Pediatric Chickenpox

Background

Varicella, commonly known in the United States as chickenpox, is caused by the varicella-zoster virus. The disease is generally regarded as a mild, self-limiting viral illness with occasional complications. Varicella is common and highly contagious and affects nearly all susceptible children before adolescence. Although most varicella infection confers life-long immunity, varicella clinical reinfections among healthy children have been described.^[1] (See Pathophysiology and Etiology.)

Before vaccination for varicella became widespread in the United States, this disease affected approximately 4 million children per year, caused as many as 100 deaths in children annually, and was responsible for an estimated $400 million in medical costs and lost wages each year. Since the varicella vaccine was introduced for children aged 12-18 months in the United States in 1995 and booster vaccine given at age 4-5 years, disease incidence has substantially decreased. (See Epidemiology.)

Chickenpox is usually a benign disease in children, and almost all children recover uneventfully. (See Prognosis.) However, varicella is not totally benign even today. A significant number of varicella cases are associated with complications, among the most serious of which are varicella pneumonia and encephalitis.

Presenting symptoms may include a history of low-grade fever, abdominal pain, a history of rash, intense pruritus, headache, malaise, anorexia, cough and coryza, and sore throat. Rash and fever are the typical findings during physical examination in pediatric patients with varicella. An ill appearance should raise concern for pulmonary or neurologic complications or serious bacterial superinfection. (See Clinical Presentation.)

Adolescents, adults, and pregnant patients are at increased risk for severe disease and are often treated with antivirals. Other groups that require specific treatment are children who are immunocompromised, those who are otherwise at risk for severe disease, and those who already have severe disease. Other treatments include supportive measures, administration of varicella zoster immune globulin (VZIG), and management of secondary bacterial infection. (See Treatment and Management.)

Go to Chickenpox for complete nonpediatric information on this topic.

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Pathophysiology

The causative organism, varicella-zoster virus, is a member of the human herpesvirus subfamily Alphaherpesvirinae and, like all herpes viruses, is a DNA virus. The virus enters through the respiratory system (conjunctival or upper respiratory mucosa) and colonizes the upper respiratory tract. Viral replication takes place in regional lymph nodes over the next 2-4 days; 4-6 days later, a primary viremia spreads the virus to reticuloendothelial cells in the spleen, liver, and elsewhere.

After a week, a secondary viremia disseminates the virus to the viscera and skin, eliciting the typical skin lesions (see the images below).^[2] This viremia also spreads the virus to respiratory sites and is responsible for the contagion of varicella before the appearance of the rash. Infection of the central nervous system (CNS) or liver also occurs at this time, as may encephalitis, hepatitis, or pneumonia.

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The pleomorphic rash characteristic of varicella. Papules, vesicles, and pustules are concurrently present.

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Papulovesicular lesions on arm in varying stages of healing in this infant with varicella. Photograph courtesy of Susan Feigelman, MD.

The usual incubation period is 10-21 days. The patient is contagious from 1-2 days before the appearance of rash until the lesions crust over, usually 5-6 days after the rash first appears.

Varicella is associated with humoral and cell-mediated immune responses. These responses induce long-lasting immunity. Repeat subclinical infection can occur in these persons, but second attacks of chickenpox are extremely rare in immunocompetent persons. Reexposure and subclinical infections may serve to boost the immunity acquired after an episode of chickenpox. This may change in the post vaccine era.

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Etiology

Transmission

Varicella is caused by the varicella-zoster virus. The infectious particles are cell-free virus particles derived from skin lesions or the respiratory tract. Transmission occurs mainly through respiratory droplets that contain the virus, making the disease highly contagious even before the rash appears. Direct person-to-person contact with lesions also spreads the virus. Papules and vesicles, but not the crusts, have high populations of the virus. In addition, maternal varicella with viremia can transplacentally spread to the fetus. This leads to neonatal varicella.

Risk factors for severe varicella

Risk factors for severe varicella in neonates are as follows:

• The first month of life: A neonate’s first month of life is a susceptible period for severe varicella, especially if the mother is seronegative.
• Early delivery: Delivery before 28 weeks’ gestation also renders a baby susceptible because transplacental transfer of immunoglobulin G (IgG) antibodies occurs after this time.

Risk factors for severe varicella in adolescents and adults are as follows:

• Steroid therapy: High doses (ie, doses equivalent to 1-2 mg/kg/d of prednisolone) for 2 weeks or more are definite risk factors for severe disease. Even short-term therapy at these doses immediately preceding or during the incubation period of varicella can cause severe or fatal varicella.^[3]
• Malignancy: All children with cancer have an increased risk for severe varicella. The risk is highest for children with leukemia. Almost 30% of patients who are immunocompromised and who have leukemia have visceral dissemination of varicella; 7% may die.
• Immunocompromised state (eg, malignancy, antimalignancy drugs, human immunodeficiency virus [HIV], other congenital or acquired immunodeficient conditions): Defects of cellular but not humoral immunodeficiency are believed to render a person susceptible to severe varicella.
• Pregnancy: Pregnant women have high risk of severe varicella, especially pneumonia.

