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Parvovirus B19 Infection
David L. Anderson, MD
Thomas P. Garigan, MD, MA
image BASICS
DESCRIPTION
  • Human parvovirus B19 is the primary cause of acute erythema infectiosum (EI, or fifth disease).
  • Complications in susceptible individuals with increased RBC turnover (e.g., sickle cell anemia [SS]) include transient aplastic crisis (TAC). In immunocompromised individuals, pure red cell aplasia (PRCA) and chronic anemia are significant complications. In normal hosts, arthritis and arthralgias are common.
  • System(s) affected: hematologic/lymphatic/immunologic, musculoskeletal, skin/exocrine, possibly central nervous system, cardiac, renal
Pregnancy Considerations
A documented acute infection during pregnancy should prompt referral to a maternal-fetal medicine specialist. Maternal parvovirus B19 infection between 9 and 20 weeks' gestation may carry a significant fetal risk.
EPIDEMIOLOGY
  • Infection is common in childhood.
  • EI has an extremely low mortality rate.
  • Peak age for EI is 4 to 12 years.
  • Males and females are equally affected.
  • Adult females are more likely to develop postinfectious arthritis.
  • No known racial predilection
  • In temperate climates, infections often occur from late winter to early summer.
  • Local outbreaks may occur every 2 to 4 years.
Prevalence
Extremely common in the United States. Based on IgG serology:
  • 1 to 5 years of age: 2-15% seropositive
  • 6 to 15 years of age: 20-40% seropositive
  • 16 to 40 years of age: 50-60% seropositive
  • >40 years of age: 70-85% seropositive
ETIOLOGY AND PATHOPHYSIOLOGY
  • Small (20 to 25 mm), nonenveloped, single-stranded DNA virus in Parvoviridae family
    • Only known parvovirus to infect humans; does not cross-infect dogs or cats
  • Natural host of B19 is human erythroid progenitor.
  • Respiratory, hematogenous, and vertical transmission are sources of human spread.
  • 4- to 14-day incubation. Rash and joint symptoms occur 2 to 3 weeks after initial infection.
  • Most contagious 5 to 10 days after exposure
  • EI rash thought to be autoimmune due to IgM complexes concurrent with viral clearance.
  • Cytotoxic infection of proerythroblasts reduces RBC production.
Genetics
Erythrocyte P antigen-negative individuals are resistant to infection.
RISK FACTORS
  • School-related epidemic and nonimmune household contacts have a secondary attack rate of 20-50%.
  • Highest secondary attack rates are for daycare providers and school personnel in contact with affected children.
  • Those with increased cell turnover (e.g., hemoglobinopathy, SS, thalassemia) are at risk for TAC.
  • Immunodeficiency (e.g., HIV, congenital) increases risk of PRAC and chronic anemia.
  • As many as 40% of pregnant women are not immune. 1.5% seroconversion rate per year
GENERAL PREVENTION
  • Respiratory spread. Standard measures include hand washing and barrier protection.
  • Droplet precautions are recommended around patients with TAC, chronic infection, or anemia.
  • Difficult to eliminate exposure because the period of maximal contagion occurs prior to the onset of clinical symptoms (rash).
  • Pregnant health care workers should avoid caring for patients with TAC.
  • No significant risk of infection based on occupational exposure. Exclusion from the workplace is neither necessary nor recommended.
  • No preventive vaccine is available.
COMMONLY ASSOCIATED CONDITIONS
  • Nondegenerative arthritis
    • In adults, 80% of patients may manifest polyarthritis and/or arthralgia (female > male).
    • In children, joint symptoms are less common.
    • Knees, hands, wrists, and ankles (frequently symmetric) are most commonly involved.
    • Joint symptoms usually subside within 3 weeks but may persist for months. Routine radiography is not necessary.
  • TAC
    • Involves patients with increased RBC turnover (SS, spherocytosis, thalassemia) or decreased RBC production (iron deficiency anemia).
    • Patients present with fatigue, weakness, lethargy, and pallor (anemia).
    • Aplastic event may be life-threatening but is typically self-limited. Reticulocytes typically reappear in 7 to 10 days and full recovery in 2 to 3 weeks.
    • In children with sickle cell hemoglobinopathies and heredity spherocytosis, fever is the most common symptom (73%). Rash is uncommon in these patients.
  • Chronic anemia
    • Seen in immunocompromised individuals (HIV, cancer, transplant) with poor IgM response
    • Usually no clinical manifestations (fever, rash, or joint symptoms)
  • Fetal/neonatal infection (1)
    • Risk of transplacental spread of virus is ˜33% in infected mothers.
