Epstein-Barr virus infections in children after transplantation of the small intestine.
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.
Finn
L
L
Department of Pathology, Children's Hospital of Pittsburgh, Pennsylvania, USA.
Reyes
J
J
Bueno
J
J
Yunis
E
E
D000293:Adolescent; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006566:Herpesviridae Infections / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D007421:Intestine, Small / Q000637:transplantation*; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D014184:Transplantation, Homologous; D014412:Tumor Virus Infections / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine; D016559:Tacrolimus