A 7-year-old boy presented with an intensely pruritic rash on the body. The rash appeared in crops. The lesions appeared initially as rose-colored papules, which progressed rapidly to papules and vesicles, and finally crusted. The parents recalled that approximately 2 weeks ago, he had contact with another child with similar lesions.

On examination, the patient was afebrile. There were macules, papules, vesicles, pustules, and crusts on the body, with the greatest concentrations on the trunk. The rest of the physical examination findings were unremarkable.

What’s your diagnosis?

(Answer and discussion on next page)

Answer: Chickenpox

Chickenpox is caused by primary infection with the varicella zoster virus (VZV), also known as herpesvirus 3—a double-stranded DNA virus of the Herpesviridae family, the subfamily Alphaherpesvirinae, and the genus Varicellovirus.¹

EPIDEMIOLOGY 

Humans are the only known reservoir for VZV.¹ Chickenpox is a highly contagious disease with secondary infection rates greater than 90% in susceptible household contacts.² Chickenpox is acquired by direct contact with varicella or zoster lesions or by inhalation of infected airborne droplets.³ In utero infection can occur as a result of transplacental passage of the virus during maternal chickenpox viremia.⁴

Prior to the introduction of varicella vaccine, the Centers for Disease Control and Prevention (CDC) estimated the yearly incidence of chickenpox in the United States at approximately 4 million cases.⁵ After introduction of the vaccine, the incidence declined by 90%. In the postvaccination era, the peak incidence occurs between 10 and 14 years of age.¹ Approximately 95% of adults have evidence of immunity to chickenpox.³ The disease affects both sexes equally and is reported in all races.

The incubation period varies from 10 to 21 days, with an average of 14 to 16 days.¹ Incubation periods are shorter in immunocompromised individuals and longer in those who have received varicella-zoster immunoglobulin. The period of infectivity is maximal in the 24 to 48 hours preceding the rash and continues with decreasing contagiousness until all the lesions have crusted.⁴

Chickenpox is most common in late winter and early spring.^1,3 Immunity usually is lifelong.

CLINICAL MANIFESTATIONS

In children, prodromal symptoms may include slight malaise and low-grade fever. These symptoms usually precede the rash by 1 or 2 days. The lesions start as rose-colored macules and progress rapidly to become papules, vesicles with the classic “dew drop on a rose petal” appearance, pustules and, finally, crusts.^3,4 New lesions appear in successive crops every 1 or 2 days, with 2 to 4 crops developing over the course of the illness. The total number of lesions typically varies between 250 and 500.^3,4 Characteristically, lesions in different stages of development are present throughout the first week of illness. Crusts generally fall off in 1 to 3 weeks, depending on the depth of skin involvement. The rash causes pruritus, which can be intense. 

The distribution of the lesions is typically central, with the greatest concentrations on the trunk. The palms and soles often are spared. Mucous membranes are commonly affected. Vesicles that develop on the oral or vaginal mucosa rapidly become macerated and form shallow and painful ulcers. Children with impaired cellular immunity tend to develop severe chickenpox, whereas children with hypogammaglobulinemia usually have an uncomplicated course. Children with cellular immunodeficiency may develop progressive varicella that is characterized by a more severe prodrome followed by widespread dissemination of the VZV.¹

Disseminated varicella infection in a newborn infant may occur if the mother develops chickenpox within 5 days before delivery or within 2 days after delivery, presumably because of insufficient time for maternal immunoglobulin G antibody to be formed and transferred to the fetus prior to delivery.¹ In this situation, the newborn usually develops chickenpox between 5 and 10 days after birth, and mortality is between 20% and 30%.^3,4

Diagnosis and laboratory investigations on next page

DIAGNOSIS AND LABORATORY INVESTIGATIONS

The characteristic rash with lesions in varying stages of development provides the basis for the clinical diagnosis of chickenpox. The presence of pruritus and low-grade fever also help in the diagnosis. Laboratory tests are rarely necessary. A Tzanck smear, performed by scraping the base of an acute lesion and staining with Giemsa, hematoxylin-eosin, or Papanicolaou stains, may demonstrate multinucleated giant cells containing intranuclear inclusions.^3,4 A Tzanck smear has poor specificity because the test is also positive in patients with infection caused by herpes simplex types 1 and 2.^3,4 False negative results may also occur. Chickenpox infection can be confirmed by testing acute and convalescent sera for VZV antibody. Direct fluorescent antibody assay and polymerase chain reaction are very sensitive and rapid methods to identify VZV in vesicular fluid, a scraping, or a scab, and are currently the diagnostic methods of choice.¹

