Roseola Infantum

Roseola is an acute, self-limiting viral exanthematous infectious disease characterized by fever of unknown origin (FUO), a maculopapular rash, and it primarily affects infants and young toddlers.

Roseola is caused by two viruses: HHV-6 and HHV-7. These viruses belong to a group (genus) called Roseolovirus, which is a type of Betaherpesvirus. They're related (subfamily) to viruses like Human Herpesviruses but have some differences. They have a round core covered by a protective layer and a center filled with proteins.

These viruses contain a large set of genetic information called DNA, which carries instructions for making more than 80 different proteins.

Roseola is typically seen in young children, often after they're around 6 months old. This is because the protective antibodies they get from their mothers start to fade around that time.

About 95% of kids who haven't reached school age will get infected by HHV-6 before they turn 2 years old. On the other hand, HHV-7 spreads more slowly and infects around 75% of children between 3 to 6 years old. By the time kids are 3 years old, only about half of them will have been infected by HHV-7.

The most common time for kids to get this infection is when they're between 6 to 9 months old. It doesn't have a specific season when it's more likely to spread—it happens sporadically throughout the year.

The virus is usually passed through saliva from adults who don't show any symptoms. However, in rare cases, around 1% of newborns can get the virus from their mothers during birth.

When someone gets infected with the virus, they experience a viraemic illness, meaning the virus enters the bloodstream and spreads throughout the body. This illness is characterized by the presence of cytopathic effects (CPE).

The CPE refers to changes that happen within infected cells. These changes include the appearance of large, refractile (shining) cells that can have either one nucleus or multiple nuclei. These cells also contain inclusion bodies, which are structures found inside the cell's cytoplasm or nucleus. These changes are a result of the virus's activity within the cells.

The infected cells live slightly longer than usual, but the virus's lytic infection, which causes the cells to burst and release more virus particles, is still the dominant process.

After the initial infection by HHV-6 and HHV-7, the virus doesn't go away completely. Instead, it enters a state of lifelong latency or persistence. This means that the virus remains in the body but doesn't cause active symptoms most of the time. It can reactivate later under certain conditions.

• Sudden onset of fever, sometimes with irritability.
• One of the most consistent features is a high fever of around 39.5°C. This fever can resolve quickly, either within 72 hours through a sudden drop (crisis), or over about 24 hours (lysis).
• There's also the appearance of a rash, which is usually around 2-3mm in size. These rash spots are usually a faint rose color or a pale pink and don't cause itching.
• Rhinorrhea (runny nose) and encephalopathy (brain-related symptoms) are rare but possible.
• Gastrointestinal complaints are not uncommon.
• Lower respiratory infection symptoms and signs are not frequently observed.
• The rash typically appears just as the fever disappears.
• The rash varies and usually lasts for 1-3 days.
• There aren't many associated physical signs, but sometimes there are Nagayama spots, which are small ulcers at the junction between the uvula, palate, and tongue. Mild redness might also be seen in the throat, eyelids, conjunctiva, and tympanic membrane (ear drum).
• Occasionally, there may be swelling of the lymph nodes at the back of the neck (suboccipital lymphadenopathy).

• Neutropenia, which is a decrease in neutrophils, is common. This affects both the total white blood cell count (around 8900/mm3) and the levels of polymorphonuclear (PMN) cells and lymphocytes. This pattern is consistent with HHV-6 and HHV-7 infections.
• Thrombocytopenia may occur. Additionally, elevated levels of transaminases and atypical lymphocytes might be observed.
• In cases of encephalitis, cerebrospinal fluid (CSF) parameters usually fall within normal ranges. However, mild pleocytosis (an increase in white blood cells) with slightly elevated protein levels might be detected in some cases.

Diagnosing roseola is primarily based on clinical observations and often involves excluding other possible causes of the symptoms.

Viral identification of either HHV-6 or HHV-7 involves detecting actively replicating viruses in the patient's blood. This is usually done through viral culture, which can be expensive.

Nuclear amplification methods, such as PCR (polymerase chain reaction), can also be used to detect the presence of the viruses.

Serology, which involves studying the patient's immune response to the viruses, is another diagnostic approach. This can be done using techniques like indirect immunofluorescence, ELISA (enzyme-linked immunosorbent assay), neutralization inhibition, or immunoblots.

A rise in virus-specific IgM (immunoglobulin M) titers is often the first specific clue in serological testing, indicating recent infection.

While complications are rare, they can include:

• Febrile convulsions, which may be prolonged; recurrent seizures could develop afterward
• Encephalitis, an inflammation of the brain
• Rare occurrences of disseminated demyelinating, cerebellitis, hepatitis, and myocarditis (these are usually seen in case reports)
• Long-term developmental disabilities, including autism, have been reported in some cases

Treatment:

• Supportive care is the main approach, focusing on managing fever symptoms.
• Specific antiviral treatment is not generally recommended.

Prognosis:

The prognosis for patients with this condition is generally good, as it tends to be self-limiting in most cases.

Prevention:

HHV6 and HHV7 are widespread viruses that are difficult to control in human populations. Currently, there is no vaccine or other effective means of curtailing their transmission.