Graft-versus-host disease (GvHD) is a medical complication following the receipt of transplanted tissue from a genetically different person.
- Type IV hypersensitivity reactino
3 criteria must be met in order for GvHD to occur.
- An immuno-competent graft is administered, with viable and functional immune cells.
- The recipient is immunologically different from the donor – histo-incompatible.
- The recipient is immuno-compromised and therefore cannot destroy or inactivate the transplanted cells.
- Classic acute GvHD (onset ≤ 100 days)
- Persistent/recurrent/late-onset GvHD (onset > 100 days)
Pleiotropic, multiorgan syndrome involving tissue inflammation and fibrosis that often results in permanent organ dysfunction. Chronic GVHD is fundamentally caused by replacement of the host’s immune system with donor cells, although the heterogeneity of clinical manifestations suggests that patient, donor, and transplant factors modulate the phenotype.
- Classic chronic GvHD (occurs at any time)
- Overlap syndrome (occurs at any time)
- Features of both acute & chronic GvHD
- Transfusion-associated GvHD
- Associated with transfusion of un-irradiated blood to immunocompromised recipient or in situations in which the blood donor is homozygous and the recipient is heterozygous for an HLA haplotype
- Thymus transplantation
- Recipient’s thymocytes would use the donor thymus cells as models when going through the negative selection to recognize self-antigens, and could therefore still mistake own structures in the rest of the body for being non-self
- Thymoma-associated multiorgan autoimmunity (TAMA)
- Patient’s own malignant thymus produces self-directed T cells (as it is incapable of appropriately educating developing thymocytes to eliminate self-reactive T cells)
- Activation of APC (antigen-presenting cells)
- Activation, proliferation, differentiation and migration of effector cells
- Target tissue destruction
- Skin (M/C affected organ): Maculopapular skin rash
- Upper GIT: Nausea and/or anorexia + positive histology
- Lower GIT: Watery diarrhoea ≥ 500ml +/- severe abdominal pain +/- bloody diarrhoea or ileus (after exclusion of infectious aetiology)
- Liver: Cholestatic hyperbilirubinemia
- Skin: Dyspigmentation, new onset alopecia, poikiloderma, lichen planus-like eruptions or sclerotic features
- Nails: Nail dystrophy or loss
- Mouth: Xerostomia, ulcers, lichen-type features, restrictions of mouth opening from sclerosis
- Eyes: Dry eyes, sicca syndrome, cicatricial conjunctivitis
- Muscles, fascia, joints: Fasciitis, myositis, or joint stiffness from contractures
- Female genitalia: Vaginal sclerosis, ulcerations
- GI tract: Anorexia, weight loss, esophageal web or strictures
- Liver: Jaundice, transaminitis
- Lungs: Restrictive or obstructive defects on pulmonary function tests, bronchiolitis obliterans, pleural effusions
- Kidneys: Nephrotic syndrome (rare)
- Heart: Pericarditis
- Marrow: Thrombocytopenia, anemia, neutropenia
- Selective damage to the liver, skin (rash), mucosa, and the gastrointestinal tract:
- GI GvHD: intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting
- Skin GvHD: Diffuse red maculopapular rash, sometimes in a lacy pattern
- IV glucocorticoids: Prednisone
- Calcineurin inhibitors: Cyclosporine & tacrolimus
- Methotrexate, cyclosporin and tacrolimus