COMPLICATIONS

The most common complication associated with chickenpox is secondary bacterial infection of the skin.^3,4 Infectious complications include impetigo, cellulitis, lymphadenitis, subcutaneous abscess, necrotizing fasciitis, and toxic shock syndrome. These infections usually are caused by Staphylococcus aureus or Streptococcus pyogenes (group A β-hemolytic streptococcus).^3,4 Postinflammatory scarring of isolated lesions is quite common.⁶

Neurologic complications include cerebellar ataxia, encephalitis, aseptic meningitis, transverse myelitis, ischemic stroke, Guillain-Barré syndrome, and Reye syndrome.^1,3,7

Pneumonia is responsible for many of the fatalities ascribed to chickenpox, particularly in adults, neonates, and immunocompromised patients.⁷ Other less commonly encountered complications include thrombocytopenia, neutropenia, anemia, purpura fulminans, Henoch-Schönlein purpura, arthritis, pericarditis, myocarditis, endocarditis, hepatitis, pancreatitis, colitis, glomerulonephritis, nephrotic syndrome, hemolytic-uremic syndrome, orchitis, keratitis, subconjunctival hemorrhage, optic neuritis, myasthenia gravis, and acute retinal necrosis syndrome.^3,4,8-10

Chickenpox during pregnancy may lead to abortion, stillbirth, congenital varicella syndrome, or varicella of the newborn.^11,12 

Herpes zoster (shingles) is caused by reactivation of VZV from a dorsal root ganglion to a cutaneous nerve and the adjacent skin.¹³ The incidence increases with age, and rises sharply after the age of 50.¹⁴ The younger a child is when he or she develops chickenpox, the greater the likelihood that he or she will develop herpes zoster in childhood or early adulthood.¹⁴ 

The socioeconomic aspect of chickenpox should not be overlooked. Considerable financial, social, and personal costs may be incurred as a result of lost wages and medical costs. The impact of these expenses may be particularly significant for families with low income.

MANAGEMENT 

Symptomatic treatment of chickenpox includes alleviating itching by the use of a topical antipruritic agent such as menthol/pramoxine, or a systemic antihistamine such as hydroxyzine. The use of topical or oral diphenhydramine has been associated with toxic encephalopathy in patients with chickenpox and is not recommended.^3,4 

Fingernails should be trimmed to reduce injury from scratching, and mittens can be worn at night to minimize nocturnal scratching. Secondary bacterial infection may be minimized by meticulous attention to hygiene. If secondary infection occurs, topical or systemic antibiotic therapy is indicated. Acetaminophen may be used to reduce fever. Salicylates are contraindicated because of their association with Reye syndrome. 

The Canadian Pediatric Society recommends that children with mild chickenpox be permitted to return to daycare or school as soon as they feel well enough to participate in normal activities, regardless of the state of their rash.¹⁵ In contrast, the American Academy of Pediatrics recommends that children with uncomplicated chickenpox may return to daycare or school when all lesions have crusted.¹ In reality, it usually is the appearance of the rash, and not the infectivity, that dictates when a child returns to school or daycare. A child covered with chickenpox lesions is unlikely to be welcomed back to a school or daycare setting before the rash subsides, even if this child is certified as being free from infection. Children with chickenpox should not be admitted to the hospital unless a serious complication develops. Hospitalized patients require strict isolation to minimize the spread of infection to immunocompromised patients.  

The use of oral acyclovir or valacyclovir in otherwise healthy children with chickenpox is not recommended.¹ Oral acyclovir or valacyclovir should be considered in high-risk individuals, such as those unvaccinated individuals older than 12 years, those with a chronic cutaneous or pulmonary disorder, and those receiving long-term salicylate or corticosteroid therapy.¹ Some investigators recommend oral acyclovir or valacyclovir for pregnant women with chickenpox, especially during the second and third trimesters.¹ Intravenous acyclovir is effective for the treatment of chickenpox in immunocompromised individuals and pregnant women with serious complications of chickenpox.^1,7 

PREVENTION

Active immunization. The Advisory Committee for Immunization Practices (ACIP) of the CDC and the American Academy of Pediatrics recommends a 2-dose varicella vaccination program for children, with the first dose administered at 12 to 15 months and the second dose at 4 to 6 years of age.¹ The ACIP further recommends 2 doses of varicella vaccine, 4 to 8 weeks apart, for all susceptible adolescents and adults and a catch-up second dose for everyone who received 1 dose of
varicella vaccine previously.³

