Graft-versus-Host Disease of the Skin and Fascia

Transcription:

[00:01] Welcome to the workshop, Graft-versus-host disease of the skin and fascia.

[00:06] My name is Michaela O'Brien, and I will be your moderator today.

[00:10] I would like to thank Incyte, whose support helped make this workshop possible.

[00:16] It is my pleasure to introduce today's speaker, Dr. Michael Stephens.

[00:21] Dr. Stephens is a dermatologist who specializes in outpatient complex medical dermatology and inpatient consultative dermatology at Mass General Brigham Cancer Institute.

[00:29] He is interested in cutaneous diseases affecting stem cell transplant recipients with a particular focus on graft-versus-host disease.

[00:41] Please join me in welcoming Dr. Stephens.

Dr. Stephens:

[00:47] Hello.

[00:47] Hello, everyone, and thank you for joining today and thank you for that introduction.

[00:53] I'm very excited to be able to speak with you today about graft-versus-host disease, specifically of the skin.

[00:59] We'll talk about a lot of hopefully helpful concepts related to thinking about skin health after a transplant and ways that you can support your skin health and think about ways that GVHD can show up in the skin.

[01:11] We'll dive in and more or less kind of take a tour through what is a bone marrow or stem cell transplant.

[01:19] It will be brief, but it is important to at least just lay a little bit of groundwork to then talk about further concepts related to acute graft-versus-host disease of the skin and then chronic graft-versus-host disease of the skin.

[01:36] In addition to some of the more common rashes that many may often think about in the context of GVHD, we'll also talk about GVHD of the skin, the nails, the fascia, and hair.

[01:44] We'll spend a lot of time talking about treatment options and ways that you as patients and family members can take care of your own skin and self-care strategies.

[01:56] We'll also spend a fair amount of time at the end reviewing any questions you have related to all of this.

[02:06] I do have to qualify, the presentation of skin diseases that can sometimes be a little bit striking.

[02:12] I'll try to give you warnings, but you may see some photographs that might be slightly graphic.

[02:18] Just be aware of that as we go through the slide deck here.

[02:26] Briefly, we're just going to spend one slide here talking about what a bone marrow transplant is, what a hematopoietic cell transplant is.

[02:30] This is a process that primarily involves high-dose chemotherapy, potentially with radiation, that is intended to address a disease of the bone marrow, such as hematologic malignancy like leukemia.

[02:48] In the process, stem cells are taken and they're infused into the bloodstream, and this is going to replace the bone marrow it's going to be.

[02:54] This is the transplant itself.

[02:54] Those cells travel into the bones and rebuild the immune system in the process.

[02:59] There are different types of transplants.

[03:06] Sometimes you might have a transplant of your own stem cells, but we're primarily going to be focusing on the context of GVHD is a transplant from a donor, from somebody else, what we call an allogeneic transplant.

[03:16] And this can come in different types of… there are different forms of these depending on who the donor is, and that's not quite as relevant to what we're going to be talking about today, just kind of highlighting here that different forms do exist.

[03:32] Of course, many of the most common conditions are conditions that you may be familiar with or have had transplants for.

[03:38] So leukemias, lymphomas, myeloma, myelodysplastic syndromes, aplastic anemia, and certain immune disorders.

[03:46] In the context of that, then what is GVHD?

[03:54] The way I want you to think about this is GVHD is when that new immune system from the donor causes manifestations of disease in different organs as it kind of sets up and starts to function.

[04:09] What is really happening in the body to trigger this?

[04:16] We talked about that infusion of the donor stem cells and what can occur in the context of everything that happens, the changes in the body that happen as a part of the transplant and the immune system activation, the signaling that occurs in the process of all of it, that those donor T cells might recognize the patient, you know, the person who's receiving the bone marrow transplant, their skin, their organs as foreign.

[04:41] And when that occurs, those T cells, these immune cells of the body, and in the process, attack host organs and tissue, and that leads to the development of GVHD symptoms.

[04:56] GVHD is really important, and it's something we think a lot about.

[04:56] It can affect many patients, and it is a leading cause of non-relapse morbidity after BMT. And so, this is a key thing that we want to minimize; we want to recognize first, and treat, and minimize as much as possible.

[05:19] The incidence, thankfully, is decreasing, but we still have more work to do, and we still want to be well aware of this.

[05:24] How does this happen?

[05:24] What are the different types?

[05:31] When should you start to think about this?

[05:31] As I mentioned very briefly on an earlier slide, there are two primary forms, acute GVHD and chronic GVHD.

[05:36] And acute, of course, the name kind of implies; it's an earlier onset.

[05:44] It's something that happens more quickly.

[05:44] And that very commonly affects the skin.

[05:51] It can affect the gut.

[05:51] It can affect the liver.

[05:51] It's characterized by a more rapid onset and a lot of inflammation.

[05:57] We used to think about this distinction of 100 days.

[06:04] Everything before that was acute and everything after day 100 was chronic.

[06:09] We've come to learn that that's not perfect, but it can be a kind of helpful general way of thinking about things.

[06:18] Chronic GVHD classically occurs later, as you know, again, as the name implies.

[06:24] It can affect many different organs, not necessarily the same organs as what's affected by acute GVHD.

[06:30] I want to highlight the predominance of skin and mucous membranes in the context of this.

[06:36] The skin is a very common location where it manifests, the eyes, the mouth.

[06:41] And then sometimes, patients may have involvement in the lungs or the liver, sometimes in their joints or their GI system.

[06:50] And the character tends to be more reflective of other types of inflammatory diseases or autoimmune diseases of these organs, including the skin.

[07:01] With that background now, we are going to migrate in and take a closer look, more detail at specifically GVHD of the skin and fascia.

[07:12] The first slide we're going to dive that we're going to first discuss acute GVHD.

[07:18] We're going to progress sequentially, you know, chronologically in time.

[07:22] With acute GVHD, what I really want, I'm going to show you some pictures.

[07:27] I would encourage you to not necessarily try to self-diagnose, always involve your providers, involve your physicians, and of course, if necessary, involve a dermatologist to help you understand if you do see something happening on your skin, but to give you the framework of what we're looking at.

