Varicella

Published on 18/03/2015 by admin

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Varicella

Christine Soon and John Berth-Jones

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Varicella, or chickenpox, is the exanthematic illness caused by infection with the herpes virus varicella zoster (VZV). Varicella has a typical incubation period of 10 to 14 days, spreading by direct person-to-person contact or by airborne droplets. The disease is infectious from 48 hours before the rash appears until the vesicles crust.

Varicella occurs most commonly in young children. Systemic symptoms are usually mild, although complications may occur. In adolescents, adults, and immunocompromised individuals of any age it is a more severe disease with a higher complication rate. Treatment is most commonly recommended in this group of individuals. Potential complications include secondary bacterial infection of the skin, bacterial pneumonia, and varicella pneumonitis. Rare complications of varicella include aseptic meningitis, encephalitis, cerebellar ataxia, myocarditis, corneal lesions, nephritis, arthritis, acute glomerulonephritis, Reye’s syndrome, bleeding diathesis, and hepatitis. Herpes zoster (shingles), a delayed complication of varicella, is the subject of a separate chapter.

Management strategy

In the US a routine, two-dose, live, attenuated vaccine program of all healthy persons 12 months of age or older who have not had varicella is now recommended. The first dose is administered at age 12–15 months and the second dose at age 4–6 years. A second dose catch-up vaccination is recommended for those who had previously received one dose, including children, adolescents, and adults. Post-exposure immunization may also be effective for household contacts if given within 3 days of the appearance of the rash in the index case. In the UK, vaccination is recommended for non-immune healthcare workers and other carers who are in frequent contact with individuals (mainly immunocompromised patients) who would be especially vulnerable to the infection, the purpose being to protect these vulnerable individuals.

In healthy children below the age of 12 years, symptomatic treatment is all that is generally required. Acetaminophen (paracetamol) is suitable. Aspirin should be avoided because of the risk of Reye’s syndrome. If a child is the second affected case in a family the illness can run a more severe course and antiviral therapy should be considered. Oral acyclovir is the antiviral of choice and should be started within 24 hours of the rash developing.

In healthy adolescents and adults, oral acyclovir commenced within 24 hours of development of the rash has been shown to be beneficial. Heavy smokers and people with chronic lung disease are at greater risk of developing complications, particularly varicella pneumonitis. Treatment with acyclovir should be given if they are seen within 24 hours of the rash developing. There is no evidence to suggest significant benefit if treatment is started after 24 hours in cases where infection is following the normal course and there are no complications. These patients should be treated symptomatically and advised to return promptly if they deteriorate. Patients with complications require hospital assessment.

Pregnant women are more likely to develop severe or complicated disease. Those who are not immune to varicella should avoid contact with varicella and zoster, and if this occurs they should report the contact immediately. Non-immune pregnant women who have had contact with a person with varicella should receive specific varicella zoster immune globulin (VZIG). VZIG is effective up to 10 days after contact. This has been shown to prevent varicella or modify disease severity. It also reduces the risk of fetal transmission if disease develops. Fetal infection between 3 and 28 weeks’ gestation may cause the fetal varicella syndrome (including developmental abnormalities of the eyes and central nervous system). This occurs in an estimated 0.91% of pregnancies complicated by chickenpox during the first 20 weeks of gestation. The risk is probably greatest when infection occurs between 13 and 20 weeks. During the first trimester the use of acyclovir carries a theoretical risk of possible teratogenesis, although it is not a recognized teratogen. Beyond 20 weeks’ gestation, oral acyclovir can be unequivocally recommended if the patient is seen within 24 hours of the onset of the rash. Pregnant women who are smokers, have chronic lung disease, are taking steroids, or are in the latter half of pregnancy are at greater risk of developing systemic symptoms. Hospitalization should be considered in late pregnancy and in women with chest or neurological symptoms, a hemorrhagic rash, bleeding, or very severe disease with a dense rash and mucosal lesions.

Neonates whose mothers had varicella 7 days before to 7 days after delivery should be given prophylaxis with VZIG. Neonates with varicella whose mothers developed varicella within 7 days prior to delivery may develop severe disease and should be treated with intravenous acyclovir. Treatment should also be considered within 48 hours of development of the rash in other infants with congenital varicella (rash within 16 days of delivery) and severe clinical disease.

