AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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

INTRODUCTION

Section 2 of 11  

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

Background

Erythema infectiosum is a common childhood exanthem caused by human parvovirus B19 (PV-B19), an erythrovirus, in which a classic 3-phased cutaneous eruption follows a rarely noticed prodrome.

Pathophysiology

The development of erythema infectiosum in children is a normal response to infection by PV-B19. Acute infection in a host who is immunocompetent leads to a Th-1–mediated cellular immune response, with the production of specific immunoglobulin M (IgM) antibodies and subsequent formation of immune complexes. Clinical signs and symptoms probably result from the deposition of the immune complexes in the skin and joints of individuals with this condition and not from the circulating virus.

Frequency

International

Worldwide, epidemics of erythema infectiosum tend to occur in the late winter or early spring, with cyclical peaks of incidence occurring every 4-7 years. Approximately 60% of adults are seropositive for PV-B19 by age 20 years. Infection rates vary from 20-50% in schools and households during outbreaks.

Mortality/Morbidity

Erythema infectiosum is a self-limited illness that resolves without complications or sequelae in its classic childhood form. Infection in adults, hosts who are immunocompromised, and patients who are anemic or pregnant can result in more significant morbidity.

Sex

Males and females are infected equally. Arthropathy is more common in women. Women may be affected by complications during pregnancy.

Age

Erythema infectiosum primarily is a disease of children aged 3-15 years, but it can occur at any age. PV-B19 infection can lead to the classic symptoms of erythema infectiosum in adults but more often manifests as an acute arthropathy without cutaneous eruption.

CLINICAL

Section 3 of 11  

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

History

• Erythema infectiosum typically has an incubation period of 4-14 days and is spread primarily via aerosolized respiratory droplets.
• Transmission also occurs through blood products and from mother to fetus.
• The prodromal phase often is mild enough to be noticed only rarely but may include headache, coryza, low-grade fever, pharyngitis, and malaise.
• Infrequently, nausea, diarrhea, arthralgias, and abdominal pain may occur.
• In hosts who are immunocompetent, the patient is viremic and capable of spreading the infection only during the incubation period.
• Classic cutaneous findings follow within 3-7 days for some patients, while other patients may manifest no findings.

Physical

• Pertinent physical findings predominantly are limited to the skin and joints.
• • Skin (first stage): The exanthem begins with the classic slapped-cheek appearance. The bright red erythema appears abruptly over the cheeks and is marked by nasal, perioral, and periorbital sparing. The exanthem may appear like a sunburn, occasionally is edematous, and typically fades over 2-4 days.
  • Skin (second stage): Within 1-4 days of the malar rash, an erythematous macular-to-morbilliform eruption occurs primarily on the extremities. While the eruption tends to favor the extensor surfaces, it can involve the palms and soles. Pruritus is rare.
  • Skin (third stage): After several days, most of the second stage eruption fades into a lacy pattern, with particular emphasis on the proximal extremities. Despite its synonym, slapped-cheek disease, the reticulate pattern is distinctly characteristic for erythema infectiosum and may be the only manifestation of the illness. The third stage lasts from 3 days to 3 weeks. After starting to fade, the exanthem may recur over several weeks following physical stimuli, such as exercise, sun exposure, friction, bathing in hot water, or stress.
  • Joints: When adults are exposed to PV-B19, an acute polyarthropathy is more likely to result than classic erythema infectiosum. Polyarthropathy may start with a typical prodromal illness and some cutaneous aspect of erythema infectiosum but more often manifests simply by a new onset of symmetric joint pain. Arthropathy is more common in women and can last for days to months. Sites most commonly affected include joints of the hands, wrists, knees, and ankles. Unlike rheumatoid arthritis, joint pain worsens over the day, and no joint destruction occurs. The synovial fluid is acellular and devoid of viral particles. An association with DR4 histocompatability alleles is recognized.
  • Rarely, patients may have some mild constitutional symptoms and/or adenopathy.

