Risk factors for tonsillar hypertrophy and post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression in solid organ transplant patients. Tonsillar hypertrophy commonly results from PTLD, and tonsillectomy is usually performed when PTLD is the suspected cause. Risk factors for PTLD-mediated tonsillar hypertrophy remain poorly defined. This study aimed to identify clinical and therapeutic factors associated with tonsillar hypertrophy following PTLD diagnosis.

We conducted a retrospective cohort study using the TriNetX Database. Pediatric solid organ transplant recipients were queried for tonsil disease, tonsillectomy, PTLD diagnosis, transplant history, and immunosuppressants using the associated Current Procedural Terminology, International Classification of Diseases, and RxNorm codes.

We identified 21,582 children with a history of solid organ transplant. Tonsil disease was found in 1833 (8.49 %), and of these patients, 193 (10.53 %) were diagnosed with PTLD within six months. Immunosuppressants associated with higher rates of tonsil disease were tacrolimus (OR 2.74, 95 % CI 2.29-3.28), mycophenolate mofetil (OR 2.72, 95 % CI 2.29-3.24), and cyclosporine (OR 1.50, 95 % CI 1.08-2.10). Sirolimus was associated with lower rates (OR 0.66, 95 % CI 0.52-0.83). EBV diagnosis was associated with both higher rates of tonsil disease (OR 1.45, 95 % CI 1.21-1.72) and PTLD diagnosis (OR 3.52, 95 % CI 2.14-5.77).

This is the largest study on tonsillar hypertrophy in PTLD and the first to identify tacrolimus, mycophenolate mofetil, and cyclosporine as significant risk factors for tonsil disease amongst pediatric transplant patients. Understanding risk factors that may predispose a patient to PTLD-mediated tonsil disease can guide decision making to help avoid this complication of immunosuppression.