Immunocompromised individuals exposed to varicella should be given prophylactic VZIG. It is most effective when given within 72 hours, but may still modify disease if given up to 10 days after exposure. All immunocompromised and immunodeficient patients who develop varicella, including those on oral corticosteroids or with a history of oral corticosteroid intake for more than 3 weeks in the preceding 3 months, should be admitted to hospital and treated with intravenous acyclovir, as they are at risk of severe disease and complications. Resistance to acyclovir can occur in immunocompromised individuals following long-term acyclovir therapy. In patients with proven acyclovir-resistant VZV strains, intravenous foscarnet is currently the antiviral agent of choice.

Newer anti-VZV drugs have been developed. These include valacyclovir, famciclovir, and brivudin, although they are currently only licensed for use in herpes zoster. Additional agents are in development.

First-line therapies

imageSymptomatic therapy C
imageAcyclovir A

The use of oral acyclovir in otherwise healthy children with varicella.

Hall CB, Granoff DM, Gromisch DS, Halsey NA, Kohl S, Marcuse EK, et al. Pediatrics 1993; 91: 674–6.

A helpful review article with treatment recommendations. Oral acyclovir is safe, but the cost–benefit ratio of treatment in otherwise healthy children remains to be established. Treatment initiated within 24 hours of onset will typically reduce fever duration by 1 day, and also reduce the severity of the eruption.

Symptomatic treatment with analgesics and topical agents such as calamine lotion or crotamiton cream and daily baths are all that is required in most children.

When required, acyclovir is the antiviral of choice for varicella infection. It is usually given orally. In children up to 12 years of age it is given at a dose of 20 mg/kg 6-hourly (to a maximum of 800 mg/dose) for 5 days. In adolescents and adults the dose is 800 mg five times daily for 7 days. Acyclovir is given intravenously in severe disease and in immunocompromised individuals.

Second-line therapies

imageFoscarnet D
imageValacyclovir D

Pregnancy

Management of varicella infection (chickenpox) in pregnancy.

Shrim A, Koren G, Yudin MH, Farine D; Maternal Fetal Medicine Committee. J Obstet Gynaecol Can 2012; 34: 287–92.

Varicella immunization is recommended for all non-immune women as part of pre-pregnancy and postpartum care. Varicella vaccination should not be administered in pregnancy. However, termination of pregnancy should not be advised because of inadvertent vaccination during pregnancy. The antenatal varicella immunity status of all pregnant women should be documented by history of previous infection, varicella vaccination, or serology. All non-immune pregnant women should be informed of the risk of varicella infection to themselves and their fetuses. They should be instructed to seek medical help following any contact with a person who may have been contagious. In the case of a possible exposure to varicella in a pregnant woman with unknown immune status, serum testing should be performed. If the serum results are negative or unavailable within 96 hours from exposure, VZIG should be administered. Women who develop varicella infection in pregnancy need to be made aware of the potential adverse maternal and fetal sequelae, the risk of transmission to the fetus, and the options available for prenatal diagnosis. Detailed ultrasound and appropriate follow-up is recommended for all women who develop varicella in pregnancy to screen for fetal consequences of infection. Women with significant (e.g., pneumonitis) varicella infection in pregnancy should be treated with oral antiviral agents (e.g., acyclovir 800 mg five times daily). In cases of progression to varicella pneumonitis, maternal admission to hospital should be seriously considered. Intravenous acyclovir can be considered for severe complications in pregnancy (oral forms have poor bioavailability). The dose is usually 10–15 mg/kg or 500 mg/m2 IV every 8 hours for 5 to 10 days for varicella pneumonitis, and it should be started within 24 to 72 hours of the onset of rash. Neonatal health care providers should be informed of peripartum varicella exposure in order to optimize early neonatal care with VZIG and immunization. VZIG should be administered to neonates whenever the onset of maternal disease is between 5 days before and 2 days after delivery.

Prophylaxis

imageVaccines A
imageVaricella zoster immune globulin B
imageIntravenous immunoglobulin C
imageAcyclovir A

Postexposure prophylaxis of varicella in family contact by oral acyclovir.

Asano Y, Yoshikawa T, Suga S, Kobayashi I, Nakashima T, Yazaki T, et al. J Pediatr 1993; 92: 219–22.

Twenty-five children were treated with oral acyclovir 40 or 80 mg/kg daily in four divided doses, 7 to 9 days after household exposure to varicella. Twenty-five age-matched control subjects who had been exposed but did not receive treatment were also followed. Twenty of the 25 treated subjects were protected from disease, but four of them failed to seroconvert. All 25 controls developed varicella.

Although its efficacy is not as well established as that of VZIG, oral acyclovir also seems likely to be effective in post-exposure prophylaxis. It is given approximately 9 days after exposure for 1 week, and may abort the disease or reduce its severity. However, seroconversion and subsequent immunity may also be suppressed.

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