Causes

Erythema infectiosum is caused by infection with PV-B19, a member of the Parvoviridae family. PV-B19 is the virus with the smallest DNA known to cause illness in humans, and it consists of a single-stranded DNA core surrounded by an unenveloped icosahedral capsid. PV-B19 requires mitotically active cells and a globoside cellular receptor for propagation, thus making erythroid cell lines a prime target. The tropism for human erythroid progenitor cells and other rare sites of the globoside receptor (eg, endothelial cells, placental cells) is responsible for the more serious complications associated with the viral infection.

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

In adult patients with acute arthropathy and rash, consider the following:

Acute rheumatic fever
Allergic-hypersensitivity reaction
Classic viral exanthems
Disseminated gonococcal infection
Epstein-Barr virus
Hepatitis
Lyme disease
Rheumatologic disorders

WORKUP

Section 5 of 11  

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

Lab Studies

• The diagnosis of erythema infectiosum usually is based on clinical presentation alone, and a workup for patients with the classic presentation is not necessary. For patients with other PV-B19–associated signs or symptoms, or for exposure in a woman who is pregnant, confirmation of infection may be helpful and can be accomplished with the following specialized tests:
• • IgM assays (enzyme-linked immunoassay, radioimmunoassay)
  • Dot blot hybridization
  • Polymerase chain reaction
  • Loop-mediated isothermal amplification

Histologic Findings

Skin biopsy is not necessary or does not aid in diagnosis but may reveal nonspecific changes, including mild basilar vacuolarization, dyskeratotic cells, and a sparse perivascular infiltrate.

TREATMENT

Section 6 of 11  

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• Medication
• Follow-up
• Miscellaneous
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Medical Care

Since erythema infectiosum most often is a benign self-limited disease, reassuring the parents often is the only intervention necessary. For patients with arthralgias or pruritus, symptomatic relief can be obtained using oral analgesics and antihistamines or topical antipruritic lotions.

Consultations

• Dermatologist: Refer patients for diagnosis and dermatologic care.
• Internal medicine specialist: Refer patients for associated conditions.
• Obstetrician/gynecologist: Due to potential complications from intrauterine PV-B19 infection, refer pregnant women who have IgM antibodies to PV-B19 or who have been exposed to the virus. Maternal alpha-fetoprotein levels and serial ultrasounds followed through the pregnancy may help predict complications.

Activity

Activities may be pursued as tolerated, with sun protection or avoidance.

MEDICATION

Section 7 of 11  

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• Miscellaneous
• Multimedia
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Symptomatic relief of erythema infectiosum may be provided using nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, and topical antipruritics, along with plenty of fluids and rest. For an acute aplastic crisis, supplemental oxygen and blood transfusions may be necessary. Intravenous immunoglobulin (IVIG) is helpful for chronic anemia in patients who are immunocompromised.

Drug Category: Nonsteroidal anti-inflammatory drugs

Provide relief for fever, malaise, headache, and arthralgia. Although the effects of NSAIDs in the treatment of pain tend to be patient specific, ibuprofen usually is the drug of choice (DOC) for initial therapy. Other options include fenoprofen, flurbiprofen, mefenamic acid, ketoprofen, indomethacin, and piroxicam.

Drug Category: Antihistamines

Provide symptomatic relief of pruritus.

Drug Category: Topical antipruritics

Help relieve the discomfort of itching skin.

FOLLOW-UP

Section 8 of 11  

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

Deterrence/Prevention

Since children with erythema infectiosum are contagious prior to the onset of the classic-appearing rash, preventing the spread of this common childhood exanthem is difficult. Attentive parents can only give their children the general good advice to frequently wash their hands and to avoid the sneezes, coughs, and discarded tissues of children who appear sick.

