A case of pure red cell aplasia complicated by Evans syndrome

A 33-year-old woman complaining of severe anemia was admitted to our hospital for polyclonal hyperglobulinemia. She was diagnosed with pure red cell aplasia (PRCA) associated with Evans syndrome. Initially, the presence of human parvovirus B19 (HPV B19) IgM appeared to indicate that the cause of PRCA was HPV B19 infection. Evans syndrome improved with steroid therapy, but PRCA was refractory. Cyclosporine was administered; consequently, the patient markedly recovered from PRCA and was discharged. PRCA complicated by Evans syndrome occurred during the course of polyclonal hyperglobulinemia. The most direct etiology for the onset of PRCA was unclear; however, immunological disorders such as polyclonal hyperglobulinemia, in addition to HPV B19 infection, may have been partly responsible for the etiology of PRCA.     

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.     

Acquired pure red cell aplasia: a study of six cases

Persistent infection by parvovirus B19 associated with pure red cell aplasia (PRCA) has been documented in immunocompromised patients. Bone marrow failure is associated with conditions in which immune surveillance is impaired, and in these instances occult parvovirus infection may be suspected. In this study we have assessed by serological and molecular methods whether parvovirus B19 infection may be a more frequent cause of PRCA than hitherto suspected and whether it may be present in the absence of a typical bone marrow picture. Six patients with PRCA — two with isolated PRCA and no apparent underlying disease, two with a lymphoproliferative disease, one with thymoma, and one with chronic myelomonocytic leukemia — have been studied. Four of the six patients had overt PCRA and were clearly immunocompromised. Parvovirus B19 was not detected in any of the six patients by PCR analysis and serology investigating the presence of IgM or IgG antibodies. Although parvovirus B19 infection needs to be ruled out in PRCA it represents only one, and probably not the most frequent, etiological factor of PRCA.     

Pure red cell aplasia and lupus

OBJECTIVE: To review the clinical and laboratory features of all reported patients with systemic lupus erythematosus (SLE) and pure red cell aplasia (PRCA). METHODS: In addition to our patient, we identified cases reported during the years 1966-2000 by searching the MEDLINE literature (Winspirs). Clinical and laboratory features were compared with those reported in large series of patients with SLE but without PRCA. RESULTS: Twenty-three additional cases were identified. In most cases, SLE was diagnosed either before or concomitantly with the diagnosis of PRCA. The clinical and laboratory features were not significantly different from those reported in large series of patients with SLE, except for less pleuritis and a trend toward less proteinuria, hallucinations, thrombopenia, and leukopenia. The natural history of PRCA and SLE was similar to that reported for PRCA alone. The disease responded to prednisone in the majority of cases, but patients frequently remained steroid dependent. CONCLUSIONS: The association between SLE and PRCA is rare. The clinical and laboratory features of SLE in such patients are similar to SLE patients without PRCA with the exception of a decreased frequency of pleuritis. Response to treatment of PRCA in those with SLE is similar to patients with PRCA but without SLE.     

Parvovirus B19 infection and systemic lupus erythematosus: Activation of an aberrant pathway?

Parvovirus B19 infection has been associated with a variety of rheumatic manifestations/diseases, mainly rheumatoid arthritis, vasculitis and systemic lupus erythematosus (SLE). B19 infection may simulate both clinical and laboratory features of SLE, presenting either as a potential first time diagnosis of SLE or as an exacerbation of previously established disease. The similarities in both clinical and serological features of parvovirus infection and SLE at presentation may hinder the differential diagnosis between these two conditions. Hence, parvovirus B19 infection mimicking SLE usually fulfils <4 ACR criteria for SLE, rarely includes cardiac or renal involvement or presents with haemolytic anaemia, and is usually associated with short-lived, low titers of autoantibodies. Rarely, cases of multisystemic involvement solely attributed to a recent parvovirus B19 infection have been reported, rendering early accurate diagnosis of particular importance and justifying the screening for evidence of parvovirus B19 involvement in newly diagnosed cases of SLE, especially the ones with abrupt onset of symptoms along with cases of SLE flares. This review describes basic features of parvovirus B19 structure and pathogenicity and expands on the parvo-associated auto-immune manifestations particularly in relation to SLE-mimicking or SLE-triggering reported cases. The proposed mechanisms for viral-induced pathologic autoimmunity are discussed with emphasis on emerging data regarding the aberrant expression and localization of autoantigens and their potential implication in alternatively activated immunological cascades.     

