Three-day feverThree-day fever is an infectious disease that primarily affects infants and young children. Most patients develop a rapidly rising high fever that lasts for about three to four days. The fever is followed by a rubella-like, non-itching exanthema.
exanthema subitum, roseola infantum, sixth disease, three-day fever, 3-day fever, three-day exanthema, pseudorubella
Three-day fever (ICD-10 B08.2) is a contagious infectious disease caused by human herpesviruses (HHV-6B, less commonly HHV-7). Other common names are exanthema subitum and roseola infantum. Older persons three-day fever is also known as sixth disease or. Sixth disease known. The mostly harmless disease affects preferably infants and toddlers. The characteristic symptom is a sudden high fever that lasts for about three to four days. About 10% of the children suffer from febrile convulsions during the course of the disease. When the fever subsides, a very small spotted rash resembling red chalk necrotic rash appears. The therapy is symptomatic. Usually remains limited to fever-reducing measures. In otherwise healthy children, three-day fever almost always heals without problems.
Three-day fever is the most common exanthem disease in infancy and early childhood. The causative herpes viruses HHV-6 and -7 occur ubiquitously. It is estimated that about 80-100% of the population is infected. The main peak of illness is between six months and two years of age.
Infections with HHV-6 occur mainly between nine and twelve months of age. By the second birthday, almost all children are seropositive.
HHV-7 is predominantly found in older children from the age of two onwards. The median age of onset of symptomatic HHV-7 infections is 26 months. By the end of the sixth year, up to 86% of children are seropositive.
Cause of the three-day fever are the human herpesviruses type 6 and 7 from the group of beta-herpesviruses. The majority of diseases (up to 90%) are based on HHV-6 infection. Type 7 HHV are responsible for exanthem disease in only about 10-30% of cases (depending on the author).
HHV-6 and-7 are double-stranded DNA viruses that are structurally closely related to cytomegalovirus (CMV).
HHV-6 isolates can be divided into two serotypes: 6A and 6B. However, according to current knowledge, practically only type B seems to be associated with three-day exanthema in Europe.
Both viruses (HHV-6B and HHV-7) persist in the organism for life after the primary infection, mainly in salivary glands and peripheral blood mononuclear cells (PBMC). Under certain circumstances, such as immunosuppression, the latently infectious viruses can become active again. These reactivations are sometimes considered to be the trigger of pityriasis rosea or pityriasis rosea. Rose lichen discussed.
The incubation period is 5 to 15 days.
Pathogen reservoir for HHV-6 and -7 is exclusively humans. Three-day fever can originate both from primarily infected persons and from – usually asymptomatic – persons with latent infections.
Transmission of the viruses occurs primarily via infectious saliva, usually after oropharyngeal contact within the family. Rarely, aerogenic transmission by droplet infection, blood products, organ transplantation, and sexual intercourse is possible. Symptomatic connatal infection is unlikely due to high immunity rate.
HHV-7 can theoretically be passed to the child via infected breast milk.
Some studies support the amption that an early infection with HHV-6 protects against a later HHV-7 infection. However, definitive proof of this hypothesis is still lacking.
After transmission, all herpes viruses use the genetic program of the host cells. T cells on. Invade them. The viral envelope fuses with the cell membrane. The capsid is transported to the nucleus, where the double-stranded viral DNA also replicates. In the lytic-productive cycle of the herpes viruses the healthy host cells die off.
In the symptomatic stage, the viruses are found lymphocyte-associated and in plasma. In the latency period, the pathogens are only present in monocytes or in the nucleus. macrophages detectable. They survive in the infected cells, but do not produce further infectious viruses. After reactivation to the lytic infection cycle, symptoms similar to the clinic of the primary infection occur.
Lifelong immunity is expected after HHV-6/7 infection in immunocompetent patients.
Children with exanthema subitum abruptly develop high fever without prior warning signs, lasting for three to four days (rarely longer). The exanthema follows only with the defibrillation. As soon as the fever drops, a macular, sometimes slightly papular skin rash forms – preferably on the trunk and neck of the body. The spots can confluence. Spread to the face and/or extremities. Generally, the exanthema is only transient. Fades relatively quickly – usually within a few hours to three days. In contrast to other exanthematous childhood diseases, the rash in three-day fever is usually not itchy.
Rare associated symptoms include:
– Diarrhea and vomiting – cervical lymphadenopathy – papular enanthem on uvula and/or soft palate (so-called Nagayama spots) – pharyngitis – cough – eyelid edema – bulging (tense) fontanelle – febrile convulsions
Occasionally, febrile courses without exanthema are observed. Completely inapparent courses are also possible, especially with HHV-7 infections (silent feiung).
