Viral exanthems of childhood: Pathology review

Definitions & Key takeaways

Viral exanthems of childhood are skin rashes that often affect children, and include varicella, hand-foot-mouth disease, roseola infantum, measles, rubella, and erythema infectiosum. Each has distinct symptoms and is caused by a different virus.

Varicella or chickenpox is caused by the varicella-zoster virus. It causes flu-like symptoms and a vesicular rash that spreads to the extremities and face. Measles caused by the measles virus leads to a high fever and a maculopapular rash that spreads in a cephalocaudal progression. There is also rubella caused by the rubella virus, which leads to flu-like symptoms and a maculopapular rash that spreads cephalocaudally, and can be transmitted by a pregnant individual to the fetus via the placenta.

Next is Hand-foot-mouth disease caused by the virus Coxsackievirus group A, which results in flu-like symptoms followed by a vesicular rash that begins in the mouth. Roseola infantum, which is human herpesvirus 6, presents with a high fever and a rose-colored maculopapular rash. There is also Erythema infectiosum caused by parvovirus B19, which presents with flu-like symptoms and a characteristic "slapped-cheek" rash, and can cause anemia in individuals with certain blood disorders or fetal anemia if contracted during pregnancy.

Chapters:

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Case study0:00–1:04

A 1 year old boy named Adam is brought to the pediatric clinic by his mother, who is concerned because Adam developed a pink skin rash that began in the trunk and has now spread to the extremities.
On physical examination, the rash appears to be maculopapular. Upon further questioning, she recalls that Adam had a high fever for the past few days, and the rash appeared after the fever went down.
Next you see Rose, a 9 year old girl who came in with her father, due to a very itchy rash all over her body. Her father claims that the rash started 2 days ago after having a mild fever, and that several of Rose’s schoolmates also have the same rash.
Upon physical examination, you notice that the rash involves her face, trunk, and extremities, and presents with different types of lesions, including papules, vesicles, and crusts.Now, based on the initial presentation, both Adam and Rose seem to have a viral exanthem of childhood, which is a group of eruptive skin rashes caused by viral infection and usually affect children.

Pathology1:04–2:17

Generally, viral exanthems can be macular, papular, maculopapular, or vesicular. A macular rash has macules, which are up to 5 mm in diameter, and completely flat, meaning that you can’t feel them if you run your finger over them.
On the other hand, a papular rash has papules, which are raised bumps that are up to 1 cm in diameter. And a maculopapular has both macules and papules.
Finally, a vesicular rash has vesicles, which are up to 5 mm in diameter, and look like clear blisters filled with fluid.
Viral exanthems of childhood include varicella; hand-foot-mouth disease; roseola infantum; measles; rubella; and erythema infectiosum.Alright, now one of the most common viral exanthems is varicella, more commonly referred to as chickenpox.

