Human parvovirus B19 is a single-stranded DNA virus with a predilection for infecting rapidly dividing cell lines, such as bone marrow erythroid progenitor cells. People with defective cell-mediated immunity (eg, severe combined immunodeficiency syndrome; acquired immunodeficiency syndrome; and patients receiving immunosuppressive therapy, ie, post organ transplant) can develop pure red cell aplasia, in which suppression of erythroid precursors is permanent. Identification of parvovirus inclusions in marrow biopsies and subsequent confirmation of infection by in situ hybridization is important in the assessment of anemia in immunodeficient patients. Our objective is to provide a general overview of the parvovirus B19 infection and its characteristics in immunocompromised patients and to summarize updated information regarding the clinicopathologic features, pathobiology, and laboratory diagnosis of this subject. The pathologist should be aware of the wide spectrum of manifestations of parvovirus B19 infection depending on the patient’s hematologic and immunologic status.

Human parvovirus B19 (PV-B19) was discovered in the United Kingdom in 1975 by Cossart et al1 and has been associated with a variety of clinical manifestations, including rash, thrombocytopenia, leukopenia, fetal wastage, hypocomplementemia, autoimmune hemolytic anemia, arthritis, and vasculitis.2,3

Parvovirus B19 infection is found worldwide in persons of all ages. Most people become infected at some time during their life, up to 15% of individuals developing infection between 1 and 5 years of age, 15% to 60% between the ages of 5 and 19 years, and 30% to 60% in adulthood.4 Around 80% of the population is immune to the virus by the age of 50 years. PV-B19 acute infection occurs mainly in school-aged children and teenagers.5

Parvovirus B19 infection can be asymptomatic or can cause a broad range of diseases, including (1) diseases found among normal, nonimmunocompromised hosts (erythema infectiosum, arthropathy, hydrops fetalis); (2) hematologic diseases in immunocompromised hosts (aplastic crisis, chronic anemia, idiopathic thrombocytopenic purpura, transient erythroblastopenia of childhood, Blackfan-Diamond anemia); and (3) a heterogeneous group of diseases in which the etiologic role of PV-B19 is less clear and sometimes putative (neurologic disease, rheumatologic disease, and vasculitic and myocarditic syndromes). Less common clinical associations of PV-B19 virus infection include various skin eruptions, hematologic disorders such as neutropenia, hepatobiliary disease, neurologic disease, and rheumatic disease, including chronic fatigue syndrome.6

Symptomatic adult PV-B19 infection typically causes a brief arthritis, often with a rash. Persistent symptoms may occur, and PV-B19 has been linked with many rheumatic diseases.7 PV-B19 infection should be considered in the differential diagnosis of ill children with myocarditis and multiple organ system dysfunction.

Conditions shown to predispose to PV-B19-induced chronic anemia include Nezelof syndrome (an extremely rare immune deficiency disorder characterized by the impairment of cellular immunity against infections), acute lymphatic leukemia, acute myeloid leukemia, chronic myeloid leukemia, Burkitt lymphoma, lymphoblastic lymphoma, myelodysplastic syndrome, astrocytoma, Wilms tumor, human immunodeficiency virus (HIV) infected patients, severe combined immunodeficiency, bone marrow (BM) transplantation, organ transplantation, systemic lupus erythematosus, immunoglobulin isotype switching defects, patients receiving cancer chemotherapy, and patients with defect immunoglobulin specificity and neutralization.8

Human PV-B19 frequently causes transient red cell aplasia in children with sickle cell disease. Although the outcome of some transient red cell aplasia episodes in children with sickle cell disease is benign, many are treated with red cell transfusions to reduce the risk of circulatory collapse from severe anemia.9

PATHOGENESIS

Human PV-B19 is a small single-stranded DNA virus classified as a member of precursors. It is the only parvovirus that has been clearly linked with disease in humans. PV-B19 virus replicates only in human cells and belongs to the family Parvoviridae, genus Erythrovirus, whose tropism is primarily for erythroid autonomous, that is, not requiring the presence of a helper virus. Specific antiviral antibody production is thought to represent the major defense against PV-B19 virus, as human normal immunoglobulin frequently clears the virus from peripheral blood and results in clinical improvement in immunosuppressed persons.6

The virus replicates in human erythroid progenitor cells of the BM and blood, inhibiting erythropoiesis. Tropism of productive PV-B19 infection is mainly due to the restrictive cellular distribution of the P blood group antigen globoside (Gb4), which is found most commonly on cells of the erythroid lineage but also on platelets; on tissues from the heart, liver, lung, kidney, and endothelium; and on synovium. Individuals who lack erythrocyte P antigens are very rare (1 in 200 000) and apparently cannot be infected by PV-B19.10