Diagnosis of varicella-zoster virus infection
Author:
Mary A Albrecht, MD
Section Editor:
Martin S Hirsch, MD
Deputy Editor:
Jennifer Mitty, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: May 31, 2017.

INTRODUCTION — Varicella-zoster virus (VZV) infection causes two clinically distinct forms of disease. Primary infection with VZV results in varicella (chickenpox), characterized by vesicular lesions in different stages of development on the face, trunk, and extremities. Herpes zoster, also known as "shingles", results from reactivation of endogenous latent VZV infection within the sensory ganglia. This clinical form of the disease is characterized by a painful, unilateral vesicular eruption, which usually occurs in a restricted dermatomal distribution.

The diagnosis of these two diseases is usually made clinically. However, the use of diagnostic assays may be important in specific situations, as discussed below.

The clinical manifestations of chickenpox and shingles are discussed elsewhere. (See "Treatment of herpes zoster in the immunocompetent host" and "Clinical features of varicella-zoster virus infection: Chickenpox" and "Clinical manifestations of varicella-zoster virus infection: Herpes zoster".)

GENERAL BACKGROUND — The diagnosis of VZV infection is usually a clinical diagnosis based on the characteristic vesicular lesions, which are seen widespread in chickenpox (varicella) or in a restricted dermatomal pattern with associated neuritis in shingles (herpes zoster).

However, additional diagnostic information may be useful in the following situations:

Atypical rash in an immunocompromised host

Possible disseminated disease in an immunosuppressed host without cutaneous lesions

In addition, serologic testing may be necessary to determine if an individual at increased risk for varicella requires immunization (eg, a healthcare worker born after 1980 who does not have a history of childhood infection).

POLYMERASE CHAIN REACTION — The real-time polymerase chain reaction (PCR) assays provide uniformly rapid and sensitive confirmation of VZV from clinical specimens obtained from skin lesions and selected body fluids such as CSF and bronchoalveolar lavage [1,2]. In a study comparing viral culture isolation to real-time PCR [2], 110 clinical specimens from dermal lesions were analyzed using both methods. VZV was isolated by culture in 15 samples (14 percent) and VZV DNA was detected by PCR in 51 (46 percent) samples. In another study of patients with a high clinical suspicion of herpes zoster, real-time PCR testing was highly sensitive compared with culture (92 versus 53 percent) [3]. In addition, PCR-based testing was highly specific; no cross-reactivity was identified when tested against several other viruses.

Real-time PCR allows for rapid viral amplification, limits risk of contamination, confers superior sensitivity in isolating VZV from an array of clinical specimens, and affords more rapid turnaround time compared with conventional culture techniques.

PCR testing is also useful for a variety of other indications, such as making a diagnosis in a patient with vaccine-modified infection [4]. PCR testing of serum or blood may also be helpful in the transplant patient who has visceral disease prior to the appearance of cutaneous lesions [5].

DIRECT FLUORESCENT ANTIBODY — Rapid diagnosis of VZV infection can usually be accomplished by using DFA on scrapings from active vesicular skin lesions that have not yet crusted. The DFA test is widely available; it has lower cost compared to culture, and is associated with more rapid turnaround time [6,7]. As noted with culture techniques above, one DFA assay can simultaneously detect HSV and VZV with a 1.5 hour turnaround time [6].

VIRAL CULTURE — Virus isolation by culture is sometimes available but is insensitive and associated with low yield (approximately 60 to 75 percent) when compared with PCR testing [8]. Specific VZV culture isolation from a swab of vesicular skin lesion or sterile body fluid, such as CSF, typically requires prolonged incubation with a turnaround time of one to two weeks [6]. Sensitivity of culture also declines when lesions progress beyond the vesicular stage.

SEROLOGIC TESTING — The presence of IgG antibodies to VZV correlates both with a history of varicella and protection against subsequent infection. Serologic testing has been employed in health care workers to assess susceptibility related to their potential risk of exposure. Serologic testing has also been employed in vaccine studies to assess response to immunization.

Many different antibody tests are available with a wide range of performance standards [9]. The fluorescent antibody to membrane antibody (FAMA) is the most extensively validated assay and correlates best with susceptibility to and protection against varicella [10]. However, this test is not widely used because it is labor intensive and requires expert interpretation.

