197.1 🎓 醫學生版

197.1.0.1 📌 一頁重點

• Virus: dsDNA virus, Herpesviridae α-subfamily
• 2 types:
  • HSV-1: oral, but increasingly anogenital (50% of new genital HSV in young adults due oral-genital contact)
  • HSV-2: classic genital, but can be oral
• Lifelong latency in sensory ganglia (trigeminal for oral, sacral for genital)
• Reactivation triggers: stress, illness, UV, immunosuppression, menstrual, fever, fatigue
• Clinical Forms:
  • Orolabial (“cold sores”, “fever blisters”) — recurrent, lip/perioral vesicles
  • Genital — recurrent painful vesicles → ulcers; majority HSV-2 globally but rising HSV-1 in 高所得
  • Neonatal — skin/eye/mouth (SEM) → CNS → disseminated; high mortality if disseminated
  • HSV encephalitis — adult: temporal lobe predilection, hemorrhagic; neurologic emergency
  • HSV keratitis — dendritic ulcer, recurrent → blindness
  • Eczema herpeticum — disseminated cutaneous HSV in atopic dermatitis
  • HSV proctitis — MSM, perianal pain + tenesmus
  • HSV esophagitis — immunocompromise (vs Candida + CMV)
  • Bell’s palsy — HSV-1 reactivation suspected in many cases
  • HSV hepatitis, pneumonia — disseminated
• Diagnosis:
  • PCR of lesion / blood / CSF — most sensitive
  • Direct fluorescent Ab (DFA) + culture — historical
  • Tzanck smear (giant cells + intranuclear inclusions) — quick bedside but low sens
  • Type-specific serology (gG1/gG2 ELISA) — past exposure
• Treatment:
  • Orolabial / genital: valacyclovir 1 g PO bid × 3-5d (acute) or valacyclovir 500 mg PO qd (chronic suppression)
  • Encephalitis: Acyclovir 10 mg/kg IV q8h × 14-21d — urgent
  • Neonatal: Acyclovir 20 mg/kg IV q8h × 14d (SEM) / 21d (CNS/disseminated)
  • Keratitis: trifluridine eye drops + oral acyclovir; ophthalmology
• Resistance: TK-mutated → foscarnet or cidofovir; immunocompromise risk
• Vaccine: in development (gB2/gD2, multi-antigen mRNA candidates 2024+)

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197.1.0.2 1️⃣ Virology

• dsDNA virus, ~ 152 kb
• ~ 75 genes
• Replicates in nucleus
• Latency in sensory ganglia (trigeminal, sacral, others)
• Latency-associated transcripts (LATs) only expressed during latency
• Lytic-latent switch tightly regulated

197.1.0.2.1 Cell Entry

• gD glycoprotein binds HVEM / nectin-1 → fusion
• gB + gH/gL fusion machinery

197.1.0.2.2 Lifecycle

• Lytic infection at site → spread → ganglia retrograde via sensory neuron
• Latency established in ganglia
• Reactivation → anterograde axonal → mucocutaneous site of original infection or new site

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197.1.0.3 2️⃣ Epidemiology

197.1.0.3.1 HSV-1

• Seroprevalence ~ 60-90% adults (varies)
• Childhood acquisition typical (mucocutaneous oral contact)
• Rising genital HSV-1 in young adults (oral-genital contact culture shift)
• Asymptomatic seroconversion common

197.1.0.3.2 HSV-2

• ~ 12% USA adults, higher in Africa, MSM
• Sexual transmission, vertical
• Lifelong recurrence

197.1.0.3.3 Co-infection

• HSV-2 + HIV: bidirectional risk increase (HSV-2 ulcers facilitate HIV transmission)
• HSV-2 PrEP: not licensed but research ongoing

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197.1.0.4 3️⃣ Clinical Forms

197.1.0.4.1 A. Orolabial HSV

• Primary: gingivostomatitis in children (often severe)
• Recurrent: “cold sores” / “fever blisters” — prodromal tingling → vesicles → crust
• Triggers: UV, stress, fever, fatigue
• Self-limit 7-10d
• Treatment for symptomatic relief or to prevent recurrences in frequent flares