The relationship between arthritis and human parvovirus B19 infection

In order to evaluate the role of human parvovirus B19 in the etiopathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), synovial fluid and blood specimens were collected at 1-month intervals from 20 patients with early synovitis (ES) and 31 with RA. Blood specimens were also collected from 25 patients with SLE, 25 with osteoarthritis (OA) as the diseased control group, and 50 healthy blood donors (HBD) as the healthy control group. Detection of B19 IgM and B19 IgG were performed by enzyme-linked immunosorbent assay from serum specimens, and B19 DNA was detected by polymerase chain reaction from synovial fluid samples. B19 IgM, B19 IgG, and B19 DNA were found in the three patients of the ES group. Subsequently, two of them were diagnosed with RA and one with SLE. B19 DNA was also detected in the synovial fluid of eight patients in the RA group. Of them, all were positive for B19 IgG and half were positive for B19 IgM. B19 IgM was not detected in either of the control groups. To define the role of B19 in the etiopathogenesis and prognosis of undiagnosed arthritis and other chronic inflammatory diseases such as RA and SLE, we need broader serial and prospective studies based on clinical and laboratory collaboration. In conjunction with case reports, these studies would also serve to detect other possible factors in the etiopathogenesis of chronic inflammatory diseases.     

Relapsing pure red cell aplasia associated with B-cell chronic lymphocytic leukemia successfully treated by intravenous immunoglobulin concentrate

Pure red cell aplasia (PRCA) is a rare syndrome characterized by a normochromic normocytic anemia and the absence of mature erythroid precursors in an otherwise normocellular bone marrow. Acquired PRCA has been associated with autoimmune, viral or neoplastic conditions. We report the case of a patient with B-cell chronic lymphocytic leukemia (B-CLL) and PRCA. Conventional antileukemic treatment had no effect on the PRCA, while the B-CLL showed partial remission according to the International Workshop on Chronic Lymphocytic Leukemia response criteria. The patient was treated with cyclosporin A that resulted in complete response of the PRCA lasting 12 months. PRCA relapse, suggested by a hemoglobin decrease and by bone marrow biopsy, did not respond to prednisone and cyclophosphamide treatment. Fludarabine treatment was started in July 1999; the B-CLL remained stable according to the International Workshop on Chronic Lymphocytic Leukemia response criteria, the PRCA did not improve. In October 1999, because of intercurrent pneumonia, the patient was treated with intravenous immunoglobulin (IVIG) concentrate. This treatment resulted in total resolution of the pneumonia and a complete response of the PRCA. Therefore the patient remained on monthly IVIG. In view of the known efficacy of IVIG in the treatment of PRCA induced by parvovirus B19 and since serial polymerase chain reaction determinations of parvovirus B19 were repeatedly negative in our subject, we hypothesize that the IVIG per se may have a therapeutic effect on PRCA. The present case suggests that IVIG may be of benefit for PRCA patients even if the disease is unrelated to parvovirus B19 infection.     

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.     