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Epidemiology

United States statistics

Before varicella vaccine use became widespread, 4 million cases of chickenpox were reported annually. National seroprevalence data for 1988-1994 indicated that 95.5% of adults aged 20-29 years, 98.9% of adults aged 30-39 years, and more than 99.6% of adults older than 40 years were immune to varicella.^[4] The disease was responsible for 11,000 hospitalizations each year and approximately 50-100 deaths.

The adoption of universal vaccination against varicella in 1995 reduced the incidence of varicella, as well as the associated morbidity and mortality rates.^{[5, 6, 7, 8]} By 2000, vaccination coverage among children 19-35 months in 3 communities in Texas, California, and Pennsylvania had reached 74-84%, and reported total varicella cases had declined 71-84%. Most of the decline occurred among children aged 12 months to 4 years; however, incidence declined in all age groups, including infants and adults.^[9]

Currently, fewer than 10 deaths occur per year, most of them in unimmunized people. Although vaccination coverage has exceeded 80% over the past few years, outbreaks of breakthrough varicella still occur in schools and daycare centers.^{[10, 11, 12]}

Children with varicella expose adult contacts in households,^[13] schools, and daycare centers to the risk of severe, even fatal, disease. Household transmission rates are 80-90%. Second cases within the household are often more severe. School or daycare center contact is associated with lower but still significant transmission rates. Children who are susceptible rarely acquire the disease by contact with adults with zoster. Maximum transmission occurs during late winter and spring.

International statistics

Varicella affects nearly all children worldwide who do not have immunity. Annual incidence is estimated at 80-90 million cases. Most developing countries have low immunization rates because of the cost involved, and varicella disease is a risk for travelers to such countries.

A survey of 1473 cases in Japan demonstrated that 81.4% involved children younger than 6 years.^[14] In Japan, the annual prevalence peaked between March and May, with subsequent lower prevalence between August and October.

The epidemiology of varicella differs between countries with temperate climates and those with tropical climates. In most countries with temperate climates, more than 90% of persons are infected by adolescence but in countries with tropical climates, a higher proportion of infections are acquired at older ages, which results in higher susceptibility among adults.

Age distribution for varicella

The maximum incidence of varicella in unvaccinated populations is in children aged 1-6 years. Persons older than 14 years account for 10% of varicella cases. In the United States, the peak age is now 9-11 years.^[5]

In tropical climates, varicella is more common in older children. Most cases in Japan were in children younger than 6 years. Approximately 9.6% of cases involved children younger than 1 year, and almost one third of these were infants younger than 5 months.

Varicella does not have a racial predilection or a sex predilection.

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Prognosis

Otherwise healthy children with varicella have excellent prognoses. In otherwise healthy children aged 1-14 years, the mortality rate is estimated at 2 deaths per 100,000 cases. The case-fatality rate in the general population is 6.7 cases per 100,000 population. Children with immunocompromised states, however, are at risk for severe disease and death. The mortality rate in children who are immunocompromised is much higher than that in otherwise healthy children. Among children with leukemia, the mortality rate of varicella is 7%.

One study suggested that nearly 1:50 varicella cases are associated with complications. Among the most serious complications are varicella pneumonia and encephalitis; both are associated with a high mortality rate. Before universal vaccination, most varicella-related deaths in the United States were from associated encephalitis, pneumonia, secondary bacterial infection, and Reye syndrome. (See Complications.) In addition, significant concerns have been raised about the association of varicella with severe invasive group A streptococcal disease.^[15]

The disease can be serious in neonates, depending on the timing of infection in the mother. Varicella during pregnancy can cause various adverse outcomes for mother and infant, depending on the stage of pregnancy. Neonatal varicella mortality rates can reach 30%.

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Patient Education

Families of children with chickenpox should be instructed to bathe the child regularly to reduce itching and prevent secondary infection. To prevent scratching, which can lead to secondary infection and scarring, the child’s fingernails should be kept short, mittens or socks may be worn on the hands at night, and medication for itching can be given as needed. Aspirin-containing medications should not be used.

Children with chickenpox should avoid nonimmune pregnant women, unimmunized young infants, and others with immunodeficiencies or who are taking prednisone long term. Children with chickenpox may not return to school or day care until all lesions are crusted over.

Parents should take children to the hospital if the following symptoms occur:

• Unusual redness, swelling, or pain over an area of the rash
• Refusal to drink fluids
• Signs of dehydration, such as scanty and yellow-colored urine, increasing drowsiness, dry mouth and lips, excessive thirst, or lethargy
• Confusion, irritability, drowsiness, or difficulty waking
• Inability to walk or unusual weakness
• Complaints of severe headache, stiff neck, and/or back pain
• Frequent vomiting
• Difficulty breathing, chest pain, wheezing, fast breathing, or severe cough
• Fever persisting more than 4 days or fever returns after defervescence
• A more sickly appearance than when last seen by the doctor

For patient education resources, see the Bacterial and Viral Infections Center, as well as Chickenpox and Skin Rashes in Children.

