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

Parvovirus B19 (B19V), the only member of the Parvoviridae family known to cause disease in humans, is a single-strand DNA virus. The most widely known clinical manifestation of B19V infection is erythema infectiosum, a mild viral illness, followed by a classic exanthem, in which both cheeks appear bright red as though they had been slapped. First described in the 1800s, erythema infectiosum was named fifth disease because it was the fifth of 6 classic exanthematous diseases of childhood to be described.

Pathophysiology

B19V enters susceptible cells via the P blood antigen receptor. Once inside the host cell, viral DNA enters the nucleus. The 3' end of the DNA strand folds back on itself, forming a hairpinlike bend that functions as a self-primer for viral DNA replication. The virus has a tropism for rapidly dividing erythrocyte precursors, particularly pronormoblasts and normoblasts, wherein they replicate to high titers, destroying infected cells. Thus, no reticulocytes (immature erythrocytes) are available to replace aging or damaged erythrocytes as they are cleared by the reticuloendothelial system.

While decreases in hemoglobin levels of greater than 1 g/dL are rare in healthy children infected with B19V, decreases of 2-6 g/dL may be observed in patients with hemoglobinopathies or hemolytic anemias. Occasionally, the virus infects leukocytes (especially neutrophils). B19V does not infect megakaryocytes, but, in vitro, B19V proteins have a cytotoxic effect on megakaryocytes. Although B19V infection may manifest with pancytopenia, it is not believed to contribute significantly to true aplastic anemia.

A small number of reports in the literature state that B19V may infect other cell types, causing encephalitis, myocarditis, and hepatitis. Information on the percentage of patients infected with B19V who go on to develop these rare sequelae is not available.

Frequency

United States

B19V infection is common. Seropositivity rates are 5-10% among young children (aged 2-5 y), increasing to 50% by age 15 years and 60% by age 30 years. Approximately 90% of adults older than 60 years are seropositive. The annual seroconversion rate among B19V-naive pregnant women is 1.5%.

International

B19V infection is common worldwide. The age distribution is similar to that observed in the United States. A small number of groups, living in remote geographical locations, have not been exposed to parvovirus.

Mortality/Morbidity

B19V infection in healthy children and adults has an extremely low mortality rate. Morbidity is as follows:

• In patients with hemoglobinopathies or hemolytic anemias, in whom the duration of erythrocyte survival is decreased, a decrease in the reticulocyte count to less than 1% (usually to 0%) may precipitate an aplastic crisis. Such a crisis is characterized by profound anemia caused by a temporary halt in new erythrocyte production. Since the reticuloendothelial system removes abnormal erythrocytes from circulating blood, abnormal erythrocytes have a short half-life. Any interruption in new erythrocyte production may trigger a crisis. B19V is the only known infectious cause of aplastic crisis.
• Patients who are immunocompromised (eg, receiving chemotherapy or immunosuppressive drugs or have immune deficits [congential and acquired]) may develop chronic B19V infection that causes chronic anemia. Anemia persists until normal immune function returns.
• Symmetric postinfectious arthritis may develop, affecting the small joints of the hands and feet. The knees and elbows are rarely involved. Arthritis is much more common in adults, particularly in women, than in children. Arthritis may persist for weeks to months or (in a small number of patients) years. The arthritis may mimic rheumatoid arthritis (RA); however, unlike RA, B19V postinfectious arthritis does not cause permanent damage to bones or joints.

Race

No racial predilection is known.

Sex

• In general, B19V infection affects males and females in equal numbers.
• In school epidemics, the incidence rate of infection in females is higher than in males. The reason for this observation is unknown.
• Females are more likely to develop postinfectious arthritis.

Age

B19V infection is common in school-aged children and younger children who attend daycare facilities. In general, children transmit the virus to parents and siblings. Infection may occur at any age, but typically occurs in childhood.

CLINICAL

Section 3 of 10  

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

History

Common symptoms include a mild prodromal illness that consists of fever, malaise, headache, myalgia, nausea, and rhinorrhea. A bright red rash appears on the cheeks 5-7 days after onset, often followed by a diffuse lacy rash (at times pruritic) on the trunk, which spreads gradually toward the distal extremities.

The cause of parvovirus B19 (B19V) rash is believed to be immunologically mediated, and the rash corresponds to the appearance of immunoglobulin M (IgM) in the serum.

