Diagnosis and Testing

Clinical Diagnosis

The signs and symptoms of herpes zoster are usually distinctive enough to make an accurate clinical diagnosis once the rash appears. However, clinical diagnosis of herpes zoster might not be possible in the absence of a rash (i.e., before a rash appears, or in cases of zoster without a rash – zoster sine herpete). Herpes zoster is sometimes confused with the following:

  • Herpes simplex, including eczema herpeticum
  • Impetigo
  • Contact dermatitis
  • Folliculitis
  • Scabies
  • Insect bites
  • Papular urticaria
  • Candida infection
  • Dermatitis herpetiformitis
  • Drug eruptions

Herpes zoster can be more difficult to diagnose in children and younger adults where the clinical presentation can be milder. Additionally, people with compromised immune systems are more likely to have atypical presentations (e.g., more severe or generalized rash).

Laboratory Testing

Laboratory testing can be useful, particularly in cases with less typical clinical presentations.

PCR is the most useful test

Polymerase chain reaction (PCR) can detect VZV DNA rapidly and sensitively. PCR is the most useful laboratory test for confirming cases of herpes zoster. PCR testing and genotyping can also distinguish between wild-type and vaccine strains of VZV.

Specimens for PCR testing

  • Swabs of unroofed vesicular lesions and scabs from lesions are ideal.
  • During acute disease, the viral DNA can also be detected in saliva, but saliva specimens are less reliable for herpes zoster than they are for varicella.
  • In cases involving atypical presentations, severe complications, or death, other specimen types (e.g., biopsied or autopsy tissue, cerebrospinal fluid) can be useful.

Other Tests

Direct fluorescent antibody (DFA) and Tzanck smear have rapid turnaround times but are not recommended because of their limited sensitivity. DFA is substantially less sensitive than PCR, and Tzanck is not specific for VZV. Moreover, real-time PCR protocols can be completed within one day.

Serologic methods have limited use for laboratory confirmation of herpes zoster and should only be used when suitable specimens for PCR testing are not available.

  • Patients with herpes zoster can mount a transient IgM response and would be expected to mount a memory IgG response.
  • However, a positive IgM ELISA result could indicate primary VZV infection, reinfection, or reactivation.
  • Primary infection can be distinguished from reactivation or reinfection with VZV IgG avidity testing:
    • High avidity IgG in the context of VZV IgM is indicative of a remote infection.
    • Low avidity IgG indicates a primary infection.

Measuring acute and convalescent sera also has limited value, since it is difficult to detect an increase in IgG for laboratory diagnosis of herpes zoster.

In instances where it is difficult to distinguish between varicella and disseminated herpes zoster in people with compromised immune systems, consider if the patient has a history of VZV exposure, history of a rash that began with a dermatomal pattern, and results of VZV antibody testing during or before the time of rash. This may help with diagnosis.