[07:42] I'll show you some pictures in the context of this.

[07:49] So what to look for?

[07:49] It's often can be a pretty diffuse salmon pink or red rash.

[07:49] It has a localization oftentimes for what we call acral surfaces.

[07:57] So that means more distal kinds of things like the palms, the soles, sometimes the ears or the tip of the nose.

[08:03] It can often involve, in addition to that, the trunk and extremities.

[08:11] It can be an itchy rash, though sometimes it might be associated with some skin pain or tenderness.

[08:16] You can often think of it in kind of mild to moderate cases similar to a sunburn.

[08:22] And then like a sunburn, if it's more severe, you might have development of blistering.

[08:27] As I mentioned, it tends to be a little bit sooner.

[08:33] So we talked about that day 100 distinction.

[08:33] Again, I usually think about a couple of weeks after transplant is classically when it develops, though.

[08:39] Nothing always follows the rules 100%.

[08:45] And I mentioned on a previous slide, you know, it can come with sometimes GI involvement, classically diarrhea, and then liver involvement.

[08:51] We always try to look out for that too if we're concerned about acute GVHD of the skin.

[08:57] The way we grade it, the way we think about it is really just in context of how much involvement there is.

[09:03] If it's more limited, it's of course grade one.

[09:09] When it's more severe, when you have that blistering kind of phenotype, that's when we label at grade four.

[09:14] The next slide, I'm going to show you some pictures here.

[09:14] You can just see some examples of something similar to a sunburn.

[09:22] We don't have to get perfectly into the fine-tuned details, but it tends to be kind of a full-body rash like this.

[09:31] I will qualify again for that previous disclaimer I made.

[09:37] Involve your providers if you're concerned or you see a rash, because there are many different types of rashes that can happen in the post-transplant period, GVHD being only one of them.

[09:49] So you want to make sure that, you know, the rash is appropriately diagnosed and then appropriately addressed.

[09:53] As I mentioned, there are other types of rashes that can develop.

[10:00] Sometimes medications can cause rashes.

[10:00] This is a very common thing that we see in the hospital, especially after transplant.

[10:05] Sometimes an infection, even something as simple as the common cold.

[10:11] We don't classically think about that as causing rashes.

[10:11] I have an availability bias doing this often, and we absolutely see viral rashes.

[10:15] Then there are other processes, something we call engraftment syndrome or rash of lymphocyte recovery.

[10:20] You don't have to worry about the nuances of these, all to say they exist.

[10:26] And again, all the more reason to just be aware of the whole array of rashes that can happen.

[10:40] On the left, I'm showing another example of acute GVHD, but this where you have more of that kind of blistering phenotype.

[10:46] We're going to transition now from acute GVHD to talking more about chronic GVHD.

[10:54] And we're going to focus on the theme of this section, on the skin.

[11:00] And so when you're thinking about chronic GVHD of the skin, it comes in several different forms.

[11:06]  I want to highlight here the way I think about it is do you have skin thickening or do you have, do you not have skin thickening?

[11:15] That's really the distinction to kind of further subdivide chronic GVHD, this form of skin GVHD.

[11:23] Many people can have kind of very transient, classic kind of rashes.

[11:29] They're red, they're scaly.

[11:31] They look a lot like a condition we treat in dermatology called lichen planus.

[11:36] It can affect the skin.

[11:36] It can affect the mouth.

[11:36] It can affect sometimes the genitalia.

[11:43] This is what we call lichenoid, the kind of medical, the kind of jargon that we use to describe this type of rash.

[11:49] Sometimes what can happen is as a complication of GVHD, the skin can harden, it can thicken, and we call that sclerotic GVHD.

[11:56] This goes by a lot of different names.

[12:03] Sometimes we call it scleroderma.

[12:03] Sometimes we call it morphea another term that's sometimes used.

[12:10] But what happens is that the skin becomes very firm.

[12:10] It can affect multiple layers and kind of go deeper down into the skin.

[12:17] It can potentially affect mobility if it's spanning a joint.

[12:22] We'll talk about that.

[12:22] And more details about the treatment of sclerotic GVHD.

[12:30] Then last, we have poikiloderma.

[12:30] This is another kind of jargon term, but it means you have a mix of dark spots and light spots.

[12:30] Hypopigmentation, hyperpigmentation and hypopigmentation with some dilated blood vessels, what we call telangiectasias.

[12:46] It's very common on sun-exposed areas.

[12:46] The upper chest, the upper back, the sides of the neck, these are areas that tend to get more sun exposure.

[12:46] You may not necessarily be thinking about putting on sunscreen.

[13:00] However, chronic GVHD can come in many, many different forms.

[13:00] You can have, there's many different symptoms that can present dryness, itching, burning, tightness.

[13:07] Sometimes people can have eczema-like presentations, just like routine eczema.

[13:14] They can have psoriasis-like presentations.

[13:20] These are very kind of generic rashes that we see in dermatology all the time and can be a manifestation of GVHD.

[13:31] These are just to give you some examples of some pictures of what to look for.

[13:35] This is that quote-unquote lichenoid presentation, that kind of more superficial rash look for chronic GVHD.

[13:44] Some of these photos, are subtle, but you can see the kind of pink and scaly rash on the back of this person's hand.

[13:52] You can see a more diffused kind of pink scaly rash on the upper shoulders of this person.

[13:59] The next slide is a little bit graphic.

[13:59] There is a picture of a wound.

[13:59] I just want to warn you up front.

[14:04] This is from a publication in the literature that shows the different ways that sclerotic GVHD can show up, all right?

[14:11] This is that tissue fibrosis, that skin thickening kind of a way that this can happen.

[14:17] Sometimes it can be very localized.

[14:17] It often likes to go to the forearms, the hips, the thighs, sometimes the lower legs, over the ankles.

[14:23] Those are some examples in the A panel in the upper left and the B panel in the upper middle section.

[14:29] Patients can have more widespread involvement, and that's when we call it scleroderma.