• Alternatively, B19V infection may manifest with purpuric rash, erythema multiforme, or pruritus of the soles of the feet. A parvovirus-associated rash may recur weeks to months after the acute infection. B19V may cause a papular-pruritic "gloves-and-socks" syndrome, in which an erythematous exanthem of the hands and feet, with a distinct margin at the wrist and ankle joints, is present along with pain and edema. This syndrome occurs exclusively with B19V infection and is uncommon in adults and rare in children.
• • Patients with severe anemia may present with pallor, fatigue, or signs of an aplastic crisis. Patients with thrombocytopenia may exhibit bruising.
  • Rarely, B19V infection manifests as myocarditis, vasculitis, glomerulonephritis, or encephalitis. B19V infection has been reported in association with idiopathic thrombocytopenia purpura, Henoch-Schönlein purpura, and pseudoappendicitis. B19V has been reported to precipitate hemophagocytic syndrome.
  • B19V infection in pregnant women may result in hydrops fetalis, particularly when infection occurs before 20 week' gestation. In the United States, the most common etiology of hydrops fetalis is B19V infection.
  • In individuals infected with B19V, 20% are asymptomatic.

Physical

• B19V infection may be indistinguishable from other viral illnesses in the absence of the classic exanthem.
• Children are often febrile, but their appearance is nontoxic.
• Splenomegaly may be present.
• Patients with aplastic crisis have pallor and tachycardia secondary to anemia. Children with aplastic crisis never have any rash. The absence of rash may result from prolonged viremia and lack of IgM. Another hypothesis is that patients in aplastic crisis often receive blood transfusions, and any rash may be attributed to a transfusion reaction.
• A friction rub may be audible if myocarditis is present. Benign flow murmurs are common in anemic children with tachycardia.
• The small bones of the hands, feet, elbows, and knees may exhibit signs of arthritis.

Causes

• Classic fifth disease, aplastic crisis, and glove-and-socks syndrome are caused almost exclusively by B19V. This virus, distributed worldwide, infects only humans. Transmission occurs via vertical transmission (birth), large droplet respiratory secretions, transfusion of blood products, and percutaneous exposure to blood.
• B19V has been spread by blood products, such as intravenous immunoglobulin (IVIG), packed RBCs, platelets, and nonrecombinant clotting factors. Since the virus lacks an outer lipid envelope and the genome is very stable, it is extremely resistant to heat, cold, and solvents.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Scarlet fever
Drug reaction
Collagen vascular disease
Rheumatoid arthritis

WORKUP

Section 5 of 10  

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

Lab Studies

• Most patients with parvovirus B19 (B19V) infection do not require laboratory studies because symptoms are mild and the illness resolves over 5-7 days.
• Parvovirus serology (IgM and immunoglobulin G [IgG]) can be determined using enzyme-linked immunoassay (ELISA), radioimmunoassay, or immunofluorescence. Results of IgM testing are particularly difficult to interpret. Standardization between laboratories is lacking. Even in a single laboratory, sensitivity and specificity are partly determined by operator skill.
• In patients with evidence of clinically significant anemia or aplastic crisis, obtain a CBC with reticulocyte count.
• • Patients infected with B19V have a low reticulocyte count (0-1%).
  • In an aplastic crisis, hemoglobin levels drop below the patient's baseline by at least 2 g/dL.
• If a pregnant woman is exposed to B19V, obtain IgG and IgM serology as soon as possible.
• • Positive IgG results and negative IgM results indicate past infection (no risk to fetus).
  • Positive IgG and IgM results indicate infection within the last 7-120 days (possible risk to fetus).
  • Negative IgG results and positive IgM results indicate acute infection (higher risk to fetus).
  • Negative IgG and IgM results indicate that the mother is not immune and that no evidence of acute infection exists.
  • Repeat serology tests in 3 weeks. Development of IgM indicates an acute infection.
• PCR (polymerase chain reaction) testing for B19V is routinely available. This test, a more useful clinical tool to diagnose infection, detects if any of the virus' DNA is present in the blood. A positive result is indicative of viremia/infection.

Imaging Studies

• Routine imaging is not necessary.

TREATMENT

Section 6 of 10  

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

Medical Care

• Acetaminophen or ibuprofen is effective for treating fever. Fever does not always require treatment with antipyretics; however, consider antipyretics if a patient appears clinically uncomfortable.
• Resolution of infection depends on the presence of immunoglobulins against B19V. No definitive evidence that cell-mediated immunity is a necessary part of the immune response has been reported. IVIG may have a role in treating chronic parvovirus infection.
• Patients in aplastic crisis require packed RBC transfusions.
• In patients receiving immunosuppressive agents, temporarily decreasing the dose of immunosuppressive agents usually enables the immune system to produce sufficient IgG to eradicate the infection and confer lifelong protection. In some individuals with human immunodeficiency virus (HIV) infection, highly active antiretroviral therapy restores immune function, enabling resolution of chronic parvovirus B19 (B19V) infection.

