Chronic GVHD Resources

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Chronic graft-versus-host disease, or GVHD, is a common immune-mediated complication of allogeneic stem cell transplantation that can affect multiple organs and have a profound impact on patients’ lives.

I can’t emphasize enough how crucial it is to identify chronic GVHD early— If diagnosis is not timely, the delay could cause irreversible tissue damage, or may worsen the patient’s prognosis.

Patients have a window of time when the disease is in the inflammatory stage, and my goal is to address it then before it progresses. If symptoms go unrecognized, patients may present with fibrotic manifestations, and at that point the damage can be irreversible.

Among patients undergoing allogeneic stem cell transplant, about 60 to 80 percent develop chronic graft-versus-host disease.

Chronic GVHD can greatly impair a patient’s quality of life. Some of my patients with ocular involvement are no longer able to do everyday activities such as driving, reading, or watching television.

For patients with skin, joint, or fascial involvement, mobility can be greatly affected, and simple actions such as getting up, bending down to tie shoelaces, or sitting down to play with children become extremely difficult. Which brings us back to the need for early identification of chronic GVHD-- the earlier we address the disease, the better the chances of limiting or improving the patients’ symptom burden.

When assessing symptoms I like to simply ask patients about their ability to do the things they've always enjoyed, making more relatable to them. I find it much more meaningful to hear responses like, “I’m able to swing the golf club almost three-quarters of the way” or “I’m able to get up from the floor by myself without any help” compared to observations such as softening of their skin or an improved range of motion during a physical examination.

The three most commonly involved organs in chronic GVHD are skin, mouth, and eyes. Other organ manifestations such as lung involvement, though very severe, are less common.

I typically examine the patient’s mouth, listen to their heart and lungs, and ask them questions about eye-related symptoms. I find simple questions such as “Do your eyes feel dry, sandy, or gritty or have any burning sensation?” or “Are your eyes sensitive to light or wind?” to be most effective in helping patients to describe what they are experiencing.

I also perform a detailed skin exam and test range of motion by having patients do a few yoga poses to assess movement of arms, wrists, shoulders, etc. This is why it is so important to see these patients live, whenever possible.

In addition to considering standard blood counts and blood chemistry, I look for anything that may signify more longterm complications, including levels of vitamin B12, vitamin D, and iron, and also thyroid function.

In my experience, one of the most important screening tests is the pulmonary function test to screen for lung graft versus host disease. This should typically be done between 3 and 6 months post transplant. If at any point my patient develops GVHD of another organ system, I have them repeat the pulmonary function test, even if they just completed one in the recent months.

Patient education is a critical component of early disease identification. Without education, patients often fail to notice their symptoms or mistake them as stemming from other causes—and valuable time can be lost. For example, I’ve had patients who thought their skin thickening was the result of weight gain and therefore didn’t report it; other patients have mistaken dry eye symptoms for seasonal allergies.

After diagnosis, I always take the time to discuss expectations and to emphasize that disease management may take a while but that chronic GVHD can improve over time.

To help improve these discussions, and to help patients perform their own assessments, I’ve collaborated with Incyte Corporation to develop a Symptom Assessment brochure that can serve as a valuable tool for any post-transplant care team member to implement in practice.

The brochure contains a tear sheet with organ-specific symptoms and information on what patients should do if they spot something new—a useful resource for not only patients but also caregivers. I’ve found that caregivers are often the first to identify signs and symptoms that are potentially new or have changed and that they don’t hold back in letting us know how their loved one is feeling, whereas patients may be more reluctant to convey the full picture.

Ultimately, with GVHD, so much depends on early identification—the sooner we identify the disease and initiate appropriate care, the better the chance for clinical improvement.

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Chronic graft-versus-host disease, or GVHD, can often manifest in the eyes, mouth, and genitals. These are some of the more common organ systems identified in patients, and they oftentimes have overlapping presentations.

When I am assessing the patient for signs of ocular GVHD, the first symptom I ask about is dry eye. This is a classic symptom that patients experience. Some patients may describe this as "pain when blinking" or say “it feels like there is something in my eyes” instead of noting it as dry eye. Patients often mistake their symptoms for seasonal allergies.

I also ask if they notice any crustiness in their eyes when they wake up or if their eyes feel sensitive to light or wind. Using relatable examples, such as discomfort with indoor lighting or a fan, can help them make an association. Another sign I look for is excessive tearing. Although dry eyes is a common manifestation, many patients with chronic GVHD have excessive tearing or watery eyes, sometimes to the point where it impairs vision.

If I strongly suspect ocular GVHD based on signs and symptoms, an ophthalmologic examination is needed for an official diagnosis and I will refer the patient to ophthalmology.

Therefore, if my patients confirm my suspicions when answering my assessment questions, I refer them to my center’s corneal specialist.

An ophthalmologist will conduct a slit lamp exam to look for characteristic findings of GVHD. Oftentimes, they will perform the Schirmer test to determine the degree of moisture in the patient’s eyes.

When assessing for oral GVHD, I look for the classic lichen planus-like changes that manifest as visible white streaks on the cheeks and tongue, and are diagnostic of chronic GVHD. I also look for ulcers and mucoceles, which are blisters frequently seen in oral GVHD but not considered diagnostic.

