AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Erythema infectiosum is usually a benign childhood condition characterized by a classic slapped-cheek and lacy exanthem. It is an infection caused by human parvovirus (HPV) B19. HPV B19 also is associated with other hematologic, rheumatologic, and neurologic conditions, including polyarthropathy, aplastic anemia, and hydrops fetalis.

Pathophysiology

HPV B19, a member of the family Parvoviridae, is a heat-stable, single-stranded DNA virus. HPV B19 was accidentally discovered in 1975; it is the only parvovirus known to infect humans. Transmission occurs through respiratory secretions, possibly through fomites, and parenterally via vertical transmission from mother to fetus and by transfusion of blood or blood products.

The incubation period is usually 7-10 days but can be 4-21 days. The mechanism producing the dermatologic and rheumatologic features is unknown but thought to represent antigen-antibody (Ag-Ab) complexes in the skin and joints.

Arthropathy is observed most commonly in adult women and occurs in fewer than 10% of children. It is a symmetric polyarthritis, usually involving finger joints. The onset of joint symptoms occurs 2-3 weeks after exposure.

The association of HPV B19 and aplastic anemia is thought to be due to the affinity and cytotoxicity of the virus for erythroid progenitor cells. This complication is primarily observed in patients with underlying hemolytic anemias (eg, sickle cell disease, thalassemia) or immunodeficiency states (eg, leukemia, HIV). These disease states depend on high red-cell production. The hematocrit of these patients may drop as much as 10-15% per day during acute infection.

Most patients have an HPV B19 aplastic crisis only once, and a rash following aplastic crisis is rare. Previously healthy patients also develop transient (and usually clinically insignificant) bone marrow suppression and reticulocytopenia. In rare cases, mild lymphopenia, neutropenia, and thrombocytopenia also may occur.

Fetal transmission may result in severe anemia with resultant congestive heart failure and fetal hydrops. This occurs in fewer than 10% of primary maternal infections. Recent studies report 1-9% risk of fetal death in pregnant women exposed to active HPV infection, with greater risk of fetal loss in early pregnancy. Approximately one half of women of childbearing age are seropositive; therefore, they are immune and are of no risk to the fetus. No evidence suggests specific congenital malformations due to in-utero exposure to HPV B19.

Associations of HPV B19 infection include encephalitis, neuropathies, myocarditis, nephritis, systemic lupus erythematosus (SLE), Henoch-Schönlein purpura (HSP), and rheumatoid arthritis. The exact role of HPV B19, if any, in these diseases is unclear.

Frequency

United States

Sporadic cases occur, but outbreaks are more common. Up to 60% of the population is seropositive for anti-HPV B19 immunoglobulin G (IgG) by age 20 years. The incidence peaks in winter and early spring. HPV B19 epidemics appear to occur in cyclical fashion every 4-7 years and are estimated to affect 30-50% of US households. Community epidemics usually last 3-6 months. Subclinical infections are common.

International

The disease occurs worldwide, especially in temperate climates.

Mortality/Morbidity

Arthropathy is observed in fewer than 10% of children with fifth disease. Incidence of HPV B19-induced aplastic crisis in patients with chronic hemolytic anemia is 2-5% per year.

Sex

Females are affected slightly more often than males.

Age

Approximately 70% of total cases occur in children aged 5-15 years. Infants and adults are affected infrequently.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Erythema infectiosum is usually a biphasic illness.

• Mild prodromal symptoms begin approximately 1 week after exposure and last 2-3 days.
• • Headache (20% of pediatric patients)

  • Fever (20%)

  • Sore throat (15%)

  • Pruritus (15%)

  • Coryza (10%)

  • Abdominal pain (10%)

  • Arthralgias (10%)

  • The symptoms above occur more frequently in adults than in children, especially joint symptoms (up to 50%).

• These symptoms precede a symptom-free period of about 7-10 days, followed by a typical exanthem that occurs in 3 phases.
• • Phase 1: A bright red, raised, slapped-cheek rash with circumoral pallor develops. The nasolabial folds are usually spared.

  • Phase 2: This phase occurs 1-4 days later and is characterized by an erythematous maculopapular rash on proximal extremities (usually arms and extensor surfaces) and trunk, which fades into a classic lace-like reticular pattern as confluent areas clear. The palms and soles usually are spared.

  • Phase 3: Frequent clearing and recurrences for weeks, and occasionally months, may be due to stimuli such as exercise, irritation, or overheating of skin from bathing or sunlight.

• The rash is often pruritic, especially in adults.
• Enanthems are virtually never observed.
• The rash is observed in approximately 75% of HPV B19 infected pediatric patients but in less than 50% of infected adults.
• The patient is no longer infectious when the rash appears. Patients with aplastic crisis continue to be viremic and infectious until RBC recovery occurs.

Physical

• Look for involved arthritis.
• In decreasing order of frequency, site of involvement are the following:
• • Metacarpophalangeal and/or interphalangeal areas

  • Knees

  • Wrists

  • Ankles

Causes

• HPV B19 is the cause.
• Complications of parvovirus infection are observed in patients with underlying chronic hemolytic anemias, congenital or acquired immunodeficiency states, and pregnancy.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pediatrics, drug eruption
Pediatrics, allergic rashes
Pediatrics, viral exanthem unspecified

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Because of the usual classic exanthem and the benign course of disease in healthy patients, routine laboratory studies are not indicated.
• • The leukocyte count is usually within the reference range. Mild eosinophilia may occur.

  • Consider determination of the CBC and serologic testing in the presence of coexisting hemolytic disease, pregnancy, or arthropathy.

