CHICKENPOX

by Prof Alexander K C Leung MB BS, FRCP(Ed), FRCP(Glas), FRCPI, FRCPC, FAAP, DCH(Lond), DCH(I), Clinical Associate Professor, Department of Pediatrics, University of Calgary; Alberta Children's Hospital, Calgary, Alberta, Canada
Prof M Robson MD, FRCPC, Clinical Associate Professor, Department of Pediatrics, University of South Carolina School of Medicine; Children's Hospital, Greenville Hospital System, South Carolina, USA

Chickenpox usually follows a benign course in children, but can have serious consequences in susceptible adults or immunocompromised individuals. The authors summarize current knowledge about this highly contagious disease and outline an approach to management.

Primary infection with varicella-zoster virus results in chickenpox (varicella). The term 'varicella' is a Latin diminutive of variola (smallpox). 'Chickenpox' is derived from pois chiche, the French word for a chick-pea, which resembles the vesicle of chickenpox.(1)

Although chickenpox usually follows a benign course in children, it can be debilitating in susceptible adults or immunocompromised individuals. Other problems include the absence from school of infected children and the loss of income to parents who stay at home to care for their children. In this article, we will review current knowledge about chickenpox and its management.

Epidemiology of chickenpox

Humans are the only known reservoir for the varicella-zoster virus. Chickenpox is a highly contagious disease with secondary infection rates in susceptible household contacts greater than 90%.(2,3)

The peak incidence occurs between 5 and 9 years of age, with most cases occurring in children under 10 years of age.(2)

Approximately 95% of adults have evidence of immunity to chickenpox. The disease affects both sexes equally and is reported in all races.(4)

Chickenpox is acquired by direct contact with varicella or zoster lesions or by inhalation of infected airborne droplets.(5)

The incubation period varies from 11 to 21 days, with an average of 14-16 days. The incubation period is shorter in immunocompromised individuals and longer in those who have received varicella-zoster immunoglobulin.(5) The period of infectivity is maximal in the 24 hrs preceding the rash and continues with decreasing contagiousness until all the lesions have crusted (7/8 days). Chickenpox is most common in late winter and early spring.(6) Immunity is usually lifelong.

Clinical manifestations

In young children, prodromal symptoms may include slight malaise and low-grade fever. These symptoms usually precede the rash by 24 hr. The lesions consist of rose-coloured macules, which progress rapidly to papules, clear then cloudy vesicles, pustules, and finally crusts. The skin rash causes pruritis, which is often intense.

The distribution of the lesions is typically central, with the greatest concentrations on the trunk. Facial and scalp lesions are also common. The palms and soles are often spared. An increase in the number of lesions occurs in areas of local pressure, irritation, friction, inflammation, or hyperaemia. Vesicles that develop on the oral or vaginal mucosa rapidly become macerated and form a shallow and painful ulcer.

New lesions appear in successive crops every 1-2 days, such that two to four crops develop during the illness. The total number of lesions is usually between 250 and 500.7 Characteristically, lesions in different stages of development are present throughout the first week of illness. Crusts fall off in 13 weeks, depending on the depth of skin involvement.

Chickenpox in adults is often associated with more severe prodromal symptoms, including irritability, headaches, anorexia, arthralgia, myalgia, and a higher and prolonged fever. Adults usually have more and deeper lesions, and have a greater risk of complications.(6)

Immunocompromised patients

Patients with impaired cellular immunity tend to develop severe chickenpox, whereas children with hypogammaglobulinaemia usually have an uncomplicated course.(8)

Immunocompromised children may develop progressive varicella, which is characterized by a more severe prodrome followed by widespread dissemination of the varicella-zoster virus. In this form of varicella, the lesions tend to be larger, deeper and umbilicated. Some of the lesions may be haemorrhagic. They are more prominent on the extremities, and the palms and soles are often affected. The patient may have a high fever for 7/10 days after the onset of the illness. New lesions may continue to occur for as long as 2 weeks. Visceral involvement is common.

Healing takes up to three times as long in immunocompromised patients. Progressive varicella is associated with significant morbidity and mortality.

Complications of chickenpox

The most common complication of chickenpox is bacterial infection of the skin, usually by group A streptococci or Staphylococcus aureus.(9) Impetigo, cellulitis and postinflammatory scarring may result. In our experience, postinflammatory scarring of isolated lesions is common. Other complications are uncommon in normal children and include otitis media, pneumonia, cerebellar ataxia, Reye's syndrome, aseptic meningitis and encephalitis.(2,6)

Complications from chickenpox tend to be more severe in adults or immunocompromised children. Adults have a 10-25 times greater risk of complications. Chickenpox pneumonia develops in 20-30% of adults. In one study, among 118 cases of chickenpox in pregnant women, 24 women developed chickenpox pneumonia and 11 of them died.(8) Pulmonary involvement is the most common cause of death. Immunocompromised children are prone to visceral dissemination of the virus, leading to pneumonia, encephalitis and hepatitis.(2,6) The mortality caused by chickenpox in immuno-compromised patients has been reported to be as high as 7%.

