MUMPS
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Acute self-limited infection, once commonplace but now unusual in developed countries because of
widespread use of vaccination.
It is characterized by fever, bilateral or unilateral parotid swelling and tenderness, and the frequent
occurrence of meningoencephalitis and orchitis.
Although no longer common in countries with extensive vaccination programs, mumps remains endemic
in the rest of the world, warranting continued vaccine protection.
ETIOLOGY
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Mumps virus is in the family Paramyxoviridae and the genus Rubulavirus.
It is a single-stranded pleomorphic RNA virusstructural proteins.
Two surface glycoproteins
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HN (hemagglutininneuraminidase) - mediate absorption of the virus to host cells
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F (fusion) - penetration into cells, respectively
*Both of these proteins stimulate production of protective antibodies. Mumps virus exists as a single
immunotype, and humans are the only natural host.
EPIDEMIOLOGY
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Occurred primarily in young children between the ages of 5 and 9 yr
In epidemics about every 4 yr.
Mumps infection occurred more often in the winter and spring months.
In 1968, just after the introduction of the mumps vaccine, 185,691 cases were reported in the USA.
Following the recommendation for routine use of mumps vaccine in 1977, the incidence of mumps in
young children fell dramatically, the disease occurring instead in older children, adolescents, and young
adults.
Outbreaks continued to occur even in highly vaccinated populations as a result of to vaccine failure and
also of under vaccination of susceptible persons.
After implementation of the 2-dose recommendation for the measles-mumps-rubella (MMR) vaccine for
measles control in 1989, the number of mumps cases declined further.
During 2001-2003, <300 mumps cases were reported each year.
In 2006, the largest mumps epidemic in the last 20 years occurred in the USA. A total of 6584 cases
occurred, 85% of them in 8 Midwestern states.
Twenty-nine percent of the cases occurred in patients 18-24 yr old, most of whom were attending college.
An analysis of 4039 patients with mumps seen in the first 7 months of the epidemic indicated that 63%
had received >2 doses of the MMR vaccine.
Mumps is spread from person to person by respiratory droplets.
Virus appears in the saliva from up to 7 days before to as long as 7 days after onset of parotid swelling.
The period of maximum infectiousness is 1-2 days before to 5 days after onset of parotid swelling.
Viral shedding before onset of symptoms and in asymptomatic infected individuals impairs efforts to
contain the infection in susceptible populations.
The U.S. Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics, and
the Health Infection Control Practices Advisory Committee recommend an isolation period of 5 days after
onset of parotitis for patients with mumps in both community and health care settings.
PATHOLOGY AND PATHOGENESIS
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Mumps virus targets the salivary glands, central nervous system (CNS), pancreas, testes, and, to a lesser
extent, thyroid, ovaries, heart, kidneys, liver, and joint synovia.
Following infection, initial viral replication occurs in the epithelium of the upper respiratory tract. Infection
spreads to the adjacent lymph nodes by the lymphatic drainage, and viremia ensues, spreading the virus
to targeted tissues.
Mumps virus causes necrosis of infected cells and is associated with a lymphocytic inflammatory infiltrate.
Salivary gland ducts are lined with necrotic epithelium, and the interstitium is infiltrated with lymphocytes.
Swelling of tissue within the testes may result in focal ischemic infarcts.
The cerebrospinal fluid (CSF) frequently contains mononuclear pleocytosis, even in individuals without
clinical signs of meningitis.
CLINICAL MANIFESTATIONS
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The incubation period for mumps ranges from 12 to 25 days but is usually 16-18 days.
Mumps virus infection may result in clinical presentation ranging from asymptomatic or nonspecific
symptoms to the typical illness associated with parotitis with or without complications involving several
body systems.
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The typical patient presents with a prodrome lasting 1-2 days and consisting of fever, headache, vomiting,
and achiness.
Parotitis then appears and may be unilateral initially but becomes bilateral in about 70% of cases.
