What is the management approach for skin Graft-Versus-Host Disease (GVHD) after Living Donor Liver Transplant (LDLT)?

Management of Skin GVHD After Living Donor Liver Transplantation

For skin Graft-Versus-Host Disease (GVHD) after Living Donor Liver Transplantation (LDLT), treatment should be based on the severity grade, with topical therapy for Grade I and systemic corticosteroids for Grade II-IV GVHD. 1, 2

Grade I Skin GVHD Management

• For Grade I skin GVHD (affecting ≤50% body surface area with non-bullous rash), continue or restart the original immunosuppressive agent used for transplant prophylaxis 1
• Apply medium to high-potency topical corticosteroids (e.g., triamcinolone, clobetasol) to affected skin areas, except on the face where low-potency hydrocortisone should be used to avoid skin atrophy 1, 2
• Consider adding topical tacrolimus as an adjunctive treatment for affected skin areas 1
• Prescribe antihistamines as needed for symptomatic relief of pruritus 1, 2
• If the rash is asymptomatic and stable, observation without additional treatment may be appropriate 1
• If complete resolution occurs, taper immunosuppressive agents and discontinue topical steroids as clinically feasible 1

Grade II-IV Skin GVHD Management

• For Grade II-IV skin GVHD (affecting >50% body surface area or with bullous lesions), systemic corticosteroids are the standard first-line treatment 1, 2
• Administer methylprednisolone at 0.5-1 mg/kg/day for Grade II and 1-2 mg/kg/day for Grade III-IV GVHD 1, 2
• Restart, continue, or escalate the original immunosuppressive agent if GVHD developed during tapering of immunosuppressive therapy 1
• If there is response to first-line therapy (complete resolution or improvement in at least one organ without progression in others), taper steroids as clinically feasible 1

Steroid-Refractory Skin GVHD Management

• For patients who fail to respond to first-line therapy, consider enrollment in a clinical trial or add other systemic agents to corticosteroids 1
• Anti-thymocyte globulin (ATG) has shown particular efficacy for skin GVHD, with response rates of 61-96% reported in studies 1
  • Thymoglobulin (rabbit ATG): 2.5 mg/kg/day for 4-6 consecutive days 1, 2
  • ATGAM (horse ATG): 15 mg/kg twice daily for 5 days 1, 2
• Basiliximab (20 mg on days 1 and 4) has shown efficacy in skin GVHD with 77% of patients experiencing at least one-grade reduction in skin GVHD 1
• Phototherapy has shown promising results for skin-limited disease 3

Special Considerations for LDLT

• GVHD after liver transplantation is rare but associated with very high mortality (>85%) 4, 5
• Skin GVHD typically presents with erythematous rashes, which occurred in 4 out of 5 cases in one case series of GVHD after liver transplantation 5
• Unlike traditional approaches that focus on increasing immunosuppression, some evidence suggests that reducing immunosuppression may allow the patient's immune system to reject the donor T cells in certain cases 4
• This approach may be more effective in patients with later onset of symptoms and lower levels of donor CD3+ T cells 4

Monitoring and Follow-up

• Regular monitoring of skin lesions and response to therapy is essential 2
• Watch for signs of infection, which is a major cause of mortality in patients with GVHD 1
• Monitor for adverse effects of systemic corticosteroids and other immunosuppressive agents 1
• If skin GVHD progresses to chronic GVHD, different treatment approaches may be needed, including calcineurin inhibitors, phototherapy, or extracorporeal photochemotherapy 3, 6

Treatment Algorithm for Skin GVHD after LDLT

1. Confirm diagnosis with skin biopsy to rule out other causes 2
2. Grade severity using modified Glucksberg criteria 2
3. For Grade I: Topical steroids + continue/restart immunosuppression 1, 2
4. For Grade II-IV: Systemic corticosteroids + continue/restart immunosuppression 1, 2
5. For steroid-refractory disease: Consider ATG, basiliximab, or other second-line agents 1, 2
6. In select cases with late-onset GVHD, consider reducing immunosuppression to allow rejection of donor lymphocytes 4