What is the next step in diagnosis and treatment for a patient presenting with a genital rash, suspected to be genital herpes (Herpes Simplex Virus, HSV)?

Genital Rash: Next Diagnostic Steps

For a patient presenting with a genital rash, immediately obtain a swab from any visible lesions for nucleic acid amplification testing (NAAT/PCR) with HSV typing, as this provides the highest sensitivity and specificity (>90%) and is the preferred diagnostic method. 1, 2

Immediate Diagnostic Approach

If Active Lesions Are Present

Collect specimens as early as possible in the disease course, as vesicular lesions yield significantly higher positivity rates than ulcerative or healing lesions. 2

Specimen collection technique:

• If vesicles are present: Open vesicles with a sterile needle, collect vesicular fluid content with a cotton-wool or Dacron swab, then vigorously swab the base of the lesion to obtain epithelial cells. 1, 2
• For ulcerative lesions: Vigorously swab the base of the ulcer using circular motions. 1
• Avoid calcium alginate swabs, which interfere with viral recovery. 2

Request NAAT/PCR with HSV typing (HSV-1 vs HSV-2 differentiation), as this is critical for counseling—12-month recurrence rates differ dramatically: HSV-2 (90%) versus HSV-1 (55%). 2 NAAT increases HSV detection rates by 24% compared to culture alone and is particularly superior for ulcerative, crusting, or healing lesions. 3, 4

If Viral Culture Is the Only Available Test

If NAAT is unavailable due to cost or laboratory limitations, viral culture is acceptable but recognize its lower sensitivity, particularly for recurrent lesions and ulcerative (versus vesicular) presentations. 1, 2 If HSV is clinically suspected and culture is negative, proceed to type-specific serology. 1

Critical Testing Pitfalls to Avoid

Do not obtain HSV molecular assays in the absence of genital ulcers—due to intermittent viral shedding, swabs without visible lesions lack sensitivity for diagnosing active genital herpes. 1

Do not use direct immunofluorescence assay or Tzanck smear, as these lack adequate sensitivity and are not recommended. 1

Differential Diagnosis Considerations

Clinical diagnosis alone is unreliable—laboratory confirmation should always be sought, as genital HSV infection is difficult to differentiate from other causes of genital ulceration. 1

Consider and test for other sexually transmitted infections:

• Treponema pallidum (syphilis) and Haemophilus ducreyi (chancroid) can present similarly, and HSV and syphilis can occasionally coexist in the same lesion. 1

Non-infectious causes to consider:

• Inflammatory bowel disease (Crohn disease), Behçet syndrome, or fixed drug eruption may mimic genital herpes. 1
• Varicella zoster virus (VZV) accounts for nearly 3% of virus-positive genital specimens and requires different counseling regarding recurrence risk and transmission. 5

When to Use Serologic Testing

Type-specific HSV serology (glycoprotein G-based) should be reserved for specific situations:

• When lesions have healed and NAAT/culture was not obtained. 1
• To distinguish between HSV-1 and HSV-2 in patients with a history of genital herpes but no current lesions. 1

Critical limitations of serology:

• HSV-1 EIA/CLIA assays have only 70.2% sensitivity, resulting in frequent false-negatives. 1
• HSV-2 EIA/CLIA assays lack specificity, particularly with index values 1.1–2.9 (only 39.8% specificity); even values ≥3.0 have only 78.6% specificity. 1
• False-positive HSV-2 results are more common in patients with HSV-1 infection. 1
• Window period for seroconversion may be up to 12 weeks after acquisition. 1

Do not use serology to diagnose acute lesions, as it cannot distinguish active from past infection. 2

Additional Diagnostic Considerations

For women with genital lesions:

• Collect specimens from the cervix (insert swab 2 cm into cervical canal) and vaginal wall, as HSV can be isolated from these sites in 88% and a significant proportion of women with first-episode genital herpes, respectively. 1, 6

For men with genital lesions:

• Consider urethral sampling (insert swab 0.5–2 cm into urethral meatus) if urethral discharge is present, as HSV can be isolated from the urethra in 28% of men with first-episode infection. 1, 6

Document lesion characteristics:

• Bilateral distribution, multiple pustular/ulcerative lesions, and systemic symptoms suggest primary first-episode infection. 6
• Unilateral, small vesicular/ulcerative lesions suggest recurrent episodes. 6