Varicella (chickenpox)2:17–9:26

It is caused by the varicella-zoster virus, or VZV for short, which is a DNA virus, and is also known as human herpesvirus 3 or HHV-3, as it belongs to the Herpesviridae family.
Now, this is a highly contagious airborne virus, meaning it’s transmitted from person to person through respiratory droplets; for example, when an infected person sneezes or coughs.
But the virus can also be transmitted by direct contact with the fluid from vesicular skin lesions of an infected person.
Because of that, an important risk factor for varicella involves going to crowded or poorly ventilated public places, such as day-care centers or school, as well as being immunocompromised.
Now, once a person inhales the virus, it travels down the respiratory mucosa and enters respiratory epithelial cells, where it starts replicating.
This is called the incubation period, where the individual is asymptomatic, and lasts 14 to 21 days. So after the incubation period, the virus gets picked up by nearby immune cells and gets transported to a nearby lymph node, so the individual may start to experience prodromal flu-like symptoms, such as a fever that’s often mild, headache, and malaise.
Keep in mind that these prodromal symptoms are typically very mild in children, but tend to be more severe in adults. About 36 to 48 hours later, the immune cells reach the skin, so the virus starts replicating within keratinocytes.
At this point, individuals develop an intensely pruritic rash, which typically starts on the trunk and then spreads to the extremities and the face, eventually covering the entire body, including the scalp.
At first, there’s a maculopapular rash, which then evolves into a vesicular rash, where vesicles come up in groups or crops.
Within 1 to 2 days, these vesicles begin to crust over and form scabs. After 5 days the scabs fall off, typically without leaving a scar, unless these individuals pick or scratch their skin.
Now, as some vesicles heal, new vesicles can pop up. So for your exams, remember that individuals with varicella typically present multiple skin lesions that are in different stages of healing.
Finally, varicella tends to resolve in about one week, providing lifelong immunity. Now, most individuals have chickenpox only once, and will develop immunity against it for the rest of their lives.
However, bear in mind that varicella zoster virus also infects sensory neurons in the skin, and travels backward, or retrogradely, through the neuron to the trigeminal ganglion and the dorsal root ganglia, where it can remain dormant in a latent state for many years.
And that’s a high yield fact! Later on, if the immune system weakens, due to aging, stress, or immunosuppressive therapy, the virus can be reactivated and travel back up, or anterogradely, through the sensory nerve to the skin.
This causes an infection in the innervated skin area, or dermatome, that’s called herpes zoster or shingles. Typically, herpes zoster leads to a rash that looks like a single stripe of vesicles around either the left or right side of the body or on one side of the face, and presents with pain, itching, or tingling of the affected area.
For your exams, remember that herpes zoster that involves the ophthalmic division of the trigeminal nerve is called herpes zoster ophthalmicus, and it presents with eye pain, redness, and swelling, along with a painful vesicular rash that can involve the forehead and the tip of the nose, and a fever.
Now, usually, the rash from herpes zoster resolves over a month, but the pain can often last for more than 90 days, called postherpetic neuralgia, and this is the most common complication of herpes zoster!
Other complications with both varicella and herpes zoster include secondary bacterial infection of the skin lesions, as well as pneumonia, and if the virus gets to the brain, it can cause encephalitis or meningitis.
Finally, in pregnant individuals, getting varicella in the first or second trimester can lead to congenital varicella syndrome in the developing fetus, which can cause limb atrophy, ocular, and neurological defects.
The diagnosis of varicella is mostly clinical, but what you need to know is that Tzanck smear can be performed by scraping a skin lesion to look for multinucleated giant cells in the fluid of the vesicles.
Finally, diagnosis can be confirmed using PCR to detect viral DNA in the fluid of skin lesions; or with a blood test by looking for IgM antibodies against the varicella-zoster virus.
Treatment of varicella can include cool baths, calamine lotions, or topical antipruritic medications to help reduce the itching, as well as anti-inflammatory medications to reduce the flu-like symptoms, but note that aspirin shouldn’t be used in children, because it can trigger Reye syndrome.
And that’s a high yield fact!In addition, immunocompromised individuals can be treated with antiviral medications, such as acyclovir, famciclovir, or valacyclovir.
In some situations, varicella-zoster immune globulin or VZIG which are anti-varicella antibodies can be given to treat immunocompromised or pregnant individuals.
Finally, varicella can be prevented with the varicella vaccine, which is a live attenuated vaccine.Another high yield vesicular rash is hand-foot-mouth disease, caused by the virus Coxsackievirus group A, which is an RNA virus that belongs to the Picornaviridae family.