The parotid gland is tender, and parotitis may be preceded or accompanied by ear pain on the ipsilateral
side.
Ingestion of sour or acidic foods or liquids may enhance pain in the parotid area.
As swelling progresses, the angle of the jaw is obscured and the ear lobe may be lifted upward and
outward.
The opening of Stensen duct may be red and edematous.
The parotid swelling peaks in approximately 3 days, then gradually subsides over 7 days.
Fever and the other systemic symptoms resolve in 3-5 days.
A morbilliform rash is rarely seen.
Submandibular salivary glands may also be involved or may be enlarged without parotid swelling.
Edema over the sternum due to lymphatic obstruction may also occur.
DIAGNOSIS
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When mumps was highly prevalent, the diagnosis could be made on the basis of a history of exposure to
mumps infection, inappropriate incubation period, and development of typical clinical findings.
Confirmation of the presence of parotitis could bemade with demonstration of an elevated serum amylase
value.
Leukopenia with a relative lymphocytosis was a common finding.
Today, in patients with parotitis lasting >2 days and of unknown cause, a specific diagnosis of mumps
should be confirmed or ruledout by virologic or serologic means.
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This step may be accomplished by isolation of the virus in cell culture, detection of viralantigen by
direct immunofluorescence, or identification of nucleic acid by reverse transcriptase polymerase
chain reaction.
Virus can be isolated from upper respiratory tract secretions, CSF, or urine during the acute illness.
Serologic testing is usually a more convenient and available mode of diagnosis.
A significant increase in serum mumps immunoglobulin G (IgG) antibody between acute and
convalescent serum specimens as detected by complement fixation, neutralization hemagglutination, or
enzyme immunoassay (EIA) tests establishes the diagnosis.
Mumps IgG antibodies may cross react with antibodies to parainfluenza virus in serologic testing.
More commonly, an EIA for mumps IgM antibody is used to identify recent infection.
Skin testing for mumps is neither sensitive nor specific and should not be used.
DIFFERENTIAL DIAGNOSIS
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Parotid swelling may be caused by many other infectious and noninfectious conditions.
Viruses that have been shown to cause parotitis include:
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parainfluenza 1 virus
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parainfluenza 3 virus
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influenza A virus
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cytomegalovirus
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Epstein-Barr virus
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Enteroviruses
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lymphocytic choriomeningitis virus
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HIV
Purulent parotitis
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caused by Staphylococcus aureus
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unilateral
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extremely tender
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associated with an elevated white blood cell count
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may involve purulent drainage from Stensen duct
Submandibular or anterior cervical adenitis due to a variety of pathogens may also be confused with
parotitis.
Other noninfectious causes of parotid swelling includes:
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obstruction of Stensen duct
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collagen vascular diseases
 Sjögren syndrome
 systemic lupus erythematosus
 tumor.
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COMPLICATIONS
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The most common complications of mumps are:
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meningitis
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with or without encephalitis
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gonadal involvement.
Uncommon complications includes:
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Conjunctivitis
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optic neuritis
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pneumonia
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nephritis
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pancreatitis
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thrombocytopenia.
Maternal infection with mumps during the 1st trimester of pregnancy results in increased fetal wastage.
No fetal malformations have been associated with intrauterine mumps infection.
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However, perinatal mumps disease has been reported in infants born to mothers who acquired
mumps late in gestation.
Meningitis and Meningoencephalitis
 Mumps virus is neurotropic and is thought to enter the CNS via the choroid plexus and infect the
choroidal epithelium and ependymal cells, both of which can be found in CSF along with mononuclear
leukocytes.
 Symptomatic CNS involvement occurs in 10-30% of infected individuals, but CSF pleocytosis has been
found in 40-60% of patients with mumps parotitis.
 The meningoencephalitis may occur before, along with, or following the parotitis. It most commonly
manifests 5 days after the parotitis.
 Clinical findings vary with age.
