Updates in the Management of Chronic GVHD: An Advanced Practice Perspective

Erin Kopp: 

Welcome to JADPRO's Roundtable discussion on chronic graft-vs.-host disease. My name is Erin Kopp and I'm a nurse practitioner at City of Hope. Joining me today are two of my colleagues, Adrianne Maurer and Katie Sellers. Adrianne, you're going to start us off, so please tell us a little bit about yourself and what we're going to dive into today. 

Adrianne Maurer: 

Thank you, Erin. My name is Adrianne Maurer. I'm a nurse practitioner at Fred Hutch Cancer Center in Seattle, Washington, and I see exclusively post-transplant patients and specialize in the treatment and management of chronic GVHD, which is perfect for our topic today. In this video, we are going to touch on the presentation and identifying features of chronic GVHD for the APP who is both experienced and inexperienced in managing this syndrome. We're going to talk about when it happens, why it happens, and what to look for. So, diving right in, I first want to talk about what chronic GVHD looks like. It's most often going to occur in the patient that is about 8 to 12 months out from completing their immunosuppression taper, but it really can occur at any time post-transplant. Personally, I tend to see this at the tail end of immunosuppression tapers, but outside of that, you can also see it triggered by some kind of immune-activating event like an illness, just bodily stress in general or vaccination, which is quite common in this population. So, if you have any patients who are undergoing any of these issues or you anticipate that that's upcoming, you certainly want to be on the lookout for a chronic GVHD presentation.  

Katie, is that what you see as well in your practice or is there anything else that I'm missing here that would be something to look for? 

Katie Sellers: 

I totally agree. I think that the stressors or something that we don't often think about, but a patient may need their gallbladder out and suddenly come in with a flare of GVHD. So, always reminding them that, "Hey, your body's going to be going through a lot and you should be on the lookout that you could be experiencing a flare perioperatively or in their recovery phase." So, absolutely, you hit the nail on the head as far as when to be looking for it and when to expect it, but it's kind of those one-off situations that require a little bit of extra education. 

Adrianne Maurer: 

And for patients too, I always tell them, "This can happen at any time to you, but we're going to be babysitting during these peak periods." So, it's also something that you can pass on to your patients. So, we know when it's going to happen. Do we know what to look for is the next question? Knowing that chronic GVHD can affect almost any organ, it sometimes is really challenging to parse out, is this actually a GVHD presentation or is this a side effect or a symptom of something else? One of the big things that is super important in identifying any of these symptoms is a review of systems, knowing what questions to ask patients. I always tell patients that I need them to be an active participant in their own care, and I trust them to know themselves better than I do. So, really knowing what questions to ask can make a big difference in identifying chronic GVHD. 

So, my thought here was to go head to toe, each organ. Let's talk about which organs it can affect, what does that look like, and what questions you should ask. So, starting with ocular GVHD, this one is often pretty hard to manage and may require an ophthalmologist to confirm, but when you see a patient for a regular exam, you should always ask them if they're experiencing any dryness, gritty feeling or sandy feeling in their eyes, any increased drainage, particularly in the mornings. Sometimes it can be so bad to where their eyes will almost seal shut and they got to kind of peel them open to get through their day, and then photosensitivity as well. On a physical exam, you might see erythema, increased tearing, and evidence of some drainage. Again, I highly recommend a referral to ophthalmology if you suspect chronic GVHD in the eyes. 

For oral GVHD, this one's probably the most common and that I see the most frequently. You want to ask your patient if they're experiencing any sensitivities to hot, cold, spicy, sweet, acidic foods or drinks, and the mint in toothpaste tends to bother them as well. It can be asymptomatic, so in absence of any of these symptoms doesn't necessarily mean that there's no oral GVHD, but it's certainly a good place to start. 

On physical exam. You might see lichen planus features. It sort of looks like a spider webby type appearance. Some erythema, hopefully not, but you may see ulceration or limited mouth opening. It's really important to check externally too, because they often can have this presentation on their external oral labia as opposed to just internally. Erin, is that what you see clinically as well? Is there anything else in either oral or ocular GVHD makes you say, "Hey, I really need to be thinking about this?" 

