Graft Versus Host Disease - Episode 2

Diagnosis of Acute and Chronic GVHD

April 13, 2021
Corey S. Cutler, MD, MPH, FRCPC, Dana-Farber Cancer Institute

,
Yi-Bin A. Chen, MD, Massachusetts General Hospital

,
Haris Ali, MD, City of Hope

Hematologist-oncologists review the typical presentation and diagnosis of acute and chronic GVHD and define how severity is classified.

Haris Ali, MD: Acute GVHD [graft-vs-host disease] risk depends on the type of the donor and the transplant type. The risk could be anywhere between 60% and 80%, but not all of it is serious or high-risk GVHD. The risk of chronic GVHD is about 50%. It depends on the circumstances of the transplant, the type of the donor, the conditioning regimen, and the GVHD profile. These are the average incidences of GVHD.

Corey S. Cutler, MD, MPH, FRCPC: Acute GVHD is a clinical diagnosis. The typical presentation involves 3 organs, and essentially only 3 organs. Those 3 organs are the skin, gastrointestinal [GI] tract, and the liver. The skin presents with an erythematous, maculopapular, and often itchy rash. The differential diagnosis includes things like drug reactions or other allergic phenomena. In the GI tract, lower GI involvement presents with copious and watery diarrhea. In the upper GI tract, it presents with persistent nausea, vomiting, and a sense of early satiety. The diagnosis of acute GVHD of the GI tract is generally made with endoscopy, either upper GI endoscopy or lower GI endoscopy, which demonstrates apoptosis in the crypt cells of the GI mucosa. The main differential diagnoses for GI GVHD are things like CMV [cytomegalovirus] or other infections, and sometimes bacterial overgrowth. The liver presents with a cholestatic jaundice. This is generally diagnosed clinically, but the main histologic findings would be a portal triaditis and loss of the biliary system. The differential diagnosis for acute GVHD of the liver is veno-occlusive disease [VOD], but these 2 syndromes present very different clinically. It’s generally not hard to differentiate the 2 on clinical grounds alone based on the pathophysiology of VOD, which presents with ascites and a hepatorenal syndrome. Those are the 3 main organs that are involved. Very occasionally, things like the eyes can be involved, but those are probably more an overlap syndrome and addressed better with chronic GVHD.

Yi-Bin Chen, MD: There really isn’t a typical presentation of chronic graft-vs-host disease. It can involve almost any organ in a patient’s body and is very heterogeneous between patients. However, the most common organs involved are the eyes, mouth, and the skin to start. For the eyes, it often presents as a feeling of dry eyes or a feeling of sand constantly in one’s eyes. In the mouth, it presents as a dry mouth, often needing to drink multiple cups of water to eat a standard meal. It often presents as trouble swallowing. Frank ulcerations can occur as well. On the skin, it’s generally a rash, and the rash is different from acute graft-vs-host disease. It’s less angry. It can appear more as mimicking eczema or psoriasis. Other organs that can be involved include the underlying fascia of the skin. This is the connective tissue between the skin and the muscles. This can become quite thickened and result in a phenomenon called scleroderma, which can limit the range of motion and become very morbid and affect the quality of life. The lungs can be involved, and this leads to a phenomenon called bronchiolitis obliterans syndrome [BOS], which not only manifests as shortness of breath on exertion, but ultimately an obstructive airway disease. The lungs, BOS, and scleroderma are oftentimes the most difficult to treat.

There are other organs that can also be involved, and we see this. There are multiple joint issues, such as arthralgias or joint pains, and muscle issues, such as myositis. The GI tract can form strictures. The esophagus can fail to move correctly as it tries to do its normal peristalsis. There is pancreatic insufficiency that can cause malabsorption and chronic diarrhea. The kidneys can often show signs of what we call nephrotic syndrome or wasting protein. It’s hard to distinguish, because a lot of these manifestations mimic what we think of as classic autoimmune disease. There’s definitely some graft-vs-host disease that we view as the attack of the donor cells on the recipient’s body. And then there are some manifestations of chronic graft-vs-host disease that are clearly showing what we call immune dysregulation, where the immune system can’t regulate itself to be normal.

Chronic graft-vs-host disease remains a clinical diagnosis. There’s no 1 test, be it a blood test or biopsy, that is the gold standard for diagnosis. It’s still looking at the patient’s clinical symptoms, laboratory tests, and where they are after transplant to make a diagnosis. Biopsy of tissues can be done. Oftentimes, when you do a biopsy, there are supportive findings of fibrosis. That’s the main hallmark in many biopsies in chronic graft-vs-host disease.

We classify chronic graft-vs-host disease is by clinical severity. There have been various staging systems that have been used throughout the years, partly to help us all communicate and partly to do clinical trials. The most recent system was developed by the NIH [National Institutes of Health] consensus group. It involves 3 categories: mild, moderate, and severe. Affected organs all receive an individual number score, and these are calculated together to create an overall grade of mild, moderate, or severe.

Haris Ali, MD: We classify acute GVHD to look at the severity. There are various grading systems that are being used. Most of them utilize the clinical data, like the extent of the skin rash, volume of the diarrhea, abnormalities of the liver function, especially the bilirubin. There are also some classifications based on the biomarker and these are validated. These are called Ann Arbor scoring, where it can be divided into low, intermediate, or high risk.

Transcript Edited for Clarity