Graft-Versus-Host Disease (GVHD): Pathological Essentials
Graft-Versus-Host Disease is a distinct immunological phenomenon occurring primarily after allogeneic hematopoietic stem cell transplantation (HSCT). Unlike transplant rejection (where the host attacks the graft), GVHD occurs when donor T-cells residing in the graft recognize and attack the recipient’s tissues.
1. Pathophysiological Requirements (Billingham’s Criteria)
For GVHD to develop, three conditions must be met simultaneously:
- The graft must contain immunocompetent T-cells.
- The recipient must be immunocompromised, preventing them from rejecting the donor cells.
- The recipient must possess foreign antigens (HLA mismatches) that the donor T-cells recognize as non-self.
2. Clinical Manifestations
GVHD is categorized into two clinical phases based on temporal progression:
| Type | Timing | Classic Clinical Presentation |
|---|---|---|
| Acute | Within 100 days | Maculopapular rash (starts on palms/soles), profuse watery diarrhea, and jaundice due to liver involvement. |
| Chronic | After 100 days | Manifests with autoimmune-like features, such as skin fibrosis (scleroderma-like), sicca syndrome, and esophageal strictures. |
3. Exam Must-Knows
Pathology Pearl: GVHD is a classic Type IV hypersensitivity reaction. The inflammatory damage is driven by donor T-cell secretion of proinflammatory cytokines (IL-2, IFN-gamma) and direct cytotoxic T-cell-mediated apoptosis of host cells.
- Prevention: Use of HLA-matched donors and immunosuppressive protocols (e.g., cyclosporine, methotrexate) to suppress donor T-cell activity.
- Transfusion-Associated GVHD: A rare but fatal complication where immunocompetent T-cells from non-irradiated blood products attack an immunocompromised patient. Prevented by irradiating all blood products prior to transfusion in at-risk populations.
- Diagnosis: Confirmed by skin or rectal biopsy, which shows lymphocytic infiltrate and characteristic apoptosis of epithelial cells.