Heart Transplant: A Mystery in the Myocardium

Abstract

Introduction Hypersensitivity myocarditis (HM) is a potentially fatal disease that can lead to refractory heart failure if left untreated. Numerous drugs have been implicated in causing HM. We present a case of HM in a heart transplant recipient treated with Rituximab for post-transplant lymphoproliferative disorder (PTLD). Case Report A 59 yo man was diagnosed with PTLD 8 months after undergoing heart transplantation. He had an early 2R acute cellular rejection that resolved with increasing baseline immunosuppression that consisted of tacrolimus, Cellcept and prednisone. An upper endoscopy done for dysphagia, anorexia and weight loss revealed a gastric ulcer and pathology consistent with high grade B cell lymphoma. PET/CT showed cervical, mediastinal, abdominal and pelvic lymphadenopathy as well as hypermetabolic liver and spine lesions consistent with stage IV metastatic disease. Bone marrow biopsy did not show any lymphoma. He was treated with 4 doses of weekly Rituximab and decreased baseline immunosuppression. He was maintained on tacrolimus with a target level around 6 ng/ml and low dose prednisone. He presented one month later with severe heart failure and allograft dysfunction. Heart biopsy showed pericellular and perivascular mixed inflammatory cell infiltrate rich in eosinophils with many degranulating forms suggestive of hypersensitivity myocarditis. There was no evidence of fungal or parasitic infection or heart involvement of the recently diagnosed B cell lymphoma. No eosinophils were seen during the prior cellular rejection. Patient was treated with high dose IV Solu-Medrol and a follow up biopsy one week later showed marked clearing of the eosinophilic infiltrate. Summary This patient presented with allograft dysfunction after receiving Rituximab, an agent putatively associated with hypersensitivity pneumonitis. Although a complete histologic distinction between HM and acute cellular rejection is not feasible, the features of this infiltrate were more consistent with HM, which was attributed to Rituximab.