Gastrointestinal Graft-Versus-Host Disease (GI GVHD) is a medical condition that can arise after certain medical procedures. It affects various parts of the digestive tract, leading to a range of bodily responses.
Understanding Graft-Versus-Host Disease
Graft-versus-host disease (GVHD) is a complication following allogeneic hematopoietic stem cell transplantation (HSCT). It occurs when transplanted donor immune cells, the “graft,” identify recipient tissues, the “host,” as foreign and attack them.
This immune reaction can affect various organs throughout the body, including the skin, liver, and gastrointestinal tract. GVHD is categorized into two primary forms based on its onset time. Acute GVHD typically manifests within the first 100 days after transplantation, though it can appear later. Chronic GVHD usually develops more than 100 days post-transplant and can even emerge years later, sometimes resembling autoimmune conditions.
Acute GVHD is estimated to affect 30-50% of patients undergoing allogeneic HSCT. While acute GVHD commonly impacts the skin, liver, and gastrointestinal tract, chronic GVHD can involve a wider array of organs, including the eyes, mouth, lungs, joints, and genitalia. A close match between donor and recipient human leukocyte antigen (HLA) markers helps reduce the likelihood of GVHD.
The Digestive System and GI GVHD
The gastrointestinal (GI) tract is frequently involved in graft-versus-host disease, with an estimated 70% of acute GVHD patients and 33% of chronic GVHD patients experiencing GI involvement. This occurs because conditioning chemotherapy and radiation treatments before a transplant can damage the intestinal wall. This damage exposes gut immune cells to bacteria from the microbiome, prompting them to produce chemicals that activate T cells.
These activated T cells instruct the cells lining the intestines to display specific molecules, increasing the likelihood of an immune response. This creates an environment for inflammation in the gut. The donor T cells then damage healthy cells lining the patient’s intestine, primarily affecting the epithelial cells within the crypts of the GI tract.
The inflammatory process can target various parts of the digestive system. The mouth may experience ulcerations and pain, while the esophagus can develop difficulty swallowing or narrowing. The stomach and small bowel are also frequently affected, leading to inflammation and cellular damage. This tissue damage in the GI tract generates an inflammatory response, releasing cytokines that promote further immune cell attack.
Damage to the intestinal mucosa can lead to a failure of fluid reabsorption, particularly in the ileum, contributing to significant fluid loss. Additionally, the destruction of mucosal cells reduces levels of disaccharidase enzymes, causing an osmotic effect due to unabsorbed carbohydrates.
Recognizing Symptoms
Symptoms of GI GVHD can vary widely in presentation and severity. Upper gastrointestinal symptoms often include loss of appetite, heartburn, nausea, vomiting, early fullness, or indigestion.
Lower gastrointestinal symptoms are also common. Diarrhea is often described as watery, green, or mucous-like, and it can contain undigested food. The diarrhea can be significant, with output potentially reaching several liters per day. Abdominal pain and cramping are often accompanying symptoms, ranging from mild discomfort to severe pain.
In some instances, the stool may become bloody, particularly in cases of severe mucosal denudation. Weight loss can occur due to malabsorption of nutrients and decreased oral intake. While these symptoms are highly suggestive of GI GVHD, they can also resemble other conditions such as infections or medication side effects, which can make diagnosis challenging.
Diagnosis and Treatment
Diagnosing GI GVHD involves a combination of clinical assessment, laboratory tests, and specialized procedures. Blood tests, particularly liver function tests, are monitored, as abnormal levels could indicate liver involvement, which often accompanies GI GVHD. Stool studies may also be ordered to rule out infections that can mimic GVHD symptoms.
Endoscopic evaluation with biopsies is an important diagnostic tool for GI GVHD. An endoscope, a flexible tube with a camera, allows visualization of the esophagus, stomach, and intestines. During endoscopy, small tissue samples (biopsies) are collected for microscopic examination. Histological findings such as apoptosis of crypt epithelial cells and crypt dropout are key indicators for diagnosis.
However, the distribution of lesions in GI GVHD can be patchy, and endoscopic findings may not always be specific or visible in all cases. Imaging tests like CT scans or MRI may show bowel wall thickening, though these findings are not specific to GVHD alone. A definitive diagnosis relies on integrating clinical symptoms with the characteristic microscopic changes observed in the biopsy samples.
Treatment for GI GVHD primarily focuses on suppressing the immune response. Corticosteroids, such as prednisone, are a common first-line treatment, working to weaken the donor immune cells and prevent them from attacking the host’s tissues. The specific dose and duration of steroid therapy are tailored to the disease’s severity and the patient’s response.
If corticosteroids are insufficient or cause side effects, other immunosuppressive medications may be introduced, such as mycophenolate mofetil, tacrolimus, or sirolimus, often in combination with steroids. For patients who do not respond to steroids, extracorporeal photopheresis (ECP), a procedure involving treating blood outside the body with light, may be considered.
Supportive care measures are also part of managing GI GVHD. These include nutritional support (dietary modifications, anti-nausea medications, IV feeding, or feeding tubes for severe cases), hydration for fluid loss, and pain management for abdominal discomfort and cramping.