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Acute severe anaemia in an elderly patient with hereditary sphaerocytosis

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Q1: Was does the bone marrow biopsy show?

The bone marrow smear shows a giant pronormoblast with cytoplasmic vacuolisation and large eosinophilic nuclear inclusion bodies characterising infected human erythroid cells.

Q2: What is the most likely diagnosis?

In patients with congenital haemolytic anaemia, such as hereditary sphaerocytosis, life threatening transient aplastic crisis may occur due to parvovirus B19 infection.

Q3: Which investigations would you perform to confirm the diagnosis?

(A) Serology for parvovirus B19 in serum

In our patient, ELISA was positive for anti-B19 IgM and anti-B19 IgG antibodies (IgM: 1:16 on day 5, 1:512 on day 11, and 1:256 on day 20; IgG 1:<64 on day 5; 1:512 on day 11, and 1: 2048 on day 20), findings consistent with acute parvovirus B19 infection.

(B) Immunohistochemical detection of parvovirus B19 in the infected cell

The giant pronormoblast showed strong immunoreactivity with a monoclonal antibody against VP1 and VP2 capsid proteins of parvovirus B19 (fig 1).

Figure 1

Strong immunoreactivity of erythroid precursor cells (including one giant pronormoblast) with monoclonal antibodies against the capsid proteins of parvovirus B19 (original magnification × 400).

(C) Polymerase chain reaction (PCR) for parvovirus B19 in the bone marrow

The PCR was not done in our patient, but it is an accurate and reliable method to diagnose an aplastic crisis due to parvovirus B19 in patients with congenital haemolytic anaemia or HIV infection.1

Outcome

Twelve days after admission, numerous cohorts of early erythroid cells were present in the bone marrow. For support, the transfusion of nine units of packed red blood cells was required during hospitalisation.

Discussion

Parvovirus B19, a small non-enveloped DNA virus first described in 1975,2 is the only pathogenic member of the family parvoviridae found in humans and is associated with a wide range of disease manifestations. Approximately 50% of children age 15 are seropositive, and the prevalence rises to more than 90% in the elderly. Most infections are asymptomatic or unrecognised. Frequent clinical manifestations include erythema infectiosum (fifth disease or slapped cheek disease) in children, polyarthropathy syndrome mimicking rheumatoid arthritis in adults, miscarriage or hydrops fetalis and eventually congenital anaemia of the newborn in pregnant women, or transient aplastic crisis in patients with underlying haemolytic disorders and chronic bone marrow failure in immunocompromised individuals.1 Pathophysiologically, the virus selectively targets human erythroid cells for propagation. In human erythroid cells derived from bone marrow, susceptibility to parvovirus B19 increases with differentiation; the pluripotent stem cell appears to be spared, and the main target cells are erythroid progenitors. Erythroid specificity results as the virus uses the blood group P antigen,3 found only on erythroid progenitors, erythroblasts, megakaryocytes, and endothelial cells, to gain entry into the cell. For this reason, individuals genetically lacking P antigen on erythrocytes are resistant to B19 infection.4 Expression of viral structural proteins results in cytotoxicity and transient erythropoietic maturation arrest. Unnoticed in normal individuals, it may become a crisis in patients with underlying haemolytic disorders or in immunocompromised patients where the virus can not be eliminated.

Due to the widespread presence of the virus worldwide, most cases of aplastic crisis associated with parvovirus B19 have been reported in children and adolescents. Nevertheless, crisis may occur in adults,5 and occasionally in the elderly, as shown in the present case. In our patient, hereditary sphaerocytosis has been diagnosed previously but remained largely asymptomatic until aplastic crisis developed. In contrast, aplastic crisis may be the initial manifestation unmasking the underlying haemolytic disorder.6

Diagnosis of acute parvovirus B19 infection is based on examination of bone marrow smears and virological studies—that is, the detection of IgM and IgG antibodies or transient viraemia. In immunocompetent patients, infection is self limited requiring only supportive therapy and blood transfusion in severe cases, whereas in immuno-compromised individuals, infection may persist; these patients may benefit from administration of immunoglobulins, but relapses may occur necessitating careful monitoring.1

Final diagnosis

Parvovirus B19 associated aplastic crisis in a patient with hereditary sphaerocytosis.

Learning points

  • Parvovirus B19 causes widespread infections, with more than 90% of the elderly being seropositive.

  • Although most infections are asymptomatic, healthy individuals may present with erythema infectiosum or polyarthropathy syndrome, and infection and in pregnant women may result in miscarriage, hydrops fetalis, or congenital anaemia in pregnant women.

  • Due to erythroid tropism, acute parvovirus infection may result in aplastic crisis in patients with haemolytic disorders or chronic bone marrow failure in immunocompromised individuals.

  • Aplastic crisis due to parvovirus B19 infection must be considered in patients with haemolytic disease presenting with severe anaemia, even in the elderly.

  • Infection is self limiting in immunocompetent individuals requiring only supportive therapy, but may persist in immunocompromised individuals.

References

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