Index
In a normal host, infection with this virus may be asymptomatic or cause infectious erythema or arthropathy.
Infections caused by human parvovirus B19 can give rise to a wide spectrum of manifestations, which are generally influenced by the immunological and hematological status of the patient.
Patients with underlying hematologic and immune disorders who become infected with this virus are at risk for aplastic anemia.
Hydrops fetalis and fetal death are complications of intrauterine parvovirus B19 infection.
Parvovirus B19 was discovered fortuitously in 1975 by Cossart and his colleagues, who unexpectedly found viral particles in the sera of asymptomatic patients screened for hepatitis B infection.
Subsequently, biochemical and molecular characteristics demonstrated that these particles were parvovirus, and since specimen 19 in panel B contained the unexpected virus, parvovirus B19 was so designated.
The development of a specific serological test for parvovirus B19 led to the first report of symptomatic infection in humans. This report, published in 1980, described two soldiers who had a brief feverish illness.
Subsequently, concurrent reports of parvovirus B19 as the etiologic agent of transient aplastic crisis among patients with sickle cell anemia and erythema infectiosum among schoolchildren established the association between parvovirus infection and these two disorders.
Epidemiological and serological data have not only confirmed the role of parvovirus B19 in infectious erythema and transient aplastic crisis, but have also established the importance of this virus as a cause of asymptomatic infection, chronic anemia in the immunocompromised host, acute arthritis and chronic and hydrops fetalis .
Although recent reports have implicated parvovirus B19 as a factor in the pathogenesis of vasculitis and neurological disease, the exact role of this virus in these entities awaits further elucidation.
Pathogenesis
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.
Experimental studies in which healthy adult volunteers were inoculated intranasally with the virus have contributed significantly to our understanding of the pathogenesis and clinical characteristics of the infection.
Viremia occurs during the first week of infection, accompanied by constitutional symptoms of fever and malaise, and by depletion of erythroid progenitor cells in the bone marrow.
At the peak of viremia, there is a precipitous drop in the reticulocyte count and is followed by anemia, which is rarely clinically evident in healthy patients, but can cause severe anemia if the red blood cell count is already low.
Reduction in reticulocyte count is occasionally accompanied by leukopenia and thrombocytopenia.
The appearance of specific IgM antibodies to parvovirus B19 in the serum in the second week after inoculation corresponds to the elimination of viremia. In the third week after inoculation, specific IgG antibodies appear in the serum and a rash of infectious erythema and arthropathy develops.
Because the appearance of the rash corresponds to the development of IgG antibodies and occurs after the viremia has disappeared, the erythema infectious rash indicates that the virus can no longer be transmitted.
epidemiology
Seroepidemiological studies from several countries show that parvovirus B19 infection is common.
Approximately 50 percent of children have detectable parvovirus B19-specific IgG antibodies by the age of 15 years, and 50 to 80% of adults are seropositive. Women of childbearing age have an annual seroconversion rate of 1.5%.
The infection appears to be most common in late winter and spring. Because parvovirus DNA has been found in respiratory secretions at the time of viremia, respiratory spread appears to be the most common route of transmission.
The virus appears to spread easily with close contact; the transmission rate with contact at home approaches 50%, while the transmission rate after exposure to school and daycare has been reported to be 10-60%.
Because the virus is present in high titers in serum and is resistant to conventional heat treatments, transmission of blood products has occurred. Nosocomial transmission of the virus has also been documented.
Clinical manifestations
Asymptomatic infection
Most people with parvovirus B19 infection remain asymptomatic.
Most people who are seropositive for the virus do not remember the above symptoms. In one study, 32% of household contacts of patients with acute parvovirus B19 infection reported no symptoms at the time they had parvovirus-specific IgM antibodies.
Infectious erythema
Fifth disease, also known as fifth disease and “slapped cheek” disease, most commonly affects children between the ages of four and ten and is the most recognizable disease associated with parvovirus B19 infection.
Although the clinical features of fifth disease have been recognized for nearly two centuries, it was not until the early 1980s that the link between this rash and parvovirus B19 was established. It is now known that parvovirus B19 is the sole etiologic agent of fifth disease.
