• Clinical diagnosis is based on the characteristic pruritic rash. It is generalized but concentrated on the head, scalp, and trunk, with fewer lesions on the extremities.
• The rash progresses from maculopapular to vesicular, to pustular, and finally scabs. Often all stages of the rash are present at the same time.
• In uncertain cases, the polymerase chain reaction (PCR) test can be used to detect VZV in vesicular fluid, scabs, throat swabs, cerebrospinal fluid (CSF), blood, or saliva.
• Uncomplicated cases in healthy children over 1 year and under 12 years can be treated symptomatically with antipyretics and antipruritics. Do not use aspirin because of the risk of Reye’s syndrome.
• Disease is more severe in infants, adolescents, and adults. Antiviral treatment is recommended in these age groups.
• Acyclovir is available in a liquid suspension. Infant dosing is 20 mg/kg (max 800 mg) every 6 hours for 7–10 days.
• In adolescents and adults, Valacyclovir (Valtrex) is preferred because of better bioavailability. It is dosed 1000 mg twice daily for 7 days.
• For disease in the immunocompromised, IV acyclovir is indicated. The recommended dosage is 10–15 mg/kg every 8 hours.
Varicella is a benign, self-limited disease in healthy children but can cause severe morbidity and mortality in infants, adolescents, adults, and the immunocompromised. Before routine vaccination beginning in 1995, varicella was an extremely common disease of childhood. In temperate climates, over 90% of people were infected before adolescence. Incidence peaked in late winter to early spring with epidemics occurring every 2 to 5 years. In tropical climates, infection was much less common and often occurred later in life.
Risk Factors and Prevention
Before the vaccine, varicella was a ubiquitous disease affecting both sexes and all races in similar climates equally. In 1995, a live attenuated varicella vaccine was licensed for use in the United States. It is now routinely used in many other countries. Initially a single 0.5 mL dose was given subcutaneously to children under 12 years of age; however, outbreaks among the vaccinated were often seen. In 2006, the Centers for Disease Control and Prevention (CDC) recommended a two-dose regimen. The first dose is given between 12 and 15 months of age, and the second between 4 and 6 years of age. It is unclear if the vaccine failures seen after only one dose were due to incomplete seroconversion or waning immunity. Though the ideal timing of the two doses is unknown, the regimen was chosen to coincide with the already established measles-mumps-rubella (MMR) vaccination schedule. In those under 12 years, doses need only be separated by 3 months. In those over 12 years, two doses given at least 4 weeks apart is advised. Most adults in the United States are immune even if they have never had the disease or vaccine. This is due to the widespread presence of the disease in the prevaccine years. It is believed they likely had a mild case that was attributed to another viral illness of childhood. However, adults who immigrated from warmer climates may not be immune and vaccination is advised. The vaccine has decreased primary varicella cases by 85% and moderate to severe cases by over 95%. The vaccine does not prevent herpes zoster.
The varicella zoster virus (VZV) is host specific, with humans being the only natural reservoir. It is a member of the herpes virus family. The virus is transmitted by aerosolized respiratory droplets or by contact with varicella or herpes zoster skin lesions. It infects a new host through inoculation of respiratory or conjunctival mucosal cells. There, the virus infects local immune cells and lymph tissues. These cells carry the virus to epithelial cells where the virus replicates, causing cutaneous lesions and viremia. The incubation period can range from 10 to 21 days, and patients are infectious up to 48 hours before the appearance of cutaneous lesions. The lesions first appear as small, erythematous papules and over 12 to 24 hours become vesicles, leading to the characteristic “dewdrop on a rose petal” appearance (Figure 1). They are highly pruritic and often first appear on the head and scalp or trunk (Figure 2). The virus can also produce ulcers in the mucous membranes of the oropharynx and vagina. Over the next 48 hours, vesicular fluid becomes cloudy and then crusts over. The virus can no longer be detected in the fluid after 72 to 96 hours. The highest contagion period is during the vesicular phase, and one is generally considered no longer contagious after all lesions have crusted over.
New skin lesions can continue to develop for an average of 3 to 5 days with a range of 1 to 7, leading to another characteristic feature of varicella: all stages of skin lesions are often present at the same time.
Later crops of lesions tend to develop on the extremities. The lesions are usually superficial and do not scar except possibly at the earliest sites, often the hairline or eyebrows. The varicella zoster virus remains latent in neurons of the dorsal root ganglia, cranial root ganglia, or autonomic ganglia. This occurs after disease or vaccination. If reactivated later in life, it causes herpes zoster (shingles).
FIGURE 1 A, “Dewdrop on a rose petal”; a thick-walled vesicle with clear fluid forms on a red base. B, The vesicle becomes cloudy and depressed in the center (umbilicated), the border is irregular (scalloped). C, A crust forms in the center and eventually replaces the remaining portion of the vesicle at the periphery.
FIGURE 2 The disease starts with lesions on the trunk and then spreads to the face and extremities.
The disease often begins with fever, malaise, headache, and anorexia, followed by the appearance of the distinctive rash. The rash is pruritic, and after 24 to 48 hours, papules, vesicles, pustules, and scabs are all present on the body at the same time. The rash is more heavily concentrated on the head, scalp, and trunk and lesions can be tender.
Lesions on mucous membranes are possible. The rash may also be accompanied by mild abdominal pain.
The diagnosis has historically been clinical, based upon the distinctive rash, associated symptoms, and possible exposures. However, because the incidence of varicella has dramatically decreased with the use of the vaccine, many newer physicians may have a difficult time recognizing varicella. Diagnosis can also be difficult in the immunocompromised, who can have a severe and atypical presentation. In the past, the gold standard for diagnosis was viral culture of vesicular or bodily fluids. However, this was time- consuming and expensive. Today, PCR is used to amplify and detect viral DNA in vesicular fluid, scabs, skin or throat swabs, blood, CSF, saliva, and even tissue biopsies.