Erin Kopp: 

Thanks for asking, because I think especially 8 to 12 months out, I see patients very hesitant to tell us things, and so I look for patients coming in wearing their sunglasses when they're in the room, they've said, "Oh, the air conditioning's bothering my eyes." So, sometimes they don't volunteer the information, but I'm looking for little clues. I like to think of it that we're detectives and with oral, the other thing is they'll say, "Oh no, I'm fine." And then you ask about, "Oh, can you eat spicy foods?" They didn't eat spicy foods before, but I'll ask them if there's any foods that they can no longer eat that they used to be able to, and it's like, "Oh, I used to eat ketchup, but now I can't." So, some of those little tools to ask those special questions when people don't want to offer it up. 

Adrianne Maurer: 

Yes, maybe it's more about how you phrase the question as opposed to just being direct. That's a really good tip. Thank you. 

Katie Sellers: 

YeahIn Texas, we ask about the overhead fan or the AC in their car. They can't use the fan in their car anymore or they have to turn it away when their spouse is driving. 

Adrianne Maurer: 

Yes, those environmental factors too. Here in Seattle, allergy season is about 9 months out the year. So, often I get patients saying, "Oh, it's just my allergies. I had allergies before. Or even if I didn't have allergies before, it's got to just be the trees." Could just be GVHD. 

Well, thanks guys. Moving on to lung GVHD. This one can be really insidious and very difficult to diagnose particularly during respiratory virus season, but you want to ask about new dyspnea. Are they coughing at all? I most often see a chronic dry cough, but it can be a little bit wetter, especially if they have some element of pneumonia mixed in there. I often ask if they're having any new difficulty climbing stairs. That elevation change can often decrease their O2 stats and really make that dyspnea a little bit more pronounced. And then the other thing to really pay attention to are changes in their pulmonary function tests. 

For chronic GVHD patients, we should be checking those every 3 to 6 months so that we catch some of those more subtle decreases in FEV1, and residual volume. Both of those might point to a lung GVHD-type situation. If you have the availability of a pulmonologist consult too, if you aren't sure, that's always a great place to just double check. 

Okay. Moving on to gastrointestinal, esophageal, and liver. This is I feel like I struggle the most with because there are so many different things that could be contributing to some of these symptoms that it's really hard to parse out if this is GVHD-driven, or is it a medication, is it something you ate. Those types of things. So, with esophageal GVHD, we can often see difficulty swallowing liquids, or food, or pills or all of the above. A lot of people will report some discomfort with swallowing as well or reflux symptoms. Again, kind of going back to what we were saying with ocular GVHD, a lot of times patients will just say, "Oh, I had acid reflux. It's fine. It's not anything else to be worried about," but anything like that always kind of rings an alarm bell in my brain. 

With upper GI GVHD, you might see persistent nausea and vomiting. Early satiety and weight loss are usually my red flags. If someone tells me, "Yeah, I am not eating as much as I used to because I take a couple of bites and I'm full and I don't want to eat anymore or it hurts to eat anymore," that's usually when I'm starting to say, "Oh, something's not right here." With lower GI GVHD, you might see abdominal cramping or chronic diarrhea, but again, thinking about all of those medications that they're on for prophylaxis or perhaps even tapering off of their general immunosuppression, it's hard to sometimes parse out, is this from GVHD or is this a medication side effect? Katie, What's your best way to distinguish between those two things? I know that's a hard question. 

Katie Sellers: 

It is really hard. For esophageal, I think that when I'm eating a piece of meat or steak, or any really hard bread or something that's really thick, that's kind of something I pick up on. So, "Nothing's getting stuck, oh, well actually when I eat sourdough bread, it gets stuck." And so, kind of knowing what other patients have said, "Okay, hey, how can I relate?" The other is that when they talk about their pills, when they're taking their potassium pill and it gets stuck, we have to talk about crushing it and all that, and that usually then prompts me to think, "Hey, we need to get our GI partners involved to do an endoscopy or at least start with a barium swallow to see what's going on there." 

