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PARVOVIRUS B19 INFECTION CAUSING PURE RED CELL APLASIA IN A RECIPIENT OF PEDIATRIC DONOR KIDNEYS1

1993; Wolters Kluwer; Volume: 55; Issue: 2 Linguagem: Inglês

10.1097/00007890-199302000-00035

1534-6080

NULL AUTHOR_ID,

Prenatal Screening and Diagnostics

Parvovirus B19, a recently discovered single-stranded DNA virus, is a known cause of chronic anemia in immunocompromised patients. This virus has been identified as the etiologic agent of the common childhood mild febrile exanthem erythema infectiosum, or “fifth disease”, as well as a chronic arthralgia in children and adults that is symptomatically similar to rheumatoid arthritis. At least one fatality from acute myocarditis in a one-year-old child has been reported (1). Transient aplastic anemia has been reported in infected patients with congenital hemolytic anemia such as sickle cell disease (2), whereas chronic anemia affects immunocompromised hosts with acquired immunodeficiency syndrome (3) and acute lymphocytic leukemia (4, 5), and it has been reported in a 14 year-old girl following bone marrow transplantation (6). Only one previous report of parvovirus B19–producing anemia in a solid-organ transplant, that of a cadaveric renal transplant recipient receiving cyclosporine, appears in the literature (7). We report the case of a pediatric en bloc renal transplant recipient on FK506 with pure red cell aplasia and peripheral pancytopenia caused by parvovirus B19 that were responsive to commercial immunoglobulin administration. The patient was a 62 year-old man with diabetic and hypertensive nephropathies and a history of gout, who underwent cadaveric renal transplantation using pediatric-donor kidneys in an en bloc fashion in February, 1990. At the time of transplant, the recipient's serologic titers were negative for hepatitis B surface antigen, anti–hepatitis B antibody, anticytomegalovirus IgM, and anti–human immunodeficiency virus antibody, while titers were positive for anticytomegalovirus IgG at 1:69, and for antihepatitis A IgG by ELISA. The donor was a 16-month-old girl who died of suspected cardiac arrest secondary to anoxia. She exhibited flu-like symptoms approximately 48 hr prior to the arrest. Donor serologic titers were negative for anti–cytomegalovirus, hepatitis, and human immunodeficiency virus antibodies. Parvovirus titers were not performed on donor or recipient sera, as they are not included in routine pretrans-plant serologic testing. The recipient was discharged 17 days posttransplant with a creatinine of 1.5 mg/dl and a hematocrit of 33.1% on an immunosuppressive regimen of FK506 (0.1 mg/kg b.i.d.) and prednisone (10 mg q.d.). He remained well until readmission one year posttransplant for an exacerbation of gouty arthritis affecting multiple joints, confirmed by fluid aspiration and treated by steroid injections and colchicine. At the time of admission, the patient was noted to be pancytopenia Total WBC count was 1700/mm3, hematocrit 22.7%, platelet count 52,000, and reticulocyte count 0.1%, with normal red cell indices. Bone marrow aspiration and biopsy at that time revealed markedly decreased erythroid maturation with normal myeloid series and megakaryocytes, and increased iron stores (Fig. 1A). No viral inclusions were present. The serum anticytomegalovirus IgG titer was positive at 1:106 and the IgM titer was equivocal at 1:15. However, urine, throat swab, and buffy coat CMV cultures and the early antigen assay remained negative. Colchicine and prophylactic trimethoprim/sulfamethoxazole were discontinued as they were thought to be likely causes of the patient's erythroid hypoplasia. His leukopenia and thrombocytopenia improved, and, following transfusion, the patient's hematocrit stabilized at 27.7%. During the subsequent month, the patient received ten outpatient transfusions of packed red blood cells. He was readmitted one month after discharge with chest pain, and subsequently a myocardial infarction was excluded by enzyme and EKG criteria. At this second admission, his hematocrit was 21.6%, his total WBC count was 1700/mm3, his platelet count was 111,000, and his reticulocyte count was 0.1%. A peripheral blood smear revealed moderate microcytosis with rare anisocytosis and hypochromia. The serum erythropoietin level was elevated at 2820 mU/ml (normal 4–26). His chest pain resolved