Herpes zoster laboratory tests

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], L. Katie Morrison, MD; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Laboratory testing may be useful in cases with less typical clinical presentations, such as in immunosuppressed persons who may have disseminated Herpes zoster (defined as appearance of lesions outside the primary or adjacent dermatomes).

Laboratory Findings

Serological Methods

Serologic methods may also be used for laboratory diagnosis of Herpes zoster, although there are challenges to interpreting the results. Herpes zoster patients may mount an IgM response and would be expected to mount a memory IgG response. However, a positive IgM ELISA result could be an indication of primary VZV infection, re-infection, or re-activation. This only appears during chickenpox or herpes zoster and not while the virus is dormant.[1] It is also difficult to detect an increase in IgG for laboratory diagnosis of Herpes zoster since patients may have a high baseline antibody titer from prior varicella disease.

In immunocompromised persons, even when VZV infection is diagnosed by use of laboratory methods, it may be difficult to distinguish between chickenpox and disseminated Herpes zoster by physical examination or serological testing. In these instances, a history of VZV exposure or of a rash that began with a dermatomal pattern, along with results of VZV antibody testing at or before the time of rash onset may help guide the diagnosis.

Direct Fluorescent Antibody Test

Direct fluorescent antibody staining of VZV-infected cells in a scraping of cells from the base of a lesion is rapid, specific, and sensitive, but it is substantially less sensitive than polymerase chain reaction (PCR). This method can also be used on biopsy material and on eosinophilic nuclear inclusions.

Polymerase Chain Reaction

PCR can be used to detect VZV DNA rapidly and sensitively in properly collected skin lesion specimens; however, PCR testing for VZV is not available in all settings. It is also possible to use PCR to distinguish between wild-type and vaccine strains of VZV. In larger laboratories, lymph collected from a blister is tested by the polymerase chain reaction for VZV DNA, or examined with an electron microscope for virus particles.[2]

In a recent study, samples of lesions on the skin, eyes, and lung from 182 patients with presumed herpes simplex or herpes zoster were tested with real-time PCR or with viral culture. [3]. In this comparison, viral culture detected VZV with only a 14.3% sensitivity, although the test was highly specific (specificity=100%). By comparison, real-time PCR resulted in 100% sensitivity and specificity. Overall testing for herpes simplex and herpes zoster using PCR showed a 60.4% improvement over viral culture.

Tzanck Smear

If the rash has appeared, identifying this disease (making a differential diagnosis) only requires a visual examination, since very few diseases produce a rash in a dermatomal pattern. However, herpes simplex virus (HSV) can occasionally produce a rash in such a pattern. The Tzanck smear is helpful for diagnosing acute infection with a herpes virus, but does not distinguish between HSV and VZV.[4]

When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), herpes zoster can be difficult to diagnose.[5] Apart from the rash, most symptoms can occur also in other conditions.

Collecting Specimens for Varicella and Zoster Virus Testing

Skin lesions are the preferable method for laboratory confirmation of varicella. Blood specimens should be used to test for varicella immunity.

There are 3 types of lesions most often seen from varicella zoster virus: a scabbed or crusted lesion; a maculopapular lesion, which is a lesion with a raised red bump; or a vesicular lesion, which is a blister-like or fluid-filled lesion.

To collect a scab for varicella zoster virus testing, begin by gently lifting the scab from the lesion. Once the scab is collected, place it in a container such as a swab specimen tube or a plastic baggie. If there is more than one scab, place each scab individually in different containers.

The most effective technique for collecting cells from a maculopapular lesion or fluid from a vesicular lesion is the same, though for maculopapular lesions it is a greater challenge to ensure that enough skin cells are collected. Lesions in vaccinated individuals are likely to be atypical, macular only or papular only, but obtaining specimens from papular lesions is possible using the following technique. Use the edge of a clean slide to loosen and collect skin cells or fluid from the lesion as shown here. Then, using a sterile swab, rub the lesion vigorously enough to ensure that skin cells or fluid are collected. To ensure an adequate amount of skin cells is collected, particularly with maculopapular lesions, it is recommended to also use the swab to wipe the skin cells off the edge of the slide used to scrape the lesion. One may also press the slide directly to the lesion to collect skin cells or fluid. This technique is especially effective for vesicles where a "smudge" should be visible. To ensure that skin cells or fluid are on the slide, compare it to a clear slide under light.

To collect a blood specimen for varicella immunity testing perform a finger stick on the individual. Soak the circle on the filter paper with blood ensuring that the circle is completely full and check to see that blood has soaked through to the other side. Then soak the remaining circle, and again ensure that blood has soaked through both sides of the filter paper. Allow the blood to dry before packaging the filter paper. Venipuncture is also an acceptable method for blood collection. Collect at least 1 ml of blood into a serum-separator vaccutainer tube. Before storage or shipping, separate the serum from the cells in a centrifuge for 15 minutes.

References

  1. Arvin AM (1996). "Varicella-zoster virus" (PDF). Clin. Microbiol. Rev 9 (3): 361–81. PMID 8809466.
  2. Beards G, Graham C, Pillay D (1998). "Investigation of vesicular rashes for HSV and VZV by PCR". J. Med. Virol 54 (3): 155–7. PMID 9515761.
  3. Stránská R, Schuurman R, de Vos M, van Loon AM. (2003). "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. 30 (1): 39-44. PMID 15072752.
  4. Oranje AP, Folkers E (1988). "The Tzanck smear: old, but still of inestimable value.". Pediatr Dermatol 5 (2): 127–9. PMID 2842739.
  5. Chan J, Bergstrom RT, Lanza DC, Oas JG (2004). "Lateral sinus thrombosis associated with zoster sine herpete". Am J Otolaryngol 25 (5): 357–60. PMID 15334402.

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