Erythema Infectiosum

Erythema infectiosum (EI) is a mild viral illness also known as "slapped-cheek" disease. It has also been called Fifth Disease because it was the fifth of six historic pediatric viral exanthems, the others being measles, scarlet fever, rubella, Filatov-Dukes disease (now recognized as a variant of scarlet fever), and roseola (1).

EI is not a reportable disease. Questions often arise from schoolteachers and parents regarding EI. Chief among these are questions of risk - risk to unexposed children, parents and in particular pregnant women. To address some of these concerns, the office of the Medical Officer of Health in Nova Scotia Districts 7 and 8 has generated recommendations, which are included at the end of this document.

Etiology
EI is caused by parvovirus B19, a single-stranded, non-enveloped DNA virus (1) that is distinct from the animal parvoviruses that affect dogs and cats (2).

Epidemiology
EI is a very common human infection, particularly among children aged five to 15. It is found worldwide with outbreaks in the winter and early spring. Based on serology, it is estimated that ~50% of the adult population has been previously exposed and thus is immune (3). If a child is infected, non-immune members of the household have ~50% risk of also becoming infected; susceptible classmates of the child have a ~60% risk (4).

Transmission
Parvovirus B19 is contagious via respiratory droplets or oropharyngeal secretions (e.g. coughing and sneezing, sharing cups and utensils). Individuals are most infectious during the week prior to the appearance of the diacritical "slapped-cheek" rash.

Incubation Period
The incubation period - from exposure to the appearance of the "slapped-cheek" rash - usually ranges from four to 14 days (5).

Signs and Symptoms
The most striking sign of EI is the "slapped-cheek" rash Ð an erythematous flush over the cheeks that spares the nasolabial folds and circumoral area. This may have been preceded by a mild prodrome of fever, headache, runny nose or sore throat. Following the "slapped cheek" rash is a diffuse, lacy, pink rash that appears on the trunk and extends to the proximal extremities. It often spares the palms and soles, may be more prominent on extensor surfaces, and may wax and wane in response to environmental temperature (e.g. hot baths), sun exposure and emotion or stress. It typically clears within three weeks. In lieu of, or in addition to, the characteristic rashes, adults and older children may experience joint symptoms ranging from arthralgias to arthritis. Most often involved are the joints of the hands, wrists, knees, and ankles, although any joint may be affected. Joint symptoms usually resolve within two to four weeks.

Complications
In almost all healthy children and adults, EI resolves without sequelae. However, there have been rare case reports of myocarditis associated with parvovirus B19 in previously healthy individuals (6). Most people infected with parvovirus B19 will experience a transient reticulocytopenia (7) because of the viral replication occurring in erythroid progenitors in the bone marrow. This temporary "slow-down" in red blood cell production usually goes unnoticed in healthy people, but for certain individuals infection with parvovirus B19 can lead to chronic anemia or aplastic crisis.

• hemolytic disorders (e.g., hereditary spherocytosis)
• hemoglobinopathies (sickle cell disease and thalassemia)
• red cell enzymopathies (glucose-6_-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and pyrimidine-5_ nucleotidase deficiency)
• autoimmune hemolytic anemias

• immunosuppressed patients, e.g.
• congenital immunodeficiency (i.e., Nezelof syndrome)
• acquired immunodeficiency syndrome (AIDS)
• lymphoproliferative disorders (especially acute lymphoblastic leukemia)
• transplant recipients

In addition, intrauterine infection with parvovirus B19 is associated with miscarriage and hydrops fetalis. The risk of fetal death, greatest if maternal infection occurred during the first half of pregnancy, has been estimated at less than 10% (8). If exposure occurs late in pregnancy, there is believed to be little risk.

Prevention and Treatment
There is no vaccine to prevent infection with parvovirus B19. Healthy children and adults require symptomatic treatment only. Individuals who develop complications may require more intensive management.

Recommendations to Family Physicians

1. It is not necessary for otherwise healthy children who have been clinically diagnosed with EI (by the appearance of the "slapped-cheek" rash) to remain out of school, as by this point in their illness they are not longer significantly infectious.As this illness is mild and typically resolves fully, there is no need for Public Health to be involved in monitoring outbreaks, implementing quarantine nor closing schools.
 

2. Individuals who have underlying medical conditions (as above) should be advised to avoid contact with ill individuals.
 

3. In a pregnant woman whose antibody status is unknown, the risk of serious fetal outcome is low. Given that her risk of being susceptible is 50%, her risk of contracting the virus given exposure is 50%, the risk of transmission to the fetus is 50% and the risk of a bad outcome in the infected fetus is 10%, her risk can be calculated:

0.5 x 0.5 x 0.5 x 0.1 = 1.25% risk of adverse outcome

4. A pregnant woman who presents to her family physician concerned about a recent exposure to parvovirus B19 can be initially offered serology. Her antibody status will determine whether she is immune, non-immune and not exposed, or infected.
 

5. If a pregnant woman is non-immune and her working environment is currently the site of an outbreak of EI (for example, a schoolteacher), it is reasonable for her to request a "sick note" from her family physician for the duration of the outbreak; however, it can be difficult for the family physician to determine when the outbreak has subsided.
 

6. If a pregnant woman is infected, it is not necessary for her to avoid outbreak situations.
 

7. If a pregnant woman is infected, she will require close follow-up in her pregnancy. The Society of Obstetricians and Gynecologists of Canada recommends considering a referral to obstetrics, and/or performing serial ultrasounds until 12 weeks after the infection (7).

- Dr. Charles Badenhorst
- Dr. Fesser

For his help in reviewing this article, our thanks to Dr. Scott Halperin, Head, Pediatric Infectious Diseases, Professor of Pediatrics and Associate Professor of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia.

References:

1. Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. 17th ed. Philadelphia, Pennsylvania: W.B. Saunders, 2004.
 

2. Gershon AA, Hotez PJ, Katz SL, editors. Krugman's Infectious Diseases of Children. 11th ed. Philadelphia, Pennsylvania: Mosby, Inc., 2004.
 

3. CDC. http://www.cdc.gov/ncidod/diseases/parvovirus/B19.htm
 

4. Kidshealth. http://www.kidshealth.org/parent/infections/skin/fifth.html
 

5. Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen's Emergency Medicine: Concepts and Clinical Practice. 5th ed. St. Louis, MO: Mosby, Inc., 2002.
 

6. Papadogiannakis N, Tolfvenstam T, Fischler B, et al. Active, fulminant, lethal myocarditis associated with parvovirus B19 infection in an infant. Clinical Infectious Diseases. Nov 1, 2002 v35 i9 p1027(5).
 

7. Long SS, Pickering LK, Prober CG, editors. Principles and Practice of Pediatric Infectious Diseases. 2nd ed. New York: Churchill Livingstone, 2003
 

8. Beers MH, Berkow R, editors. Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck & Co., 2004.
 

9. Crane J. Parvovirus B19 infection in pregnancy. J Obstet Gynaecol Can. Sept 1, 2002; 24(9): 727-43

You can search for abstracts of the above references by following this link: PubMed