Description

• Human parvovirus B19 is the cause of erythema infectiosum (fifth disease, morbus quintus).
• Individuals with increased red blood cell (RBC) turnover (sickle-cell anemia, spherocytosis, thalassemia) are more susceptible to transient aplastic crisis (TAC). In immunocompromised individuals, pure red cell aplasia may lead to transfusion-dependent anemia. In immunocompetent individuals, arthritis and arthralgias are common complications of parvovirus B19 infection.
• Systems affected: hematologic/lymphatic/immunologic, musculoskeletal, skin/exocrine, central nervous system, cardiac, renal, hepatobiliary

Pregnancy Considerations
Documented acute infection during pregnancy should prompt referral to maternal-fetal medicine specialist. There is a 30% chance of fetal transmission with acute maternal infection—this may be higher during epidemic outbreaks. 30–40% of pregnant women do not have antibodies to parvovirus B19 and thus are considered susceptible to infection (1).

Epidemiology

• Common in childhood; may be asymptomatic
• Erythema infectiosum has an extremely low mortality rate.
• Peak age for erythema infectiosum is 4 to 12 years.
• Males and females are equally affected.
• Women 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 5 years.
• Parvovirus B19 DNA has been isolated from human remains over 6,900 years old.

Prevalence
Based on serologic studies, infection with parvovirus B19 is extremely common throughout the world. By age 5 years, 2–15% of individuals in the United States and Western Europe are IgG positive. This steadily increases to 70–85% seropositivity by >40 years of age.

Etiology and Pathophysiology

• First described in 1974, parvovirus B19 is a small (20 to 25 nm) nonenveloped, single-stranded DNA virus in the Erythrovirus genus of the Parvoviridae family
• Parvovirus B19 spreads primarily through respiratory droplets.
• Children 4 to 10 years of age are most often affected.
• The incubation period is typically 4 to 14 days.
• Prodromal symptoms are usually mild and include low-grade fever, headache, malaise, and myalgia. The characteristic rash usually presents in several stages. The first stage is the characteristic “slapped cheek.” During the second stage, the rash spreads to the trunk and extremities in a diffuse, macular, erythematous pattern sparing the palms and soles. Central clearing leads to a commonly seen lacy/reticulated appearance. Within 3 weeks, the rash typically resolves.
• Rash and joint symptoms usually occur 2 to 3 weeks after initial infection. These are thought to be due to immune complex formation and are associated with viral clearance (and decreased risk of transmission).
• Patients infected with parvovirus B19 are most contagious 5 to 10 days after exposure, well before the rash typically manifests.
• Cytotoxic infection of erythroid progenitor cells decreases RBC production, which can lead to TAC in patients with increased RBC turnover.

Genetics
Erythrocyte P antigen–negative individuals (approximately 1 in 200,000 people) 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.
• Conditions with increased RBC turnover (spherocytosis, sickle-cell anemia, thalassemia) increase the risk of TAC.
• Immunodeficiency (congenital, due to HIV or malignancy) increases risk of pure red cell aplasia and chronic anemia.
• As many as 40% of pregnant women are not immune; 1.5% seroconversion rate per year

General Prevention

• Respiratory spread; hand washing, cough/sneeze hygiene, and barrier precautions
• Droplet precautions are recommended around patients with TAC and in immunocompromised patients.
• Difficult to eliminate exposure because the period of maximal contagion occurs prior to the onset of the typical rash
• No significant risk of infection based on occupational exposure if proper isolation precautions are followed; exclusion from the workplace is neither necessary nor recommended.
• No preventive vaccine is currently available.

Commonly Associated Conditions

• Nondegenerative arthritis
  • In children, joint symptoms are uncommon and typically involve the knees and ankles (symmetric or asymmetric joint involvement).
  • In adults, joint symptoms are much more common, usually symmetric, involving the hands, with less frequent involvement of larger joints. Women are affected with joint symptoms more often than men.
  • Joint symptoms generally resolve within 3 weeks but may persist for months or years. Longer duration symptoms are more common in women. Routine radiography is not necessary.
• TAC
  • Involves patients with increased RBC turnover (sickle-cell disease, spherocytosis, thalassemia) or decreased RBC production (iron deficiency anemia)
  • Presents with fatigue, weakness, lethargy, and pallor (symptoms of anemia); may have dyspnea/shortness of breath
  • Aplastic event may be life-threatening but is typically self-limited. Reticulocytes typically reappear in 7 to 10 days with full recovery in 2 to 3 weeks.
  • In children with sickle cell hemoglobinopathies and hereditary 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 antibody response
  • Usually no clinical manifestations (fever, rash, or joint symptoms)
  • Patients may be transfusion-dependent.
• Fetal/neonatal infection (1)
  • Risk of transplacental spread of virus is ~30% in infected mothers.
  • Up to 50% of infected pregnant women may be asymptomatic, but vertical transmission can still occur.
  • Check IgM and IgG levels in pregnant women with symptoms consistent with parvovirus B19 infection.
  • Test pregnant women with known exposure to individuals with acute parvovirus B19.
    • If IgG positive and IgM negative, consider immune, and no further intervention is needed.
    • If IgM and IgG negative, repeat serologic testing in several weeks to look for seroconversion.
    • If IgM positive, test further to determine if acute infection is present (false-positive result).
  • Overall fetal death may occur in 5–10% of fetal infections and can occur with or without fetal hydrops.
  • Fetal bone marrow is primarily impacted. RBC survival is shortened resulting in anemia and (potentially) high-output cardiac failure. Other complications can result from fetal hypoalbuminemia, myocarditis, hepatitis, and placentitis.
  • The risk of fetal loss is highest in 1st trimester (19%).
  • Intrauterine fetal RBC transfusion can decrease fetal loss rate if fetal hydrops is present.
  • Infants who have undergone intrauterine transfusions are at risk for delays in psychomotor development.
• Parvovirus has also been associated with a gloves and socks syndrome (2).
  • Typically in younger adults, there is symmetric painful erythema and edema of feet and hands.
  • Gradually progresses to petechiae/purpura/vesicles/bullae and then skin sloughing
  • May have no other symptoms but can have fevers or arthralgias
  • Generally resolves in 1 to 3 weeks without scarring