197.1.0.4.2 B. Genital HSV

• Primary: severe extensive vesicles + ulcers + dysuria + fever + LAP
• 1st recurrence often within 4 mo
• Recurrence rate: HSV-2 4-5/yr, HSV-1 1/yr
• Asymptomatic shedding common (silent transmission)
• Counsel re transmission risk + condom + suppressive Tx

197.1.0.4.3 C. Neonatal HSV

• Vertical from infected mother (mostly intrapartum, some in utero)
• Higher risk if primary infection in 3rd trimester
• 3 patterns:
  • SEM (Skin / Eye / Mouth) — milder, ~ 50%, treat 14d
  • CNS — encephalitis, seizure, high mortality, 21d Tx
  • Disseminated — multi-organ, sepsis-like, very high mortality, 21d Tx
• Cesarean if active maternal genital lesions
• 母 antiviral suppression in late pregnancy if recurrent genital HSV
• Acyclovir 20 mg/kg IV q8h × 14-21d
• Suppressive PO acyclovir after IV completion in some

197.1.0.4.4 D. HSV Encephalitis (Adult)

• Most common cause of sporadic encephalitis in USA
• HSV-1 in 90%+ adults
• Temporal lobe predilection — bilateral or asymmetric
• Hemorrhagic, necrotizing
• Sx: fever, headache, altered mental status, seizures, focal neuro deficits
• MRI: T2 hyperintensity in temporal lobe + insula + cingulate
• EEG: PLEDs (periodic lateralized epileptiform discharges) in temporal region
• CSF: lymphocytic pleocytosis (1-2 cells × 10^6/L) + mildly ↑ protein + normal glucose
• HSV PCR of CSF = gold standard (sens 95%+ in first week)
• Treatment: Acyclovir 10 mg/kg IV q8h × 14-21d — start immediately on suspicion, don’t wait for PCR result
• Mortality 70% untreated, ~ 20% treated
• Long-term sequelae: memory + behavioral changes 在 survivors

197.1.0.4.5 E. HSV Keratitis

• HSV-1 mostly
• Dendritic ulcer (branching pattern) on cornea — fluorescein staining
• Pain, photophobia, foreign body sensation, blurred vision
• Recurrent → corneal scarring → blindness
• Treatment: topical trifluridine + oral acyclovir/valacyclovir; ophthalmology
• NO topical steroid unless ophthalmologist (can worsen)

197.1.0.4.6 F. Eczema Herpeticum

• Disseminated HSV in atopic dermatitis
• Punched-out vesicles + erosions over eczematous skin
• Risk of bacteremia, viremia, dissemination
• Acyclovir IV + supportive

197.1.0.4.7 G. HSV Proctitis

• MSM common
• Perianal pain + tenesmus + ulcers + LAP + fever
• HSV-2 typical
• Oral / IV antiviral

197.1.0.4.8 H. HSV Esophagitis

• Immunocompromise
• Odynophagia, dysphagia
• Endoscopy: clean-based ulcers (vs Candida thrush, vs CMV linear)
• Biopsy + PCR
• Acyclovir IV / PO

197.1.0.4.9 I. Disseminated HSV in Immunocompromise

• HSCT, leukemia, AIDS
• Hepatitis, pneumonia, encephalitis
• High mortality
• Acyclovir IV high-dose

197.1.0.4.10 J. Bell’s Palsy

• HSV-1 reactivation suspected in many cases
• Treatment: steroid +/- antiviral (mixed evidence on antiviral benefit; some advocate)

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197.1.0.5 4️⃣ Diagnosis

197.1.0.5.1 A. PCR

• Most sensitive — lesion swab, blood, CSF (encephalitis)
• HSV-1 vs HSV-2 distinguishable
• Quick (hours)
• Replaces older culture + DFA

197.1.0.5.2 B. Tzanck Smear

• Quick bedside test
• Scraping vesicle base → giemsa → multinucleated giant cells + intranuclear inclusions
• Sensitivity 40-60% — low
• Doesn’t distinguish HSV-1 vs HSV-2 vs VZV
• Mostly historical

197.1.0.5.3 C. Culture

• Viral culture (Vero cells, etc.)
• 1-3d
• Less sensitive than PCR; declining use