You're right, the upper and lower GI are tough because they could just be common side effects of medications, but I think especially the lower, thinking more of the qualifying factors, it's loose, it's dumpy, it's high volume, or at least fills the toilet every time, it's frequent, no matter if it's associated with a meal or not. So, I think part of really learning about that is also knowing what other patients have experienced. We know the classifications, but hearing what other patients have said before, "Oh, it's no longer a form stool, it's more like peanut butter or, oh, now it's even a little bit softer and more like applesauce." So, kind of knowing some of those key phrases that patients can relate to helps. 

Adrianne Maurer: 

Wonderful. Thank you.  

Okay, so liver GVHD often presents just as a lab abnormality or not frequently going to see any symptoms associated with it unless their LFTs or bilirubin are sky-high and they present with jaundice. But this is another good reason for us to frequently check labs on these patients.  

Skin GVHD can take a variety of different forms and is pretty variable. I always ask patients, "Are you having anything new that we haven't discussed previously? So, new itching, any color changes, either lighter or darker, or a rash? Any texture changes, does it feel more dry? Does it feel flaky? Does it feel tight as you move around?" The changes in flexibility are super important and can be very subtle, but these are really key in identifying early sclerotic changes or myofascial changes. So ,it's really important to do those types of exams and catch those subtlety changes early on. 

You might see a maculopapular rash for chronic skin GVHD, hypo- or hyperpigmentation, lichen planus changes, or morphia. But again, the big thing we're looking out for here are sclerodermatous changes. that tightening or fasciitis-type distinguish. And these are very subjective findings overall. So, sometimes it can be really hard to truly identify is the skin GVHD or is this something else that I need to be worried about? Never be afraid to consult with dermatology or even just grab a friend. Somebody else who has a second set of eyes and can take a look at this with you. 

This kind of smooths right into the myofascial realm as well. That limited range of motion is a big indicator of something funky going on. And I always ask patients, "Is it more difficult to reach something on the top of your shelf, or when you bend down and touch your toes. When you squat down to pick something up off the floor, is that uncomfortable? Does it feel like you can't get as far as you used to?" As opposed to just saying something like, "How are your muscles feeling?” or “Do you have any limits in your wrists and your elbows and your shoulders?" That sort of deal. 

For genital GVHD, this is often really hard to define without a good pelvic exam for females. Most often patients will present with difficulty or discomfort during sexual activity, but they can also notice some increased dryness or discharge. In males, they can notice some skin sensitivity and maybe even ulceration or difficulty with urination because the urinary meatus has started to close up a little bit. That's called phimosis. These are really sensitive topics for patients to discuss, so it's important as the provider to make sure that we're investigating and prompting patients to report these changes before they become too advanced.  

Erin, what did I miss? Anything else that I've missed? 

Erin Kopp: 

Just if I see somebody who has oral GVHD, I'm automatically prompting the question for any kind of genital GVHD because sometimes they go hand in hand. And again, like you said, we don't like to talk about it, patients don't like to talk about it. So, it's really up to the APP to create a safe space for patients to understand, and especially I see it with a lot of my postmenopausal women. They were already in menopause, so they may have been experiencing some of these symptoms already. I loved how you gave the point with skin that it's like, "What's your baseline? Have you seen anything new?" Just because they're postmenopausal, they may have already had some issues. Is there anything different or new? And again, making a connection with somebody in the community who's a great GYN, who's comfortable and familiar with it, so the patient feels comfortable going to them. 

Adrianne Maurer: 

Really quickly, I want to touch on some more rare presentations of chronic GVHD, just to have your mind thinking about those. You can see GVHD in the kidneys. It often presents as nephrotic range proteinuria. So again, just keeping an eye on those labs. And then I've also had patients with serositis or anasarca, and often those are more diagnoses of elimination than a true easy chronic GVHD diagnosis. 

Erin Kopp: 

All right. And I know we've talked so much, ladies, about what GVHD looks like. It's so important before we can make any decision about treatment, is to really have that differential diagnosis. So, thank you both so much for talking about this. It brings us to the end of our discussion.  

I really want to thank Katie and Adrianne for taking time out of your busy day to talk to us. But for more information and to view our other discussions on chronic GVHD, please visit JADPRO online at JADPRO.com. Thank you so much and have a great day.