Graft versus Host Disease (GVHD) is a serious, potentially fatal infection that can happen after bone marrow or stem cell transplantation. This condition arises when the donated immune cells from the transplant (the graft) perceive the recipient’s body (the host) as foreign and stage an immune attack against it.
GVHD can affect multiple organs and tissues, resulting in a wide range of symptoms that may vary in severity based on the level and kind of immune response. GVHD is one of the most difficult aspects of allogeneic transplants, so understanding its types, causes, and symptoms is essential to identifying and treating the issue early on.
The following article explores Graft vs. Host Disease, including its various types, underlying causes, and the wide range of symptoms that the host might experience.
What is Graft vs Host Disease (GVHD)?
Graft vs. Host Disease (GVHD) is a serious medical condition that can develop after a stem cell or bone marrow transplant. In this condition, the donated immune cells (the graft) recognise the recipient’s body (the host) as foreign and launch an attack.
This immune response can lead to significant damage to various organs and tissues, creating a complex interplay between the donor’s immune cells and the host’s immune defences. GVHD is a major complication following an allogeneic transplant, which involves receiving stem cells from a donor rather than from the patient’s own body.
Types of Graft vs Host Disease
GVHD is commonly categorised into two main types according to its emergence and type of symptoms:
Acute Graft Vs Host Disease
Acute GVHD generally shows itself in the first 100 days after a bone marrow or stem cell transplant. It usually affects the liver, gastrointestinal system, and skin. Symptoms often appear suddenly. Acute GVHD can have a wide range of severity, from moderate symptoms that are generally manageable to severe cases that may be fatal. The early signs of symptoms necessitate seeking medical assistance promptly in order to avoid serious medical issues.
Chronic Graft Vs Host Disease
Chronic GVHD usually appears during the first 100 days following transplant and can persist for months or even years. In contrast to acute GVHD, which typically targets a single organ, chronic GVHD can impact several organ systems at once, such as the skin, eyes, mouth, lungs, liver, and joints. Chronic GVHD can display symptoms similar to autoimmune disorders, and managing this condition requires long-term treatment and monitoring.
Causes of Graft vs Host Disease
Below are the underlying causes of graft vs host disease:
HLA Matching
The degree of donor-recipient human leukocyte antigen (HLA) matching is positively correlated with both the risk and severity of GVHD. Cell surface proteins called HLAs help the immune system distinguish between the body’s cells and external invaders.
Due to small variations in histocompatibility antigens, GVHD can occur even in cases where there is a perfect HLA match. The chance of the recipient’s tissues being attacked by the donor’s immune cells increases with the level of HLA mismatch between the donor and recipient.
Donor Source
The source of the donor cells is a major factor in the development of GVHD. GVHD is more common in transplants from unrelated or mismatched donors than in transplants from HLA-matched sibling donors.
The threat may also be influenced by the type of cells used in the transplant. Bone marrow and peripheral blood stem cells contain a higher concentration of mature immune cells, which can cause an immunological response in the recipient’s tissues. Therefore, they are more likely to cause GVHD than umbilical cord blood.
Age and Gender of Donor
The development of GVHD is greatly affected by the donor’s age and gender. Older donors tend to have a higher risk of causing GVHD due to the presence of more mature immune cells that are more likely to recognise the recipient’s tissues as foreign.
Female donors, particularly those who have had pregnancies, are also known to be associated with a higher risk of GVHD. It is probably because immune sensitisation during pregnancy raises the possibility of recipient-specific immune cell reactions from the donor’s immune system.
Conditioning Treatment
Patients undergo conditioning treatment prior to a transplant, which usually consists of radiation or chemotherapy to weaken their immune systems and make room for the donor cells to engraft. The degree to which this conditioning procedure is followed can affect the possibility of developing graft versus host disease.
Symptoms of Graft vs Host Disease
The symptoms of GVHD vary depending on whether it is acute or chronic and which organs are affected.
