Symptom Scoring Criteria and Assessment for Chronic GVHD

Diya Sabnani

When we discuss scoring for chronic graft-versus-host disease (GVHD), we look at each of the organ systems involved and score the severity of the symptoms using the 2014 National Institutes of Health (NIH) consensus criteria.¹ The scores range from 0 to 3 based on severity, with 3 being the highest. We score criteria, symptoms, or manifestation in each organ system and then add up those numbers to get a global severity score.

The first assessment is the patient’s overall performance status from 0 to 3, based on either ECOG or Karnofsky performance status, depending on which scoring system your institution uses. We look at patients and assess how they're doing. Are they symptomatic? Are they slightly symptomatic but able to still do their daily living activities and physically strenuous activities, or are they 50% debilitated or completely debilitated?

Jaime Shahan

Absolutely. How much are they in and out of bed? How much are they able to take care of themselves, and are they restricted when they try to be active?

Next, we score skin features based on two different things. One is the body surface area of involvement. Body surface area score follows the pattern of acute GVHD grading, but instead of grading on 0-25, score 1 correlates with 1% to 18% body surface area involved, while score 2 is between 19% and 50% involvement, and score 3 is over 50% body surface area involved.

The second thing we use to score chronic GVHD of the skin is whether the diagnostic features of chronic GVHD are present, including redness, maculopapular rash, lichen planus, small red plaque, or sclerotic features where there is scarring or decreased mobility of the skin. We might see an inability to pinch the skin, or sometimes there's dry skin where the skin has something like chill bumps, called keratosis pilaris. Then we also look at the sclerotic features specifically. No sclerotic features would have a score of zero, but if a patient had "hidebound" features, meaning we're not able to pinch it at all, that would be scored a 3.

Diya Sabnani

One thing I want to mention, Jaime, is that when we talk about the skin changes, there are features we could potentially see in patients with chronic GVHD but that we don't factor into the scoring for body surface area. These include hyper- or hypopigmentation of the skin—also known as poikiloderma—and generalized itching. Patients may have hair or nail involvement, usually patchy growth of their hair or ridging of their nails.

Jaime Shahan

Next, let’s talk about the mouth. Like we said, patients can have lichenoid changes on their skin, but they can also have them in their mouth. How do we go about scoring oral GVHD?

Diya Sabnani

The scoring range goes from no symptoms, to mild to moderate, and then to severe. We're looking for lichen planus—changes in the mouth, potentially mucoceles, erythema, ulcerations, and how symptomatic they are. Are they experiencing mild symptoms that don't affect their oral intake, which would be graded as 1, moderate where they're having more severe symptoms that partially limit how much they're able to eat and drink, or are the symptoms severe?

Jaime Shahan

If they have major limitations, then they're going to get a score of 3.

Eyes can also be affected by chronic GVHD. Sometimes patients have dry eyes or keratoconjunctivitis. These patients are primarily being seen by an ophthalmologist, but we score their GVHD based on how often they have to use eye drops or whether they have to wear specific eyewear to get through their day. Zero is no symptoms. A score of 1 would just be mild, dry eyes, but they're not having to use eye drops more than three times a day. Two is when they're using eye drops more than three times a day, or sometimes they actually have to use punctal plugs to try to keep the tears from leaving their eyes. And then a score of 3 would be when symptoms are so severe that patients have to wear special eyewear to relieve the pain or potentially lose their vision due to the severity of the dry eye.

Diya Sabnani

Moving on to scoring chronic GVHD in the GI tract—esophageal webbing and constriction being one of the main concerns. We can also see dysphasia, anorexia, nausea, vomiting, and weight loss. So when we talk about scoring, grade 1 is symptoms without significant weight loss, which is defined as less than 5%. Grade 2 is moderate symptoms with about 5% to 15% weight loss, and then grade 3 is severe symptoms with over 15% weight loss. Grade 2 can also include moderate diarrhea without it affecting daily life versus grade 3, which can include severe diarrhea affecting their daily life or even the need for esophageal dilation.

Jaime Shahan

Then with liver involvement, we're looking at not only the total bilirubin, but also the ALT and the alkaline phosphatase. If these labs are between normal and three times the upper limit of normal, that’s a score of 0. Between three and five times the upper limit of normal is a score of 1. Elevated total bilirubin less than 3 mg/dL or ALT above five times the upper limit of normal is going to get a score of 2. A score of 3 is going to be over 3 mg/dL for the total bilirubin.