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History

The following are the most common presenting symptoms of varicella:

• Low-grade fever preceding skin manifestations by 1-2 days
• Complaints of abdominal pain by some children
• Pleomorphic rash, usually starting on the head and trunk and spreading to the rest of the body
• Typically, complaints of intense pruritus
• Headache
• Malaise
• Anorexia
• Cough and coryza
• Sore throat

Children with eczema or dermatitis may have severe skin manifestations during varicella.

The history should elicit if a recent outbreak of chickenpox in the community has occurred and if any exposure to varicella at school, daycare, or among family members has occurred. Most patients have a history of exposure in one or more of these three settings. It should also be noted whether the child has previously received varicella vaccine or if the child is immunocompromised (including recent systemic steroid use) to help guide management.

Immunocompromised children often have severe and complicated varicella, and their mortality rate is higher than that in immunocompetent children. Such children are at high risk for developing progressive varicella with multiple organ involvement. These children may have prolonged high fever, prolonged extensive rashes, and hepatitis.

The following categories of patients should be considered immunocompromised:

• Children with any malignancy
• Children on cancer chemotherapy
• Children undergoing high-dose corticosteroid therapy
• Children with congenital cellular immunodeficiencies
• Children on immunosuppressive therapy
• Children with HIV infection

Ask parents whether their child had chickenpox previously. Recently, the validity of reported varicella history as a marker for immunity among unvaccinated individuals has come into question. A recent study recommended that a reported history is no longer highly predictive of seropositivity, suggesting that universal vaccination regardless of history may be prudent.^[16]

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Physical Examination

Rash and fever are the typical findings during physical examination in pediatric patients with varicella. An ill appearance should raise concern for pulmonary or neurologic complications or serious bacterial superinfection. (See Complications.)

Examination of rash

The diagnosis of varicella is made upon observation of the characteristic chickenpox rash. This rash appears in crops. Skin lesions initially appear on the face and trunk, beginning as red macules and progressing over 12-14 days to become papular, vesicular, pustular, and finally crusted. New lesions continue to erupt for 3-5 days. Lesions usually crust by 6 days (range 2-12 d), and completely heal by 16 days (range 7-34 d). Prolonged eruption of new lesions or delayed crusting and healing can occur with impaired cellular immunity.

An otherwise healthy child usually has 250-500 lesions but may have as few as 10 or as many as 1500. The lesions predominate in central skin areas and proximal upper extremities with relative sparing of distal and lower extremities but spread to other skin areas. Some lesions may appear in the oropharynx. Eye lesions are rare.

Each lesion starts as a red macule and passes through stages of papule, vesicle, pustule, and crust. The vesicle on a lesion’s erythematous base leads to its description as a pearl or dewdrop on a rose petal. Vesicles may occur on mucous membranes and break down to form shallow aphthous ulcers. Vesicles can be hemorrhagic. Redness or swelling around a lesion should lead to suspicion of bacterial superinfection. Dermatomal distribution of lesions is characteristic of reactivation rather than primary infection.

The hallmark of the disease is the simultaneous presence of different stages of the rash.

Assessment of fever

Fever is usually low grade (100-102°F) but may be as high as 106°F. In otherwise healthy children, fever typically subsides within 4 days. Prolonged fever should prompt suspicion of complication or immunodeficiency. Although tachypnea may be seen with fever alone, respiratory distress might represent pneumonitis.

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Complications

Pneumonia

Perhaps the most serious complication of varicella is viral pneumonia, which primarily occurs in older children and adults. Respiratory symptoms usually appear 3-4 days after the rash. The pneumonia may be unresponsive to antiviral therapy and may lead to death.

Secondary bacterial infections

Varicella may predispose patients to secondary bacterial infections. Signs and symptoms of such infections can be indistinguishable from uncomplicated varicella during the first 3-4 days. Skin lesion infections are common and occur in 5-10% of children. These lesions provide a portal of entry for virulent organisms; rapidly spreading cellulitis, septicemia, and other serious infections may occur. Superficial infection with impetigo is suggestive of potential bacterial superinfection.

The most common infectious organisms are group A streptococci and Staphylococcus aureus. Varicella places the patient at high risk for acquiring invasive group A streptococcal disease.^{[17, 18, 19]} In addition to toxic shock syndrome, group A streptococci may cause necrotizing fasciitis, bacteremia, osteomyelitis, pyomyositis, gangrene, subgaleal abscess, arthritis, and meningitis in patients with varicella.

Staphylococci reportedly cause cellulitis, impetiginous pox infections, staphylococcal scalded skin syndrome, toxic shock syndrome, pericarditis, and osteomyelitis in these patients.