First case report of acquired pure red cell aplasia associated with micafungin

A 70-year-old Japanese man with chronic kidney disease under treatment with oral prednisolone for organizing pneumonia developed pulmonary aspergilloma. The patient was started on micafungin (MCFG), with no addition of any other new drug. About 5 weeks later, aggravation of his normocytic anemia associated with a low reticulocyte count was observed. Bone marrow puncture and biopsy revealed intense hypoplasia of the erythroblasts. As there was no evidence of malignancy, human parvovirus B19 infection, autoimmune diseases or hemorrhage, the patient was diagnosed as having acquired pure red cell aplasia (PRCA). The anemia improved along with an increase of the reticulocyte count to the normal level within 12 weeks of discontinuation of the MCFG therapy. The patient showed no evidence subsequently of any recurrence of the normocytic normochromic anemia or relapse of the PRCA. This is the first reported case of PRCA associated with MCFG.     

Human parvovirus B19 infection: its relationship with systemic lupus erythematosus.

OBJECTIVES: The clinical presentation and outcome of four cases of human parvovirus-B19 (HPV-B19) infection, initially diagnosed as systemic lupus erythematosus (SLE), were reviewed and compared with similar cases previously reported in the literature. The relationship between HPV-B19 infection and SLE is discussed. METHODS: The medical records of four patients with documented HPV-B19 infection, initially diagnosed as SLE, were reviewed and studied in detail. A Medline search from 1985 to 1997 was performed to identify other cases reported in the literature in which a relationship between HPV-B19 and SLE had been identified in both adults and children. RESULTS: In all of our cases, the clinical findings (fever, rash, arthritis and malaise) and hematologic data (leukopenia, thrombocytopenia, anemia, presence of autoantibodies, hypocomplementemia, etc.) had initially suggested a diagnosis of juvenile SLE. Subsequently, evidence of HPV-B19 infection at the time of clinical presentation was ascertained. In three of these cases, the disease course was self-limiting with complete clinical remission and normalization of hematologic abnormalities within 18 months; one case, however, had persistent disease activity and repeated exacerbations. CONCLUSIONS: The occurrence of HPV-B19 infection has been documented in patients with SLE, in particular in relation to disease onset. Similarities in clinical and immunological features of viral infections and SLE at presentation may hinder the differential diagnosis between these two conditions. The family history, a self-limiting disease course and certain disease specific clinical aspects may help the pediatrician formulate an accurate diagnosis. In our patients, HPV-B19 infection may have mimicked the onset of SLE in three cases, but triggered the disease in one.     

Novel cytomorphology of the giant proerythroblasts of parvovirus B19 infection

The morphology of the giant proerythroblasts (GPE) in air-dried and Wright-Giemsa-stained smears of bone marrow in 16 patients with pure red cell aplasia (PRCA) caused by parvovirus B19 infection is described. B19 infection was diagnosed by the presence of the virus or viral DNA and/or IgM antibodies. Twelve patients had chronic hemolytic anemia and aplastic crisis and 4 patients had AIDS with chronic PRCA. In patients with chronic hemolytic anemia and aplastic crisis, GPE were not detectable in bone marrow biopsies that showed any degree of recovery of erythropoiesis. The GPE morphology was quite variable. The early (basophilic) GPE measured 25 to 35 μm in diameter, had a narrow rim of intensely blue and often vacuolated cytoplasm with pseudopodia, round nuclei with compact uncondensed chromatin, and an indistinct and inclusion-like purple-colored tinctorial change. The “intermediate” and “late” GPE measured 25 to 45 μm in diameter and showed cytoplasmic swelling, gradual loss of cytoplasmic basophilia, and fraying of the cytoplasm with focal rupture; the nuclei showed an increase in volume, a highly uncondensed and coarse sieve-like chromatin, and 1 to 3 prominent, pale to moderate purple inclusion-like nucleoli or inclusions. Bare nuclei similar in size and chromatin pattern to those of the GPE were present in proximity to the GPE and may have arisen from the GPE by dissolution of the cytoplasm. The glassy intranuclear inclusions with central clearing, the so-called lantern cells described in formalin-fixed tissues of patients with B19 infection, were absent in all cases. These findings suggest that direct toxic cell injury rather than apoptosis may be involved in the pathogenesis of erythroid aplasia in B19 infection. Am. J. Hematol. 58:95–99, 1998. © 1998 Wiley-Liss, Inc.     

