S5795 Acute Cellular Rejection Secondary to Topical Imiquimod for Squamous Cell Carcinoma Skin Cancer: A Rare and Underrecognized Causation

Introduction: Acute liver injury following liver transplant can be multimodal. Initial concern includes immunological etiologies such as T-cell mediated rejection and antibody-mediated rejection. The systemic effect of topical therapies is rarely considered due to the expected low absorption; however, topical medications like imiquimod are immunomodulators and pose risk for stimulating immune response and potentially organ rejection. One prior study has shown hepatic injury due to topical imiquimod in setting of transplant patient, though overall data is limited. Case Description/Methods: A 62-year-old White man with history of liver transplant secondary to MASH on January 9, 2018, melanoma post-resection and squamous cell carcinoma of the right upper back presented to the clinic for general follow up. One month prior he was started on topical imiquimod by dermatology for treatment of squamous cell carcinoma in situ of skin on his back. An attempt had been made to switch immunosuppression from tacrolimus to everolimus given potential benefit of everolimus in reducing skin cancer risk in post-transplant patients, however he only took 1 dose of everolimus and developed a chest pain episode. He never decreased the tacrolimus dosing. He denied any recent infections, fevers, chills, sick contacts or recent antibiotic exposure. Laboratory assessment showed aspartate aminotransferase 213/ alanine aminotransferase 560/ t bili 1.4/ alkaline phosphatase 269. Given concern for rejection, methylprednisolone followed by a steroid taper was ordered. Topical imiquimod was stopped. A liver biopsy was performed and revealed moderate to severe acute cellular allograft rejection. MRCP was normal. Transaminases resolved rapidly following initiations of steroids and have since returned to tacrolimus monotherapy without further recurrence of rejection. Discussion: Here we present the case of a 62-year-old man, status post liver transplant in 2018, who presented with acute cellular rejection following initiation of topical imiquimod, an immunomodulator that acts as a toll-like receptor 7 agonist. In the only study examining imiquimod in post-transplant patients, one patient required medication discontinuation due to elevated liver enzymes. Given the timing of imiquimod therapy and onset of rejection weeks later we believe our patient developed acute T-cell mediated rejection related to immunomodulator therapy. This case implied significant importance given the high incidence of skin cancer post-liver transplant and may have implications when considering treatment options of skin cancers.