197.1.0.5.4 D. Direct Fluorescent Ab (DFA)

• Smear-based, monoclonal Ab
• Quick
• Sens lower than PCR

197.1.0.5.5 E. Serology

• Type-specific glycoprotein G (gG1/gG2 IgG ELISA) distinguishes HSV-1 vs HSV-2
• Past exposure / serologic status
• Doesn’t help acute lesion diagnosis usually

197.1.0.5.6 F. Imaging

• MRI for encephalitis (temporal lobe)
• Slit lamp + fluorescein for keratitis

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197.1.0.6 5️⃣ Treatment

197.1.0.6.1 A. Orolabial Recurrent (Mild)

• No treatment + reassurance for occasional mild
• Valacyclovir 2 g PO bid × 1 day (one-day high-dose, FDA-approved)
• Acyclovir 400 mg 5×/d × 5d
• Famciclovir 1500 mg PO × 1 dose

197.1.0.6.2 B. Genital HSV (Acute)

197.1.0.6.2.1 Primary

• Valacyclovir 1 g PO bid × 7-10d
• Acyclovir 400 mg PO tid × 7-10d
• Famciclovir 250 mg PO tid × 7-10d

197.1.0.6.2.2 Recurrent

• Valacyclovir 500 mg PO bid × 3d OR 1 g PO qd × 5d
• Acyclovir 400 mg tid × 5d
• Famciclovir 1 g bid × 1d (single-day option)

197.1.0.6.3 C. Suppression (Frequent Recurrences, ≥ 6/yr)

• Valacyclovir 500 mg PO qd (or 1 g qd if HIV +)
• Acyclovir 400 mg PO bid
• Reduces episodes + asymptomatic shedding + transmission (~ 50%)

197.1.0.6.4 D. HSV Encephalitis

• Acyclovir 10 mg/kg IV q8h × 14-21d
• 不 wait for PCR confirmation — start ASAP
• Pediatric: 10-20 mg/kg q8h
• Monitor renal function + hydrate
• Repeat CSF PCR at end of treatment (~ end-of-treatment LP — controversial; some advocate continuing if still + )

197.1.0.6.5 E. Neonatal HSV

• Acyclovir 20 mg/kg IV q8h × 14-21d
• SEM: 14d
• CNS / Disseminated: 21d
• Post-IV PO acyclovir suppression × 6 mo (reduces neurologic relapse)
• Maternal: acyclovir 36 wk gestation if recurrent genital HSV

197.1.0.6.6 F. HSV Keratitis

• Topical trifluridine 1% drops or ganciclovir gel
• Oral acyclovir / valacyclovir
• Ophthalmology — corneal scraping if needed

197.1.0.6.7 G. Eczema Herpeticum

• Acyclovir IV (severe) or PO valacyclovir (mild)
• Treat underlying eczema
• Address bacterial superinfection

197.1.0.6.8 H. Immunocompromise

• IV acyclovir
• Long course
• Consider resistance — foscarnet if refractory

197.1.0.6.9 I. Resistance

• TK mutation → acyclovir resistance
• More common in immunocompromise (HSCT, HIV)
• Foscarnet (direct polymerase) or cidofovir
• Pritelivir (helicase-primase inhibitor) — in Phase 3 trials for refractory mucocutaneous HSV

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197.1.0.7 6️⃣ Prevention + Transmission Reduction

197.1.0.7.1 Asymptomatic Shedding

• Asymptomatic shedding common (40%+ of days in HSV-2)
• Major source of transmission
• Suppressive therapy reduces shedding ~ 50%

197.1.0.7.2 Condoms

• Reduce transmission ~ 30%
• Not 100% (genital area beyond condom coverage)

197.1.0.7.3 Disclosure

• Counsel partner re HSV+ status
• Avoid sex during prodromal/active lesions
• Suppressive Tx + condom = ~ 50%+ reduction

197.1.0.7.4 Pregnancy

• 1st-trimester HSV: low fetal risk
• 3rd-trimester primary HSV: high neonatal HSV risk
• Acyclovir 36 wk gestation for recurrent → reduces neonatal exposure + cesarean if active
• Cesarean if active genital lesions at delivery

197.1.0.7.5 Vaccine

• In development
• gB2/gD2 subunit, mRNA candidates, multi-antigen
• Phase 1-2 trials 2024
• Therapeutic + prophylactic approaches
• No licensed vaccine yet

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