Erythema infectiosum, often referred to as fifth disease, is caused by human parvovirus B19. The name "fifth disease" is used because it is considered the fifth viral infection that commonly causes rash in children (the first four are measles, rubella, chicken pox, and roseola). It is also sometimes called slapped-cheek disease.
It occurs mostly during the spring, commonly causing localized outbreaks every few years among children (particularly children aged 5 to 7 years).
Spread seems to be by respiratory droplets and by percutaneous exposure to blood or blood products, with high rates of secondary infection among household contacts; infection can be asymptomatic.
Infection may also occur in adults and may cause various clinical syndromes, including papular-purpuric gloves-and-socks syndrome, arthropathy, transient aplastic crisis, and pregnancy loss or hydrops fetalis Hemolytic Disease of the Fetus and Neonate Hemolytic disease of the fetus and neonate is hemolytic anemia in the fetus (or neonate, as erythroblastosis neonatorum) caused by transplacental transmission of maternal antibodies to fetal... read more . Based on seroprevalence surveys, 50 to 80% of adults have evidence of prior parvovirus B19 infection, which likely confers protective immunity for immunocompetent people.
Pathophysiology of Erythema Infectiosum
Parvovirus B19 is a single-stranded DNA virus that causes transient suppression of erythropoiesis that is mild and asymptomatic except in children with underlying hemoglobinopathies Overview of Hemoglobinopathies Hemoglobinopathies are genetic disorders affecting the structure or production of the hemoglobin molecule. Hemoglobin molecules consist of polypeptide chains whose chemical structure is genetically... read more (eg, sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more 
) or other red blood cell (RBC) disorders (eg, hereditary spherocytosis Hereditary Spherocytosis and Hereditary Elliptocytosis Hereditary spherocytosis and hereditary elliptocytosis are congenital red blood cell (RBC) membrane disorders that can cause a mild hemolytic anemia. Symptoms, generally milder in hereditary... read more 
), who may develop transient aplastic crisis. Also, immunocompromised children can develop protracted viremia (lasting weeks to months), leading to severe anemia (pure RBC aplasia Pure Red Blood Cell Aplasia Acquired pure red blood cell aplasia is a disorder of erythroid precursors that results in an isolated normocytic anemia. White blood cells and platelets are not affected. Symptoms result from... read more ). See table .
Parvovirus B19 infection in pregnancy
Erythema infectiosum can be transmitted transplacentally, sometimes resulting in miscarriage Spontaneous Abortion Spontaneous abortion is pregnancy loss before 20 weeks gestation. Threatened abortion is vaginal bleeding without cervical dilation before 20 weeks in a confirmed viable intrauterine pregnancy... read more , stillbirth Stillbirth Stillbirth is fetal death (fetal demise) at ≥ 20 weeks gestation (> 28 weeks in some definitions). Management is delivery and postpartum care. Maternal and fetal testing is done to determine... read more , or severe fetal anemia with widespread edema (hydrops fetalis Hemolytic Disease of the Fetus and Neonate Hemolytic disease of the fetus and neonate is hemolytic anemia in the fetus (or neonate, as erythroblastosis neonatorum) caused by transplacental transmission of maternal antibodies to fetal... read more ). However, about half of pregnant women are immune because of previous infection.
The risk of fetal death is approximately 2 to 6% after maternal infection, with risk greatest during the first half of pregnancy (1 Pathophysiology reference Erythema infectiosum is caused by acute infection with human parvovirus B19. In children, it causes mild constitutional symptoms and a blotchy or maculopapular rash beginning on the cheeks and... read more 
).
Pathophysiology reference
1. Enders M, Weidner A, Zoellner I, et al: Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: Prospective evaluation of 1018 cases. Prenat Diagn 24(7):513–518, 2004. doi: 10.1002/pd.940
Symptoms and Signs of Erythema Infectiosum
The incubation period of parvovirus B19 infection is 4 to 14 days. Typical initial manifestations of erythema infectiosum are nonspecific flu-like symptoms (eg, low-grade fever, slight malaise).
