Exanthema Subitum
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Roseola, also known as sixth disease, is an
infectious disease An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
caused by certain types of human herpes viruses. Most infections occur before the age of three. Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash. The fever generally lasts for three to five days, while the rash is generally pink and lasts for less than three days. Complications may include febrile seizures, with serious complications being rare. It is caused by ''
human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host. HHV-6 ...
'' (HHV-6A, HHV-6B) or ''
human herpesvirus 7 Human herpesvirus 7 (HHV-7) is one of nine known members of the ''Herpesviridae'' family that infects humans. HHV-7 is a member of ''Betaherpesvirinae'', a subfamily of the ''Herpesviridae'' that also includes HHV-6 and ''Cytomegalovirus'' (HHV ...
'' (HHV-7). Spread is usually through the
saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...
of those who are otherwise healthy. However, it may also spread from the mother to the baby during pregnancy. Diagnosis is typically based on symptoms and does not need to be confirmed with blood tests (PCR or antigen). Low numbers of
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s may also be present. Treatment includes sufficient fluids and medications to treat the fever. Nearly all people are infected at some point. Males and females are affected equally often. The disease may reactivate in those with a
weakened immune system Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affec ...
and may result in significant health problems. The disease was first described in 1910 while the causal virus was isolated in 1988. The name "sixth disease" comes from its place on the standard list of rash-causing childhood diseases, which also includes
measles Measles (probably from Middle Dutch or Middle High German ''masel(e)'', meaning "blemish, blood blister") is a highly contagious, Vaccine-preventable diseases, vaccine-preventable infectious disease caused by Measles morbillivirus, measles v ...
(first),
scarlet fever Scarlet fever, also known as scarlatina, is an infectious disease caused by ''Streptococcus pyogenes'', a Group A streptococcus (GAS). It most commonly affects children between five and 15 years of age. The signs and symptoms include a sore ...
(second),
rubella Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and ...
(third),
Dukes' disease Dukes' disease, named after Clement Dukes (1845–1925), also known as fourth disease, Filatov-Dukes' disease (after Nil Filatov), ''Staphylococcal'' Scalded Skin Syndrome (SSSS), or Ritter's disease is an exanthem (rash-causing) illness primari ...
(fourth, but is no longer widely accepted as distinct from scarlet fever), and
erythema infectiosum 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 cause other diseases besides fifth disease. Fifth ...
(fifth).


Signs and symptoms


Fever

Symptoms begin with a three to six-day febrile illness. During this time, temperatures can peak above 40 °C and children can experience increased irritability with general malaise. Many children in the febrile phase feel well, engaged, and alert. For these patients, fever is usually diagnosed incidentally. The most common complication (10-15% of children between 6 and 18 months) and most common cause of hospitalization in children with primary infection of HHV-6B is
febrile seizure A febrile seizure, also known as a fever fit or febrile convulsion, is a seizure associated with a high body temperature but without any serious underlying health issue. They most commonly occur in children between the ages of 6 months and 5 ye ...
s which can precipitate
status epilepticus Status epilepticus (SE), or status seizure, is a medical condition with abnormally prolonged seizures. It can have long-term consequences, manifesting as a single seizure lasting more than a defined time (time point 1), or 2 or more seizures over ...
due to the sudden rise in body temperature.


Rash

Once the
febrile Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range caused by an increase in the body's temperature set point in the hypothalamus. There is no single agre ...
phase subsides, a rash develops. The rash sometimes presents one or two days after the fever resolves. The rash is classically described as an erythematous
morbilliform The term morbilliform refers to a rash that looks like measles. The rash consists of macular lesions that are red and usually 2–10 mm in diameter but may be confluent in places. A morbilliform rash is a rose-red flat ( macular) or slightly ...
exanthem An exanthem is a widespread rash eruption occurring on the outside of the body, usually presents in children, the rash is typically associated with constitutional symptoms including fever and fatigue. It is usually caused by a virus, but an exanth ...
and presents as a distribution of soft pink, discrete, and slightly raised lesions each with a 2-5mm diameter. It classically begins on the trunk (torso) and spreads outward to the neck, extremities, and face. This pattern is referred to as a centrifugal spread. Usually, peeling and itching are not characteristic of this rash. This phase can last anywhere from several hours to 2 days.


Other symptoms

A small percentage of children acquire HHV-6 with few signs or symptoms of the disease. Children with HHV-6 infection can also present with myringitis (inflammation of the tympanic membranes), upper respiratory symptoms, diarrhea, and a bulging fontanelle. In addition, children can experience pharyngitis with lymphoid hyperplasia seen on the soft palate and swelling of the eyelids. These symptoms usually present during the febrile phase of roseola. Cervical and postoccipital
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In c ...
can also be seen, but this generally presents 2–4 days after the onset of the febrile phase. In rare cases, HHV-6 can become active in an adult previously infected during childhood and can show signs of
mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adu ...
.


Cause

There are nine known human herpesviruses. Of these, roseola has been linked to two: ''
human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host. HHV-6 ...
'' (HHV-6) and ''
human herpesvirus 7 Human herpesvirus 7 (HHV-7) is one of nine known members of the ''Herpesviridae'' family that infects humans. HHV-7 is a member of ''Betaherpesvirinae'', a subfamily of the ''Herpesviridae'' that also includes HHV-6 and ''Cytomegalovirus'' (HHV ...
'' (HHV-7), which are sometimes referred to collectively as
Roseolovirus ''Roseolovirus'' is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpesvirinae''. There are currently six species in this genus. Diseases associated with this genus include: HHV-6: s ...
. These viruses are of the
Herpesviridae ''Orthoherpesviridae'', previously named and more widely known as ''Herpesviridae'', is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are commonly known as herp ...
family and the ''
Betaherpesvirinae ''Betaherpesvirinae'' is a subfamily of viruses in the order '' Herpesvirales'' and in the family ''Herpesviridae''. Mammals serve as natural hosts. There are 26 species in this subfamily, divided among 5 genera. Diseases associated with this su ...
'' subfamily, under which
Cytomegalovirus ''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...
is also classified. HHV-6 has been further classified into HHV-6A and HHV-6B, two ''distinct'' viruses that share 88% of the same DNA makeup, with HHV-6B the most common cause of roseola. After infection, these viruses enter a latent phase. Roseola caused by HHV-7 has been linked to the ability of HHV-7 infection to reactivate latent HHV-6.