[14:37] That's when all of the skin can really become very thickened and firm.

[14:41] Then there's another phenotype where it's a little bit deeper, what we call fasciitis in the D panel in the lower left.

[14:48] The middle lower panel, E, and the lower right panel, F, are intended to demonstrate some things we really want to look out for to stop as much as possible and as early as possible.

[15:03] If the process goes across a joint, it can become difficult to use that joint.

[15:09] So this person is having difficulty stretching their fingers all the way out.

[15:15] And then over time, that thickening makes it very hard for the skin to heal.

[15:23] And so if you develop a wound of the skin, it's hard for the body, the healing mechanisms, to close that wound up.

[15:28] As a result of that, they might become progressive and develop, those wounds might progress and become larger and larger.

[15:33] We really, really want to avoid this.

[15:38] We do everything we can.

[15:38] I work closely with the, you know, transplant oncologists to address this, manage wound care, to help this heal, because this is, this is a serious problem that we want to fix.

[15:51] Now we're going to transition and talk a little bit about some specific areas that chronic GVHD, in particular classically, can show up in other domains.

[16:05] We talked a lot about the skin, and now we're going to talk about hair, nails, and fascia, okay?

[16:10] First, I'm going to show you some examples of GVHD in the nails, and these are some kind of classic ways that it shows up for patients that I take care of.

[16:25] The first is nail ridging, or what we call onychorrhexis, and this is where you have  these lines, basically ridges that develop along the length of the nail.

[16:31] They can be a nuisance.

[16:39] Understandably, people can be bothered by this.

[16:39] Generally speaking, it's not a problem.

[16:39] It doesn't damage the nail or the nail function.

[16:46] It is challenging to manage.

[16:46] If I'm honest, it's difficult to make it go away.

[16:51] The other two slides, the other two panels here, though, I really want to emphasize because this is where we want to intervene.

[16:57] Sometimes as a manifestation of GVHD, the skin around the nail that kind of folds along the edges of it can become inflamed and scar into the nail, just like a scar anywhere else on your body, a wound or something you had cut.

[17:21] When it happens in the nail, and especially in the nail factory, kind of the apparatus that our body uses to grow a nail, the nail can eventually go away.

[17:26] Once it's completely scarred, we can't bring it back.

[17:32] So the panels, the two right panels are kind of showing two stages of a spectrum where the fancy term we use is pterygium, which is just jargon for scarring.

[17:44] When that pterygium, that scarring progresses to damage the nail factory, we call it anonychia.

[17:50] This means no nail.

[17:50] Sometimes we can try creams, sometimes we can try steroid injections.

[17:57] These can help to minimize the inflammation that's driving this process.

[18:03] Know that this process can affect both fingernails and toenails.

[18:03]  I really encourage you to seek out a dermatologist, especially a specialist in this condition.

[18:10] If you're able to, if your oncologist or you are concerned about development of this scarring process, please, please, please let us work on this and try to reverse it as much as we can.

[18:28] Moving from nails into some of the deeper tissues of the skin, we're going to talk about GVHD of what we call the fascia.

[18:33] The fascia is this connective tissue that exists underneath the skin.

[18:37] It wraps around your muscles, your tendons; you can develop inflammation of that layer as well.

[18:46] In the process, it can cause inflammation, scarring, and that same tightening kind of reaction that I showed you an earlier picture of.

[18:55] How do you know this is happening?

[18:56] What are some signs or symptoms you should look out for?

[18:59] The skin may feel what we call indurated, bound down, tight, really hard to; it just feels tight.

[19:05] It feels like something is pulling it.

[19:10] Just like more superficial scleroderma, you might have involvement across a joint that affects the ability to bend that joint.

[19:16] Sometimes imaging can help to demonstrate this MRI or even a deep biopsy of the fascia can show it.

[19:23] There often can be overlying sclerotic skin GVHD.

[19:30] So that's a key thing.

[19:30] There's a dermatologic condition called eosinophilic fasciitis that it can mimic.

[19:36] I won't belabor that just to state that there is a lot of overlap with skin conditions, autoimmune skin diseases that happen in patients who have not had a transplant.

[19:50] Why does this matter?

[19:50] Why is it important?

[19:50] It matters because it can be functionally impacting.

[19:57] If you have that tightening of your skin, it can be hard to use that part of your body.

[20:02] You may have difficulty stretching an arm all the way out or difficulty stretching a leg all the way out.

[20:08] It can lead to swelling in the arms and legs and associated discomfort and pain.

[20:13] We can address this.

[20:15] These symptoms do not have to; we do not just let this go.

[20:21] Identifying it, recognizing it, making that diagnosis lets us then pursue treatment options that can either arrest this process or ideally start to reverse it.

[20:31] Physical therapy and immunosuppression are critical to preserving function.

[20:39] All right, so we've talked about acute GVHD.

[20:41] We talked about the skin.

[20:43] We talked about chronic GVHD of the skin.

[20:45] We discussed nails.

[20:47] We discussed fascia.

[20:48] We're now going to talk about hair as the last domain, if you will, of GVHD.

[20:54] I want to highlight that hair loss happens for many reasons, and it's a consult that we often have in dermatology.

[21:00] In my clinical practice, you want to keep an awareness.

[21:00] You don't want to anchor on a single diagnosis because the reality is there are many reasons to have hair loss.

[21:14] The two most common ones that we primarily think about after a bone marrow transplant would be chemotherapy-related and then GVHD-related.

[21:21] zzthis is important.

[21:21] Chemotherapy-related hair loss is kind of what you classically think about in the context of getting chemotherapy.

[21:34] It usually begins about two to four weeks after the conditioning regimen.

[21:34] It's the stress on the body, the kind of effect of the medication on rapidly turning over cells, like essentially the hair factory in the scalp, leads to hair shedding.

[21:46] It does regrow.

[21:46] It does not cause any scarring.

[21:46] It can grow differently afterwards.

[21:58] Sometimes we do see that, but generally speaking, it returns, and the hair is recoverable.