Complications

Complications of PV-B19 infection include the following:

• Aplastic crisis: The parvovirus infects erythroid cells, causing a reticulocytopenia that lasts 7-10 days. A healthy host experiences no consequences, since the normal lifespan of a red blood cell is 120 days. In patients with a background of shortened red blood cell survival, such as hemolytic anemia, an acute aplastic crisis ensues. At-risk conditions in patients include the following:
  
  
  • Sickle cell anemia
  • Hereditary spherocytosis
  • Thalassemia
  • Glucose-6-phosphate dehydrogenase deficiency
  • Pyruvate kinase deficiency
  • Autoimmune hemolytic anemia
• Chronic bone marrow failure: In patients who are immunocompromised and have little defense against PV-B19, a prolonged viremia may occur, affecting all cell lines of the bone marrow. Immunodeficient states include the following:
  
  
  • HIV infection
  • Congenital immunodeficiency syndromes
  • Acute lymphocytic leukemia
  • Immunosuppressive or cytotoxic therapy
• Congenital infection: PV-B19 can cross the placenta during pregnancy and have a direct cytotoxic effect on fetal red blood cells. Infection may lead to the following:
  
  
  • Severe anemia
  • Congestive heart failure
  • Hydrops fetalis (PV-B19 responsible for 10-15% of cases)
  • Intrauterine death (miscarriage or stillborn) in 3-10% of mothers who are infected
• Papular-purpuric gloves and socks syndrome: This is an acute self-limited exanthem with fine palpable purpura usually located on the hands and feet, with sharp demarcation at the wrists and ankles. The eruption may be accompanied by fever and aphthous ulcers and occurs more commonly in adults. Rarely, this eruption can involve the perioral and chin area in an acropetechial variant.
• Other potential illnesses that occasionally may be linked to or triggered by PV-B19 include the following:
  
  
  • Viral-associated hemocytophagia
  • Rheumatoid arthritis
  • Systemic sclerosis
  • Systemic lupus erythematosus
  • Autoimmune-like pulmonary disease
  • Idiopathic thrombocytopenic purpura
  • Diamond-Blackfan–like anemia
  • Acute vasculitic syndromes
  • Atypical and nonspecific erythematous exanthem
  • Myocarditis
  • Hepatitis
  • Uveitis
  • Seizures, encephalitis, and other neurologic manifestations
  • Glomerulonephritis/nephrotic syndrome

Prognosis

The prognosis is excellent for typical childhood cases.

Patient Education

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 11  

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

Medical/Legal Pitfalls

• Usually, erythema infectiosum is a self-limited childhood exanthem that resolves without complications in the classic cutaneous form; however, PV-B19 infections in adults who are pregnant, immunocompromised, or have a chronic hemoglobinopathy can lead to a significant increase in morbidity. Therefore, discussing these negative consequences with parents of the children with the exanthem is important. Parents should warn potentially at-risk people who may have been exposed to the virus and the serious sequelae of infection.

Special Concerns

• Public health and infection control
• • Since children with erythema infectiosum are contagious only during the asymptomatic viremic period (occurring approximately 1 wk before rash appears), restricting them from attending school is not necessary by the time the clinical diagnosis is made.
  • Patients with PV-B19–induced aplastic crisis or chronic anemia may be actively viremic during the illness. Patients require routine respiratory isolation, since the virus can be spread via aerosolized respiratory droplets.
  • Potential risk of infection through Parvovirus B-19 contaminated blood products and subsequent consideration to screening blood destined for high risk patients.

MULTIMEDIA

Section 10 of 11  

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

Media file 1:  Classic slapped-cheek appearance of fifth disease.
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Media type:  Photo

Media file 2:  Pathognomonic reticulated lacy-appearing eruption of fifth disease.
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Media type:  Photo

REFERENCES

Section 11 of 11

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

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• Revilla Grande AI, Carro García T, Sánchez de Dios M, Galán Calvo MJ, Nebreda Mayoral T. [Outbreak of infectious erythema at a urban health center]. Aten Primaria. Jul-Aug 2000;26(3):172-5. [Medline].
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• Takeda S, Takaeda C, Takazakura E, Haratake J. Renal involvement induced by human parvovirus B19 infection. Nephron. Nov 2001;89(3):280-5. [Medline].
• Veraldi S, Rizzitelli G. Erythematous exanthem associated with primary infection by human parvovirus B19. Int J Dermatol. Feb 1995;34(2):119. [Medline].
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Article Last Updated: Jul 24, 2007