 Infants and young children have fever, malaise, and lethargy, whereas older children, adolescents, and
adults complain of headache and demonstrate meningeal signs.
 In 1 series of children with mumps and meningeal involvement, findings were:
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fever in 94%
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vomiting in 84%
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headache in 47%
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parotitis in 47%
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neck stiffness in 71%
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lethargy in 69%
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seizures in 18%
 In typical cases, symptoms resolve in 7-10 days.
 CSF in mumps meningitis has a white blood cell pleocytosis of 200-600/mm3 with a predominance of
lymphocytes.
 The CSF glucose content is normal in most patients, but a moderate hypoglycorrhachia (glucose content
20-40 mg/dL) may be seen in 10-20% of patients.
 The CSF protein content is normal or mildly elevated.
 Less common CNS complications of mumps includes:
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transverse myelitis
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aqueductal stenosis
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facial palsy
 Sensorineural hearing loss is rare but has been estimated to occur in 0.5- 5.0/100,000 cases of mumps.
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There is some evidence that this sequela is more likely in patients with meningoencephalitis.
Orchitis and Oophoritis
 In adolescent and adult males, orchitis is 2nd only to parotitis as a common finding in mumps.
 Involvement in prepubescent boys is extremely rare, but after puberty, orchitis occurs in 30-40% of males.
 It begins within days following onset of parotitis in the majority of cases and is associated with moderate
to high fever, chills, and exquisite pain and swelling of the testes.
 In ≤30% of cases the orchitis is bilateral. Atrophy of the testes may occur, but sterility is rare even with
bilateral involvement.
 Oophoritis is uncommon in postpubertal females but may cause severe pain and may be confused with
appendicitis when located on the right side.
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Pancreatitis
 Pancreatitis may occur in mumps with or without parotid involvement.
 Severe disease is rare, but fever, epigastric pain, and vomiting are suggestive.
 Epidemiologic studies have suggested that mumps may be associated with the subsequent development
of diabetes mellitus, but a causal link has not been established.
Cardiac Involvement
 Myocarditis has been reported in mumps, and molecular studies have identified mumps virus in heart
tissue taken from patients with endocardial fibroelastosis.
Arthritis
 Arthralgia, monoarthritis, and migratory polyarthritis have been reported in mumps.
 Arthritis is seen with or without parotitis and usually occurs within 3 wk of onset of parotid swelling.
 It is generally mild and self-limited.
Thyroiditis
 Thyroiditis is rare following mumps.
 It has not been reported without parotitis and may occur weeks after the acute infection.
 Most cases resolve, but some become relapsing and result in hypothyroidism.
TREATMENT
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No specific antiviral therapy is available for mumps.
Management should be aimed at reducing the pain associated with meningitis or orchitis and maintaining
adequate hydration.
Antipyretics may be given for fever.
PROGNOSIS
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The outcome of mumps is nearly always excellent, even when the disease is complicated by encephalitis,
although fatal cases due to CNS involvement or myocarditis have been reported.
PREVENTION
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Immunization with the live mumps vaccine is the primary mode of prevention used in the USA.
It is given as part of the MMR 2-dose vaccine schedule, at 12-15 mo of age for the 1st dose and 4-6 yr of
age for the 2nd dose.
If not given at 4-6 yr, the 2nd dose should be given before children enter puberty. Antibody develops in
95% of vaccinees after 1 dose.
One study showed vaccine effectiveness of 88% for 2 doses of MMR vaccine, compared with 64% for a
single dose. Immunity appears to be long lasting.
However, studies from the United Kingdom and the recent epidemic in the USA suggest that both
antibody levels and vaccine effectiveness may decline, contributing to mumps outbreaks in older
vaccinated populations.
As a live-virus vaccine, MMR should not be administered to pregnant women or to severely
immunodeficient or immunosuppressed individuals.