[22:06] GVHD-related hair loss is a phenomenon where the same inflammation that's affecting the skin and causing the rashes that we were discussing on earlier slides similarly can affect the apparatuses, the apparati in the skin that produce hair.

[22:19] We do want to recognize this and address it because, again, we do not want the irreversible damage to the hair follicles where it would be difficult to regrow hair later.

[22:34] Generally speaking, the treatment of the GVHD, generally, all of the different manifestations of it will address any component of the process affecting hair and promote hair regrowth.

[22:47] I mention here that it's possibly irreversible, but generally speaking, it is readily reversible.

[22:54] We're able to fix this.

[23:02] I do want to spend some time before we dive into the Q&A about treatment, and especially I want to spend a lot of time talking about things that you can do, non-pharmacologic kind of interventions, ways that you can take care of your skin as best as possible.

[23:14] The first thing I have to say is that the treatment decisions are very individualized.

[23:20] It's all dependent on what involvement you have, the domains that are affected, even beyond your skin.

[23:27] GVHD can involve internal organs and manifest in other ways.

[23:34] It's best to identify a therapy plan that addresses all of this, kind of targeting multiple different domains, even potentially with a single medication.

[23:47] A first disclaimer is that it's very personalized.

[23:47] The severity, we tailor how aggressively we go after things based on how severe it is and how rapidly evolving it is.

[24:00] And then, of course, what's already been tried.

[24:03] You won't necessarily just continue to do the same thing forever.

[24:03] You may need to change up the treatment plan.

[24:08] We're going to talk a little bit about systemic treatments.

[24:08] Basically, these are internal, these are pills, these are infusions, whole body treatments for GVHD.

[24:19] Then we'll talk about more skin-directed kinds of things, things that go either onto the skin or into the skin.

[24:24] The first-line treatment generally for GVHD is going to be corticosteroids.

[24:32] It's really the cornerstone of management.

[24:32] This is a medication, the most common medication we give in this way, something called prednisone.

[24:41] You may be on what we call a calcineurin inhibitor.

[24:41] This is classically tacrolimus.

[24:48] This is commonly given after a transplant and then slowly tapered.

[24:48] That taper might be extended or restarted if there is GVHD that this tacrolimus then might be able to target.

[25:02] You cannot be on prednisone forever.

[25:02] The medication can create side effects.

[25:02] We often are looking for a medication to replace the prednisone, what we call a steroid sparing agent, or if the process is persistent and we need to come off a prednisone to limit the side effects, then we would consider doing one of these medications I have in the second box.

[25:24] There's a few of them.

[25:24] These are FDA approved.

[25:24] The only one that's off label is the extracorporeal photopheresis, but ruxolitinib, or what we call Jakafi, belumosudil, or Rezurock, axatilimab, or Niktimvo.

[25:40] This is a newer targeted therapy and infusion treatment.

[25:46] And then Ibrutinib is not as commonly used anymore.

[25:46] I do have to say that I generally am not reaching for it, but it is FDA approved as well.

[25:52] And then extracorporeal photopheresis.

[25:59] This is going to be a conversation with your oncologist if there's a dermatologist involved in your care, about the risks and benefits of these logistics.

[26:10] It depends on how easy it is for you to come into the office on a regular basis.

[26:16] It's not one size fits all, and there's going to be discussion is really what I want to communicate.

[26:23] There are many other agents.

[26:23] If you've tried these, I don't want you to feel like you've reached the end of the line.

[26:23] We have other options.

[26:23] This is an area of very active research.

[26:23] It's an area that I'm very interested in.

[26:23] I'd love there to be more therapeutics.

[26:39] We're constantly leveraging and trying different things.

[26:44] There's newer data every day.

[26:46] I want to tell you that this is not the end of the line.

[26:50] This is not the end of the story.

[26:51] We're still working on it, and there's more to come.

[26:56] In terms of topical or targeted treatments, many of my patients probably think I'm a broken record with the topical corticosteroids.

[27:06] This is essentially like prednisone as a cream or an ointment.

[27:11] They're great because they're very localized.

[27:13] They act where we want them to go, and they don't have that systemic side effects that prednisone does.

[27:20] Which medication to use?

[27:23] Let us help you kind of guide that.

[27:24] There are many of them.

[27:25] There are dozens, if not maybe over 100 topical corticosteroids out there.

[27:32] Tacrolimus, the same oral tacrolimus also comes as a cream.

[27:35] a medication called Protopic, and a cousin of it called pimecrolimus or Elidel.

[27:35] Think of these as kind of quote-unquote steroid sparing agents in a topical version.

[27:42] They're not topical corticosteroids, but they are anti-inflammatory.

[27:48] Then I briefly talked about extracorporeal photopheresis on the previous slide.

[27:54] It's a great treatment.

[27:54] It can be quite effective.

[27:54] It's a treatment of the blood directly.

[28:01] And so you come to an infusion center, you receive the treatment in the infusion center, the blood is basically, your own blood is transfused back into your body after treatment with a light therapy.

[28:13] It's all kind of your own blood, your own, everything is kind of yours.

[28:20] And in the process, it creates this anti-inflammatory milieu, anti-inflammatory effect in the blood.

[28:27] A few other important topical and targeted treatments.

[28:27] Sometimes patients will go for a treatment called phototherapy.

[28:38] This is different from extracorporeal photopheresis, but essentially what it is a targeted light treatment.

[28:43] You do have to come into the office somewhat regularly for this.

[28:50] It's usually done with a dermatology office.

[28:50] So you might have to find a facility nearby you.

[28:56] Then other important things, it's really crucial if you have any joint involvement to involve, you know, have a physical therapist that you're seeing, stretches, kind of skin massage.

[29:08] All of these things can help to keep your skin as pliable as possible to prevent that thickening and, you know, the further tightening of the skin and limit any joint involvement.

[29:21] The earlier we intervene with this, the better.

[29:21] I just want to put a plug there for physical therapists, for occupational therapists.

[29:26] Then nail-specific care, I would just say you're going to likely need an experienced dermatologist, and I'll give you some guidance on how to find people who might have experience with this and know how to take care of the nails.