Neurological complications

Acute postinfectious cerebellar ataxia is the most common neurological complication, with an incidence of 1 case per 4000 patients with varicella. Ataxia has sudden onset that usually occurs 2-3 weeks after the onset of varicella. Manifestations may range from mild unsteadiness to complete inability to stand and walk, with accompanying incoordination and dysarthria. Manifestations are maximal at onset; a waxing and waning course suggests another diagnosis. The sensorium is clear, even when the ataxia is profound.

The condition may persist for 2 months. The prognosis for patients with ataxia is good, but a few children may have residual ataxia, incoordination, or dysarthria.

Encephalitis occurs in 1.7 patients per 100,000 cases of varicella among otherwise healthy children aged 1-14 years. The disease manifests during acute varicella a few days after rash onset. Lethargy, drowsiness, and confusion are the usual presenting symptoms. Some children may have seizures, and encephalitis can rapidly progress to deep coma. This serious complication of varicella has a 5-20% mortality rate.

Reye syndrome was associated with varicella when aspirin use was common. Identification of this association now has made acetaminophen the preferred drug, and Reye syndrome has become rare.

Other neurological complications include aseptic meningitis, myelitis (including Guillain-Barré syndrome), polyradiculitis, and meningoencephalitis. A careful neurologic examination can identify associated meningoencephalitis.

Herpes zoster

A delayed complication of varicella, herpes zoster infection, occurs months to years after the primary infection in about 15% of patients. The complication is caused by virus that persists in the sensory ganglions.

Herpes zoster consists of a unilateral vesicular rash, limited to 1-3 dermatomes. The rash is often painful in older children and adults. Among the health benefits of routine varicella immunization in childhood may be a lifelong decreased risk for reactivation of the virus as shingles.

Other complications

About 5% of children with varicella develop otitis media, caused by the usual pathogens.

Hepatitis is a self-limited accompaniment of varicella. Severe hepatitis with clinical manifestations is infrequent in otherwise healthy children with varicella. Liver involvement is independent of the severity of skin and systemic manifestations. Identify right upper quadrant pain with or without associated jaundice.

Retinitis and optic neuritis have been reported as rare complications of varicella in children who are immunocompetent.^[20]

Other reported complications include glomerulonephritis,^[21] hemorrhagic varicella, thrombocytopenia, myocarditis, appendicitis, pancreatitis, Henoch-Schönlein purpura, orchitis, iritis, and keratitis. Extracutaneous complications increase proportionately to the age of the patient.

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In Utero Varicella Infections

Outcomes of in utero varicella infections vary based on the timing of the infection.

The Royal College of Obstetricians and Gynaecologists recently released revised guidelines for treating chickenpox in pregnancy, summarized below.^{[22, 23]}

Clinicians should ask women presenting for antenatal care about previous chicken pox or shingles infection.

Pregnant women who have not had chicken pox, or who are known to be seronegative for chicken pox, should avoid contact with persons who have chicken pox or shingles and should promptly inform their clinician of potential exposure.

Clinicians should confirm potential exposure by careful history to confirm the significance of the contact and the susceptibility of the patient, as well as by blood test to determine VZV immunity or nonimmunity.

Pregnant women may need a second dose of varicella-zoster immunoglobulin if there is further exposure and 3 weeks have elapsed since the last dose.

Pregnant women who develop the characteristic rash should immediately inform their clinician, and they should be isolated from other pregnant women and neonates until the lesions have crusted over (usually about 5 days after rash onset).

Symptomatic treatment and hygiene are helpful to prevent secondary bacterial infection.

Aciclovir is not licensed for use in pregnancy. Clinicians should advise their patients of the risks and benefits.

Clinicians should consider hospital assessment of women at high risk for severe or complicated chicken pox, regardless of clinical status.

Clinicians should refer pregnant women who develop chicken pox to a fetal medicine specialist, virologist, and neonatologist for decision regarding treatment.

Clinicians should individualize the timing and mode of delivery of the pregnant woman with chicken pox.

Women with chicken pox should breast-feed if they so desire and are in sufficiently good health.

Congenital varicella syndrome

Congenital varicella syndrome occurs in 2% of children born to women who develop varicella during the first or second trimester of pregnancy.^[24] It manifests as intrauterine growth retardation, microcephaly, cortical atrophy, limb hypoplasia, microphthalmia, cataracts, chorioretinitis, and cutaneous scarring. Fetal injury risk is unrelated to the severity of disease in the mother. Zoster exposure during pregnancy has not been associated with fetal injury.

Infantile zoster

Infantile zoster is caused by maternal varicella infection after 20 weeks’ gestation. It usually manifests within the first year of life and commonly involves the thoracic dermatomes.^[25]

Neonatal varicella

Neonatal varicella can be a serious illness, depending on the timing of maternal varicella and delivery. After the initial viremia, the mother develops antibodies against the varicella virus. The severity of the disease in the newborn depends on whether transplacental passage includes only the virus or includes both the virus and the antibodies.

