Herpes Simplex
Infection with herpes simplex virus type 1 (orolabial) or type 2 (genital), causing painful vesicular lesions. Establishes lifelong latency in sensory ganglia with periodic reactivation. HSV encephalitis is a medical emergency requiring urgent IV aciclovir.
Key Facts
HSV-1: predominantly orolabial (cold sores); HSV-2: predominantly genital herpes — but either can cause either HSV encephalitis: most common sporadic viral encephalitis — temporal lobe predilection; mortality >70% untreated, ~20% with IV aciclovir Neonatal herpes: devastating infection acquired during delivery — mortality up to 30% even with treatment Treatment: oral aciclovir 400mg TDS for 5 days (genital primary); IV aciclovir 10mg/kg TDS for 14–21 days (encephalitis) Suppressive therapy: aciclovir 400mg BD long-term for frequent recurrences (≥6/year) Eczema herpeticum: widespread HSV in atopic eczema — medical emergency requiring IV aciclovir Erythema multiforme: HSV is the most common trigger for recurrent erythema multiforme Diagnosis: HSV PCR on vesicle swab (gold standard) or HSV PCR on CSF (encephalitis)
Overview
Key Facts
HSV infections are extremely common, affecting over two-thirds of the global population. Most infections are asymptomatic or mild, but severe manifestations including encephalitis and neonatal herpes can be life-threatening.
Epidemiology
- HSV-1 seroprevalence: ~50–80% of UK adults
- HSV-2 seroprevalence: ~10–15% of UK adults
- Genital herpes: ~30,000 new diagnoses/year in UK sexual health clinics
- HSV encephalitis: ~2–4 per million/year in UK
- Neonatal herpes: ~1.65 per 100,000 live births in UK
Aetiology
- HSV-1 and HSV-2: double-stranded DNA viruses (Herpesviridae, Alphaherpesvirinae)
- Transmission: direct contact with infected secretions (saliva, genital secretions)
- Asymptomatic shedding accounts for most transmission
- Incubation: 2–12 days
Pathophysiology
- Virus enters through mucosal surfaces or skin breaks → replicates in epithelial cells → vesicle formation
- Retrograde axonal transport to sensory ganglia (trigeminal for HSV-1, sacral for HSV-2)
- Establishes latency in neuronal cell bodies
- Reactivation: stress, UV light, immunosuppression, menstruation → anterograde transport → recurrent lesions
- HSV encephalitis: typically reactivation (HSV-1) → temporal lobe inflammation and necrosis
Clinical Presentation
Primary Orolabial Herpes (Gingivostomatitis)
- Children/young adults; fever, malaise
- Painful vesicles and ulcers on lips, gums, tongue, palate
- Lymphadenopathy, dysphagia
- Duration: 10–14 days
Recurrent Orolabial Herpes (Cold Sores)
- Prodrome: tingling/burning at lip margin
- Grouped vesicles on vermilion border → crust → heal in 7–10 days
- Milder and shorter than primary
Primary Genital Herpes
- Painful vulval/penile vesicles and ulcers; dysuria
- Bilateral inguinal lymphadenopathy
- Systemic symptoms: fever, malaise, headache
- Duration: 2–3 weeks
Severe Manifestations
- HSV encephalitis: fever, headache, confusion, seizures, temporal lobe signs (dysphasia, personality change)
- Eczema herpeticum: widespread vesiculopustular rash in atopic eczema
- Neonatal herpes: skin/eye/mouth disease, CNS disease, or disseminated disease
- HSV keratitis: dendritic ulcer on fluorescein staining
Red Flags
- New confusion/seizures with fever (encephalitis)
- Widespread vesicles in eczema (eczema herpeticum)
- Genital herpes in late pregnancy (neonatal risk)
- Eye pain with HSV (keratitis)
- Immunocompromised with HSV (dissemination risk)
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| VZV (chickenpox/shingles) | Dermatomal (shingles) or widespread different stages (chickenpox) | VZV PCR |
| Aphthous ulcers | Recurrent, non-vesicular, no systemic symptoms | Clinical |
