Membrane Bound IgG on Erythroblasts in Pure Red Cell Aplasia following Thymectomy

A case of pure red cell aplasia appearing 6 months following thymectomy is reported in a 43-year-old man. Immunofluorescence studies of the patient's bone marrow have demonstrated the presence of membrane-bound IgG on the majority of erythroblasts and some mature erythrocytes. It is suggested that the IgG represents anti-erythroid autoantibodies. The number of Ig-bearing lymphocytes in peripheral blood was decreased as was the level of immunoglobulins indicating a B-lymphocyte deficiency. T-lymphocyte functions were without remarks. The patient was initially treated with corticosteroids and oxymetholone. He responded well to this therapy but relapsed 9 month later. Cyclophosphamide treatment was started and followed by a complete haematologic remission.     

Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation

Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed.     

Pure Red Cell Aplasia in a Patient with Trrisomy X Chromosome Abnormality and Reactivated Epstein-Barr Virus Infection

We describe a woman with a congenital chromosome anomaly, 47,XXX, who developed chronic pure red cell aplasia (PRCA). The patient had serologic reactivity consistent with that of reactivated Epstein-Barr virus (EBV) infection, as judged by high titers for anti-EBV viral capsid antigen (VCA) immunoglobulin G (IgG) and anti-early antigen (EA) IgG. Detection of EBV genome in peripheral blood cells and cell-free serum also supported the diagnosis. Although EBV infection has been implicated in the pathogenesis of acute PRCA, the viral infection rarely results in a chronic disease state. So far, only 1 case of EBV-associated chronic PRCA has been reported, to the best of our knowledge. Chronic PRCA also is known to occur on an autoimmune basis. Individuals carrying an extra X chromosome, such as XXY and XXX, are prone to development of immune abnormalities. Our patient had an anti-DNA autoantibody and a positive result of the direct Coombs test. The pathogenesis of PRCA in this case seemed to involve multiple factors. In addition to the infectious agent, host factors may have played a role. Although the etiologic link between chronic PRCA and trisomy X remains to be elucidated, our findings suggest the importance of karyotype analysis as well as search for infectious agents in patients with chronic PRCA.     

Spectrum of adult Parvovirus B19 infection according to the underlying predisposing condition and proposals for clinical practice

The virological diagnosis of Parvovirus B19 (PvB19) infection is currently based on sero‐diagnosis, molecular methods or both, yet without clear recommendations. We retrospectively identified patients with polymerase chain reaction‐positive PvB19 and/or positive serological assay between 2007 and 2013. Eighty‐two adults with at least one diagnostic criterion of recent PvB19 infection (IgM antibodies, viral DNA in blood and/or in marrow) were included and classified into three homogeneous groups: 30 patients had no underlying predisposing condition, 25 a hereditary haemolytic anaemia, 27 an underlying immunodeficiency. The classical PvB19‐related manifestations were less frequent in immunocompromised than in immunocompetent patients (arthromyalgia: 5 vs. 14; erythema: 4 vs. 17, respectively). Only 41·4% of patients with no underlying disease were anaemic. Bicytopenia and pancytopenia were observed mainly in immunocompromised patients. Classical pure red cell aplasia was observed in only 9 of the 27 marrow smears performed. Specific IgM were found in 93% of immunocompetent patients, whereas only 58% had detectable viral DNA in blood. IgM and DNA were present alone or together in all patients with hereditary haemolytic anaemia. In immunocompromised patients, the diagnosis was confirmed by marrow analysis in 91% of cases. We make some proposals based on this large series of PvB19‐infected patients.     

Parvovirus B19 as a cause of acquired chronic pure red cell aplasia

Parvovirus B19 infection causes chronic anaemia in immunodeficient individuals by selective suppression of erythropoiesis. The bone marrow morphology is character-istic of pure red cell aplasia (PRCA). To determine the frequency of B19-induced PRCA we retrospectively analysed a series of 57 PRCA patients. B19 DNA was present in serum of eight patients (14%) and could be extracted from bone marrow aspirate slides from five of these patients. Recent exposure to the virus was confirmed by the presence of anti-B19 IgM in sera from four and by the finding of giant pronormoblasts in marrow aspirates from five of the B19 DNA-positive patients. The sensitivities of anti-B19 IgM and of giant pronormoblasts were only 50% and 63%, respectively; specificites were 90% and 92%. Unexpectedly, PRCA in two B19 DNA-positive patients remitted after antilymphocyte globulin or cyclosporin A therapy, suggesting that the clinical course of B19-induced PRCA may be indistinguishable from other forms of PRCA. As therapy with immunoglobulin is uniformly effective for treatment of B19-associated anaemia, our data suggest that all patients with acquired PRCA should be evaluated for evidence of B19 infection. B19 DNA analysis is the most reliable method to demonstrate infection.     