Historically, smallpox was the most serious possibility. There have been no documented cases of smallpox since 1949, and it retains only minimal concern today as a result of the threat of bioterrorism. The main differentiating feature is that smallpox lesions are larger and present in the same stage of evolution. Other conditions similar to varicella include impetigo, eczema herpeticum, herpes simplex infection, hand-foot-mouth disease, herpes zoster, insect bites, drug reactions, and atypical measles. Coxsackievirus and echovirus also cause similar viral exanthems. Hemorrhagic varicella can appear similar to meningococcemia. Stevens-Johnson syndrome and toxic shock syndrome could also present similarly. The main differentiating features are the distribution of rash, simultaneous presence of multiple stages of skin lesion evolution, associated symptoms, and exposures.
The decision to treat depends on the age and health status of the patient and the time since the development of the rash. Studies have shown that, if acyclovir therapy is initiated within 24 hours of the onset of rash, a shorter duration of fever and a modest decrease in skin lesions are seen. Overall, the duration of illness may be shortened up to 24 hours. Improvement in clinical course is relatively small and the window for treatment is short; therefore antiviral therapy is still considered optional in otherwise healthy children. Often, supportive treatment with acetaminophen and antipruritics is all that is needed.
Aspirin should be avoided, however, because of the risk of Reye’s syndrome. Infants, adolescents (over age 12), and adults are at a much higher risk of complications and often have more severe disease.
Treatment of these groups with antiviral medication is advised. Studies have shown treatment with antiviral medication to be of benefit for up to 48 hours, possibly even longer, after the appearance of the rash. Both acyclovir and valacyclovir (Valtrex) can be used.
Valacyclovir is preferred because of better bioavailability and is dosed 20 mg/kg up to 1000 mg twice daily for 7 days. Acyclovir is dosed 800 mg 5 times daily for 5 days. For infants and children who require liquid suspension, acyclovir is the only option. Liquid acyclovir is dosed 20 mg/kg every 6 hours for 7 to 10 days. Pregnant women appear to be particularly vulnerable to pulmonary complications, and any pregnant woman with varicella and evidence of pulmonary involvement (cough, shortness of breath, or abnormal chest X-ray) should be treated. Though not specifically approved for varicella in pregnancy, both acyclovir and valacyclovir have been used in pregnancy for treatment of herpes simples without evidence of maternal or fetal toxicity. Immunocompromised people, such as those with HIV, cancer, organ transplant recipients, or those on immunocompromising drugs are very vulnerable to severe complications and should receive IV treatment as soon as the disease is diagnosed. IV acyclovir is given at 10 to 15 mg/kg twice daily for 7 to 10 days. A switch to orals can be considered when the patient is afebrile and no new lesions appear for at least 24 hours. If acyclovir or valacyclovir cannot be used, either because of resistance or allergy, IV foscarnet (Foscavir) is available. This is not first line, however, given the much lower safety profile, most notably nephrotoxicity, hypocalcemia, and other electrolyte disturbances. Foscarnet can be given at a dose of 40 mg/kg every 8 hours or 100 mg/kg every 12 hours. To prevent adverse effects, it must be infused over at least 1 hour. Currently, famciclovir (Famvir) is primarily used in herpes simplex and herpes zoster outbreaks and not routinely used in varicella infections.
The most common complication in healthy children is secondary bacterial infection from scratching the skin lesions. Keeping nails trimmed can be helpful. The most common infecting agents are Staph. aureus and Strep. pyogenes. If this occurs, antibiotics may be needed.
Serious complications are more likely to occur in adolescents, adults, or the immunocompromised. Pneumonitis or viral pneumonia is the most common, followed by subclinical hepatitis. Neurologic complications are estimated to occur in 1 to 3 per 10,000 cases and include encephalitis, meningitis, cerebellar ataxia, and transverse myelitis. Stroke syndromes, hemorrhagic rashes, and Guillain-Barré syndrome are rarer, but also possible. Infection during the first or second trimester of pregnancy can result in severe congenital malformations. Infection in the third trimester can lead to disseminated severe disease in the newborn.
A common long-term consequence of varicella zoster infection is reactivation later in life, manifesting as herpes zoster, or shingles.
Zoster affects over 1 million people in the United States each year, and most are over age 60. It begins with a prodromal phase that includes pain, paresthesias, and dysesthesia in a dermatomal distribution.
Within a few days, a unilateral, dermatomal macuolopapular rash appears. The rash evolves into vesicles, which usually scab over in 10 days. Complete resolution of the rash and accompanying pain and dysesthesias generally occurs over 4 to 6 weeks. If pain persists after resolution of the rash, this is called postherpetic neuralgia.
Postherpetic neuralgia can be severe, difficult to treat, and last from months to years. In 2006, the FDA approved a zoster vaccine for VZV- seropositive adults over age 60. It is the same live, attenuated vaccine given to children, but at a higher dosage. It increases cell-mediated immunity to the varicella virus. Initial studies showed that the zoster vaccine resulted in a 61% decrease in illness among the vaccinated compared to placebo groups. In those who still developed shingles after receiving the vaccine, there was a shortened severity and duration of the illness as well as a twofold reduction in the occurrence of postherpetic neuralgia. Herpes zoster does recur in 3% to 5% of affected individuals, and those with a history of herpes zoster can still be vaccinated and benefit from the further boost in immunity. The vaccine is generally well tolerated, with minor injection site reactions and headache being the most common adverse effects. The vaccine is contraindicated in pregnant women and those with severe immunodeficiency.
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