Fulminant mixed humoral and cellular rejection in a cardiac transplant recipient: a review of the histologic findings and literature

Mixed acute cellular and humoral rejection is diagnosed uncommonly among heart transplant recipients and usually occurs within the first post-transplant month. We report a case of fatal, fulminant, mixed, acute cellular and humoral rejection in a 33-year-old woman 6 weeks after orthotopic heart transplantation. She had been treated with intravenous methylprednisolone for International Society for Heart and Lung Transplantation (ISHLT) Grade 2 rejection at post-operative Day 28. Despite intensification of immunosuppression therapy, she developed fever and progressive hemodynamic instability. Autopsy results revealed ISHLT Grade 4 mixed cellular and humoral rejection. Cellular rejection is a well-described mechanism of graft failure early after heart transplantation. Although humoral rejection also is recognized as contributing to early graft failure, its characteristics and clinical implications are not as well characterized. We describe a patient with fulminant mixed rejection, despite intensified immunosuppression therapy, early after orthotopic heart transplantation who presented with high-grade fever. We include a review of the literature on humoral and mixed rejections.