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Graft versus host disease

Authors: Dr Amritpreet Singh, Advanced Trainee in General Medicine, Wellington Regional Hospital; Honorary Associate Professor Paul Jarrett, Dermatologist, Middlemore Hospital and Department of Medicine, The University of Auckland, New Zealand. Copy edited by Gus Mitchell. February 2022.


What is graft-versus-host disease?

Graft-versus-host disease (GVHD) is a condition that occurs after organ transplantation, most commonly bone marrow transplantation. It is a multi-system condition where the donor’s immune cells (graft) recognise the recipient (host) as foreign, and attack the recipient’s tissue and organs.

The organs most affected are the skin, gastrointestinal tract, liver, eyes, and lungs.

The most common cause of GVHD is allogeneic haematopoietic stem cell transplant (HSCT), which is used for the treatment of haematological malignancies and some immune system disorders (eg, bone marrow transplantation).

There are two main types, acute graft-versus-host disease and chronic graft-versus-host disease.

Who gets graft-versus-host disease?

Most patients with GVHD are recipients of allogeneic HSCT (stem cells come from a person other than the patient). The incidence of GVHD after allogeneic HSCT is as high as 40–60%.

Risk factors for GVHD following allogeneic HSCT include:

  • Immune mismatch between donor and recipient
  • Older age of donor or recipient
  • Gender disparity between donor and recipient
  • History of pregnancy or transfusions in the donor
  • Use of peripheral blood stem cells
  • Prior acute GVHD in the recipient
  • Splenectomy in the recipient.

Although extremely rare, GVHD may also occur after transfusion of non-irradiated blood products, solid organ and lymphoid tissue transplant, or after autologous HSCT (stem cells come from the patient themselves).

What causes graft-versus-host disease?

T lymphocytes in the donated tissue (graft) recognise the recipient (host) as foreign, and attack the recipient’s tissue and organs.

What are the clinical features of graft-versus-host disease?

There are two main types.

Acute GVHD (within 100 days of transplant)

  • Skin (most common and earliest organ involved):
    • Maculopapular rash on the nape of the neck, shoulders, palms, soles, pinnae, and cheeks; it can be painful and pruritic
    • Erythroderma
    • There may be blister formation and desquamation
    • Median time of onset is 19 days post transplantation.
  • Gastrointestinal tract:
    • Mouth: Erosions, ulcers, lichenoid lesions, xerostomia, and pain
    • Bloody or watery diarrhoea, cramping abdominal pain, nausea, vomiting, loss of appetite.
  • Liver:
    • Jaundice and rise in serum alkaline phosphatase.

Chronic GVHD (After 100 days of transplant)

  • Skin:
  • Nails:
  • Hair:
    • Scarring or non-scarring scalp alopecia, scaling, papulosquamous lesions, loss of body hair.
  • Mouth
    • Lichen planus-like features, hyperkeratotic plaques, restriction of mouth opening from sclerosis
    • Xerostomia, mucocele, mucosal atrophy.
  • Eyes
    • Dry, gritty, painful eyes, cicatricial conjunctivitis, keratoconjunctivitis sicca, confluent punctate keratopathy.
  • Genitalia
    • Lichen planus-like features, vaginal scarring, or stenosis
    • Erosions, fissures, ulcers.
  • Musculoskeletal system
    • Fasciitis, joint stiffness, or contractures due to sclerosis
    • Myositis, polymyositis. 

Itchy skin, dry mouth, diarrhoea, dry eyes, reduced vitality, and psychological stress are the most commonly reported symptoms of GVHD. 

What are the complications of graft-versus-host disease?

  • Impaired sleep due to itchy skin involvement.
  • Genital involvement can result in sexual dysfunction.
  • Hospitalisation is often required for immunosuppression titration and restoration of nutrition due to gastrointestinal tract involvement.
  • Immunosuppressive treatment increases the risk of infection, and depending on which agent is used, can cause:
    • Skin thinning, bruising, striae, weight gain, adrenal insufficiency, renal dysfunction, and neutropenia

Acute GVHD is associated with an increased risk of:

  • Infectious and noninfectious pneumonia
  • Pleural effusions
  • Haemorrhagic cystitis
  • Thrombocytopenia
  • Anaemia.

Chronic GVHD is associated with an increased risk of:

  • Streptococcal pneumonia
  • Haemophilus influenzae bacteraemia
  • Sinopulmonary infections.

How is graft-versus-host disease diagnosed?

Acute GVHD is diagnosed by a combination of clinical signs and biopsy. For the histological features, see graft-versus-host disease pathology

Chronic GVHD requires the presence of at least one diagnostic manifestation or one distinctive manifestation, in the same or separate organ. 

What is the differential diagnosis for graft-versus-host disease? 

What is the treatment for graft-versus-host disease?

General measures

  • Soap avoidance and emollients
  • Avoidance of UV light

Specific measures

Topical treatments

Systemic treatments

What is the outcome for graft-versus-host disease?

GVHD can persist for months to years requiring long-term immunosuppression. It may regress after one year due to the production of white blood cells in the recipient. 

Patients report impaired physical, social, and psychological wellbeing and impaired quality of life. Mortality may be as high as 15%.

However, the same immune response responsible for GVHD may also destroy any surviving cancer cells. This is called the graft versus tumour effect. Patients who develop GVHD have lower relapse rates of their original malignancy.



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