Many commercially available ELISAs are available that are considered generally less sensitive than FAMA, although specificity appears comparable [9]. Persons 60 years of age and older may not have been exposed to varicella for many years; consequently, waning antibodies may lead to a false negative result and result in misclassification of the person as susceptible. In contrast, latex agglutination testing has been associated with false positive test results and failure to vaccinate susceptible healthcare workers, who subsequently developed varicella after exposure [11].

Some experts have concluded that commercial ELISA assays are suitable for screening for VZV susceptibility among healthcare workers [9]. The rationale for this is that the risk of vaccinating an adult with a false-negative test result is much lower than the risk of natural infection in an individual falsely identified as seropositive.

Routine screening for varicella in individuals born in the United States before 1980, who are not healthcare workers, is not recommended because of extremely high rates of seropositivity in this population.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Varicella-zoster virus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Shingles (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Varicella-zoster virus (VZV) infection causes two clinically distinct forms of disease. Primary infection with VZV results in varicella (chickenpox), characterized by vesicular lesions in different stages of development on the face, trunk, and extremities. Herpes zoster (shingles) results from reactivation of endogenous latent VZV infection and is characterized by a painful, unilateral vesicular eruption. (See 'Introduction' above.)

VZV infection is usually a clinical diagnosis based on the characteristic vesicular lesions, which are seen widespread in chickenpox (varicella) or in a restricted dermatomal pattern with associated neuritis in shingles (herpes zoster). No further diagnostic testing is necessary in a patient with typical clinical presentation. (See 'General background' above.)

Additional diagnostic testing may be useful when considering VZV in an immunocompromised host or in the evaluation of atypical lesions. (See 'General background' above.)

When further testing is needed, real-time PCR allows viral amplification of VZV from an array of clinical specimens and affords more rapid turnaround time compared to conventional culture techniques. (See "Tools for genetics and genomics: Polymerase chain reaction".)

Rapid diagnosis of VZV infection can also be accomplished by using direct fluorescent antibody (DFA) on scrapings from active vesicular skin lesions that have not yet crusted. (See 'Direct fluorescent antibody' above.)

Virus isolation by culture is associated with low yield and requires prolonged incubation. (See 'Viral culture' above.)

Serologic testing with ELISA is used to determine susceptibility to varicella and the need for immunization. Testing is not necessary in individuals born in the United States before 1980 due to the high rates of seroprevalence among this age group. (See 'Serologic testing' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. Stránská R, Schuurman R, de Vos M, van Loon AM. Routine use of a highly automated and internally controlled real-time PCR assay for the diagnosis of herpes simplex and varicella-zoster virus infections. J Clin Virol 2004; 30:39.
  2. Schmutzhard J, Merete Riedel H, Zweygberg Wirgart B, Grillner L. Detection of herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus in skin lesions. Comparison of real-time PCR, nested PCR and virus isolation. J Clin Virol 2004; 29:120.
  3. Harbecke R, Oxman MN, Arnold BA, et al. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol 2009; 81:1310.
  4. Leung J, Harpaz R, Baughman AL, et al. Evaluation of laboratory methods for diagnosis of varicella. Clin Infect Dis 2010; 51:23.
  5. de Jong MD, Weel JF, van Oers MH, et al. Molecular diagnosis of visceral herpes zoster. Lancet 2001; 357:2101.
  6. Chan EL, Brandt K, Horsman GB. Comparison of Chemicon SimulFluor direct fluorescent antibody staining with cell culture and shell vial direct immunoperoxidase staining for detection of herpes simplex virus and with cytospin direct immunofluorescence staining for detection of varicella-zoster virus. Clin Diagn Lab Immunol 2001; 8:909.
  7. Dahl H, Marcoccia J, Linde A. Antigen detection: the method of choice in comparison with virus isolation and serology for laboratory diagnosis of herpes zoster in human immunodeficiency virus-infected patients. J Clin Microbiol 1997; 35:347.
  8. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med 2002; 347:340.
  9. Breuer J, Schmid DS, Gershon AA. Use and limitations of varicella-zoster virus-specific serological testing to evaluate breakthrough disease in vaccinees and to screen for susceptibility to varicella. J Infect Dis 2008; 197 Suppl 2:S147.
  10. Williams V, Gershon A, Brunell PA. Serologic response to varicella-zoster membrane antigens measured by direct immunofluorescence. J Infect Dis 1974; 130:669.
  11. Behrman A, Schmid DS, Crivaro A, Watson B. A cluster of primary varicella cases among healthcare workers with false-positive varicella zoster virus titers. Infect Control Hosp Epidemiol 2003; 24:202.
Topic 8329 Version 14.0