If the mother develops varicella within 5 days before or 2 days after delivery, the baby is exposed to the secondary viremia of the mother. The baby transplacentally acquires the virus but acquires no protective antibodies because of insufficient time for antibodies to develop in the mother. In these babies, neonatal varicella is likely to be severe and disseminated. Hemorrhagic lesions of the liver and lungs characterize this potentially fatal disease.

Onset of maternal varicella more than 5 days ante partum provides the mother sufficient time to manufacture and pass on antibodies along with the virus. Full-term neonates of these women usually have mild varicella because of the attenuating effect of the transplacentally acquired antibodies.

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Approach Considerations

In general, laboratory studies are unnecessary for diagnosis, because varicella is clinically obvious. However, some tests and procedures may be helpful in confirming the diagnosis or identifying complications. Imaging studies are typically not required for varicella unless secondary complications are a concern (eg, chest radiography for varicella pneumonia).

Go to Chickenpox for complete nonpediatric information on this topic.

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Blood Studies

White blood cell count

Most children with varicella have leukopenia in the first 3 days, followed by leukocytosis. Marked leukocytosis may indicate a secondary bacterial infection but is not a dependable sign. Most children with significant secondary bacterial infections do not have leukocytosis; neutrophilic leukocytosis and neutrophilia occur in only a few cases involving serious bacterial infections. Investigations cannot be relied on to diagnose or exclude bacterial infection.

Alanine aminotransferase level

Significant elevations of alanine aminotransferase (ALT) occur in 20-50% of children and adolescents with varicella complicated by hepatitis, but elevations return to normal within one month in almost all cases.

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Staining

Tzanck smear

A Tzanck smear involves scraping the base of the lesions and then staining the scrapings to demonstrate multinucleated giant cells. The presence of multinucleated giant cells suggests a herpes virus infection but is not specific for varicella-zoster virus. Infections with other herpes viruses, such as herpesvirus 1 and 2, also display similar multinucleated giant cells. Thus, this finding is not sufficiently sensitive or specific for varicella and should be replaced by the more specific immunohistochemical staining of such scrapings, if available.

Immunohistochemical staining

Immunohistochemical staining of skin lesion scrapings can confirm varicella. The procedure is useful for high-risk patients who require rapid confirmation.

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Serologic Studies

Serology is mainly used to confirm past infection to assess a patient’s susceptibility status. This helps determine preventive treatment requirements for an adolescent or adult who has been exposed to varicella.

Among the many serologic studies, the most sensitive are the indirect fluorescent antibody (IFA), fluorescent antibody to membrane antigen (FAMA), neutralization test (NT), and radioimmunoassay (RIA). These time-consuming tests require specialized equipment that renders them unsuitable for routine use.

Commercially available latex agglutination (LA) and enzyme-linked immunosorbent assay (ELISA) tests are sensitive and rapid. Although the complement fixation test is often used, its sensitivity is low.

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Polymerase Chain Reaction

Polymerase chain reaction (PCR) examination of skin scrapings is quick and sensitive. This test is replacing other methods as the equipment becomes more widely available.

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Culture

Bacterial culture of lesions may be indicated if signs of superinfection are present.

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Chest Radiography

Children with high temperatures and respiratory signs should have chest radiography to confirm or exclude pneumonia. Chest radiographic findings may be normal or may show diffuse bilateral nodular infiltrates in primary varicella pneumonia. Radiography may also detect focal infiltrates suggestive of secondary bacterial pneumonia.

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Lumbar Puncture

Children with neurological signs should have their cerebrospinal fluid (CSF) examined. The CSF of patients with varicella encephalitis may have few or as many as 100 cells that are polymorphonuclear or mononuclear, depending on the timing of the lumbar puncture. Glucose levels are within the reference range. Protein levels are within the reference range or are slightly elevated.

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Approach Considerations

Treatment approaches include supportive measures, antiviral therapy, administration of varicella zoster immune globulin (VZIG), and management of secondary bacterial infection. Early recognition of secondary bacterial infection and appropriate follow-up are major issues. Failure to recognize occult infection may result in serious illness and even death.

Isolate patients with varicella because the disease is highly contagious and airborne spread can occur. Isolation is especially important if the hospital also admits patients who are immunocompromised because their exposure to the disease can be serious and even fatal.

Go to Chickenpox for complete nonpediatric information on this topic.

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Supportive Therapy

Manage pruritus in patients with varicella with cool compresses and regular bathing. Discourage scratching to avoid scarring. Trimming the child’s fingernails and having the child wear mittens while sleeping may reduce scratching.

Warm soaks and oatmeal or cornstarch baths may reduce itching and provide comfort. Topical calamine lotion may produce caking of lesions and excessive drying of the skin, causing the child to scratch. Oral antihistamines, such as diphenhydramine and hydroxyzine, are used for severe pruritus. Caution must be used with topical diphenhydramine; toxicity may occur from systemic absorption if it is applied to the entire body.