HIV-infected patients who are not severely immunocompromised may receive the vaccine, because the
risk for severe infection with mumps outweighs the risk for serious reaction to the vaccine.
Individuals with anaphylactoid reactions to egg or neomycin may be at risk for immediate-type
hypersensitivity reactions to the vaccine.
Persons with other types of reactions to egg or reactions to other components of the vaccine are not
restricted from receiving the vaccine.
In 2006, in response to the multistate outbreak in the USA, evidence of immunity to mumps through
vaccination was redefined.
Acceptable presumptive evidence of immunity to mumps now consists of 1 of the following:
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(1) documentation of adequate vaccination
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(2) laboratory evidence of immunity
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(3) birth before 1957
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(4) documentation of physician-diagnosed mumps.
Evidence of immunity through documentation of adequate vaccination is now defined as 1 dose of a live
mumps virus vaccine for preschool-aged children and adults not at high risk and 2 doses for school-aged
children (i.e., grades K-12) and for adults at high risk (i.e., health care workers, international travelers,
and students at post–high school educational institutions).
All persons who work in health care facilities should be immune to mumps.
Adequate mumps vaccination for health care workers born during or after 1957 consists of 2 doses of a
live mumps virus vaccine.
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Health care workers with no history of mumps vaccination and no other evidence of immunity should
receive 2 doses, with >28 days between doses.
Health care workers who have received only 1 dose previously should receive a 2nd dose.
Because birth before 1957 is only presumptive evidence of immunity, health care facilities should
consider recommending 1 dose of a live mumps virus vaccine for unvaccinated workers born before 1957
who do not have a history of physician diagnosed mumps or laboratory evidence of mumps immunity.
During an outbreak, health care facilities should strongly consider recommending 2 doses of a live
mumps virus vaccine to unvaccinated workers born before 1957 who do not have evidence of mumps
immunity.
Adverse reactions to mumps virus vaccine are rare.
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Parotitis and orchitis have been reported rarely.
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Other reactions such as febrile seizures, deafness, rash, purpura, encephalitis, and meningitis
may not be causally related to the strain of mumps vaccine virus used for immunization in the
USA.
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Higher rates of aseptic meningitis following vaccination for mumps have been associated with
vaccine strains used elsewhere in the world, including the Leningrad 3 and Urabe Am 9 strains.
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Transient suppression of reactivity to tuberculin skin testing has been reported after mumps
vaccination.
PARVOVIRUS B19
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Cause of erythema infectiosum or fifth disease.
ETIOLOGY
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Parvovirus B19 (B19) is a member of the genus Erythrovirus in the family Parvoviridae.
Parvoviruses are small DNA viruses that infect a variety of animal species.
As a group, parvoviruses include a number of important animal pathogens, such as canine parvovirus
and feline panleukopenia virus.
B19 does not infect other animals, and animal parvoviruses do not infect humans.
B19 is one of only two parvoviruses that are pathogenic inhumans.
The other such virus is the newly described human bocavirus.
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Although the clinical significance of human bocavirus is not yet fully defined, this virus may be
associated with upper and lower respiratory tract infection in young children and will not be further
discussed in this chapter.
B19 is composed of an icosahedral protein capsid without an envelope and contains a single-stranded
DNA genome of approximately 5.5 kb.
It is relatively heat and solvent resistant.
It is antigenically distinct from other mammalian parvoviruses and has only one known serotype.
Parvoviruses replicate in mitotically active cells and require host cell factors present in late S phase to
replicate.
B19 can be propagated in vitro only in erythropoietin-stimulated erythropoietic cells derived from human
bone marrow, umbilical cord blood, or primary fetal liver culture.
EPIDEMIOLOGY
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Infections with parvovirus B19 are common and occur worldwide.
Clinically apparent infections, such as the rash illness of erythema infectiosum and transient aplastic
crisis, are most prevalent in school-aged children, 70% of cases occurring in patients between 5 and 15
yr of age.
