Fifth disease


Fifth disease, also known as erythema infectiosum and slapped cheek syndrome, is a common and contagious disease caused by infection with parvovirus B19. This virus was discovered in 1975 and can also cause other diseases besides fifth disease. Fifth disease typically presents as a rash and is most common in children. Parvovirus B19 can affect people of all ages; about two out of ten persons infected will have no symptoms.

Pathogenicity

Parvovirus B19 is the only virus within the Parvoviridae family to cause disease in humans, especially in children. The most common disease derived from parvovirus B19 is fifth disease. This disease is spread in close contact through respiratory droplets, which can be from the nose, mouth, or direct contact with an infected person. Fifth disease is most commonly spread in the winter and spring seasons among children aged six to fourteen years old. Parvovirus B19 begins replicating anywhere from four to eighteen days after infection. Infected children are most contagious during this period, before they develop the most notable sign—a red rash on their cheeks—along with other symptoms.
Since parvovirus B19 is a single stranded DNA virus, replication can only occur in dividing cells. This is also why populations other than children can become infected with parvovirus B19, develop fifth disease, and experience complications. Certain populations are at higher risk if they have more dividing cells or a weakened immune system than the typical person. These populations include pregnant women, fetuses, adults, and immunocompromised individuals. Over the last few years, first-time infections in pregnant women have been increasing throughout the world. About 1-5% of pregnant women can become infected. Typically, having the virus will not impact the outcome of the pregnancy, and 90% of cases of infected fetuses do not lead to any serious outcomes. However, complications can still occur in both the fetus and mother. For example, if fetuses contract parvovirus B19, possible complications can include or intrauterine fetal death. Additionally, infected adults have been documented to develop , or joint pain. Also, a specific group of immunocompromised people with bone marrow failure and infected with parvovirus B19 have been shown to develop . Other notable complications caused by infection from parvovirus B19 can include gloves and sock syndrome.

Signs and symptoms

The symptoms of fifth disease are usually mild and may start as a fever, headache or a runny nose. These symptoms pass, then a few days later, the rash appears. The bright red rash most commonly appears in the face, particularly the cheeks. Children infected typically go through 3 stages; first when the rash appears on the face. This is a defining symptom of the infection in children. In addition to red cheeks, the second stage consists of children developing a red, lacy rash on the rest of the body, with the upper arms, torso, and legs being the most common locations. The rash typically lasts a few days and may itch; some cases have been known to last for several weeks. People are usually no longer infectious once the rash has appeared. Lastly the third stage consists of recurring rashes due to hot showers, sun exposure, or minor injuries lasting about 11 days.
In children, the risk of Parvovirus B19-related arthralgia is less than 10%, but 19% of those with new-onset arthritis may have developed the B19 infection within the previous 10 weeks. Teenagers and adults may present with joint pain or swelling, out of which 60% infected females and 30% of infected males reported these symptoms. Out of these, 20% of the females may experience continuous joint stiffness for several months or years. Symptoms can persist up to 3 weeks since onset. Sometimes, fifth disease can also cause serious complications, especially if the person is pregnant, has anemia, or is immunocompromised; affecting the blood system, joints or nerves. Adults with fifth disease may have difficulty in walking and in bending joints such as wrists, knees, ankles, fingers, and shoulders.
The disease is usually mild, but in certain risk groups and rare circumstances, it can have serious consequences:
  • In pregnancy, infection in the first trimester is considered more detrimental for the mother but contraction of the infection in the second trimester has been linked to hydrops fetalis, a condition causing excessive build up of fluid in the fetus' tissues and organs causing edema, and thus causing spontaneous miscarriage.
  • Those who are immunocompromised may be at risk for complications if exposed.
  • In less than 5% of women with parvovirus B19 infection, a baby may develop severe anemia leading to miscarriage. This occurs most often during the first half of pregnancy.