Because of the association of varicella and aspirin therapy leading to Reye syndrome, acetaminophen is recommended for use for the reduction of fever. Studies have also tried to find an association between ibuprofen and risk of fasciitis; the results have not been conclusive.

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Antiviral Therapy

The routine use of acyclovir or valacyclovir in healthy children is recommended by the AAP if it can be given within 24 hours after the rash first appears in children older than 12 years, those with chronic cutaneous or pulmonary disorders, those on long-tern salicylate therapy, and children receiving corticosteroids.^[26] Intravenous acyclovir is recommended only for the treatment of varicella in immunocompromised children or in healthy children with varicella pneumonia or encephalitis. In some instances, acyclovir may be considered for teenagers and adults with otherwise uncomplicated varicella. Additionally, antiviral therapy should be considered for patients with recent steroid use or those with extensive eczema.

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Varicella-Zoster Immune Globulin Therapy

Varicella zoster immune globulin (VariZIG by Cangene) was approved by the FDA in December 2012. It is indicated for high-risk individuals within 10 days (ideally within 4 days) of chickenpox exposure. This agent reduces complications and the mortality rate of varicella, not its incidence. It is used as postexposure prophylaxis in high-risk individuals; for immunologically normal patients, postexposure prophylaxis using varicella vaccine is preferred.^[27] High risk groups include:

• Immunocompromised children and adults
• Newborns of mothers with varicella shortly before or after delivery
• Premature infants
• Infants less than one year of age
• Adults without evidence of immunity
• Pregnant women

VariZIG is administered intramuscularly, never intravenously. The dose is 125 U/10 kg body weight. Administration as soon as possible after exposure is best, but it can prevent or attenuate varicella if administered within 10 days (ideally within 96 hours) of contact. The expected duration of protection is approximately 3 weeks.

Intravenous immunoglobulin (IVIG) has been used to prevent varicella after exposure when VariZIG is not available. Clinical efficacy is not exactly known. Patients already on replacement IVIG do not need VariZIG if their most recent IVIG infusion was within 3 weeks.

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Treatment of Neonatal Varicella

When maternal varicella has developed within 5 days before or 2 days after delivery, neonatal varicella is likely to be severe and disseminated. Prophylaxis or treatment is required with VZIG and acyclovir. Without these drugs, mortality rates may be as high as 30%. The primary causes of death are severe pneumonia and fulminant hepatitis.

If the onset of maternal varicella is more than 5 days ante partum, a full-term neonate will usually have only mild varicella. Treatment with VZIG is not recommended in such cases, but acyclovir may be used, depending on individual circumstances.

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Treatment of Secondary Bacterial Infections

A high level of suspicion is necessary for early recognition and timely appropriate treatment of secondary infections. Suspect secondary infection if systemic manifestations do not improve in 3-4 days, the fever returns or worsens, or the child’s condition deteriorates after initial improvement. Suspicion of secondary bacterial infection should prompt early institution of empirical antibiotic therapy until the results of culture studies become available.

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Varicella Vaccination

Varicella vaccine consists of live attenuated Oka strain varicella virus. The vaccine is safe and highly immunogenic. It was approved for use in the United States in 1995 and has greatly reduced the incidence and mortality due to varicella.^[6] The vaccine has a protective efficacy of 71-100% against varicella. However, it affords a much greater degree of protection against moderate and severe varicella (95-100%).^[28]

Babies are born with protective maternal antibodies to varicella. The half-life of these antibodies is about 6 weeks, and most children have very low levels beyond age 5 months.^[29] However, the varicella vaccine is recommended after age 1 year. A single dose provides protection to approximately 85% of recipients. Vaccine-conferred immunity to varicella wanes over time, making more vaccine recipients susceptible to the disease.

The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) now recommend 2 doses of this vaccine for all children.^{[30, 5, 31]} After the first dose at age 12-15 months, the second should be administered at age 4-6 years. All persons who have received one dose at any time in the past should be offered a second dose. Two doses of the vaccine provide 98% protection against varicella and 100% protection against severe disease.^[5] These children also have a lower incidence of breakthrough varicella.^[28]

A study by Su et al reported that pyrexia, headache, or vomiting occurred in 494 (3%) out of 14,641 adverse events after second-dose vaccination. No new or unexpected safety concerns for second-dose varicella vaccination were found.^[32]

Breakthrough disease involves varicella that occurs after 42 days of immunization. When it occurs, it is usually mild disease but can spread to other susceptible individuals. These children usually have less than 50 skin lesions, and fever is low and quickly subsides. Headache, sore throat, malaise, and anorexia are less frequent.^[33]

Some studies have found that breakthrough disease is more common if the vaccine was given prior to age 14 months, within 28 days after the measles-mumps-rubella (MMR) vaccine, and if the child was on oral steroid therapy.^[34] Duration between vaccination and exposure has also been found to be significant.^[35] Other studies have not found such associations.^[33]

Research study protocols allow varicella vaccine administration to patients with leukemia while they are in remission. Seroconversion is good among children with leukemia.^[36]

Even with high levels of vaccination, varicella outbreaks do occur. Outbreaks can be controlled by offering catch-up vaccination to unimmunized children and adolescents in the area.^[37] Postexposure prophylaxis with the vaccine, if provided within 36-72 hours of contact, can prevent or attenuate disease in the exposed individual.^[38] Although vaccinated children develop milder disease, they are still infectious.

