(218) Post-Transplant Lymphoproliferative Disorder and its Treatment Presenting with Psychosis: Case Report and Literature Review

Abstract: Background/Significance: 
Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation (Samant et al 2023). Rituximab is a mainstay treatment for those who do not respond to immunosuppressant reduction alone.  It has been infrequently associated with psychiatric side effects (Kami et al 2004, Ceïde & Rosenberg 2011, Essali et al 2019). Here, we present a case of PTLD and rituximab-associated psychosis.


Case:  
A 34-year-old male with a history significant for primary sclerosing cholangitis (PSC) status post repeat liver transplantation in the setting of recurrent PSC complicated by PTLD was admitted for encephalopathy. He received his fourth induction rituximab treatment for PTLD two weeks prior to admission; there were no other known precipitating factors. Collateral suggested that he developed new visual hallucinations and confusion soon after his recent rituximab infusion and was found unresponsive ten days later, prompting hospitalization. Extensive work-up, including brain magnetic resonance imaging, flow cytometry, electroencephalogram, urine toxicology, metabolic, infectious, and autoimmune and paraneoplastic serum and cerebrospinal fluid studies, was unrevealing. With low clinical suspicion for posterior reversible encephalopathy syndrome and delirium, he was maintained on tacrolimus and low-dose prednisone.
Transplant psychiatry was consulted on day 7 of hospitalization due to concerns for catatonia. Initial evaluation revealed a Bush Francis Catatonia Rating Score of 10 notable for mutism, staring, waxy flexibility, and autonomic instability. Though catatonic symptoms lysed with lorazepam (up to 8 mg/day), psychotic symptoms, including paranoid and nihilistic delusions, audiovisual hallucinations, and gross disorganization with marked irritability soon became apparent, culminating in psychiatric hospitalization. Benzodiazepines were tapered off and his symptoms improved significantly with olanzapine 10 mg and valproate 500 mg. Transplant psychiatry follow-up one month after discharge revealed no decompensated psychiatric symptoms.  Fluorodeoxyglucose-positron emission tomography scan and flow cytometry suggested complete resolution of PTLD, and maintenance rituximab treatment was considered. He was thus advised to taper off of valproate while continuing olanzapine until further assessment.
Discussion:
Given the absence of prodrome and temporal relationship, we suspect our case represents the first known manifestation of catatonia and psychosis with rituximab. Cytokine disruption may underlie these effects, but overall, a review of the literature suggests there is a limited understanding of the neuropsychiatric effects of PTLD and rituximab.
Conclusion/Implications:
Consultation-liaison psychiatrists would benefit from a better understanding of PTLD and the potential neuropsychiatric effects of its treatment. Further characterization of rituximab-associated psychosis is necessary for early identification and management, mitigating the risk of post-transplant complications, and optimizing support for patients, families, and transplant teams. 
References: 

1. 
   Samant H, Vaitla P, Kothadia JP. Posttransplant Lymphoproliferative Disorders. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513249/
   


2. 
   Kami M, Hamaki T, Kusumi E, et al. Recurrent psychotic episodes in a patient who received rituximab for the treatment of non-Hodgkin's lymphoma. Hematol J. 2004;5(1):90. 
   


3. 
   Ceïde ME, Rosenberg PB. Brief manic episode after rituximab treatment of limbic encephalitis. J Neuropsychiatry Clin Neurosci. 2011;23(4):E8. 
   


4. 
   Essali N, Goldsmith DR, Carbone L, et al. Psychosis as an adverse effect of monoclonal antibody immunotherapy. Brain Behav Immun. 2019;81:646-649. 
   

Presentation Eligibility: Not previously published or presented

Diversity, Equity, and Inclusion: Our patient had multiple structural vulnerabilities including limited family support, financial instability, and limited education which resulted in poorly controlled medical conditions years prior to his transplantation.

Additionally, in our poster, we emphasize the importance of identifying psychiatric side effects of medications used to treat physical conditions. Misattributing symptoms to a primary psychiatric disorder can be harmful, as the underlying, potentially reversible, issue goes unaddressed. Equally as important, misattribution may perpetuate stereotypes and lead to mislabeling and misdiagnosis--this is especially relevant given that Black Americans already over 2 times more likely to receive a diagnosis of schizophrenia.