Parvovirus B19

Parvovirus B19 infection is common worldwide, and usually results in mild symptoms. Infections usually occur in children in the form of erythema infectiosum or fifth disease, which features a classic "slapped cheek" rash. While most infections are mild, some serious clinical conditions have been linked to the virus. Infection can trigger an acute cessation of RBC production, which may result in a transient aplastic crisis, red blood cell aplasia, hydrops fetalis, or congenital anemia. 

Etiology

  • The parvovirus is a small, single-stranded DNA virus. 
  • The virus targets erythrocyte precursors in bone marrow, the liver, the umbilical cord, and the peripheral blood. 
  • Most symptoms of parvovirus B19 occur because of immune complex formation. 

Epidemiology

  • Parvovirus B19 infections occur worldwide. 
  • Most patients are infected with parvovirus by age 15. 
  • Infection is more common in the late winter and early spring. 
  • The virus is transmitted via respiratory droplets and blood products. It can also be transmitted vertically from mother to fetus. 
  • The incubation period lasts from four to 21 days. 
  • Patients are no longer contagious once the rash appears.  

Clinical Manifestations

  • Most patients with a parvovirus B19 infection are asymptomatic or have mild, non-specific cold symptoms. There are, however, a number of specific clinical conditions that have been linked to the virus:

Fifth Disease, aka Erythema Infectiosum

  • Usually occurs in children ages 4-10.
  • Mild prodrome consists of fever, coryza, headache, and nausea.
  • Rash: 
    -First appears as red, "slapped cheeks" with circumoral pallor. 
    -After 1-4 days, a maculopapular rash develops over the limbs and trunk. The rash may later develop a lacy, reticular pattern. 
    -The rash may vary with exposure to sunlight, exercise and heat. It may disappear and return. 
    -The rash may persist for one to nine weeks. 
    -The rash is usually not pruritic and tends to spare the palms and soles.
  • Patients are no longer contagious once the rash appears. 

Arthropathy 

  • Arthopathy can occur as a part of erythema infectiosum or as the primary presentation of a parvovirus infection. 
  • Eight percent of children with parvovirus have arthralgias, while 60 percent of adults/teens report arthralgias. 
  • Adults tend to have symmetric, polyarticular involvement, usually of the finger joints. The knees, wrists and ankles can also be involved, but this occurs less often. 
  • Children may have symmetric or asymmetric joint involvement, and most often report pain at the knee or ankle. 
  • Arthropathy usually resolves in three weeks, but can persist for much longer (months to years). Persistent joint pain is more common in women. 

Transient Aplastic Crisis

  • Patients with a shortened erythrocyte life span at baseline (those with HIV, iron deficiency anemia, sickle cell disease, thalassemia, or hereditary spherocytosis) are at risk for an aplastic crisis if infected with parvovirus B19. 
  • Parvovirus leads to a transient cessation in erythrocyte production, which may be life-threatening. 
  • The sudden drop in a patient's hemoglobin level may lead to splenic sequestration, CVA, or congestive heart failure. 
  • Patients may require multiple transfusions. 
  • Patients are highly contagious during an aplastic crisis, so it is imperative that they be isolated while in the hospital. 
  • Most patients recover fully in two weeks. 

Chronic Red Blood Cell Aplasia

  • In immunocompromised patients, parvovirus B19 infection may persist. 
  • Rashes and arthropathy do not develop in these patients, because these symptoms are secondary to the development of immune complexes (of which they are deficient). Instead, these patients present with pallor and fatigue.
  • Patients may suffer from profound anemia, which can be chronic and recurrent. Multiple transfusions may be necessary. 
  • Patients with persistent, profound anemia may require treatment with IV immune globulin. 

Gloves and Socks Syndrome

  • Parvovirus B19 has been associated with a papular, purpuric "gloves and socks" rash, which most often occurs in young adults. 
  • The rash is usually symmetric, initially consisting of painful erythema and edema of the hands and feet. Petechiae and purpura develop later, as may vesciles, bullae, and skin sloughing.
  • The rash is classically sharply demarcated at the wrists and ankles, but other body parts can also be involved.
  • Patients may feel well or suffer from non-specific cold symptoms and arthralgias.  
  • Symptoms usually resolve in one to three weeks without scarring. 

Hydrops Fetalis

  • When pregnant women are infected with parvovirus B19, their presentation is the same as a non-pregnant adult. The infection can be transmitted vertically to the fetus, however, which can be much more dangerous. 
    -The estimated risk of vertical transmission is 30 percent.
    -There is a two to six percent risk of fetal loss. 
    -Second trimester pregnancies are at the greatest risk because of the high rate of RBC development in the fetal liver. 
  • Infected fetuses may develop severe anemia, as fetuses already have a shortened RBC lifespan. The virus can also directly infect the heart muscle, leading to myocarditis. Together, the anemia and myocarditis may lead to congestive heart failure and hydrops fetalis. 

Diagnosis 

  • Erythema infectiosum is usually diagnosed clinically. If laboratory confirmation is needed, the following may be used:
    -B-19 specific antibody testing: used in immunocompetent patients
         -IgM antibodies will become elevated and remain detectable for 2-3
         months after an acute infection
         -Serum IgG indicates the presence of prior infection and immunity
    -Viral DNA testing (via PCR assay): used for patients who are not immunocompetent and for those in transient aplastic crisis
    -Peripheral blood smear or bone marrow aspirate may show giant pronormoblasts, but this is non-specific 
  • Pregnancy: If a pregnant woman is exposed to parvovirus B19, she should be tested for acute infection.
    -IgM levels will be elevated during the acute phase, and IgG will mark seroconversion. 

Treatment

  • Most parvovirus B19 infections are mild and self-limited. 
  • In erythema infectiosum, patients may return to school or work once the rash appears. They are no longer contagious at that point. 
  • Arthralgias may be treated with NSAIDs. 
  • Patients in aplastic crisis may require blood transfusions, but most recover fully. 
  • Immunocompromised patients may require treatment with IV immune globulin, especially if they develop a chronic infection. 
  • A vaccine against parvovirus B19 is in development, but is not yet approved for use.
  • Treatment in Pregnancy
    -If an acute infection is confirmed, the woman should be followed with weekly or bi-weekly serial ultrasounds for 12 weeks to monitor for signs of hydrops fetalis. 
    -The risk of developing hydrops virtually disappears 12 weeks after the mother developed symptoms. 
    -If signs of hydrops are detected, then fetal blood sampling and transfusion may be required. 

References

  1. Servey JT, Reamy BV and Hodge J. Clinical presentations of parvovirus B19 infections. American Family Physician. 2007; 75(3). 
  2. Young NS and Brown KE. Mechanisms of Disease: Parvovirus B19.  NEJM. 2004; 350(6). 

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