Consultations

• Hematologist: Patients who present with aplastic crisis require intensive monitoring and RBC transfusions to prevent death and should be evaluated by a hematologist.
• Pediatric infectious disease specialist or immunologist: Patients with long-term or unusual B19V infections can benefit from consultation with a pediatric subspecialist in infectious diseases or immunology. These patients may benefit from treatment with IVIG.

Diet

No dietary restrictions are necessary.

Activity

No activity restrictions are necessary.

MEDICATION

Section 7 of 10  

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

No antiviral therapy is available to treat parvovirus B19 (B19V) infections. Children rarely require specific therapy other than acetaminophen for fever.

In patients with postinfectious arthritis, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) usually provide symptomatic relief. Because the use of aspirin in children with other viral illnesses has been associated with Reye syndrome, aspirin use is not recommended in children with B19V infection. If children have pruritus from the B19V rash, oral antihistamines (eg, diphenhydramine) and starch baths typically provide relief.

Drug Category: Antipyretic agents

These agents decrease or eliminate fever by acting at the level of the hypothalamus (acetaminophen) or by decreasing the activity of the enzyme cyclooxygenase, thereby decreasing the production of prostaglandins (NSAIDs).

Drug Category: Immunologic effectors

These agents are purified preparations of gamma globulin. Immunologic effectors are derived from large pools of human plasma and comprise 4 subclasses of antibodies, approximating the distribution of human serum.

Immunity to B19V infection appears to be purely humoral (ie, mediated via immunoglobulins). The role, if any, that cell-mediated immunity plays in providing immunity to B19V is unknown. As a result of the high seroprevalence of IgG against parvovirus among adults in the general population who have recovered from infection, the antiparvovirus IgG titer in IVIG is probably sufficient to provide passive immunity for the clearance of virus in immunocompromised hosts with chronic B19V infection.

Drug Category: Antihistamines

These agents decrease or prevent allergic symptoms caused by histamine receptors from mast cells.

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Patients rarely require admission for parvovirus B19 (B19V) infections unless they have underlying disease.
• Consider the following factors for purposes of infection control:
• • B19V is spread via small respiratory droplets.
  • The attack rate in susceptible populations is 60%.
  • B19V is contagious from 24-48 hours before developing the viral prodrome and until the rash appears. The appearance of serum IgM coincides with the appearance of the rash.

Further Outpatient Care

• Patients with aplastic crisis or with a rash are no longer infectious. Patients are no longer infectious after other symptoms resolve (usually by day 7 of illness). Thus, patients with a classic B19V rash may return to school or daycare.

Transfer

• Patients with an aplastic crisis may require transfer to centers that provide pediatric critical care and hematology services.

Deterrence/Prevention

• Phase I clinical trials are currently evaluating vaccine candidates against B19V.
• Preventing secondary cases of B19V illness is difficult because the virus can be transmitted before the appearance of symptoms in the index case.

Complications

• Complications include hydrops fetalis, chronic anemia, aplastic crisis, and death. Immunocompetent individuals with a prolonged course of rash, fatigue, and arthralgias caused by persistent viremia have been reported. Symptoms in some of these patients respond to IVIG therapy.

Prognosis

• Most patients recover without sequelae.

Patient Education

• B19V infects only humans. Approximately 60% of adults aged 30 years are immune to B19V, although few recall having had the infection. Symptoms include a low-grade fever, myalgias, arthralgias, headache, nausea, and rhinorrhea. As the symptoms disappear, children often develop a bright red rash on the cheeks (as if they had been slapped). The infection is contagious in children for a few days before symptoms begin and until the symptoms disappear. When the rash appears, the infection is no longer contagious. The presence of the B19V rash is not a reason to keep children home from daycare or school.
• If a woman who is pregnant and not immune to B19V becomes infected, a small probability (2-5%) exists that hydrops fetalis will develop. Any pregnant woman who is exposed to an individual in whom B19V infection is suspected should contact the obstetrician immediately.
• In healthy adults and children, B19V is not a serious infection. Exceptions include patients with cancer who are receiving chemotherapy, as well as patients with HIV infection and/or acquired immunodeficiency syndrome (AIDS), organ transplants, and other immunodeficient states.
• For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Fifth Disease.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Parvovirus B19 (B19V) infection is not a reason to terminate a pregnancy, and B19V is not teratogenic. Less than 20% of fetuses exposed before 20 weeks' gestation have severe symptoms. Interuterine RBC transfusions have been used to treat infectious and noninfectious hydrops. A minority of hydrops fetalis cases may spontaneously resolve.

