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Graft versus host disease

Author: Vanessa Ngan, Staff Writer, 2003.

Graft versus host disease — codes and concepts

What is graft-versus-host disease?

Graft-versus-host disease (GVHD) is a condition where following transplantation the donor's immune cells in the transplant (graft) make antibodies against the patient's tissues (host) and attack vital organs. Organs most often affected include the skin, gastrointestinal (GI) tract and the liver.

Ninety per cent of bone marrow transplants lead to GVHD. Solid organ transplantation, blood transfusions, and maternal-fetal transfusions have also been reported to cause GVHD less frequently.

Types of graft-versus-host disease

There are two forms of GVHD.

  • Acute GVHD
    • An early form of GVHD that occurs within the first three months of transplantation
    • The first sign is usually a skin rash appearing on the hands, feet and face
    • Gastrointestinal and liver dysfunction symptoms may follow
  • Chronic GVHD

What are the signs and symptoms of graft-versus-host disease?

Acute GVHD and chronic GVHD are distinct diseases. One common factor is that they both increase the patient's susceptibility to infection.

Acute GVHD Chronic GVHD
  • Tender, red spots usually appear 10-30 days post-transplantation
  • Face, hands and feet affected first then spreading to the whole body (erythroderma)
  • Nails can be lost or develop Beau lines
  • Spots may coalesce to form widespread red rash
  • The rash may develop into raised spots or blisters that resemble toxic epidermal necrolysis
  • Fever may be present
  • Watery or bloody diarrhoea with stomach cramps indicates GI involvement
  • Jaundice (yellowing of the skin and eyes) indicates liver involvement
  • Abnormal liver function tests
  • A dry, itchy raised rash develops over the whole body (erythroderma)
  • Dry mouth and sensitivity to spicy or acid foods leading to mouth lesions
  • Dry eyes causing irritation and redness
  • Skin thickening, scaling, hyper- or hypopigmentation (resembling lichen planus)
  • Loss of skin colour without thickening (vitiligo)
  • Hardening of skin (scleroderma) may interfere with joint mobility
  • Hair loss (including typical alopecia areata) or premature greying
  • Nail dystrophy
  • Genital disease, including painful vulval and vaginal ulceration with scarring
  • Decreased sweating
  • Liver involvement causing jaundice
  • Lung and GI disorders may occur

How is graft-versus-host disease diagnosed?

Graft-versus-graft disease may be suspected in patients who have received a transplant and develop cutaneous or systemic complications. It must be confirmed by a tissue biopsy. See graft-versus-host disease pathology for the cutaneous histological features. 

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

Patients recovering from bone marrow transplantation are usually hospitalised for several weeks following transplant and are monitored closely for signs of developing GVHD or infection. The best treatment for GVHD is prevention. This consists of a cocktail of immunosuppressive drugs such as:

The combination of ciclosporin and methotrexate has been found to significantly decrease the severity of GVHD. These drugs weaken the ability of the donor's immune cells to launch an attack on the patient's organs.

Treatment for patients who do develop GVHD depends on the severity of the disease. Mild cases with only skin involvement of acute GVHD may settle without treatment. More severe acute or chronic GVHD predisposes the patient to infection, and overwhelming sepsis (blood poisoning) is the main cause of death in patients with GVHD. The aim is to treat GVHD before life-threatening sepsis occurs.

  • Local skin care should include emollients and topical steroids
  • The vulvovaginal disease should also be managed using oestrogen cream, intravaginal corticosteroid or tacrolimus and dilators.
  • High dose corticosteroids are usually added to the immunosuppressive regime.
  • Targeted monoclonal antibodies such as rituximab appear very effective but are very costly.
  • In 2019, ruxolitinib was approved by the Food and Drug Administration (FDA) in the US for treatment of steroid-resistant GVHD in adults and children over the age of 12 years.
  • Photochemotherapy (PUVA) and high dose long-wave ultraviolet radiation (UVA1) may reduce the severity of skin problems.
  • Extracorporeal photopheresis is available in a few centres and can be very effective

Because GVHD affects so many different organs, treatment is usually delivered by a multi-disciplinary team of transplant doctors, dermatologists, respiratory doctors, gastroenterologists, ophthalmologists, and other specialists.

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  • Book: Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth edition. Blackwell Scientific Publications.

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