Postexposure prophylaxis. Varicella vaccine is recommended for healthy, VZV-nonimmune individuals within 3 to 5 days of exposure.³ Individuals who have a history of only 1 dose of vaccine should be offered a second dose of vaccine for completion of their series, as long as 3 months have elapsed since the first dose.¹⁶ Varicella-zoster immunoglobulin is indicated following significant exposure to chickenpox for immunocompromised and susceptible persons, newborns whose mothers had chickenpox within 5 days before delivery or within 48 hours of delivery, premature infants of 28 or more weeks of gestation whose mothers do not have a history of chickenpox or who are seronegative, and premature infants of less than 28 weeks of gestation or with a birth weight of 1000 g or less, regardless of the maternal history of chickenpox or VZV serostatus.^1,16 The period after exposure to VZV during which a patient may receive the varicella-zoster immunoglobulin is 10 days.¹⁷

PROGNOSIS

Chickenpox in otherwise healthy children usually is a self-limiting disease with an excellent prognosis.⁷ Fatalities are rare and usually result from complications in neonates, adults, and immunocompromised individuals.³ The mortality rate of chickenpox in immunocompromised individuals has been as high as 7% in some reports.³ The most common cause of death is pneumonia, followed by secondary bacterial infection, neurologic complications, and hematologic complications.^3,4

Alexander K. C. Leung, MD, is clinical professor of pediatrics at the University of Calgary and pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada.

Benjamin Barankin, MD, is a dermatologist and the medical director and founder of the Toronto Dermatology Centre in Toronto, Ontario, Canada.

References on the next page

REFERENCES

1. American Academy of Pediatrics. Varicella-zoster virus infections. In: Kimberlin DW, Brady MT, Jackson MA, et al, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:846-860.

2. Leung AKC, Kao CP. The truth about chickenpox. Can J Diagn. 1999;16(2):79-87.

3. Leung AKC, Kellner JD, Davies HD. Chickenpox: an update. J Pediatr Infect Dis. 2009;4(4):343-350.

4. Leung AKC, Sauve RS, Robson WLM. Congenital varicella syndrome. In: Lang F, ed. The Encyclopedia of Molecular Mechanisms of Disease. Berlin, Germany: Springer-Verlag; 2009:2167-2168. 

5. Centers for Disease Control of Prevention (CDC). Decline in annual incidence of varicella-selected states, 1990-2001. MMWR Morb Mortal Wkly Rep. 2003;52(37):884-885.

6. Leung AKC, Kao CP, Sauve RS. Scarring resulting from chickenpox. Pediatr Dermatol. 2001;18(5):378-380.

7. Cohen J, Breuer J. Chickenpox: treatment. BMJ Clin Evid. 2015;2015. pii: 0912.

8. Cameron JC, Allan G, Johnston F, Finn A, Heath PT, Booy R. Severe complications of chickenpox in hospitalised children in the UK and Ireland. Arch Dis Child. 2007;92(12):1062-1066.

9. Robson WLM, Leung AKC, Kaplan BS. Hemolytic-uremic syndrome. Curr Probl Pediatr. 1993;23(1):16-33.

10. Leung AKC, Eneli I, Davies HD. Necrotizing fasciitis in children. Pediatr Ann. 2008;37(10):704-710.

11. Leung AKC, Sauve RS. Congenital varicella syndrome. Consultant. 2004;44:81-89.

12. Sauve RS, Leung AKC. Congenital varicella syndrome with colonic atresias. Clin Pediatr. 2003;42(5):451-453.

13.Leung AKC, Rafaat M. Photo quiz: Vesicular rash on the flank and buttocks. Am Fam Physician. 2003;67(5):1045-1046.

14. Leung AKC, Robson WLM, Leong AG. Herpes zoster in childhood. J Pediatr Health Care. 2006;20(5):300-303.

15. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. School and daycare exclusion policies for chickenpox: a rational approach. Paediatr Child Health. 1999;4(4):287-288.

16. Albrecht MA. Post-exposure prophylaxis against varicella-zoster virus infection. UpToDate. http://www.uptodate.com/contents/post-exposure-prophylaxis-against-varicella-zoster-virus-infection. Accessed January 10, 2016.

17. Centers for Disease Control of Prevention (CDC). FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella. MMWR Morb Mortal Wkly Rep. 2012;61(12):212.