Seasonal peaks occur in the late winter and spring, with sporadic infections throughout the year.
Seroprevalence increases with age, 40-60% of adults having evidence of prior infection.
Transmission of B19 is by the respiratory route, presumably via large droplet spread from
nasopharyngeal viral shedding.
The transmission rate is 15-30% among susceptible household contacts, and mothers are more
commonly infected than fathers.
In outbreaks of erythema infectiosum in elementary schools, the secondary attack rates range from 10%
to 60%.
Nosocomial outbreaks also occur, with secondary attack rates of 30% among susceptible health care
workers.
Although respiratory spread is the primary mode of transmission, B19 is also transmissible in blood and
blood products, as documented among children with hemophilia receiving pooleddonor clotting factor.
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Given the resistance of the virus to solvents, fomite transmission could be important in child-care centers
and other group settings, but this mode of transmission has not been established.
PATHOGENESIS
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The primary target of B19 infection is the erythroid cell line, specifically erythroid precursors near the
pronormoblast stage.
Viral infection produces cell lysis leading to a progressive depletion of erythroid precursors and a
transient arrest of erythropoiesis.
The virus has no apparent effect on the myeloid cell line.
The tropism for erythroid cells is related to the erythrocyte P blood group antigen, which is the primary cell
receptor for the virus and is also found on endothelial cells, placental cells, and fetal myocardial cells.
Thrombocytopenia and neutropenia are often observed clinically, but the pathogenesis of these
abnormalitiesis unexplained.
Experimental infection of normal volunteers with B19 revealed a biphasic illness.
From 7 to 11 days after inoculation, subjects had viremia and nasopharyngeal viral shedding with fever,
malaise, and rhinorrhea.
Reticulocyte counts dropped to undetectable levels but resulted in only a mild, clinically insignificant fall in
serum hemoglobin.
With the appearance of specific antibodies, symptoms resolved and serum hemoglobin returned to
normal.
Several subjects experienced a rash associated with arthralgia 17-18 days after inoculation.
Some manifestations of B19 infection, such as transient aplastic crisis, appear to be a direct result of viral
infection, whereas others, including the exanthem and arthritis, appear to be postinfectious phenomena
related to the immune response.
Skin biopsy of patients with erythema infectiosum reveals edema in the epidermis and a perivascular
mononuclear infiltrate compatible with an immunemediated process.
Individuals with chronic hemolytic anemia and increased red blood cell (RBC) turnover are very
sensitive to minor perturbations in erythropoiesis.
Infection with B19 leads to a transient arrest in RBC production and a precipitous fall in serum
hemoglobin, often requiring transfusion.
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The reticulocyte count drops to undetectable levels, reflecting the lysis of infected erythroid
precursors.
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Humoral immunity is crucial in controlling infection.
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Specific immunoglobulin M (IgM) appears within 1-2 days of infection and is followed by anti-B19
IgG, which leads to control of the infection, restoration of reticulocytosis, and a rise in serum
hemoglobin.
Individuals with impaired humoral immunity are at increased risk for more serious or persistent infection
with B19, which usually manifests as chronic RBC aplasia, although neutropenia, thrombocytopenia, and
marrow failure are also described.
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Children undergoing chemotherapy for leukemia or other forms of cancer, transplant recipients,
and patients with congenital or acquired immunodeficiency states (including AIDS) are at risk for
chronic B19 infections.
Infections in the fetus and neonate are somewhat analogous to infections in immunocompromised
persons.
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B19 is associated with nonimmune fetal hydrops and stillbirth in women experiencing a primary
infection but does not appear to be teratogenic.
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Like most mammalian parvoviruses, B19 can cross the placenta and cause fetal infection during
primary maternal infection.
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Parvovirus cytopathic effects are seen primarily in erythroblasts of the bone marrow and sites of
extramedullary hematopoiesis in the liver and spleen.