The classic course of infectious erythema can be divided into three distinct stages. The first stage, which occurs after an incubation period of four to 14 days, consists of a mild prodromal illness characterized by low-grade fever, headache, and gastrointestinal symptoms.
This stage, which is often not recognized, corresponds to the period of viremia and the period of contagion.
Classic course of parvovirus B19 infection and infectious erythema:
Stage 1:
- Period of transferability.
- Mild prodromal disease.
- Viremia.
- Erythroid progenitor cell depletion.
- Development of specific IgM antibodies for parvovirus B19.
Stage 2:
- Facial rash or “slapped cheek” appearance.
- Clearance of viremia.
- Development of specific IgG antibodies for parvovirus B19.
Stage 3:
- Erythematous maculopapular rash on the trunk and extremities.
- Evanescent course of rash for 1 to 3 weeks.
- Arthropathy.
The second stage of the disease, which occurs 3 to 7 days after prodrome, is characterized by the appearance of a bright erythematous facial rash.
Because this rash most often involves the malar eminences and preserves the nasal bridge and perioral areas, the characteristic “slapped cheek” appearance becomes apparent.
This stage is seen more commonly in children than adults, and the rash may become more marked with exposure to sunlight.
The third stage of the disease occurs 1 to 4 days after the appearance of the facial rash and is characterized by the appearance of a lacy, erythematous, and maculopapular rash on the trunk and extremities.
This rash may be itchy and is often evanescent, recurring for one to three weeks. Because the appearance of the rash is matched by the development of antibodies, patients with the fifth disease rash are no longer contagious.
Although it is useful to classify the stages of fifth disease, the different characteristics can be variable. For example, the facial rash may be pronounced in some patients but not in others. Similarly, the third stage of the disease can range from a very faint erythema to a flowery confluent rash.
Arthropathy
It has become increasingly clear in recent years that parvovirus B19 causes arthritis and arthralgia in adults and children. Although parvovirus infections in adults are usually asymptomatic, it is estimated that 60% of women with symptomatic disease manifest arthropathy. Men seem to be affected much less frequently.
The most common presentation of parvovirus-related arthropathy in adults is the acute onset of arthralgia or frank arthritis affecting the hands, knees, wrists, and ankles.
Symptoms generally subside within one to three weeks, although about 20% of affected women have persistent or recurrent arthropathy for months and years.
Concurrent constitutional symptoms, such as fever, are rare, but half of patients have an associated generalized skin rash, and about 15% have the typical facial rash.
The incidence of parvovirus-related arthropathy is lower in boys than in adults, and girls have more symptoms than boys of having joint symptoms.
Reports from a series of 22 children presenting to a pediatric rheumatology clinic with serological or clinical evidence of an acute parvovirus B19 infection have shed light on the clinical features of arthropathy in children.
Unlike adults, arthropathy in children most often affects large joints, such as the knees, ankles, and wrists, primarily in an asymmetrical pattern.
In the series of 22 children, half of the children had concurrent constitutional symptoms but, surprisingly, only a third had a concurrent rash.
Although joint symptoms resolved quickly in most of the children, eight of the 22 children had prolonged symptoms, and their disease would have met the criteria for juvenile rheumatoid arthritis had the diagnosis of parvovirus infection not been made.
Aplasia eritrocitas
Because parvovirus B19 infects erythroid progenitor cells in the bone marrow and causes a temporary cessation of red blood cell production, patients who have underlying hematologic abnormalities (and thus depend on an elevated rate of erythropoiesis) are prone to cessation of red blood cell production if they become infected.
This can lead to a transient aplastic crisis, which can occur in people with chronic hemolytic anemia and bone marrow stress conditions. Therefore, patients with sickle cell anemia, thalassemia, acute bleeding, and iron deficiency anemia are at risk.
Typically, these patients have a viral prodrome followed by anemia, often with hemoglobin concentrations falling below 5.0 g per dL (50 g per L) and reticulocytosis. Although recovery is usually spontaneous and there is no recurrence, serious illness with heart failure and death is possible.