[29:48] We're going to move on now and talk about some self-care strategies for skin GVHD.

[29:55] I want to recommend moisturize aggressively.

[29:55] I usually recommend; they may not feel great on the skin.

[30:01] I'm going to be completely candid with you, but it's better if they're thicker.

[30:06] I really like things that don't have fragrance in them.

[30:06] They tend to be very gentle on the skin.

[30:10] They're not irritating.

[30:10] They don't trigger any kind of allergies.

[30:14] Some products that I usually recommend.

[30:14] CeraVe has a great lineup.

[30:14] There is a type called Vanicream that is more readily accessible online.

[30:20] It's specially made by dermatologists without really any additives or anything.

[30:27] There's no disclosures that I have.

[30:27] I have no stake in any of these products, but I really do like Vanicream a lot.

[30:34] It's a really go-to for a lot of dermatologists.

[30:40] And you can't overdo it.

[30:40] This is what I tell people all day, every day.

[30:40] Just keep when you apply, apply, apply, and, you know, it's carry it with you.

[30:46] There's no, it's not possible to really put on too much.

[30:53] This second panel here, I really want to emphasize.

[30:53] I'm going to spend a second here, a little bit on this, on this topic, because it is cliche.

[31:00] I am a dermatologist, but sun protection is important for everyone.

[31:06] It is really crucial after a transplant.

[31:06] The sun and ultraviolet light can trigger GVHD.

[31:14] It can trigger GVHD, and in the process, that triggering of GVHD can even trigger GVHD in your body.

[31:21] Even beyond your skin health, your overall general health, you really have to be very diligent about protecting from the sun.

[31:27] If you're going outside, wear a hat, sun protective clothing, anything that's exposed.

[31:31] I recommend SPF 50 is usually my go-to.

[31:39] Even on cloudy days, it's critical.

[31:39] I'm going to be completely honest.

[31:39] I really like the sun protective clothing.

[31:46] Just keeping the sun off of your skin is the, you're not going to miss a spot.

[31:53] You don't have to worry about reapplying.

[31:53] That's going to be the easiest way to make sure you're protected.

[31:57] I will say you don't have to hide from the sun.

[31:57] As you get further out from transplant, you have to live your life.

[32:03] You have to enjoy things.

[32:03] You have to do things that bring you joy.

[32:09] There's a mental health component to all of this too.

[32:09] So just use common sense about it.

[32:17] Be diligent.

[32:17] Be careful.

[32:17] Do not burn your skin.

[32:17] Just simple measures, sun protective clothing, sunscreen, and you'll be able to do what you enjoy doing.

[32:24] In terms of bathing, we often recommend kind of lukewarm water.

[32:32] You don't need to scrub your skin.

[32:32] You don't need to aggressively rub your skin.

[32:37] Then in terms of wound care, if you do notice any skin breakdown, alert your providers.

[32:47] If there are any signs that are concerning for infection, if it's red, if it's painful, If you have a wound that's draining, let your care team know immediately.

[32:57] Good exercise is great.

[32:59] You know, within reason, don't overdo it.

[33:03] Staying active will help to keep your body moving, will help to prevent if there is any risk for joint involvement.

[33:11] That'll help to keep them functioning well.

[33:14] And then just staying hydrated.

[33:17] It also sounds cliche, but drink plenty of water.

[33:20] It's good for your skin health.

[33:21] This is kind of common recommendations that I give to all of my patients.

[33:28] A few important points related to the skin and when you need to contact your care team about findings that you see on your skin.

[33:36] The beauty of skin is you can see it.

[33:38] You know, it's easy to self-monitor.

[33:40] It's not something where you need a scan or you need any invasive testing.

[33:45] It's readily visible.

[33:47] If you see a rapidly spreading rash, certainly with blisters or skin peeling, if you have a new fever with a rash, if you have any kind of open areas or open wounds that are expanding, they're painful, they're draining.

[34:03] If you have any other signs of skin infection, expanding redness, swelling, these are signs that you need to contact your team and really do it quickly.

[34:12] contact your team today, or frankly, even if it's really dramatic, very severe, progressing very fast. If you have a lot of concern, obviously escalate to, you know, potentially an urgent care or even the emergency department.

[34:24] When should you schedule an appointment?

[34:24] You know, when should you kind of make a time to maybe not immediately, but kind of look into seeking care?

[34:29] If you do see any new skin rashes, nail changes, hair loss, skin tightness, any joint stiffness.

[34:44] Certainly, if you're very impacted by any skin symptoms, even in the absence of visible rash, if you're really itchy and it's keeping you up at night, it's impacting your ability to take care of your family or go to work, let us help you.

[34:55] You don't have to suffer in silence.

[34:59] We have so many treatments for these things, and we'll be able to fix it and help you kind of reclaim your life.

[35:03] So again, I really want to emphasize, let us be involved.

[35:10] How do you find us?

[35:10] Obviously your transplant oncologist will often have potentially a dermatologist with whom they've worked with in the past and may be able to give you some guidance.

[35:22] In the BMT InfoNet provider directory, there is an ability to look for you can search by criteria and specifically pull down skin, specify your state, and you'll be able to find, it'll usually be a dermatologist who is local or in your area who can be able to help you.

[35:46] I'd encourage you to do that.

[35:46] I'd also make a plug; there is a very big mental health component.

[35:51] I'll talk about this on the next slide, but this is another, I'll put a plug here as well that leverage this directory.

[35:56] If you need it, you know, beyond the skin from a mental health perspective, you know, feel free to take advantage of this resource.

[36:09] So what are some key takeaways?

[36:09] And just to kind of, this is kind of concludes my talking at your component.

[36:15] Thank you for following along with me.

[36:15] And I'm just going to summarize some of the key points I made before we dive into the question and answer.

[36:20] Just know that So GVHD of the skin, of the nails, fascia, hair, the mouth, the eye, these are very, GVHD of the skin and mucous membranes is very common after transplant, especially after the allogeneic transplant, the donor, you know, where you have donor cells.

[36:39] You're not alone in this.

[36:43] We have a lot of experience with it.

