GVHD After Orthotopic Liver Transplant: Successful Treatment With High Dose Steroids and Anti Thymocyte Globulin (ATG)

Abstract

Introduction: Graft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1-2%, but an 80-100% mortality rate. We present two cases of GVHD that resolved with high dose systemic steroids and anti thymocyte globulin (ATG). Case 1: A 66 year old male with HCV cirrhosis complicated by hepatocellular carcinoma underwent OLT. 4 weeks later, he presented with a generalized erythematous maculopapular eruption. Biopsy demonstrated evidence of vacuolar type interface dermatitis with follicular involvement consistent with GVHD. Labs showed mild pancytopenia without any evidence of viral infections. Peripheral blood chimerism was negative for donor cells. He received intravenous (IV) methylprednisolone and three doses of ATG with subsequent resolution of symptoms. The patient was followed up to two years without any recurrence. Case 2: A 53 year old male with HBV cirrhosis who underwent orthotopic liver transplant presented five weeks later with fever and generalized maculopapular rash and oral ulcers. Skin biopsy showed interface dermatitis with follicular involvement consistent with GVHD. peripheral blood chimerism study did not show any donor cells. The patient received high dose IV methylprednisolone and ATG. The patient subsequently improved and had complete resolution of cutaneous findings without any recurrence on follow up. Discussion: Graft-versus-host disease after OLT usually presents 2 to 8 weeks postoperatively with bone marrow aplasia, skin rash and diarrhea. Detection of donor lymphocytes in skin and a nonspecific lichenoid reaction pattern with basal vacuolar changes, dyskeratosis and epidermal apoptotic cells may be seen. Although published literature describes the role of corticosteroids in management, treatment beyond steroids has been heterogeneous and has included antimetabolites, alkylating agents, anti-T cell antibodies, anti-B cell antibodies, intravenous immunoglobulin, cytokine inhibitors, immunostimulants and cellular therapy, including T cell infusions and hematopoietic stem cell transplantation. Despite aggressive treatment, reported mortality rate exceeds 80%. Conclusion: GVHD is a rare clinical entity but carries a high mortality. Reducing the risk factors for development of GVHD, identifying the disease promptly, preventing infection, and starting treatment as early as possible as seen in our cases may improve the dismal outcome associated with this disease.2444_A Figure 1. Papular rash seen on lower extremity2444_B Figure 2. Vacuolar type interface dermatitis with follicular involvement