Herpes Zoster Workup

Updated: Jul 21, 2021
  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
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Approach Considerations

Diagnosis of herpes zoster (shingles) is based primarily on the history and physical findings—specifically, the characteristic location and appearance of the skin eruption in association with localized pain. Systemic manifestations are uncommon and usually are confined to patients in whom the immune system has been compromised by other disease processes or chemotherapy.

In most patients, confirming the diagnosis via laboratory testing usually has no utility, because most tests are time consuming, lack specificity, or are unavailable outside of research facilities. In select patient populations, however, the presentation can be atypical and may require additional testing. This is particularly true in immunocompromised patients.

Zoster has been considered a harbinger of other occult disease (eg, malignancies in older patients). Both zoster and malignancy are common in elderly individuals; therefore, most experts currently consider the association to be purely coincidental. There also appears not to be an increased incidence of malignancy in children with herpes zoster. Approximately 3% of pediatric cases occur in children with malignancies. Accordingly, a malignancy workup is not indicated in an otherwise healthy child who has herpes zoster.


Laboratory Studies

Although varicella-zoster virus (VZV) can be cultured, its growth rate is usually too slow for culturing to make a timely contribution to diagnosis.

One of the least expensive and simplest laboratory diagnostic methods for VZV and other herpesviruses is the Tzanck smear. The Tzanck smear is performed by obtaining a scraping from the base of a fresh vesicular lesion after it has been unroofed, spreading and drying the collected material on a glass slide, staining the result with Giemsa, and examining the material with a microscope for the characteristic presence of multinucleated giant cells.

The Tzanck smear confirms that the lesion is herpetic but cannot differentiate between VZV and other herpesviruses. Further, this test has a limited sensitivity compared with other diagnostic methods, such as polymerase chain reaction (PCR) assay. Therefore, a negative result does not rule out a herpes virus infection and should not preclude empiric treatment in patients. [76]

When acute diagnostic confirmation is desired, modern tests, such as direct fluorescent antibody (DFA) testing or PCR (if available), are preferred to the Tzanck smear. DFA testing of vesicular fluid or a corneal lesion can yield the VZV antigen. Both DFA and PCR have far greater sensitivity and specificity than the Tzanck smear and allow differentiation between herpes simplex virus (HSV) and VZV infections.

PCR assay of vesicular fluid or a corneal scraping can yield the VZV nucleic acid. Detection of VZV DNA in plasma can facilitate the early recognition of VZV infection in immunocompromised hosts. [77] [#WorkupSkinBiopsyFindings]In cases of zoster sine herpete, DNA analysis by means of PCR appears more useful than the standard assays, especially for early diagnosis.

It is seen approximately 7 times more frequently in patients with HIV infection; therefore, when clinically indicated, an HIV test should be ordered.


Other Studies

No imaging tests are indicated in typical cases of cutaneous herpes zoster infection. Magnetic resonance imaging (MRI) may be used in cases of myelopathy or encephalopathy as a means of excluding other etiologies.

A small percentage of patients, particularly those with cranial nerve (CN) involvement, may develop headache and neck stiffness, necessitating a lumbar puncture to exclude meningitis. Because the inflammatory response involves the leptomeninges, cerebrospinal fluid (CSF) may show increased protein and a pleocytosis.

Because the diagnosis can almost always be made on clinical grounds, skin biopsy is seldom necessary; as a rule, it is reserved for cases that are difficult to diagnose (eg, atypical lesions).


Histologic Findings

On rare occasions when skin biopsy is necessary, histologic findings are similar to those of herpes simplex and varicella. Ballooning degeneration and acantholysis of keratinocytes result in an intraepidermal vesicle. Multinucleated giant cells with accentuation of nuclear material at the periphery of nuclei are characteristic. [78] Underlying leukocytoclastic vasculitis often is a prominent finding and helps differentiate zoster from other herpetic infections.

Lymphocytes may be found in the lower part of the epidermis, accompanied by a combination of spongiosis and vacuolar alteration. The papillary dermis is often edematous. Extravasated erythrocytes in variable numbers are a common finding. A brisk lymphocytic infiltrate is present in the upper dermis.

Some of these lymphocytes may have large and polygonal nuclei. They are dense, perivascular, and sparse interstitial, superficial, and deep collections, sometimes assuming a patchy, lichenoid pattern. The lymphocytes may be prominent in and around adnexal structures, often peppering follicles, sebaceous glands, and eccrine glands.

Neutrophils and nuclear dust are occasionally seen; eosinophils are rare.

Conventional microscopy is routinely used to confirm infection by herpesviruses, though on occasion, PCR assay may then be used to demonstrate herpesvirus-specific DNA.