Parvovirus B19 infections

Parvovirus B19 is transmitted through respiratory droplets and has a wide range of clinical presentations. Infections occur most frequently in children, with peak incidence between 5 and 15 years of age (infection provides lifelong immunity). While most infections are asymptomatic, erythema infectiosum (fifth disease) is the most common clinical manifestation in symptomatic children. Erythema infectiosum begins with a mild febrile illness followed 7–10 days later by a rash with macules and papules that is especially noticeable on the cheeks (slapped‑cheek rash) and trunk and spreads to the extremities. The rash may be pruritic. Once the rash has appeared, the infection is no longer contagious and the patient usually feels well again, although the rash may persist for weeks, especially with heat and exposure to sunlight. In adults, the rash is typically absent and patients may develop acute-onset polyarthralgia (parvovirus B19-associated arthritis). Individuals who are immunocompromised and/or have preexisting hematological disease may develop severe anemia or pancytopenia because the virus affects the bone marrow. Diagnosis of erythema infectiosum is usually clinical; confirmatory studies are recommended for atypical presentations, pregnant patients (because of the risk of congenital TORCH infection), and immunocompromised individuals. Management is supportive.

• 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).

Incubation period ^[2]

• Average: 4–14 days
• May be up to 21 days

References:^[3][4]

• 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 ^[5][6]
• Parvovirus B19 can also bind to and infect endothelial cells via the P antigen, potentially causing cardiovascular complications. ^[7][8]

Individuals with parvovirus B19 infection may be asymptomatic or have any of the following presentations (see “Subtypes and variants” for additional details). ^[2][9]

• Mild respiratory symptoms
• Rash
  • Erythema infectiosum (fifth disease)
  • Papular-purpuric gloves-and-socks syndrome
    • Painful, pruritic, papular, petechial, and/or purpuric rash affecting the hands and feet
    • Fever and oral lesions may be present.
• Parvovirus B19-associated arthritis
• Severe anemia or transient aplastic crisis
• Hydrops fetalis
  • Parvovirus B19 is a TORCH infection that can cause fetal death and miscarriage.
  • See also “Congenital parvovirus B19 infection.”

Children with parvovirus B19 infection often present with an exanthem, while adults are more likely to present with arthritis. ^[2][10]

General principles ^[11][12]

• Erythema infectiosum and parvovirus B19-associated arthritis are diagnosed clinically.
• Confirmatory studies for parvovirus B19 are recommended in: ^[9]
  • Diagnostic uncertainty
  • Immunocompromised individuals
• Additional testing may be indicated for:
  • Suspected anemia or aplastic crisis (e.g., in immunocompromised individuals)
  • Exclusion of alternative diagnoses (e.g., rheumatologic disease in patients with arthritis)
  • See “Subtypes and variants” for details.

Congenital infection with parvovirus B19 can cause severe complications; for more information on diagnosis during pregnancy, see “Parvovirus B19 infection during pregnancy.”

Confirmatory studies for parvovirus B19

• Immunocompetent individuals: IgM and IgG antibodies ^[2]
  • IgM: usually detectable when the rash appears; remains positive for 2–3 months
  • IgG: positive after approx. 2 days; remains positive for life
• Immunocompromised individuals: NAAT ^[2]

Immunocompromised patients may have falsely negative serum IgM and IgG. ^[2]

Erythema infectiosum (fifth disease) ^[2]

• Clinical features
  • Prodromal stage: systemic symptoms occurring 7–10 days before rash ^[2]
    • Fever (often mild)
    • Myalgia and/or arthralgias
    • Malaise
    • Headache
  • Exanthem stage: characteristic rash
    • Slapped-cheek appearance; diffuse redness of the face with perioral sparing
    • Reticular rash originating on the trunk and spreading to the extremities
    • Often pruritic
    • May recur with environmental changes (e.g., sunlight, heat exposure) over several weeks or months
• Diagnosis: clinical diagnosis
• Differential diagnoses
  • Other infectious rashes in childhood
  • Drug hypersensitivity reaction
• Management
  • Management is supportive.
  • See “Management of parvovirus B19 infection” for details.

Parvovirus B19-associated arthritis ^[2][10]

• Clinical features
  • Adults ^[10]
    • Acute-onset arthralgia with symmetrical, nondestructive polyarthritis, particularly in small joints (fingers, hands), ankles, and knees
    • Affects ♀ > ♂ ^[2]
    • Rash: absent or atypical
    • May be accompanied by systemic symptoms (e.g., fever, malaise)
    • Usually resolves within 2 weeks; may last months or years ^[10]
  • Children (uncommon): most commonly affects the knees
• Diagnosis
  • Clinical diagnosis
  • In patients with diagnostic uncertainty:
    • Obtain confirmatory testing for parvovirus B19 infection.
    • Consider additional studies to exclude alternative diagnoses (e.g., diagnostics for rheumatoid arthritis).
• Differential diagnoses
  • Rheumatoid arthritis
  • Differential diagnoses of infection-associated arthritis
• Management
  • NSAIDs for pain management
  • See “Management of parvovirus B19 infection” for details.

Parvovirus B19-associated anemia ^[2]

• Clinical features
  • Symptoms of pancytopenia (e.g., symptoms of anemia, symptoms of thrombocytopenia)
  • May be preceded by fever, malaise, and myalgia
  • Chronic pure red cell aplasia occurs in immunocompromised individuals.
  • Transient aplastic crisis occurs in patients with chronic hemolytic diseases (e.g., sickle cell disease)
• Diagnosis
  • Perform confirmatory testing for parvovirus B19 infection in all patients. ^[2]
  • CBC and reticulocyte count ^[2]
    • ↓ Reticulocytes
    • ↓↓ Hemoglobin
    • Thrombocytopenia and leukopenia in transient aplastic crisis
• Management
  • Refer patients with severe anemia or transient aplastic crisis to hematology.
  • Blood transfusion and IVIG may be required.
  • See also “Management of parvovirus B19 infection.”

• Offer symptomatic treatment. ^[13]
  • Arthralgia: NSAIDs (for dosages, see “Oral analgesics” for adults and “Nonopioid oral analgesia in children”)
  • Pruritus: Consider antihistamines.
  • Fever (e.g., antipyretics, supportive care for pediatric fever)
• Provide specialist referral as indicated, e.g.:
  • Obstetrics: all pregnant patients (and pregnant contacts); see also “Congenital parvovirus B19 infection.”
  • Hematology: patients with severe anemia and aplastic crisis
• Educate on appropriate infection control measures. ^[2]
  • Advise hand hygiene and respiratory hygiene for all patients and caregivers.
  • Use droplet precautions for hospitalized patients with : ^[2][14]
    • Aplastic crisis ^[2]
    • PPGSS
    • Immunosuppression and pure red cell aplasia

Children with the rash of erythema infectiosum are not contagious and do not require exclusion from school or daycare. ^[2]

• Hepatitis
• Myocarditis
• Aseptic meningitis and/or encephalitis
• Hemophagocytic lymphohistiocytosis
• Nephrotic syndrome

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