Hand-foot-mouth disease9:26–12:25

Hand-foot-mouth disease is very contagious, and it’s transmitted via person-to-person skin contact, as well as through respiratory droplets or feces, or via direct contact with a contaminated surface.
Now, when a person becomes infected by this virus, they initially present with flu-like symptoms along with oral pain. After a few days, a rash breaks out.
The first lesions appear as painful vesicles and ulcers in the oral mucosa, and remember this is called herpangina. Soon after, individuals develop small painful oval-shaped vesicles involving the palms of the hands and soles of the feet.
Fortunately, most of the time, hand-foot-mouth disease resolves in a week, but keep in mind that there are rare complications like viral meningitis and encephalitis.
For your exams, remember that there’s only a few conditions that cause a rash on the palms and soles. Besides hand-foot-mouth disease caused by Coxsackievirus A, there’s Rocky Mountain spotted fever caused by the bacterium Rickettsia rickettsii, and secondary Syphilis caused by the bacterium Treponema pallidum.
To help you remember this, think that you drive CARS using your palms and soles. Now, to set these three conditions apart, check the distribution of the rash.
With hand-foot-mouth disease, there’s a painful rash distributed on the skin of the hands and feet, and the mucosa inside the mouth.
On the other hand, with Rocky Mountain spotted fever, there’s a painless erythematous macular rash that starts around the wrist and ankles and then spreads to the palms and soles, as well as to the rest of the body, but generally sparing the face.
Finally, with secondary syphilis, the rash usually appears as painless, rough, reddish spots on the palms and soles, and can spread throughout the body, including the face.
And that’s very high yield!Now, diagnosis of hand-foot-mouth disease can be made using a throat swab or stool specimen, which can be taken for viral culture or PCR.
Treatment is usually pain medications and adequate hydration, especially because the mouth pain can make eating uncomfortable.

Roseola infantum (exanthem subitum)12:25–14:31

The next viral exanthem of childhood is roseola infantum, also known as exanthema subitum or sixth disease. This is caused by human herpesvirus 6, or HHV-6, and less commonly by HHV-7; both of which are DNA viruses that belong to the Herpesviridae family.
Roseola infantum is most common in young children aged between six months and two years, and is primarily transmitted through saliva or via respiratory droplets.
The disease has an incubation period of 1 to 2 weeks, followed by a high fever that may exceed 104 degrees Fahrenheit or 40 degrees Celsius, and usually lasts for several days.
As a consequence, what’s important to remember is that some children may develop febrile seizures. Luckily, the fever tends to resolve quickly, and after it’s over, the child will develop a rose-colored maculopapular rash that begins on the trunk and then spreads to the extremities.
This rash typically clears itself within a few days. You can remember the main features of Roseola with the mnemonic: fever first, Rosy later.
Diagnosis of roseola infantum is usually based upon clinical presentation, and can be confirmed with viral culture or PCR, or by demonstrating a rise in IgG antibodies against HHV-6 or HHV-7.Treatment is usually supportive, and fever can be controlled with antipyretic medications, such as acetaminophen.
Finally, immunocompromised individuals can be treated with antivirals like ganciclovir.Okay so then there’s measles, also called rubeola, which is one of the most contagious infectious diseases.

