AUTHOR INFORMATION

Section 1 of 11

Authored by Dennis Cunningham, MD, Assistant Professor of Pediatrics, Section of Infectious Diseases, Children's Hospital, Ohio State College of Medicine

Dennis Cunningham, MD, is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Disease Society, and Phi Beta Kappa

Edited by Glenn J Fennelly, MD, MPH, Director, Division of Pediatric Infectious Diseases, Jacobi Medical Center; Associate Professor, Department of Pediatrics, Albert Einstein College of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Joseph Domachowske, MD, Associate Professor, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University; Robert W Tolan, Jr, MD, Chief of Allergy, Immunology and Infectious Diseases, The Children's Hospital at St Peter's University Hospital, Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; and Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center

Author's Email:	Dennis Cunningham, MD
Editor's Email:	Glenn J Fennelly, MD, MPH

eMedicine Journal, November 9 2006, VOLUME 7, Number 11

INTRODUCTION

Section 2 of 11

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:

• In the US: 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%.

• Internationally: 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 11

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 11

Rubella

Other Problems to be Considered:

Scarlet fever
Drug reaction
Collagen vascular disease
Rheumatoid arthritis

WORKUP

Section 5 of 11

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

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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 11

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 Name	Acetaminophen (Tylenol, Feverall, Tempra, Aspirin Free Anacin, Panadol) -- Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.
Adult Dose	650 mg PO q4-6h or 1000 mg q6h; not to exceed 4 g/d
Pediatric Dose	<12 years: 10-15 mg/kg/dose PO/PR q4-6h prn; not to exceed 5 doses/d and 2.6 g/d >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hepatotoxicity is possible in chronic alcoholism following administration of various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; acetaminophen is contained in many OTC products, and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose; avoid alternating acetaminophen with NSAIDs to reduce fever because no evidence exists proving greater effectiveness in reducing fever over use of acetaminophen or ibuprofen alone

Drug Name	Ibuprofen (Motrin, Ibuprin, Advil) -- One of the few NSAIDs indicated for reduction of fever.
Adult Dose	Fever: 400-600 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d Arthritis: 400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose	10 mg/kg/dose PO q4-6h while symptoms persist; not to exceed 2.4 g/d
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI tract bleeding or perforation; renal insufficiency; high risk of bleeding
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when concurrently administered
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy; can trigger asthma in some patients with asthma (especially if patient has aspirin insensitivity)

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 Name	Immune globulin, intravenous (Gammagard S/D, Carimune NF, Gammar-P) -- Provides passive immunization against a broad spectrum of infectious agents. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Adult Dose	Limited data suggest using a dose of 400 mg/kg/d IV for 5 days. Use of IVIG to treat chronic anemia resulting from B19V is off label; use should be limited to prescription by infectious disease specialists, immunologists, hematologists, or transplant surgeons
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Decreases immunogenicity of vaccines, especially live-attenuated vaccines
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	IgA deficiency occurs in 1 in 300-500 patients; check serum IgA before IVIG (use IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine headaches, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Drug Category: Antihistamines -- These agents decrease or prevent allergic symptoms caused by histamine receptors from mast cells.

Drug Name	Diphenhydramine (Benadryl) -- First-generation antihistamine that binds to H1 receptors in the CNS and the body. Competitively blocks histamine from binding to H1 receptors. As a result of CNS penetration, diphenhydramine frequently causes drowsiness. A small percentage of children paradoxically respond to diphenhydramine with agitation.
Adult Dose	25-50 mg PO q6-8h prn; not to exceed 400 mg/d 10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d
Pediatric Dose	1.25 mg/kg/dose PO/IV/IM q6h as needed for pruritus; not to exceed 5 mg/kg/d or 50 mg q6h
Contraindications	Documented hypersensitivity; MAOIs
Interactions	Potentiates effect of CNS depressants; due to alcohol content, do not administer elixir to patients taking medications causing disulfiramlike reaction
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer disease, or urinary tract obstruction; xerostomia may occur

FOLLOW-UP

Section 8 of 11

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 11

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.
  