Spread

After exposure to roseola, the causative virus becomes latent in its host but is still present in saliva, skin, and lungs. HHV-6 is thought to be transmitted from previously exposed or infected adults to young children by shedding the virus through saliva. Even so, most cases of roseola are transmitted without known exposure.


Diagnosis

The diagnosis of roseola is made clinically based on the presence of the two phases: fever and rash. Laboratory testing is seldom used as the results do not alter the management of the disease. An exception is in people who are immunocompromised in whom serologic tests with viral identification can be used to confirm the diagnosis. Roseola should be differentiated based on symptoms from other similar-appearing illnesses, such as
rubella Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and ...
,
measles Measles (probably from Middle Dutch or Middle High German ''masel(e)'', meaning "blemish, blood blister") is a highly contagious, Vaccine-preventable diseases, vaccine-preventable infectious disease caused by Measles morbillivirus, measles v ...
,
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 cause other diseases besides fifth disease. Fifth ...
,
scarlet fever Scarlet fever, also known as scarlatina, is an infectious disease caused by ''Streptococcus pyogenes'', a Group A streptococcus (GAS). It most commonly affects children between five and 15 years of age. The signs and symptoms include a sore ...
, and drug reactions.


Prevention

Many viruses can cause roseola and are shed by carriers without symptoms. Because of this and the fact that most children with the disease are not seriously ill, there is no particular method of prevention. Proper hygienic measures, like regular handwashing, can be implemented as a routine prevention method. Those exposed or infected have been shown to shed the virus for the rest of their lives. No current guidelines exist regarding children staying home or away from child care when infected.


Treatment

Most cases of HHV-6 infection improve on their own. Because of this,
supportive care Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the co ...
is the mainstay treatment. The febrile phase can be managed using
acetaminophen Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
to control fever and prevent spikes in temperature which can lead to
febrile seizure A febrile seizure, also known as a fever fit or febrile convulsion, is a seizure associated with a high body temperature but without any serious underlying health issue. They most commonly occur in children between the ages of 6 months and 5 ye ...
s. In the case of febrile seizures, medical advice should be sought, and treatment aggressively pursued. Antiepileptic drugs are not recommended for patients who develop seizures from roseola. Once children have entered the rash phase, reassurance is important as this indicates the resolution of the infection. If
encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...
occurs in
immunocompromised Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
children,
ganciclovir Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections. Ganciclovir was patented in 1980 and approved for medical use in 1988. Medical use Ganciclovir is indicated ...
or
foscarnet Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate Structural analog, analog ...
have inconsistently shown usefulness in treatment. Treatment of children who are immunocompromised centers around decreasing their levels of immunosuppression as much as possible.


Prognosis

Children infected with roseola generally have a good prognosis. Most recover without intervention or long-term effects.


Epidemiology

Between the two human herpesvirus 6 types, HHV-6B has been detected much more frequently in hosts. HHV-6B has been shown to affect about 90% of children before the age of 3. Out of these, 20% develop symptoms of roseola, also known as exanthem subitum. Roseola affects girls and boys equally worldwide year-round. Roseola typically affects children between six months and two years of age, with peak prevalence in children between 7 and 13 months old. This correlates with the decrease in maternal antibodies, thus virus protection, that occurs at the age of 6 months. Out of all emergency department visits for children between ages 6 months and 12 months who have a fever, twenty percent of these are due to HHV-6. Many children exposed and infected can present without symptoms, which makes determining the incidence within the population difficult.


History

John Zahorsky MD wrote extensively on this disease in the early 20th century, his first formal presentation was to the St Louis Pediatric Society in 1909 where he described 15 young children with the illness. In a JAMA article published on Oct 18, 1913, he noted that "the name 'Roseola infantilis' had an important place in the medical terminology of writers on skin diseases" but that descriptions of the disease by previous writers tended to confuse it with many other diseases that produce febrile rashes. In this JAMA article, Zahorsky reports on 29 more children with roseola and notes that the only condition that should seriously be considered in the differential diagnosis is German measles (
rubella Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and ...
) but notes that the fever of rubella only lasts a few hours whereas the
prodromal In medicine, a prodrome is an early Medical sign, sign or symptom (or set of signs and symptoms, referred to as prodromal symptoms) that often indicates the onset of a disease before more diagnostically specific signs and symptoms develop. More spe ...
fever of roseola lasts three to five days and disappears with the formation of a
morbilliform The term morbilliform refers to a rash that looks like measles. The rash consists of macular lesions that are red and usually 2–10 mm in diameter but may be confluent in places. A morbilliform rash is a rose-red flat ( macular) or slightly ...
rash.


Names


Research

HHV-6 has been tentatively linked with
neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
s.


See also

*
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 cause other diseases besides fifth disease. Fifth ...


References


External links

* {{DEFAULTSORT:Exanthema Subitum Virus-related cutaneous conditions Pediatrics Wikipedia medicine articles ready to translate