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy

Abstract

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.     

Development of pure red cell aplasia by transmission and persistent infection of parvovirus B19 through a kidney allograft

We report a case of pure red cell aplasia (PRCA) caused by parvovirus B19 (PVB19) infection, which was transmitted through a kidney allograft. The patient underwent a living‐donor kidney transplant from his wife at the age of 60. Despite successful engraftment with a normal creatinine level, he developed severe anemia that required frequent blood transfusions 2 months after transplantation. Renal anemia was unlikely as his serum erythropoietin level was extremely high. A bone marrow aspiration test demonstrated the existence of large proerythroblasts. Although anti‐PVB19 IgM antibody levels were not increased, polymerase chain reaction (PCR) detected PVB19 DNA in his serum. Thus, he was diagnosed as having PRCA induced by PVB19 infection. PCR analysis of total DNA isolated from 0‐hour biopsy sections showed the existence of PVB19 DNA. Furthermore, PVB19 proteins was detected on renal tubules of 0‐hour allograft by immunoperoxidase staining. Thus, transmission of PVB19 through the allograft was confirmed. A single course of intravenous immunoglobulin (IVIG) therapy resulted in substantial improvement; however, the effect was limited, and severe anemia relapsed after 5‐6 months. Several courses of IVIG with adjustment of immunosuppressive drugs resulted in long‐term remission. Our case demonstrates that donor‐transmitted PVB19 infection should be suspected in kidney transplant recipients who develop refractory anemia during the early post‐operative phase.     

Pure Red Cell Aplasia in a Three-Months-Old Infant Possibly Secondary to Cytomegalo Virus Infection

We report a 3 months old child who presented with severe anemia due to pure red cell aplasia (PRCA). After ruling out other known causes of PRCA, congenital cytomegalovirus (CMV) infection was diagnosed to be the cause. The child responded to Ganciclovir and is doing well. CMV infection should be considered as differential diagnosis in PRCA during infancy.     

Parvovirus B19-related anemia in HIV-infected patients

Persistent infection with parvovirus B19 (B19) is an important treatable cause of anemia in HIV-infected patients. B19 has a tropism for erythroid progenitors and causes pure red cell aplasia (PRCA). The failure to produce neutralizing antibodies to the virus following B19 infection in immunodeficient persons may result in persistent viremia and chronic PRCA (B19-PRCA). The seroprevalence rates for B19 in unselected persons with HIV infection are high, similar to those seen in the general population. Reports of B19-related anemia in HIV infected patients, however, are infrequent. A partial explanation may be that B19-PRCA is predominantly a complication associated with advanced immunodeficiency. The condition is probably underdiagnosed as well. The finding of an unexplained normocytic anemia with absent reticulocytes, in an afebrile HIV-infected patient without renal dysfunction suggests a diagnosis of B19-PRCA. The diagnosis is established when the following criteria are met: (1) bone marrow biopsy showing PRCA, (2) serum or bone marrow positivity for B19 DNA by PCR or dot-blot hybridization, and (C) no alternate explanation for the PRCA. Serological methods are unreliable for the diagnosis because these patients often lack IgM and IgG antibodies to B19. Nearly all patients with B19-PRCA respond to treatment with intravenous immunoglobulin (IVIg) with a rise in the hemoglobin to levels appropriate for the clinical condition of the patient. An alternative explanation for the anemia must be sought in patients not responding to IVIg. Most patients with CD4+ T-lymphocyte counts of < or = 100 cells/mm3 relapse to anemia, usually within 6 months of IVIg therapy. Such patients must be retreated with IVIg 2 g/kg given over 2 to 5 days. The routine use of maintenance IVIg 0.4 g/kg q 4wk may be considered in these patients to prevent relapse.     