[36:43] We can help you.

[36:43] Early recognition is important.

[36:50] The sooner we can intervene, the greater likelihood that we can prevent any irreversible changes that might occur.

[36:54] We can manage this.

[36:54] There's many new treatments.

[37:01] There are kind of new ones coming out every day.

[37:01] Make sure you prioritize self-care, moisturizing, sun protection, sun protection, sun protection.

[37:06] I know I'm a broken record, but it's just that crucial.

[37:11] Gentle skincare.

[37:11] And then again, I just want to emphasize that your mental health is just as important as your physical health.

[37:17] Don't ever lose sight of that.

[37:17] And lean on support systems, lean on your providers when you need it, because that's what we're here for.

[37:28] With that, we'll kind of migrate now to the question-and-answer component of this.

Moderator:

[37:36] Thank you, Dr. Stephens, for this excellent presentation.

[37:36] If you have a question for Dr. Stephens, please type it into the question box on the lower left-hand side of the screen.

[37:46] we will answer as many questions as possible.

[37:46] The first question is, what is the difference in indications for NB-UV-B and UVA treatments?

Dr. Stephens:

[38:00] Yeah, that's a great question.

[38:00] So NB-UV-B is what we call narrowband ultraviolet B therapy.

[38:11] This is essentially what we call phototherapy.

[38:14] And phototherapy is a treatment that I really like.

[38:18] I have many of my patients do this.

[38:20] It can be quite effective.

[38:23] It's a light treatment.

[38:24] It's the light treatment that I was referencing on an earlier slide, where you go into usually a dermatologist's office.

[38:30] It's three times a week.

[38:32] You stand in front of very specialized types of light bulbs.

[38:39] They shine a type of light that has an anti-inflammatory effect on the skin.

[38:46] The treatment can sometimes be done at home if we're able to get the device approved.

[38:46] Usually, I'm going to be completely candid, there's usually a little bit of back and forth with insurance companies to be able to get this, but it's great if you can do it at home because it saves you all of these trips into the office three times a week.

[39:05] My threshold for sending someone for ultraviolet B therapy again it's a very personalized conversation. One is how realistic is it for the patient if they're coming you know someone is driving an hour and a half to see me I'm not going to tell them that they have to come in three times a week and it just wouldn't be there's no way that someone can spend 12 10 12 hours out of their week commuting but if we're able to get a home unit where they live close by and it's not too inconvenient.

[39:34] Other considerations I have around pursuing narrowband phototherapy, is do they have contraindications to other treatments?

[39:40] There are really limited side effects to phototherapy.

[39:46] The main thing is just preventing a burn, just like a sunburn.

[39:46] It's very carefully controlled and calibrated.

[39:53] There's a lot of algorithms that go into it.

[39:53] I actually run our phototherapy unit at Mass General Hospital.

[39:58] When you are coming in, really, we do minimize that side effect.

[40:06] If someone has a contraindication to other treatments, then this might be a very reasonable option to pursue insofar as the risk tends to be thought to be pretty low.

[40:18] Otherwise, other instances where you might pursue this treatment is layering it on top of other things.

[40:27] If you're on something like Jakafi or you're on something like Ruxolitinib or you're on belumosudil, Rezurock, and things are getting better, but they're not perfect, then it would be very reasonable to kind of add this on top of those.

[40:39] It's a kind of augmentative effect, synergistic.

[40:43] There's no interaction or contraindications to layering these things.

[40:49] That would be kind of the context in which I would consider sending a patient

[40:54] for phototherapy.

[40:54] A great question.

Moderator:

[40:54] Is there anything that can thicken skin after it has been excessively thinned by long-term prednisone use?

Dr. Stephens:

[41:09] That is a great question.

[41:09] I am going to be completely honest that short of stopping the prednisone. If it's safe to do, I'm certainly not advocating that without a conversation with the prescriber of the prednisone.

[41:22] The short answer is it's difficult to reverse that, certainly if the steroids are still on board.

[41:30] Overtime skin on its own, the atrophy caused by steroids can start to reverse, but it's not perfect.

[41:38] I'm talking a little bit more circularly because the truth is there's just not otherwise great ways to reverse the atrophy if it doesn't do it on its own.

[41:50] Another area where I think very smart people hopefully are looking into it and down the road, there might be newer things that come out.

Moderator:

[42:03] Okay.

[42:03] You talked about sun exposure earlier in the presentation.

[42:03] Can that exacerbate GVHD in organs other than the skin?

[42:10] If so, which organs would most be affected by sun exposure?

Dr. Stephens:

[42:17] Yeah, great question.

[42:17] This really kind of ties into why it's so, so, so crucial to be careful about the sun, because the answer to your question is yes.

[42:17] The ultraviolet from the sun can trigger an immune reaction locally in the skin, but it's all one immune system.

[42:17] Your body is all connected.

[42:35] The skin is an organ like any other organ.

[42:35] Damage in that area can trigger damage in other areas.

[42:35] I don't know if we have granular enough data to be able to say very confidently that a sunburn increases your risk of GVHD potentially in the eyes or in the mouth may very well exist.

[42:35] If I'm honest, off the top of my head, I don't know.

[43:04] I will say, though, broadly speaking, that it is a well-known thing that skin GVHD, skin exposure to the sun can trigger skin GVHD, and in the process also trigger GVHD in other places.

[43:18] So, again, all the more important to make sure you're careful in protecting yourself.

Moderator:

[43:25] Can massage help loosen tissue affected by sclerotic GVHD or make it worse by creating more inflammation?

Dr. Stephens:

[43:33] The former.

[43:33] So massage, I'm perfectly fine with people doing that.

[43:33] I recommend it.

[43:33] The more you kind of stretch your skin, the more you try to stay as supple as possible, the better.

[43:48] It's encouraged.

[43:48] I would always say if you're having any sclerosis in your skin, it's a good idea just to involve a physical therapist or an occupational therapist, because they'll be able to give you a very personalized way of approaching a regimen and at-home kind of therapy plan.

[44:07] That would be probably the safest way to do things.

