bring it on back in here because there's going to be a great presentation during the lunch. Finally, before you go, how about a wonderful round of applause for our speakers.