Diya Sabnani

Next in chronic GVHD scoring is the lungs. With severe chronic lung GVHD, we may see bronchiolitis obliterans syndrome or sometimes cryptogenic organizing pneumonia. Our scoring is based on symptoms and the forced expiratory volume. With a score of 1, we're looking at mild symptoms where a patient is climbing a flight of stairs and, after that, they feel that they're having some shortness of breath, but their forced expiratory volume percentage is slightly decreased, between 60% and 79%. With a score of 2, forced expiratory volume is between 40% to 59%, and patients will complain of shortness of breath just from walking. A score of 3 would be FEV1 less than 39% and shortness of breath at rest.

Jaime Shahan

Right. And sometimes patients with a score of 3 will require oxygen.

Next in our scoring assessment is joints and fascia. With scoring for joints, there's actually a photographic range of motion picture that we follow. We give patients a range of motion score from 1 to 7 for the shoulder, elbow, and wrist joints. Like with the shoulder, how close can they get their elbows to their ears when they raise their arms straight over their head? A 7 would be full range of motion, and 1 would be if they're not able to lift their arms at all. With elbows, we have the patient straighten their arms and then have their elbow completely flapped. If they're able to get their elbow at a 180-degree angle, that's a 7, but if they're so limited that they have joint contracture, then they'll have a limited range of motion score with their elbow. It's the same with the wrists and the fingers. We ask them to hold a prayer sign—palms pressed together—and see if they have a full range of motion with the fingers fully extended and touching each other, and the wrists fully extended. With the ankles, we have patients raise their ankle (dorsiflexion) and see whether they're able to point their toe as well. The ankle joint is on a range between 1 and 4.

Diya Sabnani

And while we're having patients do these different photographic range of motion exercises, we're also looking at whether there is mild tightness in the joint. We're actually putting our hands on their skin and feeling at each of the joints, pinching the skin. As you mentioned earlier, Jaime, it's so important for us to feel the actual skin.

A score of 1 is mild tightness with normal or mild decrease in range of motion versus tightness with moderate changes or decrease in range of motion. But if we're seeing contractures, that's going to be a score of 3, because that means they're significantly impaired in their range of motion, and usually at that point, it's limiting their activities of daily living.

Jaime Shahan

Yes. And then lastly, we score symptoms of the genital tract through a physical exam, usually with a gynecologist. Mild symptoms without discomfort during the exam is a score of 1. When patients experience discomfort during the physical exam and have moderate symptoms, they're going to get a score of 2. A score of 3 signifies severe signs, even when a patient doesn't have discomfort with the exam. At that point, they may have scarring in that area.

Although that is the last item we check for, according to the 2014 NIH consensus criteria, there are some other indicators for chronic GVHD that we look out for. Sometimes patients have ascites or pericardial fusions. Sometimes they have plural effusions or nephrotic syndrome. Others include myasthenia gravis, peripheral neuropathy, polymyositis, and weight loss without GI symptoms. We can sometimes see eosinophilia in our chronic GVHD patients too. I tell the patients it's kind of like inflammatory white blood cells; they will see that rise when they have an allergic-type reaction. Sometimes we do see a rise in those eosinophils, and then sometimes we see a drop in the platelets as well. Those are indicators that we do score if they are present, but they're separate from the organ scoring.

Diya Sabnani

Yes, and after we score each individual body system and check for these other outlying issues, then we categorize organ scoring into a global severity score. For this, we're looking at the number of organs involved and the severity of the disease—the 0 to 3 score—in these organs. The global score is defined as mild, moderate, or severe. Mild disease is when one or two organs are involved with a maximum score of 1. Moderate disease is defined as three or more organs involved with a score of 2 in any individual organ or with lung involvement grading with a score of 1. And a severe global score is defined as an individual score of 3 in any organ or a lung score of 2.

Jaime Shahan

Yes, there is a lot of close and careful assessment that goes into scoring chronic GVHD—partly because of all the potential organ systems that can be involved, and partly because it's vital that our patients are treated appropriately based on their individual signs and symptoms. Chronic GVHD can severely impair quality of life in many ways, and it's our duty as APPs to help patients understand, manage, and treat their symptoms.