[44:11] Generally speaking, as a broad answer to the question, the more you do stretches, the more you exercise, the more you massage your skin, the better, the more likely that you'll be able to keep things as loose as possible within reason.

Moderator:

[44:26] This patient has ocular GVHD, and they're wondering if there's any SPF products that they could use that are tear-free.

[44:37] Great question.

[44:37] It's difficult for them to use sunscreen.

Dr. Stephens:

[44:40] Yeah, yeah.

[44:42] There are so many sunscreen products out there that I do think to some extent it requires a little bit of trial and error.

[44:49] There are some that are a little bit thicker, like zinc oxide, that leave a residue on the skin and might run a little bit if you're sweating or you're swimming.

[45:00] Those are usually my favorite, if I'm frank, because they don't really cause any reactions.

[45:06] Zinc oxide is very inert.

[45:08] Your skin won't react to it in any meaningful way.

[45:12] The truth is that anything that you're going to be putting onto your skin is going to come in the form of a vehicle.

[45:17] It's going to be a cream.

[45:18] It's going to be a lotion.

[45:19] It's going to be a spray.

[45:21] And those kinds of things can run.

[45:24] And so just trying to protect your eyes as much as possible, you know, obviously avoid applying it directly into the area.

[45:31] But it is difficult to really completely mitigate that 100%.

[45:36] The follow-up I would say is even better than sunscreen is just keeping the sun off of your skin.

[45:43] So we talked about the hats, the sun protective clothing, gloves.

[45:49] If it's, depending on where you live, if it's 100 degrees outside and it's the middle of the day, you can't go out in a parka.

[45:57] It's just not realistic.

[46:00] Some of these sun protective articles of clothing are quite loose. They're not thin, but they're light.

[46:09] They don't feel like heavy clothing.

[46:11] The technology is great.

[46:12] There's really a lot of great stuff out there.

[46:14] And then for your face, just wearing a hat.

[46:17] And ideally, the one that has a broad brim around it that will protect the back of your neck, your ears.

[46:23] If you're well protected, if you're wearing a hat, then the amount of sun exposure on your face is obligatorily going to be decreased, if not non-existent.

[46:31] Those are kind of some general principles.

[46:34] But I wish I had a foolproof way of keeping the sunscreen out of your eyes completely.

[46:39] It's difficult just by virtue of the vehicles that the manufacturers make these things in, but you might be able to, you have my blessing, for lack of a better term, that if you are having a lot running into your eyes, then I would recommend trying a hat and seeing if that can keep your skin protected in lieu of the sunscreen.

Moderator:

[47:00] Is it possible to have chronic skin GVHD post-autologous stem cell transplant in the setting of an autoimmune condition?

[47:09] specifically systemic sclerosis.

[47:09] This person is 14 months full transplant for scleroderma.

Dr. Stephens:

[47:20] I will say that my general impression after an autologous transplant is GVHD is very uncommon.

[47:29] Many of the consults that I have gotten where there is a question about GVHD, we often do unravel a different condition as the cause.

[47:35] Developing scleroderma or systemic sclerosis after an autologous stem cell transplant would be a very atypical kind of presentation.

[47:51] I will tell you that many of these types of rashes happen in people who did not get transplants.

[47:58] Scleroderma does not only happen in people who have had a bone marrow transplant.

[47:58] So the short answer is how common is chronic GVHD of the skin after an autologous transplant?

[48:07] In my opinion, very low, if not, frankly, next to impossible.

[48:15] How likely is systemic sclerosis in the context, or how would you think about developing systemic sclerosis after an autologous transplant.

[48:28] I would recommend having evaluation by a dermatologist or a rheumatologist in that context, because there are some clues, there are some exam features that can help you differentiate scleroderma that would happen to anybody with or without a transplant and sclerotic or scleroderma that's GVHD.

[48:50] That can be helpful because the treatments might be different, the way you think about it might be different.

[48:55]  I would just say that the short answer to your question is it's very, very, very, very, very uncommon.

[49:01] If someone did have systemic sclerosis after an autologous transplant, I would be looking very carefully at certain exam features to make sure that it is in fact GVHD.

[49:13] Otherwise, it very well could have been just de novo unrelated scleroderma.

Moderator:

[49:23] When decreasing prednisone, deep wrinkles sometimes follow.

[49:23] Is there anything that can be done to reduce these wrinkles?

Dr. Stephens:

[49:32] Yeah.

[49:32] Wrinkles that happen, so wrinkles happen for a lot of reasons.

[49:38] It's obviously a well-established thing that happens just as collagen in the skin breaks down over time.

[49:48] There are a lot of management options for wrinkles.

[49:52] There are a lot of cosmetic interventions that can be done.

[49:57] I have to admit; I am not quite up to date with all of the different lasers that exist now and injections that people do.

[50:03] It's not a super common part of my own practice, but I do refer a lot of people who are interested in pursuing treatments.

[50:12] But what I would say is consult with a cosmetic dermatologist if you'd like to talk about treatment options.

[50:19] There are certain types of retinol and retinoid creams, both over the counter and prescription, that can have a tightening effect.

[50:27] There are, again, certain types of lasers that are quite effective.

[50:30] You want to wait.

[50:31] In terms of doing these cosmetic interventions, I really would prioritize waiting well after your transplant, ideally at least six months to one year, and tell your oncologist before you pursue any of this.

[50:44] If you have active GVHD, especially of the skin, of your face, then I would be very careful.

[50:51] I would be very, very, very cautious about doing these things because you don't want to make an inflammatory process worse.

[50:57] So the short answer is that there are cosmetic interventions, over the counter and prescription.

[51:04] And talk to a dermatologist, talk to your oncologist, and feel free to pursue those if appropriate.

Moderator:

[51:13] Okay.

[51:13] How helpful is regular exercise for GVHD dermatology issues?

[51:13] In addition to the skin and fascia effects from moving and stretching, what happens at the cellular level to explain these benefits?

Dr. Stephens:

[51:28] Yeah, no, that's a great question.

[51:28] You're pushing me a lot on the basics, the kind of really getting granular in the microscopic and cell biology level.

