24th July 2024

Graft-versus-host disease

GvHD is a complication of allogeneic HSCT when donor T-lymphocytes respond to histoincompatible antigens on host tissue.

Higher degree of HLA-mismatch, older donor/recipient age and sex disparity all increase the risk of GvHD.

GvHD can be acute, chronic or exhibit an overlap syndrome. They are differentiated by clinical findings.

Prophylaxis is generally with ciclosporin/tacrolimus and methotrexate/mycophenolate mofetil. There can be complications from these medications, e.g. gingival hyperplasia with ciclosporin and renal failure with tacrolimus.

Acute GvHD

Classic acute GvHD occurs <100 days post-HSCT; if it occurs after this, it is classified as late onset acute GvHD.

• Skin: maculopapular rash on neck, ears, shoulders, palms and soles
• Gastrointestinal tract: can affect the upper and lower gastrointestinal tract causing nausea, vomiting, anorexia, diarrhoea and abdominal cramps
• Liver: damage to bile canaliculi causing cholestasis and elevated bilirubin and deranged liver function tests

Isolated skin acute GvHD affecting <50% of the skin is treated with topical treatments, including steroids.

Any other acute GvHD is treated with systemic oral steroids and ciclosporin/tacrolimus.

Chronic GvHD

Chronic GvHD normally occurs >3 months after HSCT but can occur at any time after it, even many years. If there are features of acute GvHD then it is an ‘overlap syndrome’.

It typically affects the skin, liver, gastrointestinal tract and lungs, but any organ system can be affected:

• Skin: erythema, plaques, desquamation, lichen planus-like, joint contractures, scleroderma-like
• Mouth: xerostomia, mucositis, gingivitis, ulcers
• Liver: acute hepatitis or slowly progressive cholestasis
• Gastrointestinal tract: can affect the upper and lower gastrointestinal tract causing nausea, vomiting, anorexia, diarrhoea, exocrine pancreatic insufficiency
• Lung: bronchiolitis obliterans causing dyspnoea on exertion, dry cough and decreased exercise tolerance
• Musculoskeletal: muscle cramps, arthralgia, arthritis

Mild disease may be managed by treatment localised to the system affected. Any other disease stage requires systemic steroids with adjunct therapy depending on the body system affected, e.g. emollients for skin and inhalers for lungs.