Chickenpox in pregnancy

Chickenpox during pregnancy may lead to abortion, stillbirth, congenital varicella syndrome, or varicella of the newborn. Fetal infection with the varicella-zoster virus in the first or early second trimester of pregnancy results in congenital varicella syndrome in approximately 5% of infants. Affected infants may have low birth weight, hypoplasia of an extremity, cicatricial skin scarring, cataract, chorioretinitis, microphthalmia, and involvement of the central nervous system, including cerebral or cortical atrophy, microcephaly, psychomotor retardation and Horner's syndrome.(9,11)

Chickenpox in the newborn

Disseminated varicella infection in a newborn infant may result if the mother develops chickenpox within 5 days before delivery or within 2 days after delivery, presumably because there is insufficient time for maternal IgG antibody to be formed and transferred to the fetus prior to delivery.(11) In this situation, the infants usually develop chickenpox between 5 and 10 days after birth and the mortality is about 30%.(12)

Herpes zoster

Following a primary infection, the varicella-zoster virus persists in a dormant form in the dorsal root ganglion until reactivated. Reactivation results in herpes zoster (shingles). Herpes zoster is rare under the age of 10 years. The incidence increases with age and rises sharply after the age of 50 years. The younger a child develops chickenpox, the greater the likelihood that he or she will develop herpes zoster in childhood or early adulthood. In young children, herpes zoster often occurs in areas supplied by the cervical and sacral dermatomes, rather than the lower thoracic and upper lumbar dermatomes, which are characteristic of herpes zoster in an adult.

Laboratory findings

The diagnosis of chickenpox is established by the presence of the typical rash in a susceptible individual. Lab-oratory tests are rarely necessary. A Tzanck smear, performed by scraping the base of an acute lesion and staining with Giemsa's, hematoxylineosin or Papa-nicolau's stain, may demonstrate multinucleated giant cells containing intranuclear inclusions.(5,11) A Tzanck smear is also positive in patients with infection caused by herpes simplex types 1 and 2. Other useful tests include fluorescent antibody against membrane antigen, immuno-adherence haemag-glutination and enzyme-linked immuno-absorbent assay.(6)

Differential diagnosis

Smallpox was historically the most important disease to differentiate from chickenpox. With smallpox, the lesions are at the same stage of development and are more prominent in a centripetal location on the face, palms and soles. The lesions are often umbilicated and scarring is common. The worldwide eradication of smallpox makes this diagnosis extremely unlikely.

The lesions in hand, foot and mouth disease involve mainly the palms, soles and oral mucosa, and do not crust.

In impetigo, the lesions do not appear in crops and do not involve the oral mucosa. A thick, golden-yellow 'stuck on' crust is the hallmark of impetigo.(13)

Generalized herpes zoster lesions are uncommon and can be distinguished from chickenpox by localization to one or several dermatomes prior to the generalized eruption. Hyperaesthesia or nerve root pain may be present in herpes zoster infection.

The lesions from insect bites are usually acral in distribution, and have a central punctum and underlying wheal. Although these lesions are pruritic and papular, they do not have a vesicular or pustular appearance.

Although scabies may also present with pruritic papules, vesicles and pustules, the lesions are mainly seen in the genital areas and the flexural creases. Linear burrows may be seen and are pathognomonic of scabies.

The lesions in ricketsialpox are smaller, deeper and randomly distributed. Constitutional symptoms such as fever, chills and headache are prominent in ricketsialpox.

Treatment of patients with chickenpox

Symptomatic treatment includes alleviating itching by the use of a topical antipruritic agent such as Pramegel (containing pramoxine and menthol) or a systemic antihistamine such as hydroxyzine hydrochloride (Atarax). The use of topical or oral diphen-hydramine has been associated with toxic encephalocephaly in patients with chickenpox and is not recommended.(14)

Fingernails should be trimmed to reduce injury from scratching. Wearing mittens at night may help to minimize nocturnal scratching.

Secondary bacterial infections may be minimized by meticulous attention to hygiene. Parents should be encouraged to bathe their children daily, preferably with an antibacterial soap. Parents may be concerned that bathing will increase the number of lesions. They should be reassured that this is unlikely, as the skin lesions develop subsequent to blood-borne spread, and the detergent effect of soap will probably inactivate the virus.(11)

If secondary bacterial infection occurs, topical or systemic antibiotic therapy is indicated. Paracetamol may be used to reduce fever. Salicylate (Aspirin) is contraindicated because of the association with Reye's syndrome.(15)

Children with chickenpox should be excluded from school or day care until the period of contagiousness has passed; this usually takes 5-7 days. They should not be admitted to hospital unless a serious complication develops. Hospitalized patients require strict isolation to minimize spread of the infection to immuno-compromised patients.

