Parvovirus Infection (Including Erythema Infectiosum)

Synonyms: erythema infectiosum, slapped cheek disease, slapped cheek syndrome, fifth disease, Parvovirus B19 (PV-B19), Sticker's disease.

Parvovirus is an extremely common infection. Approximately 60% of adults are sero-positive to PV-B19 by the age of 20 years. The commonest clinical encounter with PV-B19 is as the causative agent of erythema infectiosum (fifth disease).

Transmission

• Transmission is usually via respiratory secretions, but it can also be passed on via blood transfusion, bone marrow transplant, other blood products (but not intramuscular immunoglobulins), and from mother to baby via the placenta.
• The incubation period for clinical erythema infectiosum is 13-20 days. The illness is infective from 10 days pre-rash until the onset of the rash. Once the rash appears it is no longer infectious.
• Infectivity is medium. For susceptible individuals during epidemics, the attack rate is 50% for household contacts and schoolchildren, and 30% for teachers.
• One attack confers lifelong immunity. Patients who are immunocompromised may remain infectious.
• Erythema infectiosum is not notifiable in the UK.

About 25% of parvovirus infections are asymptomatic,² and nonspecific coryzal symptoms only are common.³

Erythema infectiosum^4,5
This is also called "fifth disease" because it is the fifth of the classic exanthems.

• This occurs commonly between ages 3-15 years. Outbreaks occur in late winter or early spring, with cyclical peaks of incidence occurring every 4-7 years.
• Prodromal symptoms are mild but may include headache, rhinitis, low-grade fever and malaise. Less commonly, nausea, diarrhoea, abdominal pain or arthropathy may develop.
• After 3-7 days, the classic 'slapped cheek' rash appears as erythema on the cheeks, sparing the nose, peri-oral and peri-orbital regions.⁶ This disappears after 2-4 days.
• About 1-4 days after the facial rash appears, an erythematous macular/morbilliform rash develops on the extremities, mainly on the extensor surfaces.⁷ It is usually not itchy in young children, but may be itchy in older children and adults. This gradually fades over the next 3-21 days, but may recur in reaction to various stimuli such as exercise, heat and sunlight.

Intra-uterine infection: see pregnancy section.

Haematological conditions:

• Transient aplastic crisis: Parvovirus has an affinity for red cell precursors, so a transient aplastic crisis can be provoked by parvovirus infection in any patient with reduced red cell production or increased red cell loss, e.g. sickle cell anaemia, thalassaemia, acute anaemia, and iron deficiency anaemia.
• Patients with a transient aplastic crisis may be highly infectious, which may be relevant to other patients in hospital wards.
• Other conditions linked to parvovirus include thrombocytopaenia, idiopathic thrombocytopaenic purpura and neutropaenia.

• Severe anaemia can occur, due to chronic pure red cell aplasia.
• These patients may be unable to eradicate the infection due to inadequate levels of IgM. They may remain infectious, yet test negative to IgM serology. Detection of the infection by alternative assays is necessary and is important for infection control.

Erythema infectiosum¹¹

• Rubella (look for suboccipital lymphadenopathy)
• Measles (look for Koplik's spots on buccal mucosa)
• Scarlet fever (look for strawberry tongue)
• Roseola infantum
• Drug eruptions
• Other infections can present with rash including meningitis and septicaemia

Older children or adults with arthropathy and rash⁵

• Acute rheumatic fever
• Allergic-hypersensitivity reaction
• Classic viral exanthems
• Disseminated gonococcal infection
• Epstein-Barr virus
• Hepatitis (parvovirus may cause transient elevations in liver enzymes)
• Lyme disease
• Rheumatological disorders

Investigations are not necessary in patients with uncomplicated erythema infectiosum, but if the clinical scenario requires confirmation of diagnosis (e.g. pregnancy, immunocompromised patients, aplastic crisis, arthropathy) the following may be helpful:

• B19-specific IgM - a positive screen indicates current or recent infection - but note that immunocompromised patients may be unable to make sufficient IgM and may test negative; they will need other tests.
• B19-specific IgG indicates immunity - it usually appears 2 weeks after infection and persists for life. IgG may also detect seroconversion in immunocompromised patients.
• Polymerase Chain Reaction (PCR) - for the specific detection of B19 virus.

For healthy and non-pregnant patients, only symptomatic treatment and explanation is needed.

To prevent transmission:²

• Advise patients to avoid contact with those at risk of complications: pregnant women, immunocompromised patients and those with haematological conditions. If contact does occur, these people should be advised to see their doctor.
• Within households and in institutions, transmission is difficult to prevent, but handwashing is recommended.
• For erythema infectiosum, the diagnostic features appear after the period of infectivity has passed, so exclusion from school has no effect on transmission.

Haematological problems¹

• Transient Aplastic Crisis: Haemoglobin levels should be restored using erythrocyte transfusion.
• Immunocompromised patients:
  • Pure red cell aplasia is treated by infusion of human immunoglobulin (which is a good source of neutralizing antibodies due to the high incidence of exposure in the adult population). This usually promotes a rapid rise in reticulocytes and haemoglobin levels.
  • Pure red cell aplasia may also resolve with temporary interruption of chemotherapy, or with antiretroviral treatment in HIV patients.

• Erythema infectiosum: This is a self-limiting condition in immunocompetent patients.
• Pregnancy: See below.
• Arthropathy: One study of 54 patients with arthropathy found no long-term sequelae.¹²
• Transient Aplastic Crisis: This is usually transient, lasting no more than 2 weeks in otherwise healthy individuals, and rapidly responds to treatment if required.
• Immunocompromised Patients: The treatment of pure red cell aplasia with immunoglobulin is frequently ameliorative and often curative.

Epidemiology, transmission and risks

• Identification of parvovirus infection in a pregnant woman is important, as parvovirus infection in the first half of pregnancy may cause fetal hydrops, but the outcome can be improved by intrauterine transfusion.
• Parvovirus affects about 1 in 400 pregnancies.
• The gestational period of risk is between 4 and 20 weeks' gestation: under 4 weeks, there is no intrauterine transmission, and over 20 weeks there is no risk of hydrops.
• The risk of adverse outcomes with infection in the first half of pregnancy is: fetal loss 15% versus 5% in controls; fetal hydrops 3%. Mortality from untreated fetal hydrops is 50%, reduced to 18% by transfusion.¹
• Rarely, neonatal infection and anaemia can occur. Parvovirus is not known to cause congenital abnormalities.

There is insufficient evidence to recommend universal screening; but screening of blood components prior to transfusion in children with malignancies, bone marrow donors prior to transplantation, and HIV patients at the time of diagnosis have all been mooted. A vaccine is currently undergoing trials.

Unselected screening of pregnant women for past infection with parvovirus B19 is not recommended, as no vaccine or prophylaxis are available. This advice will need reconsideration if a licensed vaccine becomes available.¹³