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Unusual bone marrow manifestations of parvovirus B19 infection in immunocompromised patients
T W Crook1, B B Rogers, R D McFarland
1Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.
Abstract:
Parvovirus B19 is responsible for a spectrum of disease in humans. The usual bone marrow findings in acute parvovirus infections are marked erythroid hypoplasia and occasional giant erythroblasts. Intranuclear inclusions in developing erythroid precursors are rarely described in children or adults with parvovirus infection, although abundant intranuclear inclusions are commonly observed in the placenta and other tissues in infected fetuses. In this study, 8 patients are reported in whom the first evidence of parvovirus infection was the recognition of numerous intranuclear inclusions in erythroid precursors on bone marrow biopsy sections. Six of the 8 patients had documented immunodeficiencies; 4 had acquired immune deficiency syndrome (AIDS), and 2 were on chemotherapy. Five of 7 patients were negative for immunoglobulin G (IgG) antiparvovirus antibodies, including all 4 with AIDS. Unlike the typical pattern in parvovirus infection, the bone marrow was hypercellular in most of the patients, and erythroid precursors were usually increased with the entire spectrum of normoblast maturation represented; abundant intranuclear inclusions were observed similar to the finding in fetuses. The inclusions were variably eosinophilic and compressed the chromatin against the nuclear membrane. In situ hybridization showed parvovirus B19 DNA in numerous erythroid precursors in all cases. The findings of erythroid maturation and abundant viral inclusions in these immunocompromised patients is consistent with the hypothesis that failure to produce effective IgG parvovirus neutralizing antibodies may lead to persistent infection through viral tolerance that allows erythroid development of infected cells past the pronormoblast stage. Identification of parvovirus inclusions in marrow biopsies and subsequent confirmation of infection by in situ hybridization can be important in the assessment of anemia in immunodeficient patients because serological studies for parvovirus B19 are frequently negative.
Insights
Parvovirus B19 infection in immunocompromised patients can present with intranuclear inclusions in erythroid precursors. Bone marrow biopsy and in situ hybridization are crucial for diagnosis when antibody tests are negative.
Area of Science:
- Hematology
- Virology
- Immunology
Background:
- Parvovirus B19 typically causes erythroid hypoplasia in acute infections.
- Intranuclear inclusions are common in fetal tissues but rarely reported in adult parvovirus infections.
- Immunocompromised individuals may exhibit atypical parvovirus B19 disease presentations.
Purpose of the Study:
- To report on 8 immunocompromised patients with parvovirus B19 infection characterized by intranuclear inclusions in erythroid precursors.
- To investigate the diagnostic utility of bone marrow biopsy and in situ hybridization in these cases.
- To explore the hypothesis of persistent parvovirus B19 infection due to impaired antibody response.
Main Methods:
- Bone marrow biopsy analysis for erythroid precursors and intranuclear inclusions.
- Immunoglobulin G (IgG) antiparvovirus antibody testing.
- In situ hybridization to detect parvovirus B19 DNA in bone marrow cells.
Main Results:
- Eight patients showed numerous intranuclear inclusions in erythroid precursors on bone marrow biopsy.
- Six patients had documented immunodeficiencies (4 with AIDS, 2 on chemotherapy).
- Five of seven tested patients were seronegative for IgG antiparvovirus antibodies.
- Bone marrow was hypercellular with erythroid maturation and abundant inclusions, unlike typical parvovirus infection.
- In situ hybridization confirmed parvovirus B19 DNA in erythroid precursors in all cases.
Conclusions:
- Intranuclear inclusions in erythroid precursors can be the primary indicator of parvovirus B19 infection in immunocompromised patients.
- Impaired IgG antibody production may lead to persistent parvovirus B19 infection and viral tolerance.
- Bone marrow examination and in situ hybridization are vital for diagnosing parvovirus B19 in immunodeficient patients with anemia, especially when serology is negative.