Parvovirus B-19 induced acute pure red cell aplasia in patients with chronic lymphocytic leukemia and neurofibromatosis type-1

Parvovirus B19 induced pure red cell aplasia (PRCA) has been previously reported in a variety of settings. We present two cases, an adult patient with chronic lymphocytic leukemia (CLL) and a child with neurofibromatosis type-1 (NF-1), where the abrupt appearance of severe anemia raised ominous clinical suspicions. Evidence of recent parvovirus B19 infection in association with the selective erythroid precursor deficiency in marrow helped exclude other etiologies.

We emphasize the importance of bearing this infectious agent in mind, even when there are associated disorders (such as CLL) that may independently cause PRCA. An association of NF-1 with acute PRCA has not been described in indexed English literature in the past.     

Parvovirus B-19 induced acute pure red cell aplasia in patients with chronic lymphocytic leukemia and neurofibromatosis type-1

Parvovirus B19 induced pure red cell aplasia (PRCA) has been previously reported in a variety of settings. We present two cases, an adult patient with chronic lymphocytic leukemia (CLL) and a child with neurofibromatosis type-1 (NF-1), where the abrupt appearance of severe anemia raised ominous clinical suspicions. Evidence of recent parvovirus B19 infection in association with the selective erythroid precursor deficiency in marrow helped exclude other etiologies. We emphasize the importance of bearing this infectious agent in mind, even when there are associated disorders (such as CLL) that may independently cause PRCA. An association of NF-1 with acute PRCA has not been described in indexed English literature in the past.     

Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis

A 47-year-old woman who had been treated for systemic lupus erythematosus (SLE) with myasthenia gravis (MG) was admitted to our hospital with acute onset of severe anemia after administration of isoniazid. Pure red cell aplasia (PRCA) was confirmed by elevated serum iron levels, reticulocytopenia and bone marrow aspiration showing a remarkable reduction of erythroblasts. Finally, cyclosporine A successfully improved PRCA. Although both SLE and MG have the potential complication of PRCA, we report here a case of isoniazid-triggered PRCA.     

Systemic lupus erythematosus due to Epstein–Barr virus or Epstein–Barr virus infection provocating acute exacerbation of systemic lupus erythematosus?

Systemic lupus erythematosus (SLE) is a rheumatologic disease characterized by an inflammatory destruction of the target organ systems of the body in an unknown way by autoantibodies formed against self-antigens. Infectious agents like Epstein–Barr virus (EBV), cytomegalovirus and parvovirus B19 may have a role in the occurrence or the exacerbation of the SLE. In this report, the clinical follow-up of a 14-year-old girl diagnosed with SLE following an EBV infection with bicytopenia, lymphadenomegaly and hepatomegaly is discussed. This case could support the role of viral infections in the etiology of SLE.     

Pure red cell aplasia due to parvovirus B19 infection after liver transplantation： A case report and review of the literature

Pure red cell aplasia （PRCA） due to parvovirus B19 （PVB19） infectiori after solid organ transplantation has been rarely reported and most of the cases were renal transplant recipients, Few have been described after liver transplantation. Moreover, little information on the management of this easily recurring disease is available at present. We describe the first case of a Chinese liver transplant recipient with PVB19-induced PRCA during immunosuppressive therapy. The patient suffered from progressive anemia with the lowest hemoglobin level of 21 g/L. Bone marrow biopsy showed selectively inhibited erythropoiesis with giant pronormoblasts. Detection of PVB19-DNA in serum with quantitative polymerase chain reaction （PCR） revealed a high level of viral load. After 2 courses of intravenous immunoglobulin （IVIG） therapy, bone marrow erythropoiesis recovered with his hemoglobin level increased to 123 g/L. He had a lowlevel PVB19 load for a 5-too follow-up period without recurrence of PRCA, and finally the virus was cleared. Our case indicates that clearance of PVB19 by IVIG in transplant recipients might be delayed after recovery of anemia.