Measles (rubeola)14:31–18:40

Now, measles is caused by the measles virus, which is an RNA virus that belongs to the Paramyxoviridae family. The measles virus is also transmitted through respiratory droplets or contact with a contaminated surface.
The incubation period is 10 to 14 days, followed by the prodromal period, which typically lasts around 3 days. During the prodromal period, individuals generally present with a high fever combined with the 3 C’s: cough, conjuntivitis, and coryza or a stuffy nose.
In addition, individuals develop Koplik spots, which are small red spots with white centers that appear on the oral mucosa.
One or two days after that, there’s a red, blotchy, maculopapular rash that spreads in a cephalocaudal progression, so from the head downwards to the extremities, but typically spares the palms and soles.
And that’s a high yield fact! This rash eventually fades after about 4 days, leaving behind a persistent cough that can last for another 10 to 14 days.
Once someone has recovered from measles, they have lifelong immunity.Now, in rare cases, measles can lead to complications, such as pneumonia, encephalitis, or severe diarrhea that may result in dehydration.
Although all these complications can lead to death, you should remember that pneumonia is the most common cause of measles-related deaths in children.
In addition, measles can suppress the immune system for up to 6 weeks, and this can contribute to bacterial superinfections like otitis media and bacterial pneumonia.
Another severe and often fatal complication is the development of subacute sclerosing panencephalitis, which can happen 7 to 10 years after the initial infection.
This is thought to be caused by a persistent measles virus infection, which leads to chronic inflammation of the entire brain.
The symptoms of SSPE are initially pretty subtle, like mood or personality changes, but eventually, symptoms can become more severe, leading to dementia and seizures.
If left untreated, subacute sclerosing panencephalitis may lead to coma and death.Another life-threatening complication of measles is giant cell pneumonia.
Fortunately, this complication is quite rare, but for your exams, keep in mind that it tends to affect immunocompromised children.
Diagnosis of measles is usually done by looking for measles-specific IgM antibodies or with PCR. There isn’t a specific antiviral medication, so treatment is mainly supportive and aimed at treating any potential complication.In addition, vitamin A supplementation can be given to young or severely malnourished children, which acts as an immunomodulator that boosts the immune response and decreases the risk of complications and death.
The good news is that measles can be prevented with the measles, mumps, rubella or MMR vaccine, which is a live attenuated vaccine.

Rubella18:40–20:55

Next is rubella, also known as German measles or 3-day measles. It’s caused by the rubella virus, an RNA virus that belongs to the Togaviridae family, and is primarily transmitted through respiratory droplets.
Now, rubella is often asymptomatic, but after a 14 day incubation period, some individuals may start presenting mild flu-like symptoms.
These can include a mild fever and arthralgias, along with postauricular lymphadenopathy, which is an enlargement of the lymph nodes behind the ears.
In addition, some individuals may develop polyarthralgia or polyarthritis, meaning joint pain or arthritis that involve at least five joints.
At the same time, or a few days later, individuals may develop a maculopapular rash that, just like measles, spreads in a cephalocaudal progression, from the face down to the trunk and extremities, but sparing the palms and soles.
The rash typically clears up in about 3 days.Now, for your tests, you must absolutely know that rubella can also be transmitted by a pregnant individual to the fetus via the placenta.
And that’s a high yield fact! And if the infection occurs during the first trimester of pregnancy, the fetus may develop congenital rubella syndrome.
This typically presents with a characteristic triad of symptoms, which includes deafness, cataracts, and congenital heart defects, like patent ductus arteriosus.
Okay, diagnosis of rubella can be done by looking for rubella-specific IgM antibodies or PCR. There’s no specific treatment available, but the good news is that rubella can be prevented with the MMR vaccine.Erythema infectiosum, or fifth disease, is caused by parvovirus B19, the smallest known DNA animal virus, which belongs to the Parvoviridae family.