Older infants or younger schoolchildren with HHV-6/7 infection occasionally present with mononucleosis-like symptoms, fulminant hepatitis, severe hemophagocytosis syndrome, and worsening idiopathic thrombocytopenia (ITP).
Three-day fever is apparently more often associated with febrile convulsions than other infectious diseases. Compared to HHV-6, HHV-7 are more likely to be associated with febrile convulsions.
In contrast to epileptic seizures with a central cause, febrile convulsions are the result of a rapid rise in body temperature to more than 39 degrees Celsius. The symptomatology shows up as a generalized tonic-clonic seizure. The children are usually pale. Lose consciousness for a short time. At first – but not necessarily – the little body cramps (tonic phase). Shortly thereafter, the muscles begin to twitch regularly (clonic phase). A little later, the muscles go limp. Being exhausted. Febrile convulsions usually last only a short time (a few minutes) and are almost always without consequences. They are usually over after a maximum of 15 minutes.
Caveat: In cases of febrile convulsions in infancy, bacterial meningitis should always be ruled out.
In up to 40% of primary infected children with florid HHV-6 infection, viruses are detectable in the cerebrospinal fluid (CSF). Characteristic changes such as pleocytosis or an increase in protein concentration, however, are absent. Rare neurological complications are Guillain-Barre syndrome and meningoencephalitis.
Immunosuppressed patients have an increased risk of complications for:
– interstitial pneumonia – graft-versus-host disease (with and without exanthema) – encephalopathy – sinusitis – retinitis – bone marrow suppression – hepatitis – meningitis
After organ transplantation, HHV reactivation occurs in about 80% of cases. This increases the risk of transplant rejection.
The diagnosis of exanthema subitum is made clinically on the basis of the typical symptoms. During the fever phase there is usually only a suspicion of illness. Only when the fever subsides and the rash begins, a reliable diagnosis can be made. Typically, the period in otherwise healthy children. Complication-free course waited until the fever was removed.
Laboratory diagnostic measures are not warranted in the diagnosis of three-day fever. If, in exceptional cases, a blood sample is nevertheless taken, leukocytosis is initially noticeable. With the onset of the exanthema, leukopenia with relative lymphocytosis is then found.
Serologically, a primary infection can be reliably proven by the detection of HHV-6/7-specific IgM antibodies and/or a seroconversion of HHV-6/7 IgG antibodies. Suitable methods for this are the enzyme-linked immunosorbent assay (ELISA) or the indirect immunofluorescence test (IFT). The viral DNA can be obtained from saliva, blood (whole blood or plasma), urine or cerebrospinal fluid using a polymerase chain reaction (PCR) and determined both qualitatively and quantitatively. However, these procedures are rather uncommon in the diagnosis of three-day fever.
If there is a suspicion of pathogen reactivation in immunosuppressed children, the corresponding antibody titer is sometimes determined in the case of known initial titers.
Caution: A positive serology and/or PCR can only be reliably evaluated with the clinical picture of the patient.
Causative, antiviral treatment of three-day fever is not possible and, on top of that, does not play a role in practice. Therapeutic measures are limited to alleviating symptoms and avoiding complications. This is also sufficient in most cases.
To reduce the fever, adequate antipyretic measures such as calf compresses or the administration of antipyretic agents such as ibuprofen and paracetamol in a dosage and form of administration suitable for children are helpful. Anticonvulsant drugs such as diazepam and clonazepam are sometimes indicated for febrile convulsions.
The younger the child, the greater the loss of fluids due to fever. This applies to accompanying symptoms such as diarrhea and vomiting. Therefore, make sure that sick children drink enough (for example, unsweetened teas made from elderberry, chamomile, lime blossom or lemon balm).
If the risk profile is elevated, for example in immunocompromised children with severe complications such as pneumonia or encephalitis, a trial of therapy with foscarnet and/or ganciclovir may be considered. Controlled studies confirming the success of the therapy are not yet available.
After organ or stem cell transplantation is possibly. infusion of HHV-specific cytotoxic T cells is an option. This adoptive cell transfer is reserved exclusively for specialized centers.
Three-day fever usually has a very good prognosis. Almost all children have survived the illness within a maximum of two weeks without any consequences. Even febrile convulsions rarely lead to serious complications. Three-day fever can occur due to the almost widespread spread of the viruses. Their extremely high contagiousness cannot be safely prevented. There is no vaccination against HHV-6/7 -. Is not to be expected in the future because of the relatively low risks.
Pregnant women form HHV-6/7-neutralizing antibodies; however, these do not protect the newborn sufficiently. A safe nest protection is not given.