Fifth disease

Erythema infectiosum (fifth disease) is one of the clinical syndromes caused by human parvovirus B19 infection. The virus is transmitted by respiratory droplets and primarily affects children between the ages of five and fifteen. Erythema infectiosum begins with a mild febrile illness followed two to five days later by a maculopapular rash that is especially noticeable on the cheeks (i.e., "slapped‑cheek" rash) and may be pruritic. Once the rash has appeared, the infected individual is no longer contagious and usually feels well again. Erythema infectiosum is self‑limited, and the rash usually resolves within seven to ten days, but may be recurrent over several weeks. Whereas adult infection is characterized much more by arthritic symptoms and less by a rash, parvovirus B19 infection also manifests with joint symptoms in a minority of children. There is no specific vaccine or treatment for parvovirus B19 infection, though symptomatic treatment for arthralgias or pruritus can be used. Previous parvovirus B19 infection results in lifelong immunity against the virus. Because of its ability to infect erythrocyte progenitor cells, parvovirus B19 can cause transient anemia in infected patients, as well as complications such as a transient aplastic crisis in patients with chronic hemolytic diseases (e.g., sickle cell disease), and chronic pure red cell aplasia in the immunocompromised. Infection with parvovirus B19 (one of the TORCH congenital infections) during pregnancy may also have serious consequences for the fetus.

• Peak incidence: 5–15 years ^[1]
• Prevalence of seropositivity
  • ∼ 10% in preschool children
  • ∼ 70% in adults

Epidemiological data refers to the US, unless otherwise specified.

Pathogen

• Human parvovirus B19 (the smallest of the DNA viruses)
  • Family: Parvoviridae
  • Single‑stranded DNA virus (linear)
  • Nonenveloped
• Humans are the only reservoir for parvovirus B19.

Route of transmission

• Main route: aerosol
• Other routes
  • Hematogenous transmission
  • Transplacental transmission: In seronegative pregnant women, transmission to the unborn fetus may occur (in up to 30% of cases).

References:^[2][3]

• Parvovirus B19 binds to the P antigen (globoside) on erythroid progenitor cells → cellular invasion → viral DNA enters the nucleus of erythroid cells → viral DNA replication → cytotoxicity → clinical manifestations + transient cessation of erythropoiesis ^[4][5][6]
• Parvovirus B19 can also bind to and infect endothelial cells via the P antigen, potentially causing cardiovascular complications. ^[7][8]

Disease course

• Incubation period: 4–14 days
• Infectivity: Only contagious before onset of rash
• Asymptomatic in ∼ 25% of cases

Clinical symptoms

• Mild cold‑like symptoms
• Exanthem: 2–5 days following the onset of cold‑like symptoms
  • Initial diffuse redness of the face with perioral sparing (slapped‑cheek rash)
  • Spread of exanthem to the extremities and trunk
    • Initially confluent and maculopapular; adopts a lace‑like, reticular appearance over time as it clears.
    • Associated with mild pruritus (in ∼ 50% of cases)
    • Fades after ∼ 7–10 days; can be recurrent over several weeks (becoming more pronounced after exposure to sunlight or heat)
  • Third phase with rash that varies with exposure to sun or heat and resolves spontaneously after several weeks.

Parvovirus B19-associated arthritis

• Epidemiology: affects < 10% of children and up to 60% of adults (♀ > ♂) infected with parvovirus B19
• Clinical findings
  • Arthralgia with symmetrical, nondestructive polyarthritis, particularly in small joints (fingers, hand, ankle) and knee
  • Usually resolves after 3–4 weeks
• Complications: In some cases, persistent arthritis may develop (see “Complications” below).

References:^{[9][10][11][12]}

The diagnostic approach for parvovirus B19 infection varies by patient group. However, all groups may be affected by transient normocytic anemia with a low reticulocyte count because of the ability of the virus to infect erythrocyte progenitor cells.

Immunocompetent children

• Erythema infectiosum is typically a clinical diagnosis (i.e., slapped‑cheek or lace‑like appearance of rash) in children.

Immunocompetent adults

• Lab tests only if the diagnosis is unclear
• Antibody testing
  • IgM antibody
    • Appears within ∼ 10 days of initial exposure, indicating acute illness
    • Remains positive for 2–3 months
  • IgG antibody
    • Appears approx. 2 weeks following infection
    • Remains positive for life
• Differentiating between parvovirus B19‑associated arthritis and acute rheumatoid arthritis may require additional tests (see diagnostics section of rheumatoid arthritis)

Patients with transient aplastic crisis and immunocompromised patients

• CBC with reticulocytes
  • ↓ Reticulocytes
  • ↓ Hemoglobin below patient's baseline by ≥ 2 g/dL (aplastic crisis) or (< 8 g/dL) (severe anemia as in pure red cell aplasia)
• Initial diagnostic test: viral DNA testing (nucleic acid amplification testing (NAAT) such as PCR of blood or bone marrow)
• Adjunctive diagnostic test: serologic antibody testing (in immunocompetent adults)

Pregnant women

• See parvovirus B19 infection during pregnancy

References:^[10]

• Other infectious rashes in childhood
• Drug hypersensitivity reaction
• Rheumatoid arthritis

The differential diagnoses listed here are not exhaustive.

• Treatment is not necessary in most cases, as the disease is often self-limited
• Analgesics and nonsteroidal anti‑inflammatory drugs (NSAIDs)
• Short course of low‑dose prednisone for parvovirus B19‑associated arthritis
• For treatment of parvovirus infection in pregnancy, see parvovirus B19 infection during pregnancy.

• Transient aplastic crisis in patients with chronic hemolytic diseases (e.g., sickle cell disease, hereditary spherocytosis, thalassemia, pyruvate kinase deficiency, autoimmune hemolytic anemia)
  • Pathophysiology: parvovirus B19 infection of stem cells
  • Treatment: blood transfusions if anemia is symptomatic
• Chronic pure red cell aplasia in immunocompromised patients
  • Pathophysiology: parvovirus B19 infection of proerythroblasts
  • Treatment: blood transfusions for severe anemia; intravenous immunoglobulin (IVIG) against parvovirus B19
• Hydrops fetalis, fetal death, and miscarriage (parvovirus B19 is a TORCH infection; see parvovirus B19 infection during pregnancy).
• Hepatitis, myocarditis, and aseptic meningitis/encephalitis (rare)

References:^[13]

We list the most important complications. The selection is not exhaustive.