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Fetal infection can presumably occur as early as 6 wk of gestation, when erythroblasts are first
found in the fetal liver; after the 4th mo of gestation, hematopoiesis switches to the bone marrow.
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In some cases, fetal infection leads to profound fetal anemia and subsequent high-output cardiac
failure.
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Fetal hydrops ensues and is often associated with fetal death.
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There may also be a direct effect of the virus on myocardial tissue that contributes to the cardiac
failure.
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However, most infections during pregnancy result in normal deliveries at term.
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Some of the asymptomatic infants from these deliveries have been reported to have chronic
postnatal infection with B19 that is of unknown significance.
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CLINICAL MANIFESTATIONS
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Many infections are clinically inapparent.
Infected children characteristically demonstrate the rash illness of erythema infectiosum.
Adults, especially women, frequently experience acute polyarthropathy with or without a rash.
Erythema Infectiosum (Fifth Disease)
 The most common manifestation of parvovirus B19 is erythema infectiosum
 Also known as fifth disease
 Is a benign, self-limited exanthematous illness of childhood.
 The incubation period for erythema infectiosum is 4-28 days (average 16-17 days).
 The prodromal phase is mild and consists of low-grade fever in 15-30% of cases, headache, and
symptoms of mild upper respiratory tract infection.
 The hallmark of erythema infectiosum is the characteristic rash, which occurs in 3 stages that are not
always distinguishable.
 The initial stage is an erythematous facial flushing, often described as a “slappedcheek” appearance.
 The rash spreads rapidly or concurrently to the trunk and proximal extremities as a diffuse macular
erythema in the 2nd stage.
 Central clearing of macular lesions occurs promptly, giving the rash a lacy, reticulated appearance.
 The rash tends to be more prominent on extensor surfaces, sparing the palms and soles.
 Affected children are afebrile and do not appear ill. Some have petechiae.
 Older children and adults often complain of mild pruritus.
 The rash resolves spontaneously without desquamation but tends to wax and wane over 1-3 wk.
 It can recur with exposure to sunlight, heat, exercise, and stress.
 Lymphadenopathy and atypical papular, purpuric, vesicular rashes are also described.
Arthropathy
 Arthritis and arthralgia may occur in isolation or with other symptoms.
 Joint symptoms are much more common among adults and older adolescents with B19 infection.
 Females are affected more frequently than males.
 In one large outbreak of fifth disease, 60% of adults and 80% of adult women reported joint symptoms.
 Joint symptoms range from diffuse polyarthralgia with morning stiffness to frank arthritis.
 The joints most often affected are the hands, wrists, knees, and ankles, but practically any joint may be
affected.
 The joint symptoms are self-limited and, in the majority of patients, resolve within 2-4 wk.
 Some patients may have a prolonged course of many months, suggesting rheumatoid arthritis.
 Transient rheumatoid factor positivity is reported in some of these patients but with no joint destruction.
Transient Aplastic Crisis
 The transient arrest of erythropoiesis and absolute reticulocytopenia induced by B19 infection leads to a
sudden fall in serum hemoglobin in individuals with chronic hemolytic conditions.
 This B19-induced RBC aplasia or transient aplastic crisis occurs in patients with all types of chronic
hemolysis and/or rapid RBC turnover, including sickle cell disease, thalassemia, hereditary spherocytosis,
and pyruvate kinase deficiency.
 In contrast to children with erythema infectiosum only, patients with aplastic crisis are ill with fever,
malaise, and lethargy and have signs and symptoms of profound anemia, including pallor, tachycardia,
and tachypnea.
 Rash is rarely present.
 The incubation period for transient aplastic crisis is shorter than that for erythema infectiosumbecause the
crisis occurs coincident with the viremia.
 Children with sickle cell hemoglobinopathies may also have a concurrent vasoocclusive pain crisis,
further confusing the clinicalpresentation.
Immunocompromised Persons
 Persons with impaired humoral immunity are at risk for chronic parvovirus B19 infection.