| Behçet disease | Oral + genital ulcers, uveitis, pathergy | Clinical criteria |
| Syphilitic chancre | Painless ulcer, inguinal lymphadenopathy | Dark-field microscopy, syphilis serology |
| Hand-foot-mouth disease | Vesicles on hands, feet, mouth; enterovirus | Enterovirus PCR |
| Impetigo | Honey-crusted, superficial, S. aureus/Strep | Wound swab |
Diagnosis / Investigation
Bedside
- HSV PCR on vesicle swab: gold standard for mucocutaneous HSV
- Viral swab in transport medium: if PCR not available
Bloods
- HSV type-specific serology: IgG for HSV-1 and HSV-2 (useful for determining primary vs recurrent)
- FBC, CRP, LFTs: if systemic illness
Special Tests
- CSF HSV PCR: gold standard for HSV encephalitis (sensitivity >95%)
- MRI brain: temporal lobe oedema, haemorrhage (HSV encephalitis)
- EEG: periodic lateralised epileptiform discharges (PLEDs) in HSV encephalitis
- Slit-lamp examination: dendritic ulcer (HSV keratitis)
- Tzanck smear: multinucleated giant cells (non-specific, rarely used)
Management
Non-pharmacological
- Avoid sexual contact during active genital herpes
- Saline bathing of genital lesions for comfort
- Topical anaesthetic: lidocaine 2% gel for pain
- Education: lifelong infection, recurrence, asymptomatic shedding
Pharmacological
Orolabial herpes:
- Primary gingivostomatitis: aciclovir 200mg 5× daily for 5 days
- Recurrent cold sores: topical aciclovir 5% cream (limited benefit); oral aciclovir if severe/frequent
Genital herpes (BASHH guidelines):
- Primary: aciclovir 400mg TDS for 5 days (or valaciclovir 500mg BD for 5 days)
- Recurrent: aciclovir 800mg TDS for 2 days (short course) or 400mg TDS for 5 days
- Suppressive therapy (≥6 recurrences/year): aciclovir 400mg BD continuously; review at 12 months
HSV encephalitis (MEDICAL EMERGENCY):
- IV aciclovir 10mg/kg TDS for 14–21 days — start EMPIRICALLY if suspected (do NOT wait for PCR result)
- Adequate IV hydration to prevent aciclovir crystalluria
Eczema herpeticum:
- IV aciclovir 5–10mg/kg TDS until improvement, then oral to complete 10–14 days
Neonatal herpes:
- IV aciclovir 20mg/kg TDS for 14–21 days
Pregnancy:
- Primary genital HSV in third trimester: aciclovir 400mg TDS from 36 weeks; consider caesarean section if active lesions at delivery
- Recurrent genital HSV: suppressive aciclovir from 36 weeks; vaginal delivery usually safe
Referral Criteria
- Ophthalmology: HSV keratitis (urgent)
- Neurology/ID: HSV encephalitis
- GUM/sexual health: genital herpes (counselling and management)
- Neonatology: suspected neonatal herpes
- Dermatology: eczema herpeticum
Prognosis
- Orolabial herpes: self-limiting; recurrences decrease over time
- Genital herpes: primary episode more severe; recurrences milder and less frequent; HSV-2 recurs more than HSV-1 genitally
- HSV encephalitis: mortality >70% untreated; ~20% with IV aciclovir; ~50% have long-term neurological sequelae
- Neonatal herpes: SEM disease ~2% mortality with treatment; CNS disease ~6% mortality; disseminated ~30% mortality
- Eczema herpeticum: good prognosis with prompt IV aciclovir
- Suppressive therapy: reduces recurrences by 70–80% and transmission by ~50%
Other Relevant Information
HSV-1 vs HSV-2 Comparison
| Feature | HSV-1 | HSV-2 |
|---|---|---|
| Primary site | Orolabial | Genital |
| Latency site | Trigeminal ganglion | Sacral ganglia |
| Seroprevalence (UK) | 50–80% | 10–15% |
| Genital recurrence rate | ~1/year | ~4–5/year |
| Encephalitis | Most common cause | Rare (neonatal) |
HSV Treatment Summary
| Condition | Treatment | Duration |
|---|---|---|
| Primary genital | Aciclovir 400mg TDS | 5 days |
| Recurrent genital | Aciclovir 800mg TDS | 2 days |
| Suppressive | Aciclovir 400mg BD | Continuous |
| Encephalitis | IV aciclovir 10mg/kg TDS | 14–21 days |
| Eczema herpeticum | IV aciclovir 5–10mg/kg TDS | 10–14 days |