completely after transfusion of two units of packed red blood cells. Repeat cytomegalovirus cultures and early antigen detection were negative. Antiparvovirus IgG was detected by western blot analysis of the patient's serum (Specialty Laboratories, Los Angeles. CA)—however, antiparvovirus IgM was undetectable. Repeat bone marrow aspiration and biopsy revealed essentially complete erythroid aplasia (Fig. 1C) except for rare giant pronormoblasts (Fig. 1B). Numerous eosinophilic intranuclear inclusions were noted in marrow cells (Fig. 1C, arrows) suggestive of viral infection. The presence of parvovirus B19 DNA was detected in the patient's serum by polymerase chain reaction (PCR), screening by dot-blot DNA hybridization, and finally by Southern blot analysis (University of Iowa, S.J.N.). The patient was treated with a ten-day course of an intravenous commercial pooled human immunoglobulin preparation with subsequent elevation of his reticulocyte count and resolution of the anemia (Fig. 2). He was discharged home seven days after completion of immunoglobulin therapy in good condition. Hematocrit rose to 30.3 and 37.9% at the time of discharge and twelve days later, respectively. Four months later, the patient's hematocrit slowly drifted down to 29.9%. Repeat bone marrow biopsy showed no evidence of viral infection. While on oral iron therapy, his hematocrit stabilized at 36.1% two weeks later, and remains at 42.1% one year after immunoglobulin therapy. Figure 1 Bone Marrow Morphology. (A) Bone marrow core biopsy on previous admission demonstrating erythroid hypoplasia. Myeloid cells and megakaryocytes are present. Intranuclear inclusions are not seen (HE ×400). (B) Giant pronormoblast present ... Figure 2 Resolution of anemia following a course of i.v. pooled immunoglobulin. Hematocrit levels are indicated by closed squares, and absolute reticulocyte counts by closed triangles. Arrows indicate transfusion of packed erythrocytes. Bone marrow biopsy specimens obtained from the patient two months prior to treatment, one week prior to treatment, and four months after treatment were removed from paraffin blocks under sterile conditions for PCR, dot-blot, and Southern Blot analysis. Parvovirus B19 DNA was detected by Southern analysis of PCR product from both bone marrow specimens obtained before immunoglobulin therapy, but it was not detected in the posttreatment specimen. Parvovirus B19 disease is now a recognized cause of aplastic crisis and anemia in patients who are immunocompromised by leukemia, hemolytic anemia, and acquired immunodeficiency syndrome. However, few cases of such infections have been reported in solid-organ transplant recipients. The shortage of available kidneys for transplantation has prompted many transplant centers to search for means of expanding the donor pool. At our institution we have utilized en bloc transplantation of pediatric cadaver kidney grafts for adult recipients. This technique uses both donor kidneys with donor aorta and vena cava intact for anastomosis to recipient iliac vessels. Periaortic and pericaval lymphatic tissue is carefully removed during preparation of the grafts for transplant. We report the case of a pediatric-donor renal transplant recipient who had pure red cell aplasia secondary to parvovirus B19 infection one year after transplantation, confirmed by PCR and Southern analysis. Serology demonstrated the lack of an IgM response, a finding that is not uncommon in immunosuppressed patients infected with this virus (8, 9). In the case reported here, the infant donor exhibited a viral prodrome prior to sudden death, and, since at least one case of death from myocarditis caused by parvovirus in an infant has been reported (1), this case raises the question of whether parvovirus B19 was transmitted from donor to recipient via the allograft. We retrieved autopsy specimens of myocardium and bone marrow from the infant donor in this case, both of which were tested by PCR and Southern-blot hybridization and found to be negative for parvovirus DNA. These tests do not, however, completely rule out the possibility of the presence of the virus in donor tissues. Further investigation into the prevalence of parvovirus B19 disease in transplant patients is warranted, as this infection may prove to be a common cause of anemia and aplastic crisis in the solid-organ transplant recipient.