What tests are used to diagnose herpes zoster?

Diagnostic Testing for Herpes Zoster

PCR (nucleic acid amplification test) from vesicular fluid or lesion swabs is the test of choice for confirming herpes zoster, offering 95% diagnostic confirmation compared to only 20% sensitivity with viral culture. 1

First-Line Diagnostic Approach

• Clinical diagnosis is typically sufficient for immunocompetent patients presenting with the characteristic unilateral vesicular eruption in a dermatomal distribution, preceded by 24-72 hours of prodromal pain 2
• Laboratory confirmation should be obtained when:
  • The presentation is atypical (nonspecific lesions, absent vesicles, faint or evanescent rash) 2
  • The patient is immunocompromised 2
  • There is diagnostic uncertainty or medicolegal considerations 3
  • The patient presents with zoster sine herpete (pain without rash) 4

Optimal Laboratory Testing Method

PCR/NAAT is the gold standard when laboratory confirmation is needed:

• Collect vesicular fluid by piercing vesicles with a sterile needle and swabbing with cotton-wool or Dacron swabs 5
• PCR detects VZV DNA with 95% sensitivity, vastly superior to the 20% sensitivity of viral culture 1
• Results are available within approximately 2 hours 5
• Less strict transportation requirements compared to viral culture (no refrigeration needed) 5
• Can differentiate VZV from HSV when genital or atypical presentations occur 6

Alternative Testing Methods (When PCR Unavailable)

• Direct immunofluorescent antigen staining from vesicle samples has 82% sensitivity but only 76% specificity 1
• Viral culture has poor sensitivity (20%) and requires 24-72 hours for results, with strict refrigeration during transport 7, 1
• Tzanck smear showing multinucleated giant cells can suggest herpesvirus infection but cannot distinguish VZV from HSV and has low sensitivity 2, 8

Serological Testing

• IgM and IgA antibodies show serological response in only 48% of cases within 4 days of rash onset 1
• Serological testing is not recommended for acute diagnosis due to poor sensitivity in the acute phase 1
• May be useful retrospectively but should not delay treatment decisions 4

Critical Sampling Considerations

• Sample early vesicular lesions for highest yield—detection rates drop dramatically as lesions progress to crusting stage 7
• For genital herpes zoster (rare S2-S3 dermatomal involvement), PCR is essential to differentiate from HSV 6
• In immunocompromised patients with chronic ulcerations, consider biopsy for histopathological examination showing ballooning degeneration, multinucleated giant cells, and eosinophilic intranuclear inclusions 4

Key Clinical Pitfalls to Avoid

• Do not wait for laboratory confirmation to initiate antiviral therapy—treatment should begin as early as possible based on clinical diagnosis, particularly in high-risk patients (elderly, immunocompromised, ophthalmic/otic involvement) 3
• Do not rely on Tzanck smear alone as it cannot distinguish VZV from HSV 2
• Do not use serological testing for acute diagnosis as it lacks sensitivity in the acute phase 1
• In patients with darker skin pigmentation, the rash may be difficult to recognize, increasing the need for laboratory confirmation 2