Varicella Health Article

Diagnosis

In most cases, the characteristic features of the vesicular varicella rash establish the clinical diagnosis. If doubt remains, a recent history of exposure to varicella (or herpes zoster) or the occurrence of secondary cases in close contacts can help diagnosis. The differential diagnosis consists mainly of allergic reactions (especially Stevens-Johnson syndrome), generalised herpes zoster or herpes simplex infections, enterovirus infections, pityriasis lichenoides et varioliformis acuta (PLEVA), and guttate psoriasis—and in newborn babies, syphilis and incontinentia pigmenti. ^3,103 Before eradication of smallpox and in posteradication surveillance, varicella was the disease most commonly confused with smallpox. ^104–106 Also, congenital histiocytosis can mimic congenital varicella syndrome. ¹⁰⁷

The most common application of laboratory testing for varicella is to confirm fatal, severe, or atypical illness. In countries with varicella vaccination programmes, laboratory testing is also needed to distinguish infection with wild-type varicella-zoster virus from vaccine strain infections (by use of restriction enzyme analyses or sequencing of amplified genomic material). ^108–110 Additionally, as the disease is controlled or eliminated, such testing is needed to confirm varicella cases, especially in vaccinated people. ^108–110 Varicella-zoster virus can be identified in clinical materials by culture (which requires 3–5 days), or indirectly by PCR or rapid antigen tests based on immunofluorescence techniques. ^{39–41,108,111} Skin scrapings are the preferred specimens for these methods; they should include cells from the base of the lesion. Crusts are useful specimens for PCR analysis, whereas varicella-zoster virus is more difficult to isolate from the nasopharynx. Other specimen sites, such as cerebrospinal fluid, lungs, liver, and brain, are more likely to be tested at autopsy. Electronmicroscopy can be used to identify individual herpesviruses in situations in which rapid diagnosis is needed (eg, to rule out suspected smallpox), and when antigen detection methods are not available. The Tzanck smear, available in many pathology departments, is a rapid and useful test for confirmation of an α-herpesvirus infection, but is not specific for varicella-zoster virus.

Serological tests are less useful than rapid antigen-detection methods for the diagnosis of acute varicella in clinical practice. Serum can test positively for IgM and IgA antibodies against varicella-zoster virus as early as 1 or 2 days after appearance of the varicella or herpes zoster rash. However, the absence of antibodies does not rule out the diagnosis. The time course of the IgM response in varicella infections has not been well described. IgG antibodies appear shortly after IgM and IgA responses, and persist throughout the patient's lifetime. There is known to be some cross-reactivity between varicella-zoster virus and herpes simplex virus type 1 (HSV-1), which is generally thought to indicate aminoacid sequence homology between glycoprotein B in varicella-zoster virus and in HSV-1. ^112–114

The fluorescent antibody to membrane antigen (FAMA) test is regarded as the gold standard for identification of varicella-zoster virus antibodies. ¹¹⁵ The FAMA test is the most reliable serological correlate of protection in non-immunised individuals. However, the method is demanding and time-consuming, and is not available in most laboratories. Second episodes of varicella have been documented in people with previous laboratory-confirmed disease, and with demonstrable IgG antibody responses. ^116,117 But for practical purposes and serosurveillance studies, ELISA tests have proven sufficiently sensitive and specific for measurement of immunity after natural varicella infection. By contrast, antibody values are about ten-fold lower in vaccinated people than in non-vaccinated people, so commercially available tests might not be sufficiently sensitive to assess vaccine-induced immunity. Moreover, the presence of antibodies is an imperfect predictor of protection in immunised people. However, the presence of antibodies 6 weeks after vaccination, as measured by both FAMA and by a specially developed ELISA test against varicella-zoster virus glycoproteins (gpEIA), are reported to relate reasonably well to protection. ^112,118–22 Additional methods for measuring IgG antibodies that are used by some laboratories include latex agglutination, neutralising antibody tests, complement fixation tests, radio-immunofluorescence assays, and immunofluorescence assays. ^{3,8,52,53,112,123}