 Chronic anemia is the most commonmanifestation, sometimes accompanied by neutropenia,
thrombocytopenia, or complete marrow suppression.
 Chronic infections occur in persons receiving cancer chemotherapy or immunosuppressive therapy for
transplantation and persons withcongenital immunodeficiencies, AIDS, and functional defects in IgG
production who are thereby unable to generate neutralizing antibodies.
Fetal Infection
 Primary maternal infection is associated with nonimmune fetal hydrops and intrauterine fetal demise, with
the risk for fetal loss after infection estimated at <5%.
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The mechanism of fetal disease appears to be a viral-induced RBC aplasia at a time when the fetal
erythroid fraction is rapidly expanding, leading to profoundanemia, high-output cardiac failure, and fetal
hydrops.
Viral DNA has been detected in infected abortuses.
The second trimester seems to be the most sensitive period, but fetal losses are reported at every stage
of gestation.
If maternal B19 infection is suspected, fetal ultrasonography and measurement of the peak systolic flow
velocity of the middle cerebral artery are sensitive, noninvasive procedures to diagnose fetal anemia and
hydrops.
Most infants infected in utero are born normally at term, including some who have had ultrasonographic
evidence of hydrops.
A small subset of infants infected in utero may acquire a chronic or persistent postnatal infection with B19
that is of unknownsignificance.
Congenital anemia associated with intrauterine B19 infection has been reported in a few cases,
sometimes following intrauterine hydrops.
This process may mimic other forms of congenital hypoplastic anemia (e.g., Diamond-Blackfan
syndrome).
Fetal infection with B19 has not been associated with other birth defects. B19 is only one of many causes
of hydrops fetalis.
Myocarditis
 B19 infection has been associated with myocarditis in fetuses, infants, children, and a few adults.
 Diagnosis has often been based on serologic findings suggestive of a concurrent B19 infection, but in
many cases B19 DNA has been demonstrated in cardiac tissue.
 B19-related myocarditis is plausible because fetal myocardial cells are known to express P antigen, the
cell receptor for the virus.
 In the few cases in which histology is reported, a predominantly lymphocytic infiltrate is described.
Outcomes have varied from complete recovery to chronic cardiomyopathy to fatal cardiac arrest.
 Although B19-associated myocarditis seems to be a rare occurrence, there appears to be enough
evidence to consider B19 as a potential cause of lymphocytic myocarditis, especially in infants and
immunocompromised persons.
Other Cutaneous Manifestations
 A variety of atypical skin eruptions have been reported with B19 infection.
 Most of these are petechial or purpuric in nature, often with evidence of vasculitis on biopsy.
 Among these rashes, the papular-purpuric “gloves and socks” syndrome (PPGSS) is well established
in the dermatologic literature as distinctly associated with B19 infection.
 PPGSS is characterized by fever, pruritus, and painful edema and erythema localized to the distal
extremities in a distinct “gloves and socks” distribution, followed by acral petechiae and oral lesions.
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The syndrome is self-limited and resolves within a few weeks.
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Although PPGSS was initially described in young adults, a number of reports of the disease in
children have since been published.
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In those cases linked to B19 infection, the eruption is accompanied by serologic evidence of
acute infection.
DIAGNOSIS
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The diagnosis of erythema infectiosum is usually based on clinical presentation of the typical rash and
rarely requires virologic confirmation.
Similarly, the diagnosis of a typical transient aplastic crisis in a child with sickle cell disease is generally
made on clinical grounds without specific virologic testing.
Serologic tests for the diagnosis of B19 infection are available.
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B19-specific IgM develops rapidly after infection and persists for 6-8 weeks.
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Anti-B19 IgG serves as a marker of past infection or immunity.
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Determination of anti-B19 IgM is the best marker of recent/acute infection on a single serum
sample; seroconversion of anti-B19 IgG antibodies in paired sera can also be used to confirm
recent infection.
