VZV has biologic and genetic similarities to HSV and is classified with HSVs in the Alphaherpesvirinae subfamily. Biologic similarities between VZV and HSV include that latency is established in sensory ganglia and infections are rapidly cytocidal. Primary infections with VZV cause varicella (“chickenpox”), whereas reactivation of the latent virus causes her pes zoster (“shingles”).

A. Epidemiology and pathogenesis

VZV is the only herpesvirus that can be easily spread from person to person by casual contact. Transmission of VZV is usually via respiratory droplets and results in initial infection of the respiratory mucosa, followed by spread to regional lymph nodes (Figure 1). Progeny virus enter the bloodstream, undergo a second round of multiplication in cells of the liver and spleen, and are disseminated throughout the body by infected mononuclear leukocytes. Endothelial cells of the capillaries and, ultimately, skin epithelial cells become infected, resulting in the characteristic, virus-containing vesicles of chickenpox that appear from 14 to 21 days after expo sure. The infected individual is contagious from 1 to 2 days before the appearance of the exanthem, implying that viruses reinfect cells of the respiratory mucosa near the end of the incubation period. The vesicular fluid from the chickenpox rash is also highly contagious and can be spread to nonimmune individuals if it becomes airborne.”

Fig1. Time course of varicella (chickenpox) in children. In adults, the disease shows a longer time course and is more severe.

B. Clinical significance

 In contrast to HSV infections, the primary and recurrent diseases (varicella and zoster) due to VZV are quite distinct. Whereas neither is usually life threatening in the normal, healthy individual, both can have severe complications in immunocompromised patients.

 1. Primary infection (varicella, or chickenpox): In a normal, healthy child, the incubation period is most commonly from 14 to 16 days. The first appearance of exanthem is often preceded by 1 to 2 days of a prodrome of fever, malaise, headache, and abdominal pain. The exanthem begins on the scalp, face, or trunk as erythematous macules, which evolve into virus-containing vesicles that begin to crust over after about 48 hours . Itching is most severe during the early stage of vesicle development. While the first crop of lesions is evolving, new crops appear on the trunk and extremities. In older adults and the immunocompromised, lesions may also appear on mucous membranes, such as in the oropharynx, conjunctivae, and vagina. New lesions continue to appear over a period of up to 6 or 7 days. Healing usually occurs without long-term consequences, but crater-like scars can remain after the lesions heal. Varicella is a more serious disease in both healthy and immunocompromised adults than it is in children. Varicella pneumonia is the most common of the serious complications, but fulminant hepatic failure and varicella encephalitis may also result. Primary infection of a pregnant woman may cause her to contract the more severe adult form of varicella and may affect the fetus or neonate as well. Fetal infection early in pregnancy is uncommon but can result in multiple developmental anomalies. More commonly, a fetus infected near the time of delivery may exhibit typical varicella at birth or shortly thereafter. The severity of the disease depends on whether the mother has begun to produce anti-VZV immunoglobulin (Ig) G by the time of delivery.

2. Reye syndrome: Reye syndrome, an acute encephalopathy accompanied by fatty liver, can sometimes follow VZV or influenza infections in children. Epidemiological evidence suggests that use of aspirin or other salicylate-containing compounds to treat pain and fever during the viral illness is associated with the development of Reye syndrome. It is also important to avoid aspirin fol lowing vaccination against chickenpox. 3. Recurrent infection (herpes zoster, or shingles): Due to the disseminated nature of the primary infection, latency is established in multiple sensory ganglia, the trigeminal, and thoracic and lumbar dorsal root ganglia being most common. Unlike most of the herpesviruses, asymptomatic virus shedding is a rare event. Herpes zoster results from reactivation of the latent virus, rather than from new, exogenous exposure. Reactivation occurs in up to 30 percent of individuals who have been infected at some point during their lifetime, and the likelihood increases with advancing age. The most striking feature of herpes zoster is that distribution of the clustered vesicular lesions is dermatomal (affecting the area of skin supplied by cutaneous branches from a single spinal nerve) . Even after the lesions heal, some individuals continue to suffer debilitating pain for months to years. This postherpetic neuralgia (PHN) is the most significant sequela of herpes zoster, but it can be mitigated by early treatment with antivirals and pain management medications. The incidence of herpes zoster and postherpetic neuralgia can be markedly reduced by using zoster vac cine in appropriate (greater than 50 years old) populations.

C. Laboratory identification

Laboratory diagnosis of uncomplicated varicella or zoster is generally not necessary and not usually done because of the typical clinical appearance and distribution of lesions. However, in the immunocompromised patient in whom therapy is warranted, it is important to distinguish VZV infection from other similar exanthems. Cell tissue cultures inoculated with a sample of vesicle fluid show gross cytopathic changes in several days. Individual infected cells can be detected within 24 hours by use of immunofluorescence or immunoperoxidase staining with antibodies against viral early proteins. More rapid diagnosis can be made by reacting epithelial cells scraped from the base of vesicles with the stains described above or by doing in situ hybridization with VZV-specific DNA probes.

D. Treatment

 Treatment of primary varicella in immunocompromised patients, adults, and neonates is warranted by the severity of the disease (Figure 25.13). Acyclovir has been the drug of choice in such patients but requires intravenous administration to achieve effective serum levels. Early administration of oral acyclovir reduces the time course and acute pain of zoster. Famciclovir and valacyclovir (base analogs similar to acyclovir) have greater activity against VZV. E. Prevention Vesicles erupt on an erythematous base and eventually dry and scab. The vesicles appear in regions supplied by the peripheral sensory nerves arising in latently infected root ganglia. Certain susceptible individuals (for example, neonates born to mothers with active chickenpox from 2 days before to 5 days after delivery, and severely immunocompromised patients) can be protected by administration of varicella-zoster immunoglobulin (VariZIG). Administration of VariZIG has no effect on the occurrence of zoster. A live, attenuated vaccine that was approved in 1995 for use in the United States by children age 1 year or older is now recommended as one of the routine childhood vaccines. Mild, breakthrough cases of chickenpox have been reported as a side effect of vaccine administration. The vaccine is also indicated for nonimmune adults at risk of being exposed to contagious individuals. Zostavax is a high potency version of the chickenpox vaccine, which also contains live, attenuated virus. Zostavax has been approved by the Food and Drug Administration for use in adults over age 50 years for prevention of zoster and, with it, the debilitating effects of PHN.