| Abstract|| |
Most persons with parvovirus B19 infection are asymptomatic or exhibit mild, nonspecific, cold-like symptoms. However, hematologic problems associated with the infection include transient aplastic crisis, chronic red cell aplasia, mild neutropenia and thrombocytopenia. A rare hematologic manifestation is in the form of dyserythropoeisis. Herein, we present the case of a 9-year-old female with severe dyserythropoeisis associated with parvovirus infection.
Keywords: Dyserythropoeisis, hematology, parvo virus
|How to cite this article:|
Jain D, Singh T. Parvovirus-induced dyserythropoeisis in a child. Indian J Pathol Microbiol 2008;51:418-20
| Introduction|| |
The spectrum of disease linked to parvovirus B19 primarily involves infection in the healthy host as well as a number of hematologic symptoms in predisposed individuals. It is known to cause transient erythroid aplasia in children with hemolytic anemia,  but has also been associated with bone marrow necrosis  and morphologic changes suggesting myelodysplasia.  Herein, we describe a pediatric age group female patient with severe anemia, thrombocytopenia and hepatosplenomegaly. Bone marrow examination showed a severe degree of dyserythropoeisis and few giant pronormoblasts signifying an evidence of parvovirus infection. Dyserythropoeisis associated with parvovirus has been documented in the literature.  This case expands the spectrum of hematologic disease associated with parvovirus infection.
| Case history|| |
A 9-year-old female patient presented with severe anemia since 2 months. In addition, she had a history of gum bleeding since 1 month and a single episode of upper GI bleed. She complained of dyspnea since 10 days' duration. On examination, she had marked pallor with petechiae and purpura all over the body. Systemic examination revealed hepatosplenomegaly. Hemogram findings were as follows: Hb 4.5 g/dl; WBC 4.5 × 10 9 /l; platelets 10 × 10 9 /l; MCV 68 fl; MCH 29 pg; MCHC 24%; RDW 22. Reticulocyte count was 0.6%. The peripheral smear demonstrated a moderate degree of anisopoikilocytosis. There were microcytes, tear drop cells, polychromatophils and few nucleated RBCs (2/100WBCs).
A moderate degree of hypochromia was present. Platelets were reduced on blood smear.
Therefore, the overall picture of bicytopenia was considered. Serology for human immunodeficiency virus was negative. Hemoglobin electrophoresis was performed in view of severe anemia and RBC morphology on peripheral blood smear; however, it did not show any abnormal band of hemoglobin. Hb F was within normal limits. A bone marrow aspirate was performed, which was hypercellular for the age of the patient, with erythroid hyperplasia. Myeloid erythroid ratio was 1:1. Differential count in the marrow includes 52 erythroblasts predominantly of late type. Erythropoeisis was predominantly micronormoblastic with marked dyserythropoeisis. Numerous bi-, tri- and multinucleated late erythroblasts were evident along with few dumbbell-shaped forms [Figure 1]. In addition, few giant pronormoblasts ('Lantern cells') were seen signifying morphologic features of parvovirus infection. These pronormoblasts were around 25 to 32 µm in size, had prominent nucleoli-like eosinophilic nuclear inclusions and at places displayed cytoplasmic blebs [Figure 2] so-called or 'dog ear projections'. Myeloid series was unremarkable. Megakaryocytes were adequately present. Bone marrow iron was absent on Prussian blue stain. No sideroblasts were seen. In view of marked dyserythropoesis and organomegaly, acidified-serum test was performed; however, it was negative. Serology of parvovirus was positive for Ig M antibodies. Titers were not available. Based on all these findings, a diagnosis of parvovirus-mediated dyserythropoeisis was considered. Cytogenetic and ultrastructural analysis was not performed. She recovered after 2 weeks with conservative management including anti-inflammatory drugs, iron therapy, red blood cell and platelet transfusions.
| Discussion|| |
The most striking feature of the case under discussion is the marked dyserythropoeisis with bi-, tri- and multinuclearity observed within the erythroid precursors, which initially suggested the diagnosis of CDA. Within the bone marrow, patients with CDA also have marked dyserythropoeisis with binuclearity, multinuclearity and internuclear bridging. Thus, it is important to do a battery of tests to diagnose CDA such as serology, cytogenetics and ultrastructural analysis.