    Causes

Fifth disease, also known as erythema infectiosum, is caused by parvovirus B19, which only infects humans. Infection by parvovirus B19 can lead to multiple clinical manifestations, but the most common is fifth disease.
Parvovirus B19 is a small, single-stranded, non-enveloped DNA virus. Binding of B19V capsid to the cellular receptor globoside results in a cascade of structural changes and subsequent signal transduction processes facilitating the entry of parvovirus B19 into the host cell. After gaining access to the host cell, B19V binds to glycosphingolipid globoside targeting erythroid lineage in the bone marrow. Replication of viral genome and release of virus from infected cells lead to various complex effects on host's cellular environment such as induction of DNA damage, hijack of cell cycle and apoptosis.
B19V DNA has been found in a wide range of tissues in healthy and diseased individuals indicates the persistence of B19V infection. According to a clinical microbiology review published by Jianming Qiu "Persistence of viral DNA has been detected in up to 50% of biopsy specimens of the spleen, lymph nodes, tonsils, liver, heart, synovial tissues, skin, brain, and testes, for decades after infection."
Recovery from parvovirus B19 infection is achieved by production of IgM antibodies which are specific for virus and are generated 10–12 days after infection. After day 16, when signs of fifth disease and arthralgia becomes apparent, specific anti B19 IgG is produced by immune cells. Production of serum anti B19 IgG keeps infection under control and facilitates the recovery of erythroid cell production in erythroid lineage cells that were targeted by parvovirus B19.

Transmission

Fifth disease is transmitted primarily by respiratory droplets such as sneezing, coughing, etc.; by direct contact through the saliva or mucus, but can also be spread by contact with infected blood either directly or through blood transfusions. The incubation period is usually between 4 and 21 days. Viremia occurs within 5 to 10 days from exposure to Parvovirus B19, and the person remains contagious 5 days following Viremia. Typically, school children, day-care workers, teachers, and parents are most likely to be exposed to the virus making them high risk population. Rates of transmission of Parvovirus B19 is highest in household settings with people living with infected persons, leading to almost 50%, moderate among adults with a 40% transmission rate, and variable in people working at daycare centers and schools with about 10-60% of transmission risk. The most common time for infection to spread in children causing fifth disease is during late winters and early spring, with outbreaks occurring every 3–4 years. Vertical transmission from maternal infection may also occur, which can lead to hydrops fetalis, a human disease of the fetuses due to the infection's detrimental effects on red blood cell production.
Parvovirus B19 can also be transmitted through blood products such as frozen plasma or cellular blood components (Red blood cells, white blood cells and platelets, as the virus is resistant to the common mechanism of solvent detergent techniques that is used to inactivate pathogens in these blood products.

Diagnosis

The most common manifestation of fifth disease is marked by a red, "slapped cheek" look on the face and a lace-like rash on the body and limbs. The "slapped cheek" appearance of the rash can be suggestive of fifth disease, however, the rash can be mistaken with other skin related disease or infections. Many other viral rashes, like measles, rubella, roseola, and scarlet fever, can look similar to erythema infectiosum. In adults, for example, joint pain caused by parvovirus B19 infection might make doctor consider conditions like the flu and mononucleosis during initial diagnosis. Doctors may also consider ruling out non-infectious causes like drug allergies and certain types of arthritis; which can present with similar symptoms as fifth disease. For this reason, blood samples testing can be definitive in confirming the diagnosis of fifth disease. These blood tests are commonly referred to as "diagnostic assays". An antibody assay uses antibodies designed to detect parvovirus antigen or protein in blood circulation. For example, anti-parvovirus B19 IgM antibody serum assay is often the preferred method to detect previous infection. The assay can result positive one week after initial infection. Negative assay results may prompt retesting in the future to rule out early sampling of blood serum. A positive assay result can also be indicative of an infection within the previous two to six months. People acquire lifetime immunity if IgG antibodies are produced in response to parvovirus B19 exposure. Infection by parvovirus B19 can also be confirmed by isolation of viral DNA detected by Polymerase Chain Reaction or direct hybridization. PCR tests are considered significantly more sensitive to detecting the viral antigen parvovirus B19 compared direct DNA hybridization. In order to diagnose fifth disease in a fetus, a PCR test is done using a sample taken from the amniotic fluid surrounding the baby. A DNA hybridization assay can better detect variants of the parvovirus B19. There exists 3 biological similar genotypes of parvovirus B19, numbered one through three. The most common genotype circulating is genotype one. Laboratory tests can indicate complications of infection, including anemia, liver damage, and low platelet count.
Aside from diagnosing fifth disease with laboratory tests, it is crucial to monitor fetal blood flow in the brain. This involves looking for signs of moderate to severe anemia using an ultrasound.