•
Demonstration of anti-B19 IgG in the absence of IgM, even in high titer, is not diagnostic of recent
infection.
Serologic diagnosis is unreliable in immunocompromised persons; diagnosis in these patients requires
methods to detect viral DNA.
•
Because the virus cannot be isolated by standard cell culture, methods to detect viral particles or
viral DNA, such as polymerase chain reaction and nucleic acid hybridization, are necessary to
establish the diagnosis.
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•
•
These tests are not widely available outside of research centers or reference laboratories.
Prenatal diagnosis of B19-induced fetal hydrops can be accomplished by detection of viral DNA
in fetal blood or amniotic fluid by these methods.
DIFFERENTIAL DIAGNOSIS
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The rash of erythema infectiosum must be differentiated from:
•
rubella, measles
•
enteroviral infections
•
drug reactions.
Rash and arthritis in older children should prompt consideration of juvenile rheumatoid arthritis, systemic
lupus erythematosus, serum sickness, and other connective tissue disorders.
TREATMENT
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There is no specific antiviral therapy for B19 infection.
•
Commercial lots of intravenous immune globulin (IVIG) have been used with some success to
treat B19-related episodes of anemia and bone marrow failure in immunocompromised children.
•
Specific antibody may facilitate clearance of the virus; it is not always necessary, however,
because cessation of cytotoxic chemotherapy with subsequent restoration of immune function
often suffices.
•
In patients whose immune status is not likely to improve, such as patients with AIDS,
administration of IVIG may give only a temporary remission, and periodic re-infusions may be
required.
•
In patients with AIDS, clearance of B19 infection has been reported after initiation of highly active
antiretroviral therapy (HAART) without the use of IVIG.
No controlled studies have been published regarding dosing of IVIG for B19-induced RBC aplasia.
•
Doses reported with good results in a limited number of cases include 200 mg/kg/day for 5-10
days and 1g/kg/day for 3 days. IVIG should not be used for treatment of B19-induced arthropathy.
B19-infected fetuses with anemia and hydrops have been managed successfully with intrauterine RBC
transfusions, but this procedure has significant attendant risks.
•
Once fetal hydrops is diagnosed, regardless of the suspected cause, the mother should be
referred to a fetal therapy center for further evaluation because of the high risk for serious
complications.
COMPLICATIONS


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Erythema infectiosum is often accompanied by arthralgias or arthritis in adolescents and adults that may
persist after resolution of the rash.
B19 may rarely cause thrombocytopenic purpura.
Neurologic conditions, including aseptic meningitis, encephalitis, and peripheral neuropathy, have been
reported in both immunocompromised and healthy individuals in association with B19 infection.
The incidence of stroke may be increased in children with sickle cell disease following B19-induced
transient aplastic crisis.
B19 is also a cause of infection-associated hemophagocytic syndrome, usually in immunocompromised
persons.
PREVENTION


Children with erythema infectiosum are not likely to be infectious at presentation because the rash and
arthropathy represent immune-mediated, postinfectious phenomena.
•
Isolation and exclusion from school or child care are unnecessary and ineffective after diagnosis.
Children with B19-induced RBC aplasia, including the transient aplastic crisis, are infectious upon
presentation and demonstrate a more intense viremia.
•
Most of these children require transfusions and supportive care until their hematologic status
stabilizes.
•
They should be isolated in the hospital to prevent spread to susceptible patients and staff.
•
Isolation should continue for at least 1 wk and until after resolution of fever.
•
Pregnant caregivers should not be assigned to these patients.
•
Exclusion of pregnant women from workplaces where children with erythema infectiosum may be
present (e.g., primary and secondary schools) is not recommended as a general policy because it
is unlikely to reduce their risk.
•
There are no data to support the use of IVIG for postexposure prophylaxis in pregnant caregivers
or immunocompromised children.
•
No vaccine is currently available.
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