Pure Red Cell Aplasia due to Parvovirus B19 Infection in a Postkidney Transplant – A Case Report

Dear Editor, Parvovirus B19 (PVB19) is a single-stranded DNA virus of Parvoviridae family and genus Erythrovirus with an affinity for human erythroid precursor cells leading to apoptosis causing pure red cell aplasia (PRCA), especially in immunocompromised patients.[1,2] In the 1st year posttransplant period, recipients are more susceptible for many primary/reactivation of viral infections.[3] Ten percent postkidney transplant recipients have measurable PVB19 DNAemia in 1st-year posttransplant.[3] PVB19 infection is defined as (a) a regenerative severe anemia (hemoglobin [Hb] <10 g/dL) after transplant, in the absence of hematologic disturbance or any active bleeding and (b) positive polymerase chain reaction (PCR) qualitative or quantitative or positive PVB19 antibody immunoglobulin (Ig) M serology.[4] A 34-year-old male had end-stage renal disease due to an unknown cause. He was on hemodialysis for 4 years following which he had a kidney transplant from a live donor. He had a course of anti-thymocyte globulin at 3 mg/kg with a cumulative dose –150 mg divided over a period of 3 days and was on tacrolimus at 2 mg BD, mycophenolate mofetil – 1000 mg BD, and prednisolone –20 mg OD as a means of immunosuppression. Tac level was done postoperatively on regular intervals and was maintained between 8 and 10 µg/L. No information was available regarding the donor’s parvovirus status. One month later, he presented with complaints of weakness, lethargy, and anemia with Hb of 3.2 g/dL. On presentation, his renal and liver functions were normal. He was afebrile, cheerful, and, apart from being very pale, was clinically well. He received a transfusion of 3 units of leukodepleted packed red blood cells. Despite this, his anemia persisted at Hb of 4.6 g/dL. The dose of immunosuppressive drugs (tacrolimus and mycophenolate mofetil) was reduced to half of the basic dose. His serum creatinine continued to remain stable at 0.8 mg/dL. Other laboratory investigations were as follows: red cell count – 2.8 × 1012/L; white blood cell – 4.6 × 109/L; platelets – 150 × 109/L; absolute reticulocyte count – 0.5; haptoglobin level – 48 mg/dL; lactate dehydrogenase level – 186; folate level – 6.8 ng/mL; Vitamin B12 – 1278 pg/mL; iron profile – iron, TIBC, Tsat, and ferritin – 74 µg/dL, 482 µg/dL, and 452 ng/mL; direct and indirect Coombs tests – negative; cytomegalovirus (CMV) DNA quantitative PCR – negative, Epstein–Barr virus (EBV) PCR – negative, PVB19 IgM antibodies – positive and PVB19 PCR – 18.6 million copies/mL; bone marrow aspiration and trephine biopsy increased myeloid series and severely suppressed erythropoiesis – normocellular marrow with erythroid aplasia [Figures 1 and 2], giant erythroblast with one inconspicuous intranuclear inclusion body, and normal megakaryocytes [Figure 3]. The above investigations show the absence of no etiology of hemolysis (immunomediated and nonimmune), iron deficiency, Vitamin B12, or folate deficiency for the anemia in this patient. The persisting anemia, with reticulocytopenia, no evidence of myelodysplasia, hemolysis nutritional deficiency, the presence of the anti-PVB19 IgM, and positive PCR confirmed the diagnosis of parvovirus PRCA. The cornerstone of treatment for this disease is reducing the immunosuppression regimen after diagnosis, as was done in our case. Intravenous Ig (IVIG) transfusion to enrich the humoral immunity of the patient supported with packed red blood cell transfusions. Our patient was treated with 0.4 g/kg/day IVIG for 5 days with packed red blood cell transfusion. However, after 8 weeks, he did not respond to treatment and was given a second course of IVIG 0.4 g/kg/day for 5 days. His Hb levels started recovering; after a week [Figure 4], his graft function remained stable over the course with serum creatinine ranging from 0.8 to 1 mg/dL. He was completely well with normal complete blood count and serum creatinine after a month, at the time of writing this report.Figure 1: Increased myeloid series and severely suppressed erythropoiesis - Normocellular marrow with erythroid aplasiaFigure 2: Increased myeloid series and severely suppressed erythropoiesis - Normocellular marrow with erythroid aplasiaFigure 3: Bone marrow biopsy: Giant erythroblast with one inconspicuous intranuclear inclusion body. Inside circle is giant erythroblast with inclusion bodyFigure 4: Hemoglobin trends during the course. IVIG: Intravenous immunoglobulinThere is an increased incidence of viral infection after solid organ transplant including PVB19, CMV, BK virus, EBV, and human herpes virus within 1st year of transplant. There have been around 51 cases of PVB19-induced PRCA reported in the literature.[5,6] Diagnosis of PVB19 can be made by PVB19 IgM antibody which can be detected in 75% of patients of solid organ transplant, so PVB19 DNA PCR holds importance in diagnosing the posttransplant patients, with unexplained anemia despite negative PVB19 serology.[6] No specific antiviral therapy exists till date for PVB19 infection; however, reducing immunosuppressant dose along with IVIG at a dose of 0.4 g/kg/session of 3–4 sessions is mainstay treatment.[5] Successful treatment with repeat doses of IVIG has been reported previously in three cases to the best of our literature search.[5,6] There are no consensus guidelines for the management of PRCA due to PVB19 infection which makes it challenging to treat. The amount of immunosuppressant reduction and the role of repeat IVIG in treating the PVB19 infection remains a mystery. Declaration of patient consent The authors certify that patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.