Synonyms: erythema infectiosum, slapped cheek disease, slapped cheek syndrome, fifth disease, parvovirus B19

Epidemiology^1,2

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

Infectivity and 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 13-18 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.
• Note:
  • Patients with aplastic crisis (see below) are highly infectious.
  • Immunocompromised patients may remain infectious.

Presentation

May be asymptomatic (about 25% of infections); or may present only with nonspecific coryzal symptoms (common).^2,3

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

• 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, perioral and periorbital regions. 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.⁵ 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.

• May present as symmetrical arthropathy, affecting the hands, wrists, knees and ankles.
• The symptoms usually resolve within a few days but in some cases persist for 2 months or longer.
• 50% of patients presenting with arthropathy would meet the criteria for rheumatoid arthritis or juvenile arthritis, had parvovirus not been detected.

Complications¹

Intrauterine infection: see Parvovirus B19 in pregnancy section (below).

Haematological conditions:

• Transient aplastic crisis: parvovirus B19 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, hereditary spherocytosis, 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 thrombocytopenia, idiopathic thrombocytopenic purpura and neutropenia.

• Parvovirus B19 can cause chronic anaemia or other cytopenias.⁸
• 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.
• Meningoencephalitis can occur with acute parvovirus infection.⁸

• Rarely, parvovirus B19 has been linked to hepatitis, myocarditis, meningitis, encephalitis and peripheral neuropathy.¹¹
• Possibly, it may cause or trigger autoimmune diseases or vasculitis.

Differential diagnosis

Erythema infectiosum¹²

• 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^1,5

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. Note: 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 parvovirus B19.

Management⁵

For healthy and nonpregnant 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 neutralising 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.

Prognosis¹

• Erythema infectiosum: this is a self-limiting condition in immunocompetent patients.
• Pregnancy: see Parvovirus B19 in pregnancy (below).
• Arthropathy: one study of 54 patients with arthropathy found no long-term sequelae.¹³
• 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.

Parvovirus B19 in pregnancy¹⁴

Epidemiology, transmission and risks

• Identification of parvovirus B19 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.

Prevention^1,16

• Screening of donated blood components before transfusion for patients with sickle cell disease and other congenital anemias, immunocompromised hosts, and women during pregnancy.
• Healthcare workers should not be caring for patients if they have flu-like symptoms, a fever or a rash. This is particularly important if they are caring for patients at risk from parvovirus B19, i.e. pregnant women, immunocompromised patients and those with hereditary anaemias.
• Infection control - special considerations are required in the following situations:
  • Confirmed parvovirus B19 (acute infection) in a healthcare worker
  • Susceptible (seronegative) healthcare workers
  • Other susceptible employees, e.g. teachers
  For these groups, specific information is given in the HPA guidance.¹⁶

Document references

1. Heegaard ED, Brown KE; Human parvovirus B19. Clin Microbiol Rev. 2002 Jul;15(3):485-505. [abstract]
2. Health Protection Agency; Parvovirus - general information. June 2008.
3. Servey JT, Reamy BV, Hodge J; Clinical presentations of parvovirus B19 infection. Am Fam Physician. 2007 Feb 1;75(3):373-6. [abstract]
4. Fifth Disease (Erythema Infectiosum) Fact Sheet
5. Zellman GL; Erythema Infectiosum (Fifth Disease). eMedicine, updated December 2009.
6. Katta R; Parvovirus B19: a review. Dermatol Clin. 2002 Apr;20(2):333-42. [abstract]
7. Cohen B; Parvovirus B19: an expanding spectrum of disease. BMJ. 1995 Dec 9;311(7019):1549-52.
8. Florea AV, Ionescu DN, Melhem MF; Parvovirus B19 infection in the immunocompromised host. Arch Pathol Lab Med. 2007 May;131(5):799-804. [abstract]
9. Posnett DN, Yarilin D; Amplification of autoimmune disease by infection. Arthritis Res Ther. 2005;7(2):74-84. Epub 2005 Feb 10. [abstract]
10. von Landenberg P, Lehmann HW, Modrow S; Human parvovirus B19 infection and antiphospholipid antibodies. Autoimmun Rev. 2007 Apr;6(5):278-85. Epub 2006 Oct 13. [abstract]
11. Douvoyiannis M, Litman N, Goldman DL; Neurologic manifestations associated with parvovirus B19 infection. Clin Infect Dis. 2009 Jun 15;48(12):1713-23. [abstract]
12. Furness C, Sharma R, Harnden A; Morbilliform rash. BMJ. 2004 Sep 25;329(7468):719.
13. Speyer I, Breedveld FC, Dijkmans BA; Human parvovirus B19 infection is not followed by inflammatory joint disease during long term follow-up. A retrospective study of 54 patients. Clin Exp Rheumatol. 1998 Sep-Oct;16(5):576-8. [abstract]
14. Guidelines on the management of and exposure to rash illness in pregnancy, Health Protection Agency (2003); (including consideration of relevant antibody screening programmes in pregnancy)
15. RCOG Infection and pregnancy, June 2001.
16. Guidelines on Parvovirus B19 (Slapped Cheek Syndrome, Fifth Disease or Erythema Infectiosum), Health Protection Agency (2008); Contains guidelines by Crowcroft et al, 1999.

Internet and further reading

• DermNet NZ; Fifth disease; Illustrations of 'slapped cheek' and lace patterns of rash
• Broliden K, Tolfvenstam T, Norbeck O; Clinical aspects of parvovirus B19 infection. J Intern Med. 2006 Oct;260(4):285-304. [abstract]
• Douvoyiannis M, Litman N, Goldman DL; Neurologic manifestations associated with parvovirus B19 infection. Clin Infect Dis. 2009 Jun 15;48(12):1713-23. [abstract]

Acknowledgements