Acute GVHD Symptoms
The Acute GVHD symptoms include:
Skin
Symptoms of acute GVHD can vary from moderate redness and itching to severe rashes that can cover significant portions of the body, with the skin frequently being the first organ to be affected. In more extreme situations, the skin may burst and peel, resembling the consequences of a serious burn. It can cause notable discomfort and increase the risk of infection, requiring intensive care and treatment.
Liver
Acute GVHD can also affect the liver, resulting in symptoms like jaundice, which is characterised by high bilirubin levels that cause the skin and eyes to turn yellow. An enlarged and tender liver can cause pain in the upper right abdomen, and unusual liver function tests can be an indication of liver disease. These symptoms require careful monitoring and management to prevent further liver damage.
Gastrointestinal Tract
Acute GVHD also frequently affects the gastrointestinal tract. Severe diarrhoea, cramping in the abdomen, and other symptoms are possible. Patients may also have nausea and vomiting, which can cause severe weight loss and dehydration. To manage gastrointestinal inflammation, supportive care and focused therapy are required because these symptoms have the potential to seriously impair the patient’s diet and overall well-being.
Chronic GVHD Symptoms
Here are the symptoms associated with chronic GVHD:
Skin
Chronic GVHD can cause a variety of skin changes, which include thickening and hardening of the skin, a condition known as scleroderma-like changes. These changes can be uncomfortable and restrict movement, mainly if they occur over joints. Additionally, chronic GVHD may lead to pigmentary changes, like darkening or lightening of the skin and hair loss. These symptoms can be persistent and may require long-term dermatological care.
Eyes
When chronic GVHD affects the eyes, it can cause symptoms like photophobia, sensitivity to light, dry eyes, and discomfort. If not treated promptly, persistent inflammation of the eyes might result in other issues, such as visual impairments. Artificial tears, anti-inflammatory drugs, and routine ophthalmological examinations are commonly used to manage these symptoms and prevent long-term damage.
Mouth
Chronic GVHD often impacts the mouth, resulting in dry mouth, excruciating ulcers, and trouble eating. Another common symptom is oral lichen planus, which is defined by white, lacy patches on the mucosal membranes.
These symptoms may impact the patient’s quality of life, making eating and speaking difficult. Management strategies often include systemic medications, topical treatments, and good oral hygiene to control inflammation.
Lungs
Bronchiolitis obliterans syndrome (BOS), a disorder that limits and scars the lungs’ small airways, is one of the more dangerous side effects of chronic GVHD. Its symptoms include shortness of breath, chronic cough, and decreased lung function.
The serious consequences of BOS can include lifelong immunosuppressive pharmaceutical treatment and pulmonary rehabilitation, as well as a serious influence on the patient’s respiratory health.
Gastrointestinal Tract
Chronic GVHD may continue to negatively impact the gastrointestinal system, which can result in recurrent symptoms such as diarrhoea, malabsorption, and trouble swallowing due to oesophagal strictures.
These symptoms might also result in significant weight loss, vitamin deficiencies, and general ill health. Dietary changes, nutritional supplements, and drugs to reduce inflammation and enhance digestion may all be part of the management process.
Liver
When GVHD causes chronic liver involvement, it can result in abnormal liver function tests, chronic liver inflammation, and, in severe cases, the development of cirrhosis, a disease where the liver tissue scars. It can cause long-term liver damage and may require ongoing monitoring and treatment to manage liver function and prevent further deterioration.
Joints and Muscles
Muscle weakness, joint stiffness, and discomfort are all symptoms of chronic GVHD that can impact the joints and muscles. These symptoms may impair the patient’s physical function and movement and may resemble those of rheumatoid arthritis. Physical therapy, pain management, and occasionally immunosuppressive drugs are used in combination to treat the inflammation and maintain joint and muscle function.
Conclusion
In conclusion, Graft vs Host Disease is a complex and potentially life-threatening complication of stem cell and bone marrow transplantation. The management of the condition necessitates the understanding of the causes, and symptoms, which helps in improving patient outcomes. Early discovery and a multidisciplinary approach to care are necessary for minimising the impact of GVHD and enhancing the quality of life for those affected by this challenging disease.
