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
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
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?
ATopical acyclovir ointment application
BIntramuscular benzathine penicillin G
CSingle-dose oral azithromycin 1 gram
DOral valacyclovir antiviral therapy
EOvernight topical permethrin application
Reveal answer & full explanation
Correct answer: D — Oral valacyclovir antiviral therapy
ATopical acyclovir ointment application
BIntramuscular benzathine penicillin G
CSingle-dose oral azithromycin 1 gram
DOral valacyclovir antiviral therapy✓
EOvernight topical permethrin application
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
Overnight topical permethrin application — Scabies trap: permethrin treats the mite, which causes burrows and pruritus, not grouped genital vesicles.
Intramuscular benzathine penicillin G — Syphilis trap: penicillin treats the painless chancre of syphilis, not painful vesicular HSV lesions.
Single-dose oral azithromycin 1 gram — Chancroid trap: azithromycin treats Haemophilus ducreyi, which causes painful, deep ulcers with a purulent base and suppurative inguinal buboes, but it has no activity against HSV.
Topical acyclovir ointment application — right-drug-wrong-route trap: acyclovir is active against HSV, but topical antiviral therapy offers minimal clinical benefit in first-episode genital herpes and is discouraged by the CDC; oral systemic therapy is needed to shorten symptoms and viral shedding.
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?
AViral culture of vesicular fluid
BTzanck smear of a lesion scraping
CType-specific HSV-2 IgG serology
DHSV PCR of a lesion-swab sample
EHaemophilus ducreyi culture of an ulcer
Reveal answer & full explanation
Correct answer: D — HSV PCR of a lesion-swab sample
AViral culture of vesicular fluid
BTzanck smear of a lesion scraping
CType-specific HSV-2 IgG serology
DHSV PCR of a lesion-swab sample✓
EHaemophilus ducreyi culture of an ulcer
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.
Haemophilus ducreyi culture of an ulcer — painful genital ulcers with tender inguinal adenopathy suggest chancroid, but chancroid ulcers are deep and ragged with undermined borders and purulent bases, without a tingling prodrome or clustered shallow ulcers on an erythematous base; chancroid is rare in the US, and the special culture media are not widely available.
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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 (usually acquired during vaginal delivery): skin-eye-mouth (SEM), CNS (encephalitis), or disseminated disease; presents at about 1-3 weeks of life (CNS disease up to 6 weeks); most mothers have no history of genital lesions because shedding is asymptomatic; transmission risk is 30-50% with genital infection acquired near delivery vs <1% with recurrent disease; CSF shows lymphocytic pleocytosis, elevated protein, and often RBCs; diagnose with HSV PCR of CSF, blood, and surface swabs and start IV acyclovir 20 mg/kg q8h empirically; 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
Neonatal HSV
IV acyclovir 20 mg/kg q8h
14 d (SEM); 21 d (CNS or disseminated)
Severe adult disease
IV acyclovir 5-10 mg/kg q8h, then oral
≥10 days total
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: neonatal HSV 20 mg/kg q8h × 14 days (skin-eye-mouth) or 21 days (CNS or disseminated); severe genital or disseminated disease in adults 5-10 mg/kg q8h until clinical improvement, then oral therapy to complete at least 10 days total; HSV encephalitis 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.
Painful clustered ulcers + TENDER inguinal nodes = HSV; single painless indurated chancre + NON-tender, rubbery (often bilateral) nodes = syphilis. Tenderness, not laterality, is the discriminator.
Serology cannot tell new from old infection without prior baseline; do not order IgM (poor performance).
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