Clinical Overview

Herpes simplex virus (HSV) infection is one of most common viral infections worldwide, affecting 60-90% of population by age 50. Two serotypes: HSV-1 predominantly causes orolabial disease (cold sores), while HSV-2 primarily causes genital herpes, though overlap exists (15% of genital HSV is HSV-1). After primary infection, virus remains latent in dorsal root ganglia, reactivating periodically causing recurrent lesions at dermatome distribution site. Despite universal prevalence, majority remain asymptomatic or minimally symptomatic.

Epidemiology

HSV-1 seroprevalence 60-90% by age 50; HSV-2 seroprevalence 10-30% varying by region/demographics. Primary infection typically childhood (HSV-1) or adolescence/early adulthood (HSV-2). Recurrence rates HSV-1: 20-40% of infected individuals have ≥1 recurrence annually; HSV-2: 50-80% have ≥1 recurrence annually (higher recurrence than HSV-1). Prodromal symptoms (tingling, burning, paresthesias) precede visible lesions by 24-48 hours in 80% of patients, permitting early antiviral initiation. Asymptomatic viral shedding occurs 10-15% of days in HSV-2+ individuals, explaining transmission despite lack of clinical disease in 60% of primary infections in partners of known HSV patients. Pregnancy: HSV infection in pregnancy increases risk of preterm labor (3-fold) and neonatal herpes in exposed infants (30-50% risk at vaginal delivery if primary infection near delivery).

Pathophysiology

HSV enters epithelial cells via glycoprotein gG/gC interaction with heparan sulfate proteoglycans and gD interaction with HVEM or nectin-1 receptors. Viral DNA replication in cytoplasm produces infectious virions within hours. Cellular apoptosis cascades create characteristic vesicles (intraepidermal with ballooned epithelial cells and multinucleated giant cells). Innate immune response (interferon-alpha, NF-kB pathway activation) and adaptive immunity (CD8+ T-cell response targeting viral antigens) establish epithelial inflammation. Primary infection: higher viral load, more severe symptoms, slower healing (7-14 days) due to absent immune memory. Recurrence: lower viral load, milder symptoms, faster healing (5-10 days) due to memory T-cell response. Latency maintained through tegument protein VP16 inhibition of immediate-early gene expression in ganglion neurons; reactivation triggers retrograde axonal transport of virions to skin.

Clinical Presentation

Primary HSV (orolabial or genital): often asymptomatic (60%) or mildly symptomatic. When symptomatic: prodromal symptoms (tingling, burning, paresthesias) for 24-48 hours followed by grouped vesicles on erythematous base. Vesicles rupture creating painful erosions within 24-48 hours. Healing with crusting/epithelialization over 5-14 days. Associated systemic symptoms: fever (30%), malaise, regional lymphadenopathy (50%). Gingivostomatitis in children: severe painful oral ulcers, difficulty eating, fever.

Recurrent HSV: prodromal phase essential, recognized by 80% of patients permitting early treatment. Fewer lesions (3-5 vs. 10-20 in primary), localized to dermatome (lip in labial HSV). Healing faster (5-10 days) than primary. Recurrence frequency: HSV-1 typically 1-2 times yearly; HSV-2 typically 4-5 times yearly. Triggers: stress, immunosuppression, illness, menstrual cycle (40% of HSV-2+ women), UV exposure (HSV-1 labial).

Diagnosis

Diagnosis clinical based on characteristic vesicles on erythematous base with prodromal symptoms. Confirmation via: viral culture (gold standard sensitivity 40-80% depending on stage; most sensitive on fluid from fresh vesicles), PCR (highest sensitivity 95%, increasingly used), Tzanck smear (shows multinucleated giant cells, non-specific but supportive, sensitivity 40%), or serology (shows HSV-1/HSV-2 IgG for confirmation of past infection; IgM less reliable for primary vs. recurrence distinction). HSV typing essential: distinguishes HSV-1 vs. HSV-2 determining recurrence risk and transmission patterns.

Treatment Algorithm

Primary HSV Infection: Initiate antiviral immediately upon presentation (not just lesions, but prodromal symptoms warrant treatment). Acyclovir 400mg 5 times daily x 7-10 days reduces duration by 1-2 days and systemic symptoms severity by 50%. Valacyclovir 1000mg 3 times daily x 7-10 days (superior bioavailability, less frequent dosing). Famciclovir 250mg 3 times daily x 7-10 days equivalent efficacy. IV acyclovir 5-10mg/kg q8h reserved for severe disease, encephalitis, immunocompromised patients.

Recurrent Herpes Labialis (Cold Sores): Early intervention critical. Prodromal symptoms trigger treatment: penciclovir 1% cream q2h x 4 days (reduces duration 1 day, lesion progression prevention), or acyclovir 5% cream 5 times daily. Systemic therapy more effective: acyclovir 400mg 5 times daily x 5 days OR valacyclovir 500mg twice daily x 3 days OR famciclovir 125mg 3 times daily x 5 days. Initiation within 24 hours of symptom onset yields maximal benefit; delayed treatment provides minimal benefit.

Recurrent Genital Herpes: Early systemic therapy: acyclovir 400mg 3 times daily x 5-10 days, valacyclovir 500mg twice daily x 3-5 days, or famciclovir 125mg twice daily x 5 days. Healing accelerated 1-3 days with early treatment. Suppressive therapy indicated for: frequent recurrences (≥6 annually), symptomatic transmission risk reduction (reduces risk 50%), or psychosocial benefit. Acyclovir 400mg twice daily, valacyclovir 500mg daily, or famciclovir 250mg daily continuous or for defined periods (winter months if UV-triggered, menstrual cycle timing if catamenial).

Immunocompromised Herpes: IV acyclovir 5-10mg/kg q8h essential for disseminated disease/encephalitis. High-dose oral therapy (valacyclovir 1000mg 3-4 times daily) for localized disease. Duration: 7-14 days or longer if immunosuppression severe. Resistance rare but possible: check for acyclovir-resistant strains via viral culture with susceptibility if treatment failure (requires testing at specialized lab). Foscarnet 40-60mg/kg IV q8h reserved for acyclovir-resistant HSV.

Herpes in Pregnancy: Suppressive acyclovir 400mg 3 times daily starting at 36 weeks gestation reduces recurrence/asymptomatic shedding and risk of cesarean delivery (for primary infection or active lesions at labor). Reduces neonatal herpes risk significantly. Acyclovir/valacyclovir category B in pregnancy (relatively safe based on available data).

Prognosis

Primary HSV: healing 7-14 days, no scarring. Recurrent: healing 5-10 days, minimal scarring (rare). 70-80% of patients experience at least one recurrence within 1 year of primary infection. Antiviral therapy reduces recurrence frequency by 20-30% if initiated early, but does not eliminate recurrence risk. Suppressive therapy reduces recurrence 70-80% while on therapy; recurrences resume upon discontinuation. Neonatal herpes (infection within first 6 weeks): severe disease with 30% mortality if untreated, 10-15% with IV acyclovir; long-term neurologic sequelae in 10-20% of survivors. Prompt delivery planning in HSV-positive pregnancies minimizes neonatal herpes risk.

When to See a Dermatologist

Dermatologists recognize