Successful re‐transplantation in patient with recurrent parvovirus B19 pure red cell aplasia

Impaired cell‐mediated, as well as antibody‐mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re‐transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re‐transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re‐consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.     

Successful high-titer immunoglobulin therapy for persistent parvovirus B19 infection in a lymphoma patient treated with rituximab-combined chemotherapy

A 40-year-old female diagnosed with follicular lymphoma was treated with rituximab-combined chemotherapy. Although she achieved complete remission, she developed progressive anemia and reticulocytopenia. Bone marrow examination revealed features of pure red cell aplasia and hemophagocytosis. In addition, the appearance of large pronormoblasts suggested that she was infected with parvovirus B19. Excess viral DNA in her bone marrow confirmed that her illness was caused by persistent parvovirus B19 infection. Serum immunoglobulin levels decreased beyond the lower normal limit, which indicated that her humoral immunity was impaired after rituximab-combined chemotherapy. Although she had been infected with parvovirus B19, she was re-infected and failed to control the viral expansion. High-titer immunoglobulin against parvovirus B19 was intravenously administrated and resulted in remarkable reticulocytosis and improvement of anemia. High-titer immunoglobulin, which contained a sufficient amount of neutralizing antibodies against parvovirus B19, likely inactivated most viruses in vivo. We successfully eradicated the virus after 2 courses of high-dose therapy at 0.5 g/kg/day every week followed by 8 courses of maintenance therapy at 0.1 g/kg/day every other week. It is important to consider that parvovirus B19 infection is a possible cause of progressive anemia in B-cell lymphoma patients treated with rituximab-combined chemotherapy. We propose that the use of high-titer immunoglobulin against parvovirus B19 may enable such immunocompromised patients to eradicate the virus before sufficient immune system reconstruction.     

Pure Red Cell Aplasia in Systemic Onset Juvenile Idiopathic Arthritis

Common causes of anemia in juvenile idiopathic arthritis are anemia of chronic disease and iron deficiency. We report a 4 year old boy with biopsy proven systemic onset juvenile idiopathic arthritis and severe anemia. Bone marrow aspiration revealed pure red cell aplasia without evidence of hemophagocytosis. This rare, unexplained but well known entity responded to corticosteroids.     

血浆置换术治疗异基因骨髓移植后纯红细胞再生障碍性贫血（附1例报告）

本文报告１例重症再生障碍性贫血患者因接受ＡＢＯ血型不合供体的异基因骨髓移植后并发纯红细胞再生障碍性贫血。采用血浆置换术２次,共置换出患者体内血浆３．２Ｌ后,血清抗＂Ａ＂血型抗体滴度由１∶６４下降至１∶８,骨髓幼红细胞比分逐渐上升,由血浆置换术前的０．００５上升至术后１２周的０．２１;红细胞输注量逐渐减少,血红蛋白逐渐升高,患者目前已完全恢复正常２年余。     

Multiple Cerebral Infarction Associated with Cerebral Vasculitis in a Patient with Ulcerative Colitis

A 40-year-old man was admitted to the hospital due to both a worsening of symptoms associated with ulcerative colitis (UC), which had been diagnosed 3 years previously, and limb paralysis. Colonoscopy revealed severe pancolitis-type UC. He was diagnosed with cerebral vasculitis with multiple white matter infarctions associated with the disease activity of UC by contrast-enhanced head magnetic resonance imaging. Mesalazine at 4,000 mg/day and prednisolone at 60 mg/day were started, and the prednisolone dosage was thereafter gradually reduced and switched to golimumab. He achieved a long-term remission from UC, and thereafter his neurological abnormalities improved significantly. He had no recurrence of cerebral infarction.     

Successful Treatment of Antibody-mediated Pure Red Cell Aplasia Induced by Continuous Erythropoietin Receptor Activator with Prednisolone

Pure red cell aplasia (PRCA) associated with erythropoiesis-stimulating agents (ESAs), which were first reported in 1998, usually occurs with subcutaneous administration of epoetin alfa (Eprex^Ⓡ). Improvements in ESA storage, handling, and administration methods have reduced the PRCA incidence. Continuous erythropoietin receptor activator (CERA) is a third-generation ESA that is rarely reported to induce PRCA. We herein report a case of CERA-induced PRCA presenting with positive anti-erythropoietin (EPO) and anti-CERA antibodies, which was successfully treated with prednisolone. Clinicians should be aware of the possibility of antibody-mediated PRCA induced by an ESA in CKD patients with anemia with reticulocytopenia and low serum EPO levels.     

