Post Transplant Lymphoproliferative Disorder in a Liver Transplant Patient with Refractory Crohnʼs Disease

Abstract

Purpose: To highlight risk factors for post transplant lymphoproliferative disorder (PTLD), clinical manifestations, treatments, and areas for research. Case Presentation: 22 year old female presents with abdominal pain. She has an 11 year history of Crohn's disease (CD), complicated by primary sclerosing cholangitis and cholangiocarcinoma who underwent an orthotic liver transplant (OLT) 3 years prior to presentation. CD had been refractory to mesalamine, budesonide, and 6-mercaptopurine. Infliximab was started in 2005 and subsequently changed to adalimumab 3 months earlier. Following OLT, she had briefly been on tacrolimus then cyclosporine. 9 months prior to admission she developed generalized colicky abdominal pain. She continued to have 10 loose stools daily with increasing hematochezia. On the day of admission, she underwent colonoscopy with biopsies and the gross appearance showed severe ileocolitis and pseudopolyps, unchanged from 3 months prior. Several hours later, her discomfort became acutely worse and she was admitted. Her exam was remarkable for a frail female with mild abdominal distention, and tenderness to palpation. Labs revealed a low albumin, and high ESR. CT showed extensive colonic wall/terminal ileum thickening. Biopsies that had been obtained at the time of colonoscopy revealed EBV associated polymorphic PTLD with CD 20 + B cells and CD3 + T cells. CT/PET demonstrated diffuse uptake in the colon and retroperitoneal/mesenteric lymph nodes. Bone marrow was negative for PTLD. A subtotal colectomy and ileostomy was performed. Pathology demonstrated PTLD and moderately active pancolitis. Adalimumab was discontinued. Rituximab was initiated with 4 weekly doses and plans to re-stage in 3 months Discussion: This case reflects the diagnostic challenges of PTLD as CD was confounding. It can present as a mono-like illness, or patients can be asymptomatic. Common GI manifestations include hematochezia, weight loss, and hypoalbuminemia. Risk factors include the degree of immunosuppression, age at transplant (less than 18 years), EBV seronegative status of the recipient, and type of allograft. The mainstay of treatment is a reduction in immune suppression. Rituximab is increasingly being utilized. Surgical intervention in select patients with localized disease can be used. Aggressive chemotherapy is reserved for those with severe, refractory, or progressive disease. This case illustrates the importance of considering PTLD in patients on aggressive immunosuppressive regimens. Further investigation is required to determine if anti-TNF agents used with other immunosuppressive agents increase the risk of PTLD.