Graft-versus-host disease !

After a stem cell transplant, the donor's immune cells can attack the patient's skin, gut, liver, eyes and mouth.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

An immune complication, most often of allogeneic haematopoietic stem cell transplantation, in which donor T cells recognise the recipient's tissues as foreign and attack them. Acute GVHD mainly targets the skin, gastrointestinal tract and liver; chronic GVHD resembles autoimmune disease and can affect almost any organ.

Who gets it

Acute GVHD affects roughly a third to a half of allogeneic transplant recipients, and chronic GVHD a similar proportion of long-term survivors; it is a leading cause of non-relapse death after transplant. It can also follow transfusion of non-irradiated blood products to immunocompromised patients, or solid organ transplants rich in lymphocytes (such as liver). Allogeneic transplant activity is growing in Colombia and Latin America, so recognising GVHD matters beyond transplant centres.

Causes

Donor T cells reacting against recipient histocompatibility antigens (HLA and minor antigens)
Allogeneic haematopoietic stem cell transplantation (most cases)
Transfusion-associated GVHD from non-irradiated cellular blood products
Rarely, after solid organ transplantation

Risk factors

HLA mismatch or an unrelated donor
Female donor for a male recipient, especially a woman with previous pregnancies
Peripheral blood stem cells as the graft source (more chronic GVHD) rather than bone marrow or cord blood
Older recipient or donor age
Intensive (myeloablative) conditioning and inadequate GVHD prophylaxis

Pathophysiology

Conditioning chemotherapy and radiation damage host tissues, releasing cytokines and danger signals that activate host antigen-presenting cells. Donor T cells recognise the recipient's antigens, multiply and release more cytokines; cytotoxic T cells and inflammatory cells then destroy epithelial cells of the skin, intestinal crypts and bile ducts. Chronic GVHD involves T and B cells, autoantibodies and fibrosis, producing changes similar to scleroderma, lichen planus and Sjögren disease. The same donor immune response provides a beneficial graft-versus-leukaemia effect.

Classification

Acute GVHD: classically within 100 days, affecting skin, gut and liver; graded I to IV by stage of each organ
Chronic GVHD: classically after 100 days, with fibrotic and autoimmune-like features; graded mild, moderate or severe
Overlap syndrome with features of both, and late-onset acute GVHD
Transfusion-associated GVHD

Symptoms and signs

Acute: itchy or painful red rash, often starting on the palms, soles and ears, which can blister
Acute: profuse watery or bloody diarrhoea with abdominal cramps, nausea and loss of appetite
Acute: jaundice from cholestatic liver injury
Chronic: dry, gritty eyes and dry mouth with painful oral lichen-like lesions
Chronic: thickened, tight skin and joint contractures
Chronic: breathlessness and dry cough (bronchiolitis obliterans), weight loss

Diagnosis

Clinical: Clinical diagnosis in the right setting: rash, diarrhoea or jaundice after allogeneic transplant, once infection, drug reactions and veno-occlusive disease have been considered. Chronic GVHD has diagnostic signs such as poikiloderma, lichen planus-like changes, sclerosis and bronchiolitis obliterans.
Tests: Biopsy of skin, gut (endoscopy) or liver confirms it, showing epithelial cell apoptosis (crypt cell apoptosis in the gut). Liver tests (cholestatic pattern), stool volume and infection studies (Clostridioides difficile, CMV and other viruses). Pulmonary function testing for bronchiolitis obliterans; Schirmer test for dry eye. In transfusion-associated GVHD, pancytopenia from marrow attack is typical.
Imaging: CT of the abdomen may show bowel wall thickening; high-resolution chest CT shows air trapping in bronchiolitis obliterans; liver Doppler ultrasound helps exclude veno-occlusive disease.

Differential diagnosis

Drug eruption or viral exanthem
Infectious diarrhoea (CMV, Clostridioides difficile, other viruses)
Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) and drug-induced liver injury
Engraftment syndrome
Chemotherapy or radiotherapy toxicity (mucositis)

Goal of treatment

Prevent GVHD where possible, control the immune attack quickly when it occurs, protect against infection and keep the beneficial graft-versus-leukaemia effect.

Treatment

Medical: Prophylaxis: calcineurin inhibitors (cyclosporine or tacrolimus) with methotrexate or mycophenolate, post-transplant cyclophosphamide, or antithymocyte globulin.
Medical: First-line treatment of acute and chronic GVHD: systemic corticosteroids, with topical steroids for mild skin disease.
Medical: Steroid-refractory disease: JAK inhibitors (ruxolitinib), BTK or ROCK2 inhibitors for chronic GVHD, or extracorporeal photopheresis.
Conservative: Supportive care: fluid and nutrition support for gut GVHD, eye lubricants, oral care, skin care and physiotherapy for contractures.
Medical: Infection prophylaxis during immunosuppression against Pneumocystis, fungi and herpes viruses, with CMV monitoring.
Follow-up: Nursing priorities: daily skin assessment, stool volume and fluid balance, weight and nutrition, liver tests, drug levels of calcineurin inhibitors and early detection of fever; irradiated blood products for at-risk patients.

Drugs for this condition

Complications

Opportunistic infections (CMV, fungi, Pneumocystis) from the disease and its treatment
Malnutrition and dehydration
Bronchiolitis obliterans with chronic respiratory failure
Skin sclerosis, contractures and ocular damage
Steroid adverse effects: diabetes, osteoporosis, myopathy

Prognosis

Mild acute GVHD responds well and is linked to fewer relapses; severe grades III–IV and steroid-refractory disease carry high mortality. Chronic GVHD often lasts years and is the main cause of late morbidity after transplant, but many patients can eventually stop immunosuppression.

Prevention

Best possible HLA matching of donor and recipient
Pharmacological GVHD prophylaxis after transplant
Irradiation of cellular blood products for transplant recipients and other at-risk patients

Test yourself

Think of the answer, then tap the question to see it.

Which three organs are classically targeted in acute graft-versus-host disease?

Skin, gastrointestinal tract and liver.

Which cells mediate graft-versus-host disease?

Donor T cells reacting against the recipient's tissue antigens.

What is the first-line treatment of moderate to severe acute GVHD?

Systemic corticosteroids.

How is transfusion-associated GVHD prevented?

By irradiating cellular blood products for at-risk patients.

Which lung complication is diagnostic of chronic GVHD?

Bronchiolitis obliterans syndrome.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Graft-versus-host disease (MedlinePlus (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

Skin highlighted on the Durgical 3D model