Recurrent painful genital vesicular ulcers caused by HSV-2 (and increasingly HSV-1) — managed with episodic or suppressive antiviral therapy.
Also known as: genital herpes, HSV-2, herpes simplex, HSV, genital HSV
Overview
Chronic, lifelong infection with herpes simplex virus (HSV) types 1 or 2, characterized by recurrent vesicular and ulcerative lesions on genital mucosa. HSV-2 historically the predominant cause; HSV-1 increasingly accounts for primary genital herpes (particularly in young adults).
Epidemiology
~12% of US adults are HSV-2 seropositive; majority of infected individuals are unaware. Most HSV-2 transmission occurs during asymptomatic shedding. HSV-1 increasingly causes new genital infections (~50% in some populations).
Try two board-style Genital Herpes questions
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Question 1Infectious DiseaseMedium
A 27-year-old man has painful grouped vesicles on an erythematous base on the penis and tender inguinal lymphadenopathy. He has never had similar lesions. Which of the following is the most appropriate treatment?
AOvernight topical permethrin application
BOral valacyclovir antiviral therapy
CIntramuscular benzathine penicillin G
DOral doxycycline for chlamydial urethritis
Reveal answer & full explanation
Correct answer: B — Oral valacyclovir antiviral therapy
AOvernight topical permethrin application
BOral valacyclovir antiviral therapy✓
CIntramuscular benzathine penicillin G
DOral doxycycline for chlamydial urethritis
Why Oral valacyclovir antiviral therapy is correct
First-episode genital herpes is treated with an oral antiviral such as valacyclovir, acyclovir, or famciclovir.
Painful grouped vesicles on an erythematous base with tender inguinal nodes is the classic HSV presentation.
Antivirals shorten symptoms and shedding but do not eradicate latent ganglionic virus.
Why the others are wrong
Intramuscular benzathine penicillin G — Syphilis trap: penicillin treats the painless chancre of syphilis, not painful vesicular HSV lesions.
Oral doxycycline for chlamydial urethritis — Chlamydia trap: doxycycline targets a urethral bacterial infection, not vesicular genital herpes.
Overnight topical permethrin application — Scabies trap: permethrin treats the mite, which causes burrows and pruritus, not grouped genital vesicles.
Question 2Infectious DiseaseMedium
A 24-year-old woman presents with a 3-day history of painful genital sores. She reports a tingling sensation in the area the day before the lesions appeared, along with low-grade fever, malaise, and burning with urination. She became sexually active with a new partner one month ago. On examination, there are several clustered shallow ulcers on an erythematous base over the labia, with tender bilateral inguinal lymphadenopathy. Which of the following is the most appropriate next diagnostic test?
AHSV PCR of a lesion-swab sample
BViral culture of vesicular fluid
CTzanck smear of a lesion scraping
DType-specific HSV-2 IgG serology
Reveal answer & full explanation
Correct answer: A — HSV PCR of a lesion-swab sample
AHSV PCR of a lesion-swab sample✓
BViral culture of vesicular fluid
CTzanck smear of a lesion scraping
DType-specific HSV-2 IgG serology
Why HSV PCR of a lesion-swab sample is correct
HSV PCR from a swab of an active lesion (deroof a vesicle to sample) is the most sensitive test and is the preferred method to confirm genital herpes in a patient with active lesions.
It both detects and types the virus (HSV-1 vs HSV-2), which guides counseling on recurrence frequency and transmission.
CDC STI guidelines recommend nucleic acid amplification (PCR) over culture as the first-line virologic test for genital ulcers when lesions are present.
Why the others are wrong
Viral culture of vesicular fluid — a valid virologic test that can also type the virus, but it is substantially less sensitive than PCR (especially as lesions crust) and is now largely historical; it is not the preferred next test when PCR is available.
Type-specific HSV-2 IgG serology — useful for confirming chronic or asymptomatic infection, or when no lesion is available to swab, but it cannot diagnose an acute lesion (seroconversion lags the primary outbreak) and cannot distinguish new from old infection without a prior baseline. With a fresh sampleable lesion, direct virologic testing is preferred.
Tzanck smear of a lesion scraping — shows multinucleated giant cells but has low sensitivity and cannot distinguish HSV from VZV; it is outdated and inferior to PCR.
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Lack of condom use; intimate contact during prodrome or active lesions
Prior HSV-1 infection partially protective against HSV-2 acquisition
Pathophysiology
Virus infects mucocutaneous epithelium, replicates locally, then ascends sensory neurons to establish latency in dorsal root ganglia (sacral for genital HSV). Reactivation triggers anterograde transport to mucocutaneous sites with recurrent lesions and asymptomatic viral shedding. HSV-2 reactivates more frequently in genital region than HSV-1.