Parovirus B19-induced red cell aplasia in solid-organ transplant recipients: Two case reports and review of the literature

Two solid-organ transplant recipients (one heart and one lung) developed severe anemia with reticulocytopenia. Both were heavily immunosuppressed. Bone marrow aspiration revealed almost complete absence of erythroid precursors. A few giant megaloblastic proerythroblasts with cytoplasmic vacuolisation and intranuclear inclusions were seen. Human parvovirus B19 (B19V)-DNA genome was found by nested-PCR assays in blood and bone marrow samples in both cases. Twelve similar cases are described in the literature. When looked for, B19V DNA was positive either in serum or bone marrow or both. Twelve of the fourteen patients were successfully treated by high dose i.v. immunoglobulin (IVIG). One patient recovered spontaneously and another after treatment with recombinant human erythropoietin (rHu-EPO) only. Transplant patients should be considered at risk for severe erythroblastopenic anemia due to B19V infection. Diagnosis is based on bone marrow examination and detection of B19V DNA by PCR in serum and/or marrow. IVIG is an effective and safe treatment. The role of erythropoietin in this indication needs further study.     

Fludarabine- and Cyclophosphamide-Based Nonmyeloablative Conditioning Regimen for Transplantation of Chronic Granulomatous Disease: Possible Correlation with Prolonged Pure Red Cell Aplasia

An 18-year-old patient with chronic granulomatous disease who had had at least 2 episodes of life-threatening Aspergillus pneumonia was treated with nonmyeloablative allogeneic stem cell transplantation (NSCT) from an HLA-identical and major ABO-incompatible sibling. The conditioning regimen consisted of cyclophosphamide at a dose of 60 mg/kg (days -5, -4) and fludarabine at a dose of 30 mg/m2 (days -5, -4, -3, -2, -1). Full donor T-cell engraftment was attained on day 28, and full myeloid engraftment was established by day 150 after tacrolimus withdrawal. The bacteriocidal activity of neutrophils, as indicated by flow cytometry with the use of a dichlorofluorescein diacetate oxidation assay, remained low until 150 days after transplantation, but no infection was detected, a finding that suggests mixed chimerism of granulocytes controlled infection. Graft-versus-host disease and severe regimen-related toxicity (grade 3 or greater) were not observed. This patient developed prolonged pure red cell aplasia, possibly caused by persistent antidonor isohemagglutinin produced by the residual host B-cells. The aplasia resolved with the combination of erythropoietin, double filtration plasmapheresis, and rituximab. In the setting of major ABO-incompatible NSCT, a fludarabine- and cyclophosphamide-based conditioning regimen may lead to prolonged PRCA.     

福建省B19微小病毒感染的病原学证据

应用套式PCR方法，对44份与B19微小病毒感染症相关的病人血清标本进行检测，其中5份血清标本和扩增产物合有B19病毒的104bpDNA生段，根据B19病毒基因组DNA核苷酸序列分析资料，使用HaeⅢ限制性内切酶切PCR扩增产物，结果产生81和23bp两段DNA，与序列分析结果一致，证实5例患者为B19病毒感染者，从病原学上支持了不久前我们使用血清学方法发现福建省B19病毒感染的报道。     

Persistent parvovirus B19 related anemia of seven years' duration in an HIV-infected patient: Complete remission associated with highly active antiretroviral therapy

A human immunodeficiency virus (HIV)-infected individual was first diagnosed with red blood cell aplasia due to B19 parvovirus infection in late 1989. Over the subsequent seven-year period, he received a total of 119 units of red blood cells (RBCs) and intravenous immunoglobulin every 2–3 weeks. In 1996 combination antiretroviral treatment with a protease inhibitor was initiated. He received four more units during the following two months and then required no more transfusions for the subsequent 24 months of follow-up. His CD4 count progressively increased and DNA polymerase chain reaction for parvovirus B19 became undetectable. Aggressive antiretroviral treatment may effectively diminish transfusion requirements among HIV-infected individuals with pure RBC aplasia resulting from parvovirus B19 infection. Am. J. Hematol. 60:164–166, 1999. © 1999 Wiley-Liss, Inc.