Treatment of immunocompromised patients

Both intravenous acyclovir (Zovirax) and vidarabine are effective for the treatment of chickenpox in an immunocompromised individual (5,16) and for serious complications of chickenpox in a normal patient. (5,16) Acyclovir and vidarabine act by inhibiting viral DNA polymerase activity.(16) Acyclovir is less toxic and is therefore the drug of choice.(17) The recommended dose of acyclovir is 500 mg/m2 every 8 h.(16) Side-effects are infrequent and include nausea, vomiting, rash, phlebitis, and precipitation of the drug in the renal tubules, particularly in the presence of dehydration.18 The child should be well hydrated when acyclovir is administered intravenously.

Oral acyclovir therapy

Oral acyclovir therapy initiated within 24 h of the onset of rash results in a decrease in the duration and magnitude of the fever and in the number and duration of skin lesions.(17,19) Oral acyclovir should be considered in high-risk individuals such as healthy nonpregnant people 13 years of age or older, children older than 12 months with a chronic cutaneous or pulmonary disorder, children receiving long-term salicylate therapy, and possibly children receiving oral or inhaled corticosteroids.(17,20) The recommended dose of oral acyclovir is 20 mg/kg four times a day, with a maximum dose of 800 mg four times a day.(19)

The use of oral acyclovir in normal children is controversial. It is not routinely recommended for the treatment of uncomplicated chickenpox in otherwise healthy children. This recommendation is based on the cost of the medication and the benign nature of chickenpox in this group of children. Notwithstanding this, secondary or tertiary cases of chickenpox within a family are usually sicker than the first case, and some doctors may decide to treat with acyclovir those children who contract chickenpox from a sibling.21

Prevention of chickenpox

The recommended dose of varicella-zoster immunoglobulin is 125 units (1.25 ml) per 10 kg of body weight, administered intramuscularly within 48 h and preferably not later than 96 h after exposure.(5,7) The maximum suggested dose is 625 units. A live attenuated varicella vaccine has been developed and preliminary studies have shown promising results. The vaccine is safe and highly protective against chickenpox in both healthy and immunocompromised children.(22,23) Vaccine-related adverse effects include a minor rash, often accompanied by fever.18 Routine immunization of children with this vaccine will probably reduce morbidity and mortality from chickenpox.

Box 1. Rare complications of chickenpox infection.(2,6,10)

Guillain Barre syndrome
Transverse myelitis
Optic neuritis
Delayed hemiparesis caused by vascular thrombosis
Subconjunctival haemorrhage
Thrombocytopenia
Purpura fulminans
Henoch Schönlein purpura
Nephritis
Hepatitis
Pancreatitis
Myositis
Myocarditis
Orchitis

Box 2. Indications for prophylaxis with varicella-zoster immunoglobulin(5,16)

Following significant exposure to chickenpox in immunocompromised and susceptible children
Susceptible adolescents and adults, particularly pregnant women
Newborn infants whose mothers have chickenpox within 5 days before delivery or within 48 h after delivery
Premature infants of less than 28 weeks gestation
Premature infants whose mothers do not have a history of chickenpox

Prognosis

Chickenpox in otherwise healthy children is usually a self-limiting disease with an excellent prognosis. Fatalities are rare and usually a result of complications in neonates, adults and immunocompromised individuals.

Conclusion

Chickenpox is a common, highly contagious viral illness characterized by a pruritic vesicular rash that appears in crops. Although it usually follows a benign course in children, it can have serious consequences in susceptible adults or immunocompromised individuals. The treatment of chickenpox in children is usually symptomatic. Prophylaxis with varicella-zoster immunoglobulin and treatment with acyclovir should be considered for susceptible high-risk individuals.

Practical points

1. The peak incidence of chickenpox is between 5 and 9 years. Nearly all adults (95%) are immune.
2. The incubation period is 11-21 days (average 14-16 days). Patients are most infectious 24 h before the appearance of the rash.
3. Rose-coloured macules change into papules, followed by vesicles, pustules and then crusts. Pruritus is usual. The rash is centrally distributed and can involve the face and scalp.
4. Prodromal symptoms are more severe in adults and there is a greater risk of complications.
5. Complications include bacterial infection, otitis media, pneumonia, cerebellar ataxia, aseptic meningitis and encephalitis.
6. Chickenpox pneumonia affects 20-30% of adults and is the commonest form of death.
7. Chickenpox during pregnancy can lead to abortion or the congenital varicella syndrome.
8. Reactivation of primary chickenpox gives rise to herpes zoster.
9. Intravenous acyclovir and vidarabine are effective for the treatment of chickenpox in the immunocompromised individual.
10. Prophylaxis with intramuscular varicella-zoster immunoglobulin is indicated following significant exposure to chickenpox in immunocompromised and susceptible children. A live attenuated varicella vaccine has been developed.

Acknowledgements

We thank Miss Katherine Campbell-Brown and Mrs Paula Pang for their expert secretarial help, and Mr Sulakhan Chopra of the University of Calgary medical library for his assistance in the preparation of the manuscript.

References

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Chicken Pox