I always ask patients if they have sensitivity in their mouth. More specifically, I ask about discomfort with toothpaste, acidic drinks, carbonated beverages, or spicy foods. Sometimes patients may present with lichenoid changes but may not have developed bothersome symptoms.

In my experience, patients with oral, ocular, or inflammatory skin GVHD are very likely to have genital involvement. I proactively ask both men and women if they have noticed any irritation or skin changes such as a rash, ulcers, sores, or pigmentary changes. If they are sexually active, I ask them about any discomfort they experience during sexual activity.

If they confirm any of these signs or symptoms, I will examine them, however female patients should be seen by their OBGYN for further exam.

The characteristics considered diagnostic for skin also apply to the external genitalia when diagnosing genital GVHD. In men, we look for the lichenoid-like rashes and an inability to retract the penile foreskin. For women, internal examination is required to assess for vaginal scarring or labial agglutination.

Once chronic GVHD has been diagnosed, it’s important to work closely with specialists to manage the care for patients. I prefer to follow-up with patients at least every two to four weeks although the frequency may vary slightly depending on the organ system involved.

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Skin is the most commonly involved organ in chronic graft-versus-host disease, or GVHD. Because of this, it may be important to involve a dermatologist to help with patient assessment and disease management.

Two types of manifestations are typical in chronic skin GVHD—the first being inflammatory changes, including lichen planus-like eruptions that present as red or purple plaques and papules. Some patients may experience pigmentary changes, which are not diagnostic but are often present along with diagnostic manifestations of other organ systems.

The second type of manifestation is deep sclerosis involving the subcutaneous layers of the skin, which presents as thickening or shiny, waxy skin.

When discussing signs and symptom recognition with my patients, I like to show them how to assess the “pinchability” of their skin. Even in areas such as the ankles, where most people don’t have a lot of body fat, I explain to them that they should be able to “pinch their skin” and bring it together.

Sometimes patients are surprised when they aren’t able to do this and realize how tight their skin really is. I also educate them that rippling or dimpling of the skin can represent sclerodermatous changes of GVHD. This can be mistaken by patients, especially by women, as cellulite.

These are some of the key signs and symptoms that I ask patients to look out for and encourage them to bring to our attention as soon as they notice these changes.

I also ask them to let us know if their skin feels dry, itchy, raw, or sore, or if they notice any changes in their skin color or texture. Likewise, thinning or greying of hair or changes to their nails, such as brittleness or ridges, can also suggest GVHD.

Patients are often unaware that these symptoms may be related to GVHD. If we provide the right education to patients and proactively look for these symptoms, we may be able to improve patient outcomes. Hence, I always encourage my patients to contact us with any subtle changes they may have noticed.

One thing I want to emphasize as a best practice for skin GVHD is the importance of documenting symptom progression by taking pictures. I encourage care team members, patients, and caregivers to implement this practice, as it can be easy to forget what a patient’s skin looked like previously, and pictures are an easy and helpful visual tool in managing skin GVHD. This can also lead to the identification of symptom progression and allow intervention in a timely manner.

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Joint or fascial involvement in chronic graft-versus-host disease, or GVHD, usually presents as tightness and a decreased range of motion. Both small joints and large joints can be involved.

Patients tend to describe this subjectively as a restriction in their daily movements, such as an inability to reach high above their head, for example, the top shelf of a cabinet, or problems bending, twisting, walking up and down stairs, or grabbing things such as doorknobs and buttons.

When assessing for joint and fascial GVHD, I ask patients if they have pain, swelling, or stiffness in their feet, ankles, or other major joints or if they are experiencing cramps, tenderness, muscle pain or weakness.

The Photographic Range of Motion assessment is a helpful tool in assessing restriction in the shoulders, elbows, wrists, and ankles. At times, MRI may be useful in diagnosing fasciitis.

Early identification is critical to avoid decreased range of motion and progression to contractures, which may be irreversible.

Joint and fascial GVHD is historically one of the most difficult organ systems to manage. After diagnosis, I see patients once a week for at least the first few weeks.

Physical therapy plays a critical role in management of joint and fascial GVHD. The physical therapist's assessment treatment plans and formal range of motion measurements are important and helpful for assessing patient improvement.

Regarding the gastrointestinal, or GI, tract, the only diagnostic manifestations include esophageal webs and strictures. Patients may have dysphagia as a presenting symptom. Often times, they will describe food, such as bread or meat, as difficult to swallow. Sometimes they may say they tend to choke on pills. These manifestations can be diagnosed through imaging such as barium swallow or through an endoscopy.

Patients with diagnostic manifestations of cGVHD may have other GI symptoms that are often common to acute GVHD.

To help uncover some of the symptoms of GI GVHD, I ask patients if they’ve noticed changes in their appetite, or if they find they are feeling full with less food. In addition to asking about the more obvious signs and symptoms of diarrhea, vomiting, and nausea, I also ask about abdominal pain, cramping, or bloating. Weight loss can be another indicator of GI GVHD.

After a confirmed diagnosis of GI GVHD, I like to follow up with patients every two to four weeks.

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