The combined MMRV vaccine (Varivax) has been shown to be associated with an increased risk of febrile seizure occurring 5-12 days following vaccination at a rate of 1 in 2300-2600 in children aged 12-23 months compared with separate MMR vaccine and varicella vaccine administered simultaneously.^{[39, 40]} As a result, the CDC Advisory Committee on Immunization Practices (ACIP) recommends that separate MMR and varicella vaccines be used for the first dose, although providers or parents may opt to use the combined MMRV for the first dose after receiving counseling regarding this risk.^[41] MMRV is preferred for the second dose (at any age) or the first dose if given at age 48 months or older.

It is estimated that there is a slightly higher risk of febrile seizures in children aged 12-23 months vaccinated with the MMRV when compared with separate MMR and varicella vaccine administration. The period of risk for febrile seizures is from 5-12 days after receipt of the vaccine. However, there is no increased risk of febrile seizures among patients aged 4-6 years receiving the MMRV. Thus, the American Academy of Pediatrics recommends that either MMR and varicella vaccines separately or the MMRV be used for the first dose of measles, mumps, rubella, and varicella vaccines administered at age 12-47 months. For the first dose of measles, mumps, rubella, and varicella vaccines administered at ages 48 months and older, and for dose 2 at any age (15 mo to 12 y), use of MMRV is preferred.^[42]

Data from postlicensure studies do not suggest that children aged 4-6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children the same age who received MMR vaccine and varicella vaccine administered as separate injections at the same visit.^[41]  

Another study by Marin et al that examined postlicensure estimates of varicella vaccine effectiveness among healthy children reported that one dose of varicella vaccine was moderately effective in preventing all varicella and highly effective in preventing moderate/severe varicella, with no differences by vaccine. The study also added that the second dose adds improved protection against all varicella.^[43]

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Admission to Intensive Care Unit

Children who develop severe and life-threatening varicella complications may require hospitalization in an intensive care unit (ICU). The following findings are indications for admission to the ICU:

• Altered consciousness
• Seizures
• Difficulty walking
• Respiratory distress
• Cyanosis
• Low oxygen saturation

Hospitalize and treat all newborns whose mothers developed varicella less than 5 days before or within 2 days after delivery. Inpatient care of varicella requires strict isolation from other patients and susceptible healthcare workers. A negative pressure room is ideal.

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Transfer to Tertiary Care Facility

Most cases of hospitalized uncomplicated varicella do not require transfer to a tertiary care pediatric facility. However, immunocompromised children with varicella may develop significant morbidity and mortality and should be transferred to a tertiary care pediatric center. Similarly, patients with complications of varicella, such as pneumonia, encephalitis, or severe skin manifestations such as necrotizing fascitis, should be transferred to a tertiary pediatric facility.

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Dietary Measures

Advise parents to provide a full and unrestricted diet to the child. Some children with varicella have reduced appetite and should be encouraged to take sufficient fluids to maintain hydration. Adequate hydration is especially important if the child is receiving acyclovir because the drug can crystallize in the renal tubules if administered to dehydrated individuals.

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Restriction of Activity

The AAP recommends excluding affected children from school until the sixth day of rash.^[30] However, this may not prevent spread of varicella, because the child is infective before the rash appears. Children with chickenpox should avoid nonimmune pregnant women, unimmunized young infants, and others with immunodeficiencies or who are taking prednisone long term. No other activity restrictions are needed for young children with uncomplicated varicella.

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Consultations

Consult with an infectious disease specialist in the following situations:

• Progressive or severe varicella
• Life-threatening complications (eg, encephalitis, pneumonia)
• Serious secondary bacterial infections, especially group A streptococcal superinfections, which may evolve rapidly into necrotizing fasciitis and toxic shock syndrome

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Medication Summary

Medications used in the treatment of varicella include antivirals, antipyretics, antihistamines, and immune globulin.

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Acyclovir (Zovirax)

• Dosing, Interactions, etc.

Clinical Context:  Acyclovir is an antiviral agent that acts by inhibiting herpes virus DNA polymerase and terminating viral replication. It reduces the number of lesions and duration of fever if it is started within 24 hours of rash appearance. In young children with uncomplicated varicella, the benefit of acyclovir therapy is only marginal, and its use is not routinely recommended. It does not affect the incidence of pruritus, complications, or secondary transmission. It is always used for complications of varicella (eg, encephalitis, pneumonia) and for immunocompromised individuals with varicella.

