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Viral exanthems of childhood: Pathology review

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Viral exanthems of childhood: Pathology review

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An 8-year-old boy is brought to the office by his parents for the evaluation of a rash. Two days ago, the patient developed fever, malaise and loss of appetite, which was followed by the appearance of multiple small “fluid filled bumps” on his trunk and face. Last night, the parents noticed a similar rash on his extremities. The rash is intensely pruritic, to the extent that the patient is unable to sleep at night. The patient has not received any vaccines since birth due to parental preference and does not have any medical conditions. He regularly goes to a community school. Temperature is 38.8°C (102°F), pulse is 98/min, respirations are 27/min and blood pressure is 90/55 mmHg. Physical examination is shown.
 
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The oropharyngeal examination is within normal limits. The patient is at increased risk of developing which of the following?

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Content Reviewers:

Antonella Melani, MD

Contributors:

Abbey Richard, Jake Ryan

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.

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. 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 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.

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.