Recurrent infections (HSV-2 averages 4-5 per year, declines over time): prodromal tingling/pain at site → small clustered vesicles → ulcers → crust; lasts 5-10 days; milder than primary
Asymptomatic shedding common — major source of transmission
Neonatal HSV (acquired during vaginal delivery): SEM (skin-eyes-mouth), CNS (encephalitis), or disseminated; high mortality without treatment
Signs / physical exam
Clustered vesicles on erythematous base evolving to shallow ulcers
Bilateral tender inguinal lymphadenopathy in primary infection
Cervicitis (women) — may be missed without speculum exam
Atypical presentations common — most infections undiagnosed clinically
Classic findings
Recurrent grouped painful vesicles/ulcers on the genitalia with prodromal tingling — classic HSV. Bilateral tender inguinal nodes with primary outbreak help distinguish from syphilis (painless chancre, non-tender adenopathy).
VZV (sacral dermatomal zoster) — Dermatomal distribution; older or immunocompromised
Diagnostic workup
Diagnostic criteria
Positive HSV PCR from lesion (preferred) or type-specific serology in clinical context.
Labs
HSV PCR from lesion swab — most sensitive (deroof vesicle to collect)
Viral culture — historical, less sensitive than PCR; useful for typing if PCR unavailable
Type-specific serology (HSV-1 and HSV-2 IgG) — for confirming chronic infection or asymptomatic status; IgM not recommended
Test for other STIs (syphilis, HIV, chlamydia, gonorrhea)
Tzanck smear historical, low sensitivity, does not distinguish HSV from VZV
Imaging
Not required for routine genital HSV
MRI brain and LP for suspected HSV encephalitis (HSV-1)
Diagnostic algorithm
Scenario
Regimen Examples
Duration
First episode
Acyclovir 400 mg TID; valacyclovir 1 g BID
7-10 days
Episodic recurrence
Valacyclovir 500 mg BID; famciclovir 1 g BID x 1 day
1-5 days
Daily suppression
Valacyclovir 500 mg daily; acyclovir 400 mg BID
Indefinite
Pregnancy (suppression from 36 wk)
Valacyclovir 500 mg BID or acyclovir 400 mg TID
Until delivery
Severe / disseminated / neonatal
IV acyclovir 10 mg/kg q8h
14-21 days
Genital HSV antiviral regimens by clinical scenario (CDC 2021).
Treatment
First-line
First episode (treat all to reduce duration and severity):
• Acyclovir 400 mg PO TID × 7-10 days
• Valacyclovir 1 g PO BID × 7-10 days
• Famciclovir 250 mg PO TID × 7-10 days
Episodic recurrent therapy (start at prodrome or within 24 hours of lesion onset):
• Acyclovir 800 mg PO BID × 5 days or 800 mg TID × 2 days
• Valacyclovir 1 g PO daily × 5 days or 500 mg BID × 3 days
• Famciclovir 1 g PO BID × 1 day (single-day course)
Daily suppressive therapy (indicated for ≥6 recurrences/year, severe outbreaks, or to reduce transmission):
• Acyclovir 400 mg PO BID
• Valacyclovir 500 mg PO daily (1 g daily if >9 recurrences/year)
• Famciclovir 250 mg PO BID
Second-line / adjunct
IV acyclovir for severe disease, neonatal HSV, encephalitis, immunocompromised disseminated infection (10 mg/kg q8h × 14-21 days)
Foscarnet — acyclovir-resistant HSV (rare, mainly in advanced HIV)
Pregnancy: suppressive valacyclovir 500 mg PO BID or acyclovir 400 mg TID from 36 weeks to delivery to reduce shedding/lesions at delivery; cesarean delivery if active lesions or prodrome at labor
Condom use reduces but does not eliminate transmission; antiviral suppression of source partner reduces transmission ~50% (Corey 2004)
Complications
Neonatal HSV with high mortality and neurologic morbidity
Sacral radiculopathy with urinary retention (Elsberg syndrome)
Disseminated HSV in immunocompromised (hepatitis, pneumonitis, encephalitis)
Increased HIV transmission risk (~3x)
Psychosocial distress, partner disclosure issues
PANCE pearls
Most HSV transmission occurs during asymptomatic shedding, not active outbreaks — counsel on this consistently.
Pregnant patients with active genital HSV at delivery require cesarean to prevent neonatal infection; suppressive antivirals from 36 weeks reduce active lesions at term.
HSV-1 increasingly causes new genital herpes — but reactivates less often in the genital region than HSV-2.
Bilateral inguinal lymphadenopathy with painful clustered ulcers = HSV; unilateral non-tender with painless ulcer = syphilis.
Serology cannot tell new from old infection without prior baseline; do not order IgM (poor performance).
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