What is Graft vs. Host Disease? Causes, Symptoms, and Treatment

What is Graft vs. Host Disease?

Graft vs. host disease (GvHD) represents a complex immune reaction following an allogeneic bone marrow or stem cell transplant. Unlike the intended healing response, GvHD happens when the donor's immune cells, particularly T lymphocytes, recognize the recipient’s body as foreign and attack healthy tissues.

This condition primarily occurs because of differences in human leukocyte antigens (HLA) between the donor and recipient. GvHD primarily affects patients who undergo bone marrow transplants for treating blood cancers, bone diseases, or severe immune deficiencies.

The severity of GvHD varies significantly among patients. Some experience mild symptoms affecting only the skin, while others develop life-threatening complications involving multiple organs.

What Happens During Graft vs. Host Disease?

During GvHD development, donor T cells become activated upon encountering recipient cells displaying different HLA markers. These activated immune cells release inflammatory chemicals called cytokines, creating widespread inflammation throughout the body. The process typically intensifies after conditioning treatments such as chemotherapy and radiation that damage host tissues and make them more visible to donor immune cells.

The inflammatory cascade affects multiple organ systems simultaneously. Graft-versus-host disease (GvHD) skin manifestations often appear first, followed by gastrointestinal and liver involvement. In chronic cases, ongoing inflammation leads to scarring, fibrosis, and autoimmune-like changes that can permanently affect organ function.

Causes of Graft vs. Host Disease

• Donor compatibility differences: Even well-matched donors may have subtle genetic variations that trigger immune responses. According to MedlinePlus, the risk of GVHD is about 35–45% with related donors and 60–80% with unrelated donors.
• Age factors: Both older donors and recipients face higher GvHD risks due to immune system changes
• Gender mismatches: Female donors who have been pregnant may carry antibodies against male recipients
• Transplant source: Peripheral blood stem cells contain more immune cells than traditional bone marrow harvests
• Conditioning intensity: Stronger chemotherapy or radiation treatments increase tissue damage and inflammation
• Previous infections: Viral reactivation can worsen immune system dysfunction
• Inadequate prevention: Insufficient immunosuppressive medications allow donor cells to attack more aggressively

Types of Graft vs. Host Disease

GvHD classification depends on timing, duration, and organ involvement:

• Acute GvHD: Develops within the first 100 days post-transplant, though late-onset acute disease can occur later. It primarily affects the skin, liver, and gastrointestinal tract, with severity graded from mild (grade 1) to very severe (grade 4).

• Chronic GvHD: Begins more than three months after transplant and can persist for years. This form affects multiple organs simultaneously and often resembles autoimmune conditions like scleroderma or autoimmune connective tissue diseases.

• Progressive GvHD: Represents a chronic disease that directly follows unresolved acute symptoms, creating a continuous spectrum of complications.

• Overlap syndrome: Occurs when patients experience both acute and chronic features simultaneously, complicating treatment decisions and requiring specialised graft vs host disease treatment approaches.

Symptoms of Graft vs. Host Disease

GvHD symptoms vary depending on the type and organs involved:

1. Acute skin symptoms include red rashes beginning on the palms, soles, or face, often accompanied by itching, burning, or blistering in severe cases.
2. Gastrointestinal manifestations include nausea, vomiting, abdominal cramps, and watery or bloody diarrhoea, sometimes resulting in large fluid losses.
3. Liver involvement causes jaundice, right upper abdominal discomfort, and abnormal liver function tests, potentially progressing to liver failure.
4. Chronic graft-versus-host disease skin changes include persistent rashes, colour changes, dryness, tightening, or scleroderma-like thickening that restricts movement.
5. Oral symptoms encompass dry mouth, sensitivity to spicy foods, mouth ulcers, and white patches inside the mouth.
6. Eye complications manifest as dryness, grittiness, burning, pain, redness, and light sensitivity due to reduced tear production.
7. Respiratory symptoms include shortness of breath, dry cough, wheeze, and exercise intolerance from bronchiolitis obliterans.
8. Musculoskeletal effects cause joint pain, stiffness, limited range of motion, and muscle weakness

Acute symptoms may resolve with treatment within weeks to months, while chronic manifestations can persist for years or become permanent without proper intervention.

How is Graft vs. Host Disease Diagnosed?

GvHD diagnosis in transplant recipients relies on combining clinical history, physical examination, and targeted investigations. Physicians first consider timing after transplant and the affected organ systems, looking for characteristic patterns such as new rashes, diarrhoea, jaundice, or dry eyes and mouth.

Differential diagnosis remains crucial, as infections, drug reactions, and disease relapse can mimic GvHD symptoms. This process often requires ruling out other conditions through comprehensive testing, including specialised bone and joint tests when musculoskeletal symptoms predominate.

