What is the initial testing algorithm for a patient presenting with suspected Herpes Simplex Virus (HSV) oral ulcers?

Testing Algorithm for HSV Oral Ulcers

For patients presenting with suspected HSV oral ulcers, nucleic acid amplification tests (NAATs) or PCR from lesion samples should be the first-line diagnostic approach, as they offer the highest sensitivity and specificity for detecting HSV infection. 1

Initial Diagnostic Steps

• Collect samples directly from vesicular or ulcerative oral lesions using proper technique for optimal diagnostic yield 1
• Open vesicles with a sterile needle and collect the content with a swab for testing 1
• For ulcerative lesions, swab the base of the ulcer to collect viral material 1
• Submit samples for HSV NAAT/PCR testing that can differentiate between HSV-1 and HSV-2 1

Sample Collection Technique

• Use cotton-wool or Dacron swabs to collect material from lesions 1
• For vesicular lesions: pierce the vesicle and collect fluid 1
• For ulcerative lesions: use Kimura scraper to sample the bases of lesions for better yield 1
• Transport samples promptly in appropriate viral transport media 1

Preferred Testing Methods (Ranked)

1. NAAT/PCR Testing (First Choice)

   • Highest sensitivity (11-71% superior to viral culture) 1
   • Can detect and type HSV in a single reaction 1
   • Provides results within approximately 2 hours 1
   • Less strict sample transportation conditions required 1

2. Viral Culture (Second Choice)

   • Traditional method but less sensitive than PCR 1
   • Isolation rate varies by lesion stage: 90% from vesicular/pustular lesions, 70% from ulcerative lesions, only 27% from crusting lesions 1
   • Results typically available in 24-72 hours but may take up to 5 days 1
   • Allows virus typing and antiviral sensitivity testing if needed 1

3. Antigen Detection Methods (Third Choice)

   • EIA-based methods have >95% sensitivity compared to viral isolation 1
   • Specificities range from 62% to 100% for symptomatic patients 1
   • Most commercial assays do not differentiate between HSV-1 and HSV-2 1

Not Recommended

• HSV direct immunofluorescence assay and Tzanck smear lack sensitivity and are not recommended 1
• Do not obtain HSV molecular assays in the absence of a genital ulcer, as intermittent viral shedding makes this approach insensitive 1

Serological Testing

• Consider type-specific HSV serologic testing if:

  • Lesions have healed and direct testing is not possible 1
  • Recurrent episodes occur but direct testing has been negative 1
  • Clinical suspicion remains high despite negative direct tests 1

• Type-specific serologic assays that differentiate between HSV-1 and HSV-2 should be used 1

• Be aware that serologic testing has limitations:

  • HSV-1 assays may lack sensitivity, resulting in false-negative diagnoses 1
  • Cannot determine the site of infection (oral vs. genital) 2
  • Requires at least 12 weeks after exposure for accurate results 2

Special Considerations

• For immunocompromised patients (HIV, cancer therapy, transplant recipients):

  • More aggressive diagnostic evaluation is warranted as lesions may present atypically 1, 3
  • Consider early biopsy and surgical debridement 1
  • Empiric antiviral therapy may be considered in life-threatening situations 1

• For suspected HSV encephalitis:

  • Detection of HSV DNA by PCR in CSF is the diagnostic test of choice 1
  • CSF cultures for HSV are usually negative 1

Clinical Pearls

• The clinical differentiation of HSV infection from other infectious and non-infectious causes of oral ulceration is difficult; laboratory confirmation should always be sought 1
• False-negative results may occur as lesions heal, so timing of sample collection is critical 1
• HSV-1 is more commonly associated with oral lesions, while HSV-2 is more commonly associated with genital lesions, but both can occur at either site 1
• Typing of HSV is important as it provides prognostic information (HSV-1 recurs less frequently than HSV-2 in the genital area) 1