  
  

TEST QUESTIONS

Section 10 of 11

CME Question 1: A pregnant woman telephones the physician. She had cared for a neighbor's child who had bright red cheeks. While performing a search on the Internet, she discovered that she could have a parvovirus B19 (B19V) infection. Which of the following actions would be most appropriate for the physician to take?

A: Reassure the patient that she is not at risk for B19V infection if she has not had any other exposure to the child.
B: Obtain maternal blood to determine titers of parvovirus immunoglobulin G and immunoglobulin M and obtain results to a B19V polymerase chain reaction (PCR) assay.
C: Immediately obtain a fetal ultrasound to evaluate for hydrops fetalis.
D: Schedule cordocentesis to evaluate fetal blood for anemia.
E: Administer oral iron, folate, and vitamin B-12 to ensure that the patient does not develop anemia.

The correct answer is A: B19V infections in children are no longer contagious once the rash appears. Obtaining maternal parvovirus titers is not unreasonable; however, PCR assay is not approved by the US Food and Drug Administration and is limited to research use. Anemia must first develop before signs of hydrops fetalis (eg, heart failure) present. At this time, ultrasound images would not demonstrate hydrops fetalis. Cordocentesis is a procedure with significant risks to the fetus and mother. Cordocentesis is indicated only if ultrasound findings suggest hydrops fetalis. Administering iron and vitamins to prevent parvoviral anemia is not effective. Anemia results from viral destruction of erythrocyte precursors, not from a nutritional deficiency.

CME Question 2: A 14-year-old boy with hemoglobin SS disease presents with mild icterus, abdominal pain, and fatigue. On examination, he appears to be in severe distress. Vital signs reveal tachycardia and hypotension. After starting an intravenous bolus, which of the following actions would be most appropriate for the physician to take?

A: Consult a surgeon because the patient may have an acute abdomen.
B: Obtain a CBC and reticulocyte count and type and crossmatch blood at once.
C: Obtain parvovirus serology.
D: A and C are correct.
E: A and B are correct.

The correct answer is E: Because this patient has tachycardia and hypotension, he may have an acute abdomen. Because the patient has a vasoocclusive crisis and possible aplastic crisis, obtaining a CBC and reticulocyte count and typing and crossmatching blood is appropriate. If the reticulocyte count is less than 1% with an extremely low hemoglobin level, parvovirus is the most likely cause. Because the patient requires transfusions, type and crossmatch is indicated. Parvovirus titers are not rapidly available; therefore, they have limited use in the setting of an acute aplastic crisis.

Pearl Question 1 (T/F): In the United States, the most common etiology of hydrops fetalis is parvovirus B19 infection.

The correct answer is True: Previously, ABO incompatibility was the most common cause of hydrops fetalis. Along with typing maternal and infant blood, administration of anti–Rh immunoglobulin (RhoGAM) to women who were Rh negative before birth or the use of obstetric procedures has drastically reduced the incidence of immune-mediated anemia. Parvovirus B19 infection is the most common cause of hydrops fetalis.

Pearl Question 2 (T/F): Postinfectious arthritis following parvovirus B19 infection is typically asymmetric and involves the elbows, shoulders, hips, and knees.

The correct answer is False: Typically, postinfectious arthritis following parvovirus B19 infection is symmetric and involves the small joints of the hands and feet. Large joint involvement is atypical.

Pearl Question 3 (T/F): Patients can spread parvovirus B19 infection at any time from the development of the first symptom until the appearance of the rash.

The correct answer is False: Parvovirus B19 infection is contagious for a 24- to 48-hour period before the onset of symptoms and until day 7 of the illness or until the classic rash appears.

Pearl Question 4 (T/F): The first-line approach to treating a patient with human immunodeficiency virus (HIV) infection and anemia that results from a chronic parvovirus B19 infection is to administer intravenous immunoglobulin (IVIG).

The correct answer is False: Use of IVIG to treat chronic parvovirus B19 infection is off label. The first step in resolving the anemia is to begin antiretroviral medication. As the patient’s immune status improves, the infection may be eradicated. IVIG is a second-line treatment in this instance.

BIBLIOGRAPHY

Section 11 of 11

• 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 2003 Feb 15; 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 1999 Nov; 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 1996 Jun; 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 2004 Feb 5; 350(6): 586-97[Medline].

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