Epstein-Barr Virus Infections in Children After Transplantation of the Small Intestine

Abstract

Epstein-Barr virus (EBV) infection in association with immunosuppressive drugs used for solid organ transplantation can produce a spectrum of illnesses. Forty-one children who ranged in age from 6 months to 18.5 years received small intestinal transplants alone or in combination with other organs while undergoing primary tacrolimus (FK506) immunosuppression between July 1990 and June 1995. We reviewed hematoxylin and eosin-stained sections from all biopsy, surgical, and autopsy material from these children to determine the incidence and morphology of EBV-associated disease. Nuclear staining with in situ hybridization for EBV early RNA transcript (EBER) using the EBER-1 probe confirmed the presence of EBV. The EBV lymphoproliferations were graded as 1 to 4 according to histopathology and EBV quantitation determined in the area of greatest positivity. Twenty-one patients (51%) had EBV documented histologically on one or more occasions; only 8 (38%) are alive; 5 of these had the highest grade of 2. Posttransplant lymphoproliferative disease (PTLD) developed in 13 patients. Three of 10 patients (30%) with grade 3 lesions (polymorphous PTLD) are alive with intermittent evidence of EBV infection; 6 died with PTLD. Monomorphic PTLD (grade 4) was the cause of death in the three additional patients. Thirteen of 20 patients (65%) with no histologic evidence of EBV are alive. The incidence of EBV infection in pediatric small intestinal transplant recipients is higher than reported for any other solid organ cohort. With the aid of frequent EBER staining we were able to diagnose EBV infections in 51% of 41 patients; PTLD (grade 3 or 4) developed in 32% of these children. Low-grade EBV infections often preceded the development of PTLD and were identified in gastrointestinal biopsy samples from patients with concurrent PTLD; however, results of gastrointestinal biopsy samples may be negative for EBV in some patients with PTLD and, thus, underestimate systemic EBV-associated lymphoproliferations. Rejection and EBV infection can occur simultaneously, therefore, attention to low-grade infection may be useful to patient management.

Post-transplant plasma cell myeloma and polymorphic lymphoproliferative disorder with monoclonal serum protein occurring in solid organ transplant recipients

“…1,2 The recipient's age, EBV seronegativity at transplant, and allograft type are recognized risk factors for PTLD. [3][4][5] PTLD have a predilection for extranodal sites, similar to lymphomas that occur in other immunocompromised patients. 6 The overall incidence of PTLD is about 1.5% in all solid organ transplant recipients [7][8][9][10] and 1% in bone marrow transplant recipients.…”

Cytolytic CD4+-T-Cell Clones Reactive to EBNA1 Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation

“…Immune dysregulation, which predisposes patients to B-cell lymphomas and EBVinduced B-cell lymphoproliferative disease (LPD), may result from genetic abnormalities affecting lymphocytes (e.g., severe combined immunodeficiency, X-linked lymphoproliferative disease), viral infection of T cells (e.g., human immunodeficiency virus infection and AIDS), or immunosuppressive medical treatments directed against T cells, such as FK506, cyclosporine A, corticosteroids, depletion of T cells, or OKT3 T-cell-toxic antibodies (14,21,32,62,76). Whether lack of NK, of CD4 ϩ , or of CD8 ϩ T-cell function allows for the outgrowth of EBV-infected B-cell lymphomas in these individuals remains unclear.…”

Autopsy Pathology of Pediatric Posttransplant Lymphoproliferative Disorder

“…1 However, PTLD is more common in children, because many children are EBV-naive at the time of transplant. [2][3][4][5] Manifestations of PTLD are protean and include signs and symptoms of both focal disease, such as graft dysfunction, as well as systemic disease, eg, viral illness.…”

“…[2][3][4][5] However, detailed autopsy reports of series of PTLD patients have not been reported. We present the pathology found at autopsy of 7 children who died with PTLD.…”