Presentations of Acute and Chronic GVHD


A panel of GVHD experts give a comprehensive overview of the presentations of acute and chronic graft-vs-host disease.


Preet M. Chaudhary, MD, PhD: Dr Tam, what are the common signs and symptoms of acute GVHD [graft-vs-host disease]?

Eric Leon Tam, MD: Acute GVHD usually occurs within the first 100 days after transplant. These are usually inflammatory, very red symptoms. If you get a skin rash, it could be very red, similar to a sunburn. Depending on how much of the part of the body, it may even peel. Sometimes it’s painful, sometimes it’s itchy, and sometimes it’s not too painful. But for the most part, it’s very evident when a patient has acute skin GVHD.

The other organ systems that are very commonly affected in acute GVHD are the GI [gastrointestinal] tract and the liver. For the liver, we usually pick it up before patients have any symptoms, based on the routine blood tests that we do so frequently. For the GI tract, you can have upper or lower. The lower GI tract usually involves a lot of diarrhea unfortunately, sometimes even cramping. As the epithelial lining of the GI tract starts to become damaged, you’re not able to absorb all that fluid and water from the colon, so that causes a lot of diarrhea. If the GVHD progresses further into the muscular layer, sometimes it invades blood vessels. That can cause bloody diarrhea and become life-threatening in its very severe form. Patients can have 5 to 6 L of diarrhea a day, sometimes bloody. For someone who’s 60 or 70 years old, that’s definitely life-threatening.

For upper GI GVHD, the symptoms typically involve nausea and then because of nausea and a low appetite, it can cause weight loss as well. It’s very hard to distinguish between these adverse effects from the chemotherapy from transplant because they happen so quickly. There are topical steroids that are not absorbed that we can take to try to help with those adverse effects when it’s GVHD. But for the most part, acute GVHD happens in those 3 organs.

Preet M. Chaudhary, MD, PhD: The critical point is that even though we routinely do a biopsy of the skin or the GI tract to establish the diagnosis, GVHD ultimately is a clinical diagnosis. I usually don’t wait to initiate treatment to get the biopsy results back if the suspicion is high. This goes back to the thing we were discussing before: it’s important to diagnose early and initiate treatment early. I prefer to get the biopsy. But on clinical suspicion, I start the treatment while the biopsy results are coming. If the biopsy shows that it’s not GVHD, you can always stop this treatment. To wait until the biopsy results come and not initiate treatment could be a dangerous route.

Eric Leon Tam, MD: That could set you back another week or so.

Preet M. Chaudhary, MD, PhD: Exactly.

Eric Leon Tam, MD: Obviously, based on the clinical picture, you need to be certain this isn’t an infection.

Lakshmi Savitala-Damerla, PA-C: I was going to say that. Especially in the acute setting, you need to rule out infections like CMV [cytomegalovirus], colitis, and things like that and not jump to the conclusion that it’s acute GVHD.

Eric Leon Tam, MD: Then of course there’s VOD [veno-occlusive disease]. But within the time frame, usually you can tell between VOD and liver disease.

Preet M. Chaudhary, MD, PhD: Lakshmi, what about chronic GVHD? How do you see chronic GVHD in your practice?

Lakshmi Savitala-Damerla, PA-C: There’s a bit of a crossover of symptoms from acute to chronic GVHD. By definition, chronic could be anything after 100 days. The interesting thing about chronic GVHD is that it can happen at any time. In Hector’s case, it happened 1 year after transplant. We have a few patients where this has happened 2 to 3 years down the line. There’s no safe way to say, “If it’s past this point, you could have chronic GVHD.” It’s true that as the days and years go by, the risk of GVHD decreases, but it can pop up at any time.

For example, in acute GVHD, in the skin, you see red visible changes. It could be subtle for chronic GVHD. Patients might notice that their skin is tighter or that they have this orange peel—what we call dimpling—and a decrease in their range of motion. If they’re going to the gym, they might feel as if things are tightening up. Reaching or bending down to pick things up or squats are hard. All these things are subtle, that you might attribute to arthritis, you can never not think about chronic GVHD in these patients.

From a lung perspective, it’s not visible, so it’s very subjective. Patients say, “I used to be able to walk 15 or 20 minutes. Now after 5 or 6 minutes, I get tired. I need to take a break and resume. Getting up a flight or 2 of stairs seems like an arduous task. I used to go 3 or 4 flights of stairs.” These things come into play. Then you have to think about a pulmonary function test and what imaging we do. From a GI perspective, it could be a little more subtle. They’ll say “When I eat, I get filled up easily. I’m not able to eat the same amounts as I used to. I get a little nausea.” We underline nausea, but there are little clues you have to pay attention to. It’s like taking a jigsaw puzzle, piecing it all together, and coming up with the diagnosis. Everything the patient says you have to put in the back of your mind. You might not be able to make a decision right then and there. Then in a few weeks you might realize, “Wait, this is a clinical picture we have for chronic graft-vs-host disease.”

For eyes, patients will say they have dry eyes. In Southern California, we can say it’s allergies, but maybe it’s not allergies. Red eyes, dryness, and needing to use lubricating drops every hour is definitely a clue that there’s something going on that warrants further treatment for GVHD.

Preet M. Chaudhary, MD, PhD: The idea is that GVHD is potentially a systemic disease. It can involve any organ, no matter which organ you see symptoms in. You mentioned the eyes. It could be allergies, but in the post-transplant or post-allotransplant patient, you have to think about GVHD. Similarly, if somebody has arthritis, it could be just arthritis or osteoarthritis. But you have to think about GVHD as an underlying cause.

The other thing you mentioned that’s critically important is that chronic GVHD can manifest at any time. In the case of Hector, even though it was a year later, the key is that if the immunosuppression has tapered off, then that’s the window of time in which the patient is at higher risk of flaring up GVHD. I’m much more vigilant in asking patients questions in the time period—a month or 2 or more—after GVHD prophylactic regimens have been stopped. That’s the time they’re going to flare up. It’s very important to catch it early on and reinitiate the therapy rather than let it smolder and affect all the other organs.

Lakshmi Savitala-Damerla, PA-C: As we’re tapering these patients off their immunosuppressive medications, each dose level that we go down, we’re educating them: “We’re going off your immunosuppressive. If you notice any signs and symptoms, let us know.” Then we review all those symptoms so the patient is aware. Some of our patients are good. They say, “Hey, I noticed this.” They may be subtle. We’re like, “Let’s monitor.” Once they’re off, we like to see them at 2 weeks, 1 month, or 6 weeks, maybe a little closer, to make sure they’re not flaring up with anything or starting with graft-vs-host disease after they’ve been off their immunosuppressive therapy.

Preet M. Chaudhary, MD, PhD: Anything else?

Eric Leon Tam, MD: One more rare chronic GVHD that we don’t usually see in organ systems, but it definitely does happen, is in the CNS [central nervous system]. This can be very scary for some patients if it happens. It’s very rare, but it could mean confusion and cause changes in personality. A primary care doctor might not know what’s going on. They might think it’s dementia setting in. The suspicion needs to be there.

Preet M. Chaudhary, MD, PhD: On the same point, there’s also the genitourinary tract.

Lakshmi Savitala-Damerla, PA-C: I was going to just say that. That’s a very under-asked question. For men, it’s genitourinary. For women, vaginal GVHD is a very real thing. As they come off transplant and get back into their sexual lives, that’s an extremely important question. It’s not on top of our list, but it needs to be addressed.

Preet M. Chaudhary, MD, PhD: Thank you.

Transcript edited for clarity.

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