    • Test pregnant women with a rash or arthralgias consistent with parvovirus B19.
    • Clinical manifestations vary. Many patients are seroconvert without symptoms and have a normal pregnancy. Other patients develop variable degrees of fetal hydrops. 2nd- and 3rd-trimester pregnancy loss can occur without hydrops.
    • Suspect B19 infection in cases of nonimmune fetal hydrops.
    • Fetal bone marrow is primarily impacted. RBC survival is shortened, resulting in anemia and (potentially) high-output cardiac failure.
    • >95% of fetal complications (fetal hydrops and death) occur within 12 weeks of acute maternal parvovirus B19 infection.
    • Risk of fetal loss is highest (2-5%) in the 1st trimester.
    • Infants requiring intrauterine transfusions due to parvovirus B19 infection are at risk for long-term neurodevelopmental impairment.
  • Papular purpuric gloves and socks syndrome (PPGSS) is an uncommon dermatosis associated with parvovirus B19 infection. It results in a petechial and ecchymotic rash of the hands and feet associated with febrile tonsillopharyngitis and oral ulcerations (2).
image DIAGNOSIS
PHYSICAL EXAM
  • “Slapped cheek” appearance is a well-known facial rash that spares the nasolabial folds.
  • A lacy, reticular rash on the trunk, buttocks, and limbs often follows 1 to 4 days later lasting 1 to 6 weeks.
  • The rash may be pruritic and recurrent, exacerbated by bathing, exercise, sun exposure, heat, or emotional stress.
  • B19 may manifest as painful pruritic papules and purpura on the hands and feet.
DIFFERENTIAL DIAGNOSIS
  • Rubella
  • Enteroviral disease
  • Systemic lupus erythematosus
  • Drug reaction
  • Lyme disease
  • Rheumatoid arthritis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • No need for routine lab studies in typical cases. Diagnosis is clinical; illness is mild and self-limiting.
  • IgG and IgM serology in immunocompetent patients
  • B19-specific DNA polymerase chain reaction (PCR) testing for fetal infection (via cord blood or amniotic fluid) as well as for patients with chronic infection or those who are immunocompromised
  • P.769

  • PCR increases diagnostic sensitivity and specificity to confirm infections in IgM-negative patients.
  • For patients with TAC, CBC with reticulocyte count shows anemia and reticulocytopenia. IgM antibodies are present by day 3, and IgG antibodies are detectable at time of clinical recovery. PCR shows high levels of viremia.
  • Pregnant women exposed to B19 require serial IgG and IgM serology to assess fetal risk.
Follow-Up Tests & Special Considerations
Fetal/neonatal infection (3)[C]
  • To exclude congenital B19 in infants with negative B19 IgM, follow IgG serology over the 1st year of life.
  • Maternal serum &agr;-fetoprotein may be increased with hydrops fetalis.
  • Documented acute maternal infection in the 1st trimester warrants serial fetal ultrasound to assess for hydrops: ascites, pericardial effusion, oligohydramnios, cardiomegaly, and placental thickening.
  • Weekly peak systolic velocity measurements of the middle cerebral artery by Doppler US is recommended to evaluate for heart failure fetal anemia and the potential need for intrauterine transfusion (>1.5 MoM).
  • Cerebral MRI to explore CNS damage in infected neonates with prolonged hydrops fetalis or hematocrit <15%.
Diagnostic Procedures/Other
  • Skin biopsy is usually normal but may show mild inflammation consisting of perivascular infiltrations of mononuclear cells.
  • In stillbirths related to maternal B19 infection, virus can be detected in all tissues.
  • In hydrops fetalis, nucleated RBCs may have intranuclear inclusion bodies.
image TREATMENT
GENERAL MEASURES
  • No therapy is usually needed (4)[C].
  • Cessation of immunosuppressive therapy allows some patients to clear chronic infections.
  • B19-associated anemia in HIV-positive patients may resolve with highly active antiretroviral therapy.
MEDICATION
First Line
  • Anti-inflammatory agents for arthritic symptoms
  • Antipyretics for fever. Avoid aspirin in children.
Second Line
  • RBC transfusions for aplastic crisis
  • Intravenous immunoglobulin (IVIG) for B19-related refractory anemia or PRAC, especially in immunodeficient states (5)[C]
  • Intrauterine RBC transfusions reduce mortality in cases of fetal hydrops.