Therefore, these patients are best monitored, usually in the hospital, for signs of congestive heart failure. Life-saving red blood cell transfusions may be required.
These patients are contagious during acute illness and therefore must be kept in respiratory isolation to avoid nosocomial transmission.
Chronic parvovirus B19 infection of the bone marrow has been described in immunocompromised hosts.
Children and adults with hematologic and solid organ malignancies, transplant recipients, and patients with human immunodeficiency virus infection are at particular risk for chronic bone marrow infection.
This can lead to severe, prolonged, or recurrent anemia, which may require red blood cell transfusions. Administration of intravenous immunoglobulin may also be beneficial. However, its efficacy has not been demonstrated in well-controlled trials.
Intrauterine infections
The probability of a healthy outcome is very high after parvovirus B19 infection in pregnancy. However, parvovirus infection can lead to fetal infection, which can result in miscarriage or non-immune hydrops fetalis.
Because most pregnant women who become infected with this virus are asymptomatic, it has been difficult to determine the risk of fetal infection, fetal loss, and non-immune dropsy. Estimates of fetal loss associated with parvovirus B19 range from 2% to 10%.
The overall risk of fetal loss as a result of parvovirus infection must take into account the mother’s susceptibility to infection and the likelihood of infection during pregnancy.
About 50% of women are seropositive for the virus before pregnancy, and the chance of infection ranges from 30 to 50% after close exposure. The overall risk of fetal loss associated with parvovirus B19 is estimated to be 1% to 2%.
Hydrops fetalis, manifested at birth by severe anemia, high output heart failure, and extramedullary hematopoiesis, is a possible consequence of congenital infection.
Parvovirus B19 has been shown to cause a congenital infection syndrome, manifested by rash, anemia, hepatomegaly, and cardiomegaly.
Diagnosis
The diagnosis of fifth disease is made clinically and laboratory studies are not required under normal circumstances.
In general, serologic tests are used to diagnose parvovirus B19 infection in patients with transient aplastic crises or arthropathy; a positive parvovirus B19 specific IgM antibody or a significant increase in the parvovirus B19 specific IgG titer is indicative of an acute or recent infection.
The finding of pronormoblasts on examination of the bone marrow of patients with anemia suggests infection with parvovirus B19. Because immunocompromised patients may not be able to develop an immune response, serological tests in these patients may not be reliable.
In such situations, isolation of viral DNA from blood or bone marrow by dot blot isolation or polymerase chain reaction may be helpful.
Treatment
Treatment of parvovirus infections should take into account the severity of the infection and the patient’s condition. Because infection in healthy children and adults is self-limited, no specific therapy is warranted.
Patients with arthropathy can be treated with non-steroidal anti-inflammatory drugs for symptomatic relief.
Patients with transient aplastic crisis may require blood transfusions to prevent congestive heart failure. Intravenous immunoglobulin has been used to treat immunocompromised patients who develop chronic anemia from parvovirus B19 infection.
Finally, intrauterine fetal blood transfusions have been attempted in cases of severe hydrops fetalis related to parvovirus B19.
Infection prevention and control
Children with fifth disease are not contagious and can attend school and daycare. In-hospital isolation measures are not necessary if admission is required for another disorder.
Hospitalized patients with transient aplastic crises of parvovirus B19 superimposed on chronic anemia should be kept in droplet isolation to avoid nosocomial spread and minimize exposure of healthcare workers.
Pregnant women who are exposed to children at home or in the workplace should be counseled about the risks of parvovirus B19 infection.
Given the high prevalence of parvovirus B19 in the community, the high rate of silent infection, and the low risk of adverse effects on the fetus, the systematic exclusion of pregnant women from the workplace where infectious erythema is present is not recommended.
Pregnant healthcare workers should be informed about preventive measures they can take to reduce the risk of transmission, such as failing to care for immunocompromised patients with acute or chronic parvovirus infection.
Serological tests may be offered, if available, to determine susceptibility in women at increased risk of exposure to parvovirus B19.