Erythema infectiosum (fifth disease)20:55–24:44

It’s primarily transmitted by respiratory droplets, but bear in mind that it can also be transmitted through transfusion of infected blood or blood products, or during pregnancy through the placenta.
Now, once inside the body, parvovirus B19 travels to the bone marrow, where it binds to the P antigen on red blood cell precursors, infecting them.
Now, erythema infectiosum has an incubation period of 4 to 14 days, after which symptoms develop.Typically, the virus causes flu-like symptoms like a mild fever, headache, and malaise, which can last for a few days.
What’s high yield is that, as the flu-like symptoms start to improve, a maculopapular rash breaks out on both cheeks, often called "slapped‑cheeks” rash.
Less frequently, individuals may develop a maculopapular, lacy rash on the body that becomes more prominent after sun or heat exposure.
However, keep in mind that adults may not present the characteristic rash, and instead are more likely to develop arthralgia and arthritis, and that’s also high yield!
Luckily, most cases of erythema infectiosum resolve in a week. In a few cases though, parvovirus B19 infection can lead to complications like anemia due to a decreased red blood cell production in the bone marrow.
This is particularly dangerous in individuals who have underlying conditions like sickle cell disease, hereditary spherocytosis, and beta-thalassemia major.
Because they already have fewer red blood cells, parvovirus B19 infection can cause transient aplastic crisis, or shutdown of red cell production in the bone marrow.
Now, parvovirus B19 infection during pregnancy can also cause anemia in the fetus. Because there are fewer red blood cells to carry oxygen, the heart will pump a larger volume of blood to give the growing fetus all the oxygen it needs.
As a result, the pressure inside the fetal blood vessels will increase, and fluid may start to leak out. This can ultimately result in hydrops fetalis, or the abnormal accumulation of fluid in soft tissues, which poses a great risk for spontaneous abortion or still-birth, especially if the infection occurs in the first half of the pregnancy.
The good news is that most fetuses survive, and the infection doesn’t cause any permanent defects or malformations. Diagnosis of erythema infectiosum can be made by identifying parvovirus B19-specific IgM antibodies or via PCR.
There’s no specific antiviral medication, so treatment is mainly supportive, and can involve blood transfusion for transient aplastic crisis and hydrops fetalis.All right, as a quick recap...

Review24:44–28:15

Viral exanthems are eruptive skin rashes that most often affect children, and include varicella; hand-foot-mouth disease; roseola infantum; measles; rubella; and erythema infectiosum.
Varicella or chickenpox is caused by the varicella-zoster virus, and initially causes flu-like symptoms, followed by an intensely pruritic vesicular rash that starts on the trunk and then spreads to the extremities and the face.
The virus can also remain latent in the trigeminal ganglion and dorsal root ganglia. Later on, it can reactivate and cause herpes zoster or shingles, which typically causes a vesicular rash that presents with pain, itching, or tingling in the affected dermatome, and may lead to postherpetic neuralgia.
Hand-foot-mouth disease is a vesicular rash caused by Coxsackievirus group A, and causes flu-like symptoms followed by a vesicular rash that begins in the mouth, called herpangina, and then moves to the palms and soles.
Roseola infantum, also called exanthema subitum or sixth disease, is caused by HHV-6 and less frequently HHV-7. It’s characterized by high fever that may last for several days, followed by a rose-colored maculopapular rash that begins on the trunk and then spreads to the extremities.
Measles, or rubeola, is caused by the measles virus, which leads to a prodromal period with a high fever and the 3 C’s: cough, conjuntivitis, and coryza; as well as Koplik spots.
This is followed by a maculopapular rash that spreads in a cephalocaudal progression, and may rarely lead to complications like pneumonia or encephalitis.
Rubella, or German measles, is caused by the rubella virus, leading to flu-like symptoms and a maculopapular rash that typically spreads in a cephalocaudal progression.
Rubella infection during pregnancy can pass onto the fetus, especially during the first trimester, causing congenital rubella syndrome with the triad of deafness, cataracts, and congenital heart defects.
Finally, erythema infectiosum, or fifth disease, is caused by parvovirus B19, and presents with flu-like symptoms and a characteristic "slapped‑cheek” maculopapular rash.
The main complication is anemia, which can lead to a transient aplastic crisis in individuals who have sickle cell disease, hereditary spherocytosis, and beta-thalassemia major.
Infection during pregnancy can cause fetal anemia, which can result in hydrops fetalis.Okay, back to our cases... Adam is a 1 year old boy who came in with a rose-colored skin rash.

Summary28:15–29:13

A very important clue here is that Adam’s rash began in the trunk and then spread to the extremities. This, combined with the fact that the rash was preceded by a high fever, should make you think of roseola infantum.
Next is Rose, a 9 year old girl who came in with an intensely pruritic skin rash that appeared after having a mild fever, and involves her face, trunk, and extremities.
A key point is that her skin rash presents with lesions of different stages, including papules, vesicles, and crusts. These are unique findings of varicella, which is supported by the fact that several of Rose’s schoolmates have the same rash.