Communicable Diseases

Chickenpox/herpes Zoster

Identification

The varicella-zoster virus (VZV) causes two distinct diseases, varicella (chickenpox) as the primary infection, and later, when VZV reactivates, herpes zoster (shingles). Varicella is an acute illness characterized by fever and generalized, pruritic, vesicular rash typically consisting of 250 to 500 lesions in varying stages of development and resolution. The rash is maculopapular for a few hours, vesicular for 3 to 4 days, then crusts, leaving granular scabs. The vesicles are unilocular and collapse on puncture, in contrast to the multilocular, non-collapsing vesicles of smallpox. Lesions commonly occur in successive crops, with several stages of maturity present at the same time; they tend to have central distribution, and are more abundant on covered than on exposed parts of the body. Lesions may appear on the scalp, high in the axilla, on mucous membranes of the mouth and upper respiratory tract, and on the conjunctivae; they tend to occur in areas of irritation, such as sunburn or diaper rash. They may be so few as to escape observation.

Mild, atypical and inapparent infections occur, especially among vaccinated individuals (breakthrough varicella). Breakthrough varicella is defined as varicella developing more than 42 days after vaccination; most breakthrough disease is mild, without fever, and with skin rash of <50 lesions that are atypical, with papules that do not progress to vesicles, and which may be so few in numbers as to escape observation.

Occasionally, especially in adults and in persons with cellular immune deficiencies such as malignancies and HIV/AIDS, fever and constitutional manifestations may be severe. Although varicella is usually a benign childhood disease, and is rarely rated as an important public health problem, varicella zoster virus may induce pneumonia or encephalitis, sometimes with persistent sequelae or death. Secondary bacterial infections of the vesicles may leave disfiguring scars, or result in necrotizing fasciitis or septicemia.

The case-fatality rate is lower for children (1:100 000 infected in the 5–9 age group) than for adults (1:5 000). Serious complications include pneumonia (viral and bacterial), secondary bacterial infections, hemorrhagic complications and encephalitis. Children with acute leukemia, including those in remission after chemotherapy, are at increased risk of disseminated disease, which is fatal in 5%–10% of cases. Neonates who develop varicella between ages 5 and 10 days are at increased risk of developing severe generalized varicella. Among neonates whose mothers develop the disease 5 days prior to or within 2 days after delivery and who do not receive VZIG (see below) or antiviral therapy, the case-fatality rate can reach 30%. Infection early in pregnancy, at 0–12 weeks, may be associated with fetal death or congenital varicella syndrome in 1% of cases, and at 13–20 weeks gestation with a 2% risk. Cases consistent with congenital varicella syndrome have been reported post 20 weeks gestation. Clinical varicella was a frequent antecedent of Reye syndrome, before the association of Reye syndrome with aspirin use for viral infections was identified.

Herpes zoster (shingles), which occurs in about 10–20% of the population, is a local manifestation of reactivation of latent varicella infection in the dorsal root ganglia. Vesicles with an erythematous base are restricted to skin areas supplied by sensory nerves of a single or associated group of dorsal root ganglia. Rash is typically unilateral, and most commonly affects thoracic, cervical, and ophthalmic dermatomes. Small numbers of lesions may appear outside the primary dermatome. Lesions are histologically identical to those of varicella, deeper seated, and more closely aggregated. The rash lasts about 7–10 days, and heals within 2–4 weeks. Complications develop in about 30% of herpes zoster cases; the most common is chronic severe pain or post-herpetic neuralgia (PHN). Although the definition of PHN has been inconsistent, PHN is defined as pain that persists after the rash heals, ranging from any duration to 30–90 days after rash resolution; it can, however, last for months, or even years. Herpes zoster may result in permanent neurological damage such as cranial nerve palsy and contralateral hemiplegia, or visual impairment following herpes zoster ophthalmia. The incidence of both herpes zoster and post-herpetic neuralgia increase with age; persons with malignant neoplasm and those infected with HIV also have a high risk of herpes zoster, with higher rates among children. Herpes zoster is more common following hematopoietic stem cell and solid organ transplants, especially in the first year. In the immunosuppressed and those with malignancies, but sometimes in otherwise healthy individuals with fewer lesions, extensive chickenpox-like lesions may appear outside the dermatome. Intrauterine infection is associated with herpes zoster in children. Occasionally, a varicelliform eruption follows shortly after herpes zoster, and rarely there is a secondary eruption of zoster after chickenpox.

Laboratory tests—such as visualization of virus by electron micrograph (EM); virus isolation in cell cultures; demonstration of viral antigen in smears using direct fluorescent antibody (DFA) of viral DNA by PCR, or of a rise in serum antibodies—are not routinely required for diagnosis, but are useful in complicated cases and in epidemiological studies. In the vaccine era, viral strain identification may be needed (e.g. to document whether herpes zoster in a vaccine recipient is due to vaccine or wild virus). Several antibody assays are now commercially available, but they are not sensitive enough to be used for post-immunization testing of immunity. Multinucleated giant cells may be detected in Giemsa-stained (Tzanck smear) scrapings from the base of a lesion; these are not found in vaccinia lesions, but do occur in herpes simplex lesions. They are not specific for varicella infections, and the availability of rapid direct fluorescent antibody testing has limited their value for clinical testing.

Chickenpox/herpes Zoster has been found in Communicable Diseases

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