Parvovirus B19 is a single-stranded DNA virus that typically has an affinity for erythroid progenitor cells in bone marrow and leads to pure red cell aplasia. This is a common pathogen in humans, and the expression of the infection depends on the host’s hematologic and immunologic status. Here, we report a female patient who developed severe and persistent anemia after kidney transplant while being on immunosuppressive therapy. The parvovirus B19 immunoglobulin M test was positive, and the virus was detected by polymerase chain reaction as parvovirus B19 (23.5 million copies/mL) in the blood sample. Bone marrow examination revealed giant pronormoblasts. She responded well to intra-venous immunoglobulin without adverse event. Hemoglobin levels gradually increased, and normal levels were achieved at 3 months posttreatment. Although her renal function did not deteriorate, severe anemia (with hemoglobin level 5 g/dL) recurred 3 times during 12 months posttransplant.
Key words : Anemia, Immunosuppression, Renal transplantation
Parvovirus B19 (PVB19) is a DNA virus that has affinity for human erythroid precursor cells. In immunocompromised individuals, PVB19 leads to a severe anemia known as pure red cell aplasia (PRCA).1 It has particular tropism for human erythroid progenitor cells and leads to apoptosis in infected erythroid progenitors, leading to acute and chronic anemia.2 This condition is particularly worse in immunocompromised individuals. Here, we present a patient who was successfully treated with intravenous immunoglobulin (IVIG) despite having 3 relapses of PRCA due to PVB19 infection after kidney transplant.
A 37-year-old female patient presented to our nephrology clinic with complaints of fatigue and palpitation. She underwent preemptive renal transplant 20 days earlier due to end-stage renal failure secondary to chronic glomerulonephritis. Physical examination was normal except for pallor. The patient was on tacrolimus 2 × 6 mg/day, mycop-henolate sodium 2 × 720 mg/day, prednisolone 20 mg/day, valganciclovir 900 mg/day, trimethoprim-sulfamet-hoxazole 400/80 mg/day, metoprolol 50 mg/day, and lansoprazole 40 mg/day. Her hyperglycemia (blood glucose of 450 mg/dL) was well controlled with insulin therapy.
Normocytic normochromic erythrocytes without fragmented erythrocytes and abnormal cells were detected in peripheral blood smears. Leukocyte distribution and platelet count were normal. Corrected reticulocyte count was 0.39%. A bone marrow aspiration and biopsy showed numerous giant pronormoblasts. Other cells were normal, and atypical cells were not detected. Serum ferritin, transferrin saturation, vitamin B12, folate, and haptoglobin levels were normal, and direct and indirect Coombs test were within normal limits. She did not use any erythropoietin treatment before and after transplant. Viral markers, including hepatitis B virus surface antigen, anti-hepatitis C virus, anti-human immunodeficiency virus, cytomegalovirus polymerase chain reaction (PCR), and BK virus PCR were negative. Parvovirus B19 immunoglobulin M and PVB19 PCR (23.5 million copies/mL) were detected.
Intravenous immunoglobulin 400 mg/kg/day was given for 5 days due to PRCA. Serum hemoglobin levels gradually increased in follow-up samples after IVIG treatment (Table 1). The patient had no complaints 2 months after the IVIG treatment. Recurrent symptomatic anemia and reticulocytopenia episodes developed at month 3 and month 7 post-transplant. Intravenous immunoglobulin treatment was given for 5 days at 400 mg/kg/day for PRCA due to recurrent PVB19. When the patient developed a second episode of PRCA, tacrolimus was changed to cyclosporine and target blood levels were maintained at a lower limit. The patient received a total of 9 units of erythrocyte suspension during the 3 PRCA episodes. The patient had no other com-plications, including renal dysfunction or anemia, at a follow-up visit at posttransplant month 17.
Transplant recipients are susceptible to viral infections and may develop primary or reactivation of latent viral infection. Frequent viral infections in the posttransplant period are influenza, adenovirus, herpes virus, cytomegalovirus, polyomavirus, Epstein-Barr virus, hepatitis B, hepatitis C, and respiratory viruses.3,4 Numerous cases of PVB19 infection after solid-organ transplant have also been reported.5,6 However, the clinical significance of PVB19 infection in the setting of renal transplantation is not fully understood. Symptomatic PVB19 infec-tion can develop after transmission from donors or the community or after reactivation of endogenous latent or persistent virus in renal transplant recipients.3
The clinical picture associated with PVB19 infection is different between immunosuppressed and immunocompetent individuals. Immunocom-promised individuals cannot produce effective cellular and humoral responses. Delayed viral clearance and even persistent and prolonged erythropoiesis suppression can occur in some people.3 There are cellular receptors of PVB19 in bone marrow erythroid precursor cells. Parvovirus B19 infects erythrocyte precursor cells by receptor binding, replication, and then destruction.7 The direct effects of PVB19 can lead to PRCA with giant pronormoblasts in bone marrow. Therefore, acute anemia and chronic PRCA may occur due to PVB19 infection in renal transplant recipients.8-10
At the time of admission, the hemoglobin level of our patient at day 20 posttransplant was 9.1 g/dL. Subsequently, hemoglobin values decreased and blood transfusion was required. Hemolysis was not detected in peripheral blood smears and biochemical tests, and kidney and liver functions were normal.
In addition to anemia, thrombocytopenia and neutropenia are other blood abnormalities. Clinical manifestations such as fever and arthralgia may occur in infected patients.5 Clinical manifestations of organ involvement such as hepatitis, myocarditis, and pneumonitis can also be seen.11 Other than anemia, neutropenia, thrombocytopenia, and organ involvement were not detected in our patient.
Parvovirus B19 infection can be diagnosed by PVB19-specific antibodies or viral PCR assays.5 In serologic tests, the false negative rate is high during acute PVB19 infection.12 In addition, immunocom-promised patients may respond to inadequate and delayed antibody-mediated immunity.5 Diagnosis by serologic tests can also be confused after blood product administration.13 In some reports, it is recommended for viral DNA to be detected by PCR.3,13 Parvovirus B19 immunoglobulin M and PVB19 PCR were both positive in our patient. Erythropoietin was never used in our patient. Although numerous giant pronormoblasts were detected, atypical cells were not detected and other cells were normal. Hemolysis, atypical cell, leu-kocyte, and thrombocyte distribution did not show any abnormalities in peripheral blood smears.
No specific antiviral treatment for PVB19 infec-tion presently exists. However, IVIG containing antiparvovirus antibodies appears to be beneficial in PVB19 infection in solid-organ transplant patients.3,5 The optimal dose and duration of treatment are not known; however, 400 mg/kg/day for 5 days is recommended.5 Our patient was successfully treated with IVIG without development of any adverse events. Progressive increases in hemoglobin values were observed during the days after IVIG treatment. The source of the infection was not known in our patient.
Parvovirus B19 infection should be suspected in renal transplant patients with nonhemolytic anemia and reticulocytopenia during the early intensive immunosuppression period. In addition to reducing immunosuppression treatment for these patients, IVIG can provide dramatic improvements without any adverse events.
Volume : 17
Issue : 1
Pages : 195 - 197
DOI : 10.6002/ect.MESOT2018.P63
From the Department of Nephrology, Cukurova University Faculty of Medicine,
Acknowledgements: The authors did not receive any funding for the present study, and they have no conflicts of interest to declare.
Corresponding author: Bulent Kaya, Cukurova University Faculty of Medicine, Department of Nephrology, Adana, Turkey
Phone: +90 553 7492065
Table 1. Summary of Patient’s Laboratory Results