Our patient presented with severe anemia and her bone marrow aspirate revealed dyserythropoeisis. Although CDA was originally suggested as the diagnosis, serologic testing documented negative acidified-serum test, thus excluding CDA II. The only other disorder which may give a positive acidified-serum test is PNH. PNH red cells are unusually susceptible to lysis by complement. These will undergo lysis in acidified normal serum and in the patient's acidified serum. However, in CDA type II, the red cells undergo lysis in only a proportion (approximately 30%) of normal sera and these RBCs do not undergo lysis in the patient's own acidified serum. Bone marrow iron stores were depleted and there was thrombocytopenia. Distinct microcytosis/hypochromia with mean corpuscular volume (MCV) below 70 fL or mean corpuscular hemoglobin concentration (MCHC) below 25 pg is not present in CDA, except in rare cases with additional iron deficiency or heterozygous thalassemia.  In the present case, hemoglobin electrophoresis did not reveal any abnormal hemoglobin, which therefore ruled out the possibility of thalassemia. Although cases of CDA with negative acidified-serum test and iron deficiency are recorded in the literature, these are rare.  Interestingly, bone marrow aspiration also showed giant pronormoblasts. Follow-up bone marrow aspiration documented complete resolution of dyserythropoeisis and suggested that all of the abnormalities seen in the initial bone marrow aspirate were due to parvovirus infection and concomitant iron deficiency anemia. The seroprevalence of parvovirus ranges from 2 to 60% in children, 30 to 60% in adults and more than 85% in the geriatric population. Women of childbearing age show an annual seroconversion rate of 1.5%.  In experimentally infected normal volunteers, bone marrow aspiration performed early in parvovirus viremia reveals a normocellular bone marrow.  In the present case, erythroid hyperplasia might have been due to co-existant iron-deficiency anemia. Erythroid aplasia occurs when the parvovirus nonstructural protein NS1 acts through the tumor necrosis factor-alpha pathway to promote apoptosis of erythroid precursors. In the present case, the patient also had thrombocytopenia. Parvovirus-related thrombocytopenia has also been reported in the literature. The infrequently reported thrombocytopenia associated with parvovirus B19 infection may consist of two types. In one type, thrombocytopenia is due to bone marrow suppression, while the other type is probably mediated by immunologic mechanisms.[ 8], The latter type has been seen in children, as can be seen in the present case. Although B19 parvovirus is widely distributed in the human population, anemia is uncommon unless there is an additional predisposing factor, as in iron-deficiency anemia, sickle cell anemia, or immunosuppression.  In our case, concomitant iron deficiency might have been the contributory factor for the development of anemia and parvovirus-related dyserythropoeisis. The most possible cause of iron deficiency in this patient was nutritional; iron supplementation recovered hemoglobin and RBC indices. Serum iron and ferritin levels were not assayed due to the cost factor. The cytopathic effect of infection of erythroid progenitor cells with B19, both in vivo and in vitro , is manifested as giant pronormoblasts. Giant pronormoblasts on a peripheral blood smear or in a bone marrow aspirate are suggestive of parvovirus B19 infection, but are not diagnostic.  Serology and ultrastructural analysis is essential for confirmatory diagnosis. This case expands the spectrum of hematologic and clinical presentations of parvovirus B19 infection to include dyserythropoeisis, with the potential for misdiagnosis. This raises the intriguing question of whether parvovirus infection may underlie some of the CDAs.
| References|| |
|1.||Heegaard ED, Brown KE. Human parvovirus B19. Clin Microbiol Rev 2002;15:485-505. |
|2.||Osaki M, Matsubara K, Iwasaki T. Severe aplastic anemia associated with human parvovirus B19 infection in a patient without underlying disease. Ann Hematol 1999;78:83-6. |
|3.||Conrad ME, Studdard H anderson LJ. Case report: Aplastic crisis in sickle cell disorders: Bone marrow necrosis and human parvovirus infection. Am J Med Sci 1988;295:212-5. |
|4.||Yarah N, Duru F, Tansu S. Parvovirus B19 infection reminiscent of myelodysplastic syndrome in three children with chronic hemolytic anemia. Pediatr Hematol Oncol 2000;17:475-82. |
|5.||Carpenter SL, Zimmerman SA, Ware RE. Acute parvovirus B19 infection mimicking congenital dyserythropoietic anemia. J Pediatr Hematol Oncol 2004;26:133-5. |
|6.||Iolascon A, Sabato V, De Mattia D, Locatelli F. Bone marrow transplantation in a case of severe, type II congenital dyserythropoietic anaemia (CDA II). Bone Marrow Transplant 2001;27:213-5. |
|7.||Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, et al . Congenital dyserythropoietic anemia type II: Epidemiology, clinical appearance and prognosis based on long-term observation. Blood 2003;102:4576-81. |
|8.||Kaplan C, Morinet F, Cartron J. Virus-induced autoimmune thrombocytopenia and neutropenia. Semin Hematol 1992;29:34-44. |
|9.||Uslu H, Kiki I, Ozbek A, Erdem F, Ayyildiz A. Seroprevalence of parvovirus B19 in patients with chronic idiopathic thrombocytopenic purpura. Mikrobiyol Bul 2007;41:597-602. |
Department of Pathology, Maulana Azad Medical College, New Delhi - 110 002
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]