Several days later, an indurated, confluent erythema appears over the cheeks (“slapped-cheek” appearance), and a symmetric rash appears prominently on the arms, legs (often extensor surfaces), and trunk, usually sparing the palms and soles. The rash is maculopapular, tending toward confluence; it forms reticular or lacy patterns of slightly raised, blotchy areas with central clearing, usually most prominent on exposed areas.
The rash and the entire illness typically last 5 to 10 days. However, the rash may recur for several weeks, exacerbated by sunlight, exercise, heat, fever, or emotional stress.
This photo shows confluent erythematous rash on the face ("slapped-cheek" appearance) with a maculopapular rash on the trunk and arms.
John Kaprielian/SCIENCE PHOTO LIBRARY
This image shows an erythematous rash on the face ("slapped-cheek" appearance) resulting from erythema infectiosum.
Image courtesy of Karen McKoy, MD.
This image shows a maculopapular rash resulting from erythema infectiosum.
Image courtesy of Karen McKoy, MD.
Other manifestations of parvovirus B19 infection
A few patients (more commonly children) develop papular-purpuric gloves-and-socks syndrome (PPGSS), which causes papular, purpuric, or petechial lesions limited to the hands and feet and is often accompanied by fever and oral and/or genital lesions.
Some adults with parvovirus B19 infection develop mild joint pain and swelling (nonerosive arthritis) that may persist or recur for weeks to months.
Diagnosis of Erythema Infectiosum
Physical examination with characteristic rash
For children with risk factors for complications, viral testing and complete blood count
For pregnant patients, antibody measurement and ultrasonography
The rash's appearance and pattern of spread are the only diagnostic features; however, some enteroviruses may cause similar rashes. Distinguishing between these viral etiologies is seldom needed for the clinical care of otherwise healthy children. Rubella Diagnosis (See also Congenital Rubella.) Rubella is a viral infection that may cause adenopathy, rash, and sometimes constitutional symptoms, which are usually mild and brief. Infection during early pregnancy... read more 
can be ruled out by serologic testing; an exposure history is also helpful. Other childhood exanthems have distinct diagnostic features.
Serologic testing is not required in otherwise healthy children; however, children with a known hemoglobinopathy or immunocompromised state should have viral and/or antibody testing as well as a complete blood count (CBC) and reticulocyte count to detect hematopoietic suppression.
In children with transient aplastic crisis or adults with arthropathy, the presence of IgM-specific antibody to parvovirus B19 in the late acute or early convalescent phase strongly supports the diagnosis.
Parvovirus B19 viremia also can be detected by quantitative polymerase chain reaction (PCR) techniques, which are generally used for patients with transient or chronic aplasia, patients who are immunocompromised, and fetuses or neonates with hydrops fetalis or congenital infection.
In pregnant patients, antibodies are measured; IgG suggests immunity due to prior infection (which is usually reassuring) and IgM indicates current or recent infection (which raises concern for potential fetal morbidity). Initial assessment of fetal status is with ultrasonography.
Treatment of Erythema Infectiosum
Supportive care
Only symptomatic treatment of erythema infectiosum is needed.
IV immune globulin has been used to curtail viremia and increase erythropoiesis in patients who are immunocompromised and have pure RBC aplasia Pure Red Blood Cell Aplasia Acquired pure red blood cell aplasia is a disorder of erythroid precursors that results in an isolated normocytic anemia. White blood cells and platelets are not affected. Symptoms result from... read more .
Key Points
Children develop low-grade fever and slight malaise followed several days later by an indurated, confluent erythema on the cheeks (“slapped-cheek” appearance) and a symmetric rash that is most prominent on the arms, legs, and trunk.
There is mild, transient suppression of erythropoiesis that is asymptomatic except sometimes in children with hemoglobinopathies (eg, sickle cell disease) or other red blood cell disorders (eg, hereditary spherocytosis), or immunosuppression.
Risk of fetal death is 2 to 6% after maternal infection, with risk greatest during the first half of pregnancy.
Testing is done mainly in children with transient aplastic crisis or adults with arthropathy.
Treatment is symptomatic, but patients who are immunocompromised may benefit from IV immune globulin.