[51:35] Exercise just in general, I do believe has an anti-inflammatory effect globally.

[51:50] The signaling that it's very complicated, exercise and metabolism are incredibly complicated.

[51:55] There's overlapping signaling mechanisms, and this cell talks to that cell.

[52:01] I wish I could give you; I think it'd be way beyond the scope of what might be helpful to hear.

[52:06] But just generally speaking, I do think that being active and staying active can absolutely have an anti-inflammatory effect.

[52:15] And so how helpful?

[52:15] I would say helpful.

[52:15] You know, you can keep your, beyond just even keeping your joints supple and preventing any contractures, it can help to just keep your overall health good and prevent kind of further complications.

Moderator:

[52:38] Okay, this person has edema in the feet that started about 95 days after transplant.

[52:44] They're now 140 days post-transplant.

[52:47] Is it possible that it could be fascia GVHD?

[52:51] They are having some edema around their eyes.

Dr. Stephens:

[52:56] Great question.

[52:57]  I would say that edema also can happen for a lot of reasons.

[53:02] I would recommend having an examination, somebody looking at it and weighing in.

[53:10] Sometimes there can be circulation problems that can cause swelling in the legs.

[53:15] Sometimes it can be lymphatic drainage.

[53:20] That would take you down one treatment path.

[53:22] I will say that certain types of inflammatory processes of the skin can cause swelling.

[53:27] And so that would take you down a different path.

[53:27] And so if there's ever any question, talk to your doctor about, talk to your care team about that and kind of get their input.

[53:36] But that would be my recommendation is if you're ever concerned about a skin manifestation that you think could be GVHD, just tell somebody and kind of pursue care for it.

Moderator:

[53:49] Could you please address GVHD concerns after having a haplotransplant?

[53:49] Is there something different that I could do about risk and surveillance?

Dr. Stephens:

[53:55] Yeah.

[53:55] After a haplotransplant,

[54:04] I would generally think about the way we approach it is very similar.

[54:04] A lot of the points that I brought up about what you should be self-monitoring for and what you should be bringing up with your care team kind of still apply.

[54:19] Not too much otherwise to say on that front than that a lot of the principles that we've discussed on previous slides would still apply, and I'd still recommend following.

Moderator:

[54:35] If chronic GVHD has been present for many years after transplant, are there any new meds or treatments that might actually reverse the fibrosis or sclerosis?

Dr. Stephens:

[54:48] Yeah, and that's a great question.

[54:48] This kind of gets to the point about when you think about a treatment plan for GVHD, what goes into that decision-making?

[54:56] And of course, it's what is involved, how severe is the disease, and then what's been tried so far?

[55:10] Sometimes it really does require kind of going through different lines of treatment, sometimes layering different lines of treatment, kind of one on top of the other.

[55:20] And so, you know, Ruxolitinib, Jakafi, Rezurock, infusions like axatilimab, you know, those either in combination with something like extracorporeal photopheresis, prednisone tapers, tacrolimus that somebody, you know, you might have already been on or been tapered off of, phototherapy that we talked about, a whole host of topical medications.

[55:41] There's a long list of treatments that are very well established.

[55:47] And then going into other things, there's all of the other kinds of systemic medications that I showed on a previous slide, rituximab, ibrutinib, methotrexate.

[55:56] The short answer is, it requires a conversation kind of sitting down and discussing with your oncologist, with the dermatologist if they're involved about what you've done and then kind of where to go from there.

[56:15] There's newer, this is again an area of active research.

[56:15] There's new kind of pharmacologic agents that are in the pipeline and in trials that hopefully will be able to kind of modify the way we approach to this or kind of change up the treatment algorithm to be able to fix the process.

Moderator:

[56:34] This is going to be our last question.

[56:34] We are running out of time.

[56:42] Certain specific probiotic strains have small clinical trials demonstrating increased circulating T regulatory cells.

[56:49] What is your opinion on probiotic supplementation?

[56:49] Is there a difference between the supplementation versus dietary intake of probiotics?

Dr. Stephens:

[56:57] Yeah, yeah, that's a great question.

[57:05] And that is such an area of, such a dynamic area.

[57:05] It seems like there's something new that comes out every day about the gut microbiome and the importance of the gut microbiome.

[57:12] I will say often after a transplant, you know, it's a timeframe when you might receive a lot of antibiotics that can have an impact on the gut microbiome.

[57:23] So it's important to be aware of that.

[57:29] The short answer to your question is, I don't, I'm going to be completely honest, I don't know the specific data about probiotics for skin health after a transplant.

[57:35] However, I do know that broadly speaking, through many immune mechanisms, cytokine signaling and the T regulatory cells that you were referencing, there's so much interplay between basically the GI immune system and the rest of the immune system.

[57:59] The gut is really a very important immunologic organ.

[57:59] Having a healthy microbiome definitely can have an anti-inflammatory effect.

[58:09] Now, in what forms that would come, whether it's probiotics that are taken by just dietary intake versus kind of a formal kind of way of getting a reset in your gut microbiome, a microbiota transplant or transfer or something like that.

[58:34] I don't know the specifics.

[58:34] I would say that eating a balanced diet, maintaining good health.

[58:41] Things like yogurt can have a lot of very healthy bacteria.

[58:48] That absolutely does have an anti-inflammatory.

[58:48] It's not a routine.

[58:48] I will qualify.

[58:54] This is not a routine thing that I tell every patient after their transplant, when they're coming in for dermatologic care, that you need to start doing X, Y, and Z to promote your gut microbiome.

[59:01] The short answer to your question is that I do think there likely is some signal there probably has some benefit, but I personally don't know the data off the top of my head.

Moderator:

[59:16] Well, thank you.

[59:16] And on behalf of BMT InfoNet and our partners, again, I want to thank Dr. Stephens for a very informative presentation.

[59:22] And thank you, the audience, for your excellent questions.

[59:27] Please stay on the line to complete a brief survey.

[59:27] Your feedback is very important.

Dr. Stephens:

[59:35] Thank you.