Tissue biopsies frequently provide a definitive diagnosis by revealing characteristic microscopic changes specific to GvHD. These histological findings, combined with clinical presentation and timing, help distinguish GvHD from other post-transplant complications and guide appropriate treatment selection.

Diagnostic Tests to Identify a Graft vs. Host Disease

• Physical examination focusing on skin changes, oral and ocular dryness, joint mobility, and abdominal assessment
• Laboratory investigations, including liver function test and complete blood count to assess organ involvement
• Histological confirmation through skin, gastrointestinal, or liver biopsies showing characteristic GvHD changes
• Endoscopic procedures with tissue sampling when significant gastrointestinal symptoms occur
• Pulmonary function testing (such as ABPA Profile - Allergic Bronchopulmonary Aspergillosis) and chest imaging to measure breathing capacity and airflow in suspected lung GvHD
• Ophthalmological assessment including tear production tests and detailed eye examinations (such as Histopathological Examination – Ocular Tissue Specimen (when clinically indicated))
• Bone profile assessments, such as bone resorption marker test or Osteomon Profile, when bone complications develop

Treatment Options for Graft vs. Host Disease

• Corticosteroids: First-line treatment for most acute cases, reducing inflammation throughout your body
• Immunosuppressive medications: Medications such as tacrolimus, cyclosporine, or mycophenolate mofetil, which suppress immune system activity
• Targeted therapies: Newer medications such as ruxolitinib for steroid-resistant cases
• Topical treatments: Steroid or immunomodulatory creams for localized skin manifestations
• Supportive care: Nutritional support, infection prevention, and symptom management
• Phototherapy: UV light treatment for certain skin manifestations
• Physical therapy: Maintains mobility, prevents contractures, and reduces joint stiffness in chronic disease

Managing Graft vs. Host Disease Long-Term

Long-term GvHD management focuses on preventing complications while maintaining quality of life. Patients require regular monitoring through comprehensive health assessments, including periodic bone profile evaluations and arthritis profile testing when joint involvement occurs. Infection prevention is critical due to prolonged immunosuppression, requiring strict attention to vaccinations, hygiene, and prompt recognition of infection symptoms.

Nutritional support, physical therapy, and psychological counselling help address the multifaceted challenges of chronic GvHD. Many patients benefit from multidisciplinary care involving specialists in dermatology, gastroenterology, pulmonology, and rehabilitation medicine.

Graft vs. Host Disease in Children vs. Adults

Pediatric patients often present with more acute symptoms but may respond better to treatment due to their robust healing capacity. However, chronic GvHD in children can significantly impact growth and development, necessitating careful monitoring and supportive interventions.

Adult patients typically face higher risks of chronic disease and may experience more severe organ involvement. Age-related factors such as pre-existing health conditions, medication tolerance, and healing capacity influence treatment decisions.

Conclusion

Understanding Graft-versus-Host Disease empowers patients and families to recognise symptoms early and advocate for appropriate care. From acute GvHD skin manifestations to chronic multi-organ complications, this condition requires comprehensive management involving transplant specialists, supportive care teams, and ongoing monitoring.

Successful GvHD management depends on early recognition, appropriate treatment selection, and long-term follow-up care. Regular health assessments help detect complications before they become severe, improving outcomes and quality of life for transplant survivors.

At Metropolis Healthcare, we understand the importance of precise diagnostic testing in managing complex conditions like GvHD. Our comprehensive portfolio of more than 4,000 tests includes specialised panels such as the arthritis profile and other bone and joint tests. Through our extensive network of over 10,000 touchpoints across India, we provide convenient at-home sample collection services, ensuring you receive reliable results when you need them most.

FAQs

Is Graft vs. Host Disease fatal?

GvHD can be life-threatening if severe and untreated, but many patients manage it successfully with appropriate medical care and monitoring.

What are the stages of Graft vs. Host Disease?

GvHD is graded from 1-4 based on severity, with grade 1 being mild and grade 4 representing severe, life-threatening disease.

How long does Graft vs. Host Disease last?

Acute GvHD may resolve within months with treatment, while chronic forms can persist for years or become permanent conditions.

Can Graft vs. Host Disease recur?

GvHD can flare or develop new manifestations, especially if immunosuppressive therapy is reduced or discontinued prematurely.

What is the survival rate for Graft vs. Host Disease?

Survival varies significantly by severity and organ involvement, but early recognition and appropriate treatment substantially improve long-term outcomes.

What lifestyle changes should I make after a GVHD diagnosis?

• Maintain excellent hygiene to prevent infections
• Follow a balanced diet with adequate nutrition support
• Protect skin from sun exposure and injury
• Attend all scheduled medical appointments
• Take medications exactly as prescribed
• Stay current with recommended vaccinations
• Engage in appropriate physical activity as tolerated

Are there any alternative treatments for Graft vs. Host Disease?

Some centers offer investigational therapies such as mesenchymal stem cell infusions, JAK inhibitors, or other emerging immunosuppressive agents through clinical trials.