Case Presentation: A 27-year-old female with Senior-Loken syndrome leading to blindness and chronic kidney disease (CKD) by the age of 19, eventually progressed to CKD stage V and had a live donor kidney transplant performed at the age of 26. Subsequently, she was started on Tacrolimus and Mycophenolate for immunosuppression (IS). Seven months later, she developed weight loss, fatigue, abdominal pain and chronic diarrhea. She underwent a colonoscopy which revealed multiple ulcers throughout her colon and biopsies revealed submucosal diffuse large B-cell lymphoma (DLBCL), CD20 positive, Epstein-Barr Virus (EBV) negative. B-cell PCR was positive for clonality confirming monomorphic post-transplant lymphoproliferative disorders (PTLD). Tacrolimus and Mycophenolate were stopped and she was started on Prednisone 5 mg/day which stabilized her kidney function with plan to start her on R-CHOP chemotherapy.
Discussion: Senior-Loken syndrome is an extremely rare autosomal recessive disease characterized by retinal dystrophy and nephronophthisis. It has an estimated prevalence of 1 in 1 million people. Patients generally develop blindness and CKD at an early age and eventually become dependent on dialysis or require transplant. After transplant, Tacrolimus is a frequent medication prescribed for IS. Tacrolimus is a macrolide calcineurin inhibitor, which inhibits interleukin-2. This inhibition leads to host IS and lower the T cell immune surveillance which decreases the chances of transplant graft rejection.
PTLD are a group of disorders that occur after solid organ or stem cell transplant due to uncontrolled proliferation of lymphoid/plasmacytic cells secondary to IS. The main risk factors are EBV, degree of IS and time after transplant. The majority of the cases happen in EBV positive patients as the latent virus reactivates with IS, leading to proliferation of B cells and clonal expansion. EBV positive PTLD usually occur early, within the first year of transplant, however, EBV negative cases, usually occur late and only represent 10-20% of PTLD. PTLD are a spectrum of disorders including early lesions like infectious mononucleosis-like disease, polymorphic disease and monomorphic monoclonal PTLD such as malignant lymphomas. The Incidence of PTLD in kidney transplant patients is about 1%, while PTLD is the second most common cancer in kidney transplant patients after skin cancer. Management of PTLD varies depending on the type of the disease, however, IS reduction is the mainstay of treatment. Patients who are CD20 positive are also started on Rituximab with or without chemotherapy. EBV negative PTLD have a more aggressive clinical course and benefit from chemotherapy.
Conclusions: Close monitoring of patients with solid organ transplants on IS is crucial due to the risk of developing PTLD, specially patients on large doses of IS and who are EBV positive. Limiting the exposure to aggressive IS therapy and antiviral prophylaxis should also be considered given the number of EBV negative cases.