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Class Summary

Chickenpox is usually a benign disease in children, and almost all children recover uneventfully. However, adulthood, adolescence, and pregnancy increase the risk for severe disease. Such patients are often treated with antiviral drugs. Other groups that require specific treatment are children who are immunocompromised, those who are otherwise at risk for severe disease, and those who already have severe disease. Acyclovir is the drug of choice for these situations. Other drugs are famciclovir (not approved for children) and foscarnet.

These agents are used for treatment of immunocompromised children or in healthy children who develop varicella pneumonia or encephalitis. The routine use of acyclovir in healthy children is not universally recommended. In some instances acyclovir may be considered for teenagers and adults with otherwise uncomplicated varicella.

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Acetaminophen (Tylenol, Feverall, Tempra, Aspirin-Free Anacin)

• Dosing, Interactions, etc.

Clinical Context:  Acetaminophen is the drug of choice because it has no association with Reye syndrome. It is available as drops containing 80 mg/0.8 mL; a suspension containing 160 mg/5 mL; a chewable tablet or capsule containing 80 mg; and a tablet containing 160 mg, 325 mg, or 500 mg.

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Ibuprofen (Motrin, Ibuprin)

• Dosing, Interactions, etc.

Clinical Context:  Ibuprofen A is a propionic acid–derivative NSAID. It acts by inhibiting prostaglandin synthesis and also has anti-inflammatory and analgesic properties. It is available as an oral suspension (100 mg/5 mL) and a tab containing 200 mg, 400 mg, 600 mg, or 800 mg.

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Class Summary

These agents inhibit central synthesis and release of prostaglandins that mediate the effect of endogenous pyrogens in the hypothalamus; thus, they promote the return of the set-point temperature to normal.

The fever is usually low grade but may be elevated. Acetaminophen is probably the safest drug to use for this purpose. Salicylate usage for varicella is associated with Reye syndrome; therefore, never prescribe these agents. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suspected of suppressing immune function and promoting infection progress in patients infected with invasive group A streptococci.

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Diphenhydramine (Benadryl)

• Dosing, Interactions, etc.

Clinical Context:  Diphenhydramine is an antihistamine that has a sedating effect and is effective for pruritus. It is available as a liquid containing 12.5 mg/5 mL, capsule containing 25 and 50 mg, and injection containing 50 mg/mL.

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Hydroxyzine (Vistaril)

• Dosing, Interactions, etc.

Clinical Context:  Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in subcortical region of the CNS. It is a second-line agent useful for pruritus when diphenhydramine is ineffective.

Hydroxyzine may only be given orally or intramuscularly (IM). It is available as a 25- or 50-mg capsule; 10 mg/5 mL suspension; 10-, 25-, or 50-mg tablet; or 25-mg/mL and 50-mg/mL for intramuscular injection.

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Class Summary

These agents may control pruritus by blocking the effects of endogenous release of histamine. Pruritus can be severe in varicella, preventing sleep and possibly leading to scarring or secondary infection. Nonsedating antihistaminics lack sufficient antipruritic action. The value of local preparations (eg, calamine, antihistamines) is unproved. Topical antihistamines can cause significant sedation from absorption through injured skin.

These agents act by competitive inhibition of histamine at the H₁ receptor and mediate wheal and flare reactions, bronchial constriction, mucous secretion, smooth muscle contraction, edema, hypotension, central nervous system (CNS) depression, and cardiac arrhythmias.

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Varicella zoster immune globulin, human (VariZIG)

• Dosing, Interactions, etc.

Clinical Context:  Varicella zoster immune globulin (VZIG) contains immunoglobulin G (IgG) varicella-zoster antibodies. It provides passive immunization to exposed individuals at high risk of complications from varicella (eg, immunocompromised children or adults, pregnant women, newborns of mothers with varicella close to delivery, premature infants, normal susceptible adults, full-term infants < 1 year). Administer by deep IM injection, preferably in deltoid muscle. For neonates or infants, administer IM in anterolateral aspect of thigh.

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Class Summary

The specific immune globulin with IgG varicella zoster antibodies provides passive immunization for susceptible individuals when administered within 10 days (ideally within 96 hours) of exposure.^[27]

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Varicella virus vaccine (Varivax)

• Dosing, Interactions, etc.

Clinical Context:  The varicella virus vaccine is indicated for children aged between 12 months and 12 years.

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Class Summary

Varicella vaccine consists of live-attenuated Oka strain varicella virus. The vaccine is safe and highly immunogenic. It was approved for use in the United States in 1995 and has greatly reduced the incidence of and mortality from varicella.^[6] The vaccine has a protective efficacy of 71-100% against varicella. However, it affords a much greater degree of protection against moderate and severe varicella (95-100%).^[28]

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