Article

Hemochromatosis in the setting of Chronic Parvovirus B-19 induced Aplastic Anemia

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Abstract

Parvovirus B19 is a ubiquitous virus typically limited to the pediatric population as erythema infectiosum or "fifth disease." In the adult populations, symptomatic Parvovirus infections can be seen in the setting of immunosuppression associated with transplant. These patients generally respond well to reduction in immunosuppression and IVIg, and do not require extended therapy. We present an interesting case of a renal transplant patient, who developed a chronic Parvovirus B19 infection after receiving a cadaveric kidney transplant. His case was additionally complicated by the diagnosis of hemochromatosis that required treatment with deferasirox due to the anemia from chronic parvovirus infection.

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Parvovirus B19 (B19) was discovered in 1974 and is the only member of the family Parvoviridae known to be pathogenic in humans. Despite the inability to propagate the virus in cell cultures, much has been learned about the pathophysiology of this virus, including the identification of the cellular receptor (P antigen), and the control of the virus by the immune system. B19 is widespread, and manifestations of infection vary with the immunologic and hematologic status of the host. In healthy immunocompetent individuals B19 is the cause of erythema infectiosum and, particularly in adults, acute symmetric polyarthropathy. Due to the tropism of B19 to erythroid progenitor cells, infection in individuals with an underlying hemolytic disorder causes transient aplastic crisis. In the immunocompromised host persistent B19 infection is manifested as pure red cell aplasia and chronic anemia. Likewise, the immature immune response of the fetus may render it susceptible to infection, leading to fetal death in utero, hydrops fetalis, or development of congenital anemia. B19 has also been suggested as the causative agent in a variety of clinical syndromes, but given the common nature, causality is often difficult to infer. Diagnosis is primarily based on detection of specific antibodies by enzyme-linked immunosorbent assay or detection of viral DNA by dot blot hybridization or PCR. Treatment of persistent infection with immunoglobulin reduces the viral load and results in a marked resolution of anemia. Vaccine phase I trials show promising results.
Article
Deferasirox is a once-daily oral iron chelator with established dose-dependent efficacy in both adult and pediatric patients with transfusional iron overload. The clinical development program has demonstrated the efficacy of deferasirox for up to 4.5 years of treatment in patients with various underlying anemias, including beta-thalassemia, myelodysplastic syndromes, sickle cell disease, aplastic anemia, and other rare anemias. In addition to reducing key indicators of total body iron levels (serum ferritin, liver iron concentration, and toxic labile plasma iron), deferasirox has also demonstrated the ability to remove cardiac iron and prevent future cardiac iron accumulation. Emerging long-term data confirm the tolerability profile of deferasirox, and data on patient compliance render deferasirox a suitable therapeutic option for patients with chronic conditions requiring ongoing iron chelation therapy. Data continue to accumulate in a wide range of patient groups, including those with non-transfusion-dependent anemias such as hereditary hemochromatosis.
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Article
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Article
Immunosuppression cannot be achieved without immunosuppressive effects. Human Parvovirus infection is known to occur after organ transplantation. We present our experience with Parvovirus infection in two cases. Two kidney transplant recipients developed symptomatic anemia requiring blood transfusions. Common causes of anemia, such as gastrointestinal bleeding, iron/vitamin deficiencies, hemolysis, and drug toxicities, were ruled out. A peripheral smear revealed low reticulocyte count. Bone marrow examination showed hypoplastic bone marrow with intranuclear inclusions suggestive of human Parvovirus. This was confirmed by immunohistochemical analysis. Treatment with i.v. immunoglobulin G resulted in a dramatic sustained response. Transplant kidney function remained stable. Human Parvovirus infections should be considered in immunosuppressed individuals with anemia with poor bone marrow response. Bone marrow examination can reveal viral inclusions and can be confirmed by immunohistochemical analysis. Intravenous immunoglobulin G results in resolution of anemia.
Article
We report an unexplained anemia that persisted for 4 months in a renal transplant patient who was receiving immunosuppression therapy that included prednisolone, tacrolimus and azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts with intranuclear inclusions, characteristic of a parvovirus B19 infection. Both the serum and bone marrow cells were positive by parvovirus B19 DNA PCR. The anemia resolved 6 weeks after the administration of intravenous immunoglobulin (IVIG). Four months later, anemia redeveloped and IVIG was infused again. Hemoglobin levels were, however, still subnormal after 1 month of treatment and tacrolimus was then switched to cyclosporin A, resulting in a clear improvement. A parvovirus B19 infection should be included in the differential diagnosis of renal transplant recipients who present with anemia associated with a low reticulocyte count. Tacrolimus may possibly impair the clearance of a parvovirus B19 infection.
Article
The treatment of iron overload by s.c. desferrioxamine (DFO) was studied in three patients with hereditary haemochromatosis in which phlebotomy treatment was not, or transiently not, possible because of their serious clinical condition or the lack of appropriate peripheral veins. Repeated non-invasive liver iron concentration measurements by superconducting quantum interference device biosusceptometry showed that DFO treatment (2 g/d for 9-11 months) was as effective (liver iron elimination rate: 12 mg/d) as normal phlebotomy treatment (5.9 or 14.3 mg/d respectively) with weekly 500-ml blood removals. This demonstrates that DFO is an effective alternative therapy for haemochromatosis when phlebotomy is not possible.
Article
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Article
Although most persons with parvovirus B19 infection are asymptomatic or have mild, nonspecific, cold-like symptoms, several clinical conditions have been linked to the virus. Parvovirus B19 usually infects children and causes the classic "slapped-cheek" rash of erythema infectiosum (fifth disease). The virus is highly infectious and spreads mainly through respiratory droplets. By the time the rash appears, the virus is no longer infectious. The virus also may cause acute or persistent arthropathy and papular, purpuric eruptions on the hands and feet ("gloves and socks" syndrome) in adults. Parvovirus B19 infection can trigger an acute cessation of red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis, or congenital anemia. This is even more likely in patients with illnesses that have already shortened the lifespan of erythrocytes (e.g., iron deficiency anemia, human immunodeficiency virus, sickle cell disease, thalassemia, spherocytosis). A clinical diagnosis can be made without laboratory confirmation if erythema infectiosum is present. If laboratory confirmation is needed, serum immunoglobulin M testing is recommended for immunocompetent patients; viral DNA testing is recommended for patients in aplastic crisis and for those who are immunocompromised. Treatment is usually supportive, although some patients may require transfusions or intravenous immune globulin therapy. Most patients recover completely.