Fifth disease

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fifth disease
Other names: Erythema infectiosum, human erythrovirus infection, slapped cheek syndrome, slapcheek, slap face, slapped face[1][2][3]
16-month-old with the typical rash
SpecialtyInfectious disease
SymptomsNone, fever, rash, runny nose[4][5][6]
ComplicationsAplastic anemia, pain in multiple joints, hydrops fetalis[4]
Usual onset4 days to 2 wks after exposure;[7][5] 5 to 15 years old[4]
Duration6 weeks[3]
CausesParvovirus B19[4]
Diagnostic methodBased on symptoms,[3] detection of parvovirus IgM or DNA[6]
Differential diagnosisMeasles, rubella, roseola, scarlet fever[4]
MedicationParacetamol (acetaminophen), NSAIDs[4]
FrequencyCommon in school children[6]

Fifth disease, also known as erythema infectiosum, is a type of viral infection that most commonly occurs in children.[4] The most common symptoms are a low grade fever and rash.[4] Other symptoms may include joint pain, diarrhea, runny nose, vomiting, and headache.[4][5] The rash generally starts in the latter part of the infection, involves the cheeks and spreads to chest and arms.[4] One in five have no symptoms.[6] Complications may include aplastic anemia, pain in multiple joints, and during pregnancy hydrops fetalis.[4]

It is caused by infection by parvovirus B19.[8] It is typically spread via the respiratory route, though may also spread from mother to child during pregnancy and via blood transfusions.[4] Diagnosis is usually based on the symptoms, though it may be confirmed with blood tests.[3]

Treatment is symptomatic and supportive which may include paracetamol (acetaminophen) and NSAIDs.[4] Symptoms generally last for 1 to 3 weeks.[9][7] After recovery people generally do not get the disease again.[5]

Fifth disease is common and typically occurs in those between the ages of 5 and 15.[3][4] Early descriptions of the disease data from at least 1889 by Tschamer and maybe as early as 1799 by Robert Willan.[10][11] In 1905 it was classified as the "fifth rash disease" in the standard list of rash-causing childhood diseases.[5][11]

Signs and symptoms

Fifth disease starts with a low-grade fever, headache, rash, and cold-like symptoms, such as a runny or stuffy nose.[4] These symptoms pass, then a few days later, the rash appears. The bright red rash most commonly appears in the face, particularly the cheeks. This is a defining symptom of the infection in children (hence the name "slapped cheek disease"). Occasionally, the rash will extend over the bridge of the nose or around the mouth. In addition to red cheeks, children often develop 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. Patients are usually no longer infectious once the rash has appeared.[1][2] The rash usually may be itchy especially on the bottom of the feet.[5]

Onset of symptoms is generally within two weeks of exposure.[5]

Teenagers and adults may present with a self-limited arthritis. It manifests in painful swelling of the joints that feels similar to arthritis. Older children and adults with fifth disease may have difficulty in walking and in bending joints such as wrists, knees, ankles, fingers, and shoulders.[1][2]


The disease is usually mild,[13] but in certain risk groups, it can have serious consequences:


Life cycle and virus-host cell interactions of B19V in EPCs[15][16]

Fifth disease is caused by parvovirus B19, which only infects humans.[17]

Parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus. Binding of B19V capsid to the cellular receptor globoside (Gb4Cer) 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 (blood group P antigen) 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 (killing of infected cells).[18][19]

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."[20]

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.[19]


Fifth disease is transmitted primarily by respiratory secretions (saliva, mucus, etc.), but can also be spread by contact with infected blood. The incubation period is usually between 4 and 21 days. Individuals with fifth disease are most infectious before the onset of symptoms ( school children, day-care workers, teachers, and parents are most likely to be exposed to the virus). When symptoms are evident, the risk of transmission is small; therefore, symptomatic individuals do not need to be isolated.[1][2]

Individuals with aplastic anemia, have a very high viral load[21]


In terms of the diagnosis for Fifth disease, we find this can be obtained via bloodwork for specific antibodies[21]


There is no vaccine or medicine that can prevent the disease.[5] The risk of disease can be reduced by washing hands, covering the mouth when you cough, not touching their eyes, nose, or mouth, avoiding close contact with people who are sick, and staying home when you are sick.[5]


Treatment is supportive, and the infection is generally self-limiting. Medications that may decrease symptoms include NSAIDs and paracetamol (acetaminophen).


Any age may be affected, although it is most common in children aged 5 to 15 years.[22] By the time adulthood is reached, about half the population will have become immune following infection at some time in their past.[1][2] Outbreaks can arise especially in nursery schools, preschools, and elementary schools. Infection is an occupational risk for school and day-care personnel.[23] No vaccine is available for human parvovirus B19,[2] though attempts have been made to develop one.[24]


A possible description of the condition by Robert Willan occurred in 1799 and was named "rubeola, sine catarrho".[10] It was better defined by Anton Tschamer in 1889 as a rubella variant (Ortliche Rotheln), identified as a distinct condition in 1896 by Theodor Escherich, and given the name "erythema infectiosum" in 1899.[25] The term "Fifth disease" was coined in 1905 by the Russian-French physician Léon Cheinisse (1871-1924), who proposed a numbered classification of the six most common childhood exanthems.[26][10][27][28][29]

The name "fifth disease" is not typically capitalized, since the name derives from its historical classification as the fifth of the classical childhood skin rashes. They are 1) measles 2) scarlet fever 3) rubella 4) Dukes' disease 5) fifth disease (erythema infectiosum) 6) roseola.

The virus was first described in 1957 at the University of Pennsylvania by Werner, Brachman et al.[30]


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