ISSUES FOR REFERRAL
  • Acute infection during pregnancy should prompt referral to a maternal-fetal medicine specialist.
  • TAC patients require treatment by a hematologist.
  • Patients with chronic or abnormal B19 infections may benefit from consultation with immunology or infectious disease specialists.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Outpatient management is typical for EI.
  • Inpatient management for aplastic crisis, which may require RBC transfusions
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Periodic blood counts for anemic patients
PATIENT EDUCATION
  • Parvovirus B19 (fifth disease): http://www.cdc.gov/parvovirusB19/fifth-disease.html
  • Parvovirus B19: What You Should Know: http://www.aafp.org/afp/2007/0201/p377.html
  • Parvovirus B19 infection and pregnancy: http://www.cdc.gov/parvovirusB19/pregnancy.html
  • March of Dimes Fifth Disease and Pregnancy: http://www.marchofdimes.org/complications/fifth-disease-and-pregnancy.aspx
  • Counsel pregnant women regarding prevention of maternal B19 infection.
  • Pregnant women should avoid exposure to patients with active/chronic infections. Exclusion of pregnant women from the workplace where EI is occurring is not recommended because they have likely been exposed.
  • Children with typical rash are no longer infectious and may attend childcare or school.
PROGNOSIS
  • Usually self-limited
  • Joint symptoms subside in weeks (often by 2 weeks but may last months).
  • ˜20% of infections result in delayed virus elimination and viremia persisting for several months to years.
  • Full recovery from aplastic crisis in 2 to 3 weeks
REFERENCES
1. de Jong EP, de Haan TR, Kroes AC, et al. Parvovirus B19 infection in pregnancy. J Clin Virol. 2006;36(1):1-7.
2. Santonja C, Nieto-González G, Santos-Briz Á, et al. Immunohistochemical detection of parvovirus B19 in “gloves and socks” papular purpuric syndrome: direct evidence for viral endothelial involvement. Report of three cases and review of literature. Am J Dermatopathol. 2011;33(8):790-795.
3. de Jong EP, Walther FJ, Kroes AC, et al. Parvovirus B19 infection in pregnancy: new insights and management. Prenat Diagn. 2011;31(5):419-425.
4. Servey JT, Reamy BV, Hodge J. Clinical presentations of parvovirus B19 infection. Am Fam Physician. 2007;75(3):373-376.
5. Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006;117(4 Suppl):S525-S553.
Additional Reading
&NA;
  • Azevedo KM, Setúbal S, Camacho LA, et al. Parvovirus B19 seroconversion in a cohort of human immunodeficiency virus-infected patients. Mem Inst Oswaldo Cruz. 2012;107(3):356-361.
  • Beigi RH, Wiesenfeld HC, Landers DV, et al. High rate of severe fetal outcomes associated with maternal parvovirus B19 infection in pregnancy. Infect Dis Obstet Gynecol. 2008;2008:524601.
  • Centers for Disease Control and Prevention. Risk associated with human parvovirus B19 infection. MMWR Morb Mortal Wkly Rep. 1989;38(6):81-88, 93-97.
  • De Jong EP, Lindenburg IT, van Klink JM, et al. Intrauterine transfusion for parvovirus B19 infection: long-term neurodevelopmental outcome. Am J Obstet Gynecol. 2012;206(3):204.e1-204.e5.
  • Heegaard ED, Brown KE. Human parvovirus B19. Clin Microbiol Rev. 2002;15(3):485-505.
  • Lamont RF, Sobel JD, Vaisbuch E, et al. Parvovirus B19 infection in human pregnancy. BJOG. 2011;118(2):175-186.
  • Snyder M, Wallace R. Clinical inquiry: what should you tell pregnant women about exposure to parvovirus? J Fam Pract. 2011;60(12):765-766.
  • Young NS, Brown KE. Parvovirus B19. N Engl J Med. 2004;350(6):586-597.
Codes
&NA;
ICD10
  • B34.3 Parvovirus infection, unspecified
  • B08.3 Erythema infectiosum [fifth disease]
Clinical Pearls
&NA;
  • Parvovirus B19 infection is usually a benign, self-limited illness with no long-term effects.
  • The rash of EI, a “slapped cheek” appearance, signifies that the patient is no longer infectious.
  • Patients with increased RBC turnover (SS, thalassemia) are at risk for TAC.
  • Immunocompromised patients may be at risk for chronic anemia.
  • Documentation of acute infection in pregnant women under 20 weeks' gestation merits maternal-fetal consultation.