Varicella

The illness usually begins 14-16 days after exposure, although the incubation period can range from 10 to 21 days. Subclinical varicella is rare; almost all exposed, susceptible persons experience a rash. Prodromal symptoms may be present, particularly in older children and adults. Fever, malaise, anorexia, headache, and occasionally mild abdominal pain may occur 24-48 hours before the rash appears. Temperature elevation is usually moderate, usually 100-102°F, but may be as high as 106°F; fever and other systemic symptoms usually resolve within 2-4 days after the onset of the rash.

Varicella lesions often appear first on the scalp, face, or trunk. The initial exanthem consists of intensely pruritic erythematous macules that evolve through the papular stage to form clear, fluid-filled vesicles. Clouding and umbilication of the lesions begin in 24-48 hr. While the initial lesions are crusting, new crops form on the trunk and then the extremities; the simultaneous presence of lesions in various stages of evolution is characteristic of varicella (Fig. 245-1). The distribution of the rash is predominantly central or centripetal, in contrast to that in smallpox, which is more prominent on the face and distal extremities. Ulcerative lesions involving the mucosa of oropharynx and vagina are also common; many children have vesicular lesions on the eyelids and conjunctivae, but corneal involvement and serious ocular disease are rare. The average number of varicella lesions is about 300, but healthy children may have fewer than 10 to more than 1,500 lesions. In cases resulting from secondary household spread and in older children, more lesions usually occur, and new crops of lesions may continue to develop for a longer time. The exanthem may be much more extensive in children with skin disorders, such as eczema or recent sunburn. Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks in some children, but severe scarring is unusual unless the lesions were secondarily infected.

Figure 245-1 A, Varicella lesions in unvaccinated persons display the characteristic “cropping” distribution, or manifest themselves in clusters; the simultaneous presence of lesions in various stages of evolution is characteristic. B, Breakthrough varicella lesions are predominantly maculopapular, and vesicles are less common; the illness is most commonly mild with <50 lesions.

(A, Courtesy of the Centers for Disease Control and Prevention [CDC]; B, Courtesy of the CDC and Dr. John Noble, Jr.)

The differential diagnosis of varicella includes vesicular rashes caused by other infectious agents, such as herpes simplex virus, enterovirus, monkey pox, rickettsial pox, and S. aureus; drug reactions; disseminated herpes zoster; contact dermatitis; and insect bites. Severe varicella was the most common illness confused with smallpox before the eradication of smallpox.

Varicella in Vaccinated Individuals (“Breakthrough Varicella”)

One dose of varicella vaccine is >97% effective in preventing severe varicella and is 85% (median; range 44-100%) effective in preventing all disease after exposure to wild-type VZV. This means that after close exposure to VZV, as may occur in a household or an outbreak setting in a school or daycare center, about 1 of every 5 children receiving 1-dose vaccination children may experience breakthrough varicella. Exposure to VZV may also result in asymptomatic infection in the previously immunized child. Breakthrough disease is varicella that occurs in a person vaccinated >42 days before rash onset and is caused by wild-type VZV. In the early stages of the varicella vaccination program, rash occurring within the 1st 2 weeks after vaccination was most commonly wild-type VZV, reflecting exposure to varicella before vaccination could provide protection. Rash occurring 14-42 days after vaccination was due to either wild or vaccine strains, reflecting breakthrough varicella or vaccine-associated rash, respectively. As varicella disease continues to decline, rashes in the interval 0-42 days after vaccination will be less commonly caused by wild-type VZV. The rash in breakthrough disease is frequently atypical and predominantly maculopapular, vesicles are seen less commonly, and the illness is most commonly mild with <50 lesions, shorter duration of rash, fewer complications, and little or no fever. However, approximately 25-30% of breakthrough cases are not mild, with clinical features more similar to those of wild-type infection. Breakthrough cases are overall less contagious than wild-type infections within household settings, but contagiousness varies proportionally with the number of lesions: typical breakthrough cases (<50 lesions) are about a third as contagious as unvaccinated cases, whereas breakthrough cases with ≥50 lesions are as contagious as wild-type cases. Therefore, children with breakthrough disease should be considered potentially infectious and excluded from school until lesions have crusted or, if there are no vesicles present, until no new lesions are occurring. Transmission has been documented to occur from breakthrough cases in household, child-care, and school settings.

Fewer studies have evaluated the performance of the 2-dose varicella vaccine regimen. One clinical trial estimated the 2-dose vaccine effectiveness for preventing all disease at 98%. Breakthrough cases have been reported among 2-dose vaccinees, although recipients of 2 doses of varicella vaccine are less likely to have breakthrough disease than those receiving one dose.

Progressive Varicella

Progressive varicella, with visceral organ involvement, coagulopathy, severe hemorrhage, and continued vesicular lesion development, is a severe complication of primary VZV infection. Severe abdominal pain, which may reflect involvement of mesenteric lymph nodes or the liver, or the appearance of hemorrhagic vesicles in otherwise healthy adolescents and adults, immunocompromised children, pregnant women, and newborns, may herald severe disease. Although rare in healthy children, the risk for progressive varicella is highest in children with congenital cellular immune deficiency disorders and those with malignancy, particularly if chemotherapy was given during the incubation period and the absolute lymphocyte count is <500 cells/mm³. The mortality rate for children who acquired varicella while undergoing treatment for malignancy and who were not treated with antiviral therapy approaches 7%; varicella-related deaths usually occur within 3 days after the diagnosis of varicella pneumonia. Children who acquire varicella after organ transplantation are also at risk for progressive VZV infection. Children undergoing long-term, low-dose systemic corticosteroid therapy are not considered to be at higher risk for severe varicella, but progressive varicella does occur in patients receiving high-dose corticosteroids and has been reported in patients receiving inhaled corticosteroids as well as in asthmatic persons receiving multiple short courses of systemic corticosteroid therapy. Unusual clinical findings of varicella, including lesions that develop a unique hyperkeratotic appearance and continued new lesion formation for weeks or months, have been described in children with untreated, late stage HIV infection. Immunization of HIV-infected children who have a CD4+ T-lymphocyte value ≥15% as well as children with leukemia and solid organ tumors who are in remission and whose chemotherapy can be interrupted for 2 wk around the time of immunization or has been terminated has reduced this problem. Since the advent of the universal immunization program, many children who would become immunocompromised later in life because of disease or treatment are protected before the immunosuppression occurs; also, due to reductions in varicella incidence, immunocompromised children are less likely to be exposed to varicella.

Neonatal Varicella