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 (PRCA) 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 (concern for fetal anemia, hydrops). There is 30% chance of fetal transmission with acute maternal infection—this may be higher during epidemic outbreaks.

Epidemiology

• Global resurgence noted in aftermath of COVID-19 pandemic
• 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.

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; has predilection for erythroid progenitor cells (temporary impact on erythropoiesis)
• The incubation period is typically 4 to 14 days.
• Prodromal symptoms are usually mild and include low-grade fever, headache, malaise, and myalgia.
• 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.

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 PRCA and chronic anemia.
• As many as 40% of pregnant women are not immune; 1.5% seroconversion rate per year

General Prevention

• Respiratory spread; handwashing, 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 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.
  • 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