Special Concerns

• If a woman who is pregnant and is not immune becomes infected with B19V, fetal infection may occur. Transplacental infection occurs in approximately 33% of pregnant women with B19V infection. As with children, B19V infects the precursors of erythrocytes in fetuses. Since fetal RBCs have a shorter half-life of 45-60 days (vs 90 d in normal erythrocytes), infection may cause severe anemia in the fetus. The fetus may develop signs of high-output cardiac failure (hydrops fetalis). Refer women who are pregnant with acute B19V infection to a specialist in maternal-fetal medicine.
• If a pregnant woman is exposed to an individual with B19V infection, serology to determine B19V IgG and IgM levels is indicated.
• • A positive IgG result indicates past infection and reassures that no risk to the fetus exists.
  • If IgG results are negative, the woman is at risk for developing B19V infection.
  • IgM serology is helpful only when results are positive. The presence of IgM antibodies indicates acute or recent infection.
• Since the incubation period of B19V infection is longer in the fetus than in healthy children, obtain serial weekly ultrasound images, which are necessary to look for signs of hydrops fetalis, for 10-12 weeks.
• • If fetal ultrasound images reveal the signs of hydrops fetalis, cordocentesis is indicated to determine the hemoglobin, hematocrit, and IgM status of the fetus' blood.
  • If IgM results are positive, the fetus has an acute infection. Severe anemia may require intrauterine transfusion of erythrocytes. Both cordocentesis and intrauterine transfusion have significant risks to the fetus and mother.
  • If ultrasound findings remain normal for 12 weeks after exposure to B19V, the prognosis is excellent.

REFERENCES

Section 10 of 10

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

• AAP. Parvovirus B19. In: 2000 Red Book: Report of the Committee on Infectious Diseases. 25th ed. American Academy of Pediatrics;2006.
• Ballou WR, Reed JL, Noble W, et al. Safety and immunogenicity of a recombinant parvovirus B19 vaccine formulated with MF59C.1. J Infect Dis. Feb 15 2003;187(4):675-8. [Medline].
• Cherry JD, Feigin RD. Parvoviruses. In: Textbook of Pediatric Infectious Diseases. Vol 2. 4th ed. WB Saunders Co;1998:1620-30.
• Gabbe SG, Niebyl JR, Simpson JL, et al, eds. Parvovirus infection. In: Obstetrics Normal and Problem Pregnancies. 3rd ed. Churchill Livingstone;1996:1225-8.
• Grilli R, Izquierdo MJ, Farina MC, et al. Papular-purpuric "gloves and socks" syndrome: polymerase chain reaction demonstration of parvovirus B19 DNA in cutaneous lesions and sera. J Am Acad Dermatol. Nov 1999;41(5 Pt 1):793-6. [Medline].
• Kuhlmann RS, Autry AM. An approach to nonbacterial infections in pregnancy. Clin Fam Pract. 2001;3(2).
• Lee GR, Paraskevas F, Foerster J, et al. Thrombocytopenia associated with infections. In: Wintrobe's Clinical Hematology. 10th ed. Waverly;1999:1627-9.
• Mandell GL, Bennett JE. Natural history of individual infections after bone marrow transplantation. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Churchill Livingstone;2000.
• Mandell GL, Bennett JE. Erythema infectiosum. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Churchill Livingstone;2000:1687-90.
• McGhee SA, Kaska B, Liebhaber, M. Persistant Parvovirus-Associated Chronic Fatigue Treated with High Dose Intravenous Immunoglobulin. Pediatr Infect Dis J. 2005;24(3):272-274.
• Mustafa MM, McClain KL. Diverse hematologic effects of parvovirus B19 infection. Pediatr Clin North Am. Jun 1996;43(3):809-21. [Medline].
• Pizzo PA, Poplack DG. Myelodysplastic syndromes. In: Principles and Practice of Pediatric Oncology. 3rd ed. Lippincott Williams & Wilkins;1997:514-8.
• Young NS, Brown KE. Parvovirus B19. N Engl J Med. Feb 5 2004;350(6):586-97. [Medline].

Article Last Updated: Nov 9, 2006