• HPV B19 does not grow in standard blood or tissue culture systems.

Other Tests

• Ab testing by means of radioimmunoassay (RIA) and/or enzyme-linked immunosorbent assay (ELISA) is most commonly used.
• • Immunoglobulin M (IgM) Ab is usually detectable within 3 days of onset of symptoms. It peaks at about 3 weeks and always indicates acute infection.
  • IgG Ab confirms previous infection and is observed 2-3 weeks after exposure.  It persists for life.
  • Ab testing usually is available only through commercial reference laboratories or state health and research laboratories.
  • These tests are unreliable for diagnosing infection in immunosuppressed patients.
• Other nonemergency diagnostic tests are antigen testing and DNA polymerase chain reaction (PCR) testing (the best method for detecting chronic infection in immunosuppressed patients).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

Patients at risk for complication from HPV B19 infection should be isolated from patients with potential erythema infectiosum in the ED.

Consultations

• Consider consultation with a hematologist and/or oncologist for patients in aplastic crisis.
• Consider consultation with an obstetrician/gynecologist if the patient is pregnant.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Immunoglobulin

Helpful in chronic aplastic crisis or infected immunocompromised patients. No evidence indicates that intravenous immunoglobulin (IVIG) is beneficial in pregnant women with HPV B19 infection.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Most children with aplastic crisis require hospitalization and probable transfusion and/or IVIG therapy.
• Hospitalized patients with erythema infectiosum need no special isolation precautions; however, patients with aplastic crisis or immunosuppression with HPV B19 infection should be isolated.
• Pregnant health care workers should be informed of the potential risks to the fetus from parvovirus B19 infections. They should not be involved in treatment of immunocompromised patients with chronic parvovirus infection or patients with HPV B19–associated aplastic crisis.

Further Outpatient Care

• Children with erythema infectiosum are not infectious and may attend childcare or school.
• Pregnant women in contact with patients in the incubation period of erythema infectiosum or with aplastic crisis have a relatively low potential risk of infection. They can be referred for obstetric follow-up care for possible serologic testing and close fetal monitoring. 
• Routine exclusion of pregnant women from the workplace where erythema infectiosum is occurring is not recommended, due to high prevalence of HPV B19 infection and low incidence of fetal effects.

In/Out Patient Meds

• Administer antipyretics, analgesics, antipruritics, and anti-inflammatories as needed.

Deterrence/Prevention

• Avoid excessive heat or sunlight, which can cause rash flare-ups.

Complications

• Arthralgias/arthropathies occur in up to 10% of pediatric patients and up to 50% of adult patients.

Prognosis

• The rash of erythema infectiosum usually is self-resolving but may last several weeks or months with exacerbations from heat or sunlight.
• Arthropathy usually lasts 2-4 weeks and on rare occasions can last months to years.
• Erythroid cell line suppression usually lasts up to 2 weeks but may be chronic and last months to years.
• The onset of erythema infectiosum rash usually indicates that reticulocytosis has returned and aplastic crisis will not occur.

Patient Education

• Emphasize in discussion with parents that otherwise healthy patients with erythema infectiosum are not infectious once the rash appears; therefore, they do not need to be isolated or restricted from school/day care.
• Infected children with hemolytic disease or immunosuppression may be quite infectious. Therefore, respiratory isolation, especially from other pregnant, chronically anemic, or immunosuppressed individuals, should be observed.
• Good handwashing and infection control techniques should be encouraged.
• For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education articles Fifth Disease and Skin Rashes in Children.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Misdiagnosis as another childhood exanthem that requires intervention (eg, scarlet fever)
• Failure to recognize special needs of patients prone to potentially serious complications of parvovirus infection

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• American Academy of Pediatrics. Red Book: 2006 Report on the Committee of Infectious Diseases. 484-487.
• Anderson LJ. Human parvovirus. In: Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology. New York: Churchill Livingston Inc; 1997:613-31.
• Cherry JD. Parvoviruses. In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. Philadelphia: WB Saunders Co; 1992:1626-33.
• Cohen B. Parvovirus B19: an expanding spectrum of disease. BMJ. Dec 9 1995;311(7019):1549-52. [Medline].
• Feder HM Jr, Anderson I. Fifth disease. A brief review of infections in childhood, in adulthood, and pregnancy. Arch Intern Med. Oct 1989;149(10):2176-8. [Medline].
• Hall CJ. Parvovirus B19 infection in pregnancy. Arch Dis Child Fetal Neonatal Ed. Jul 1994;71(1):F4-5. [Medline].
• Hammond GW. Parvovirus. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. New York: Churchill Livingston Inc; 1997:1205-9.
• Heegaard ED, Hornsleth A. Parvovirus: the expanding spectrum of disease. Acta Paediatr. Feb 1995;84(2):109-17. [Medline].
• Jones MF, Wold AD, Espy MJ, Smith TF. Serologic diagnosis of parvovirus B19 infections. Mayo Clin Proc. Nov 1993;68(11):1107-8. [Medline].
• Keeler ML. Human parvovirus B-19: not just a pediatric problem. J Emerg Med. Jan-Feb 1992;10(1):39-44. [Medline].
• Kirchner JT. Erythema infectiosum and other parvovirus B19 infections. Am Fam Physician. Aug 1994;50(2):335-41. [Medline].
• Qari M, Qadri SM. Parvovirus B19 infection. Associated diseases, common and uncommon. Postgrad Med. Jul 1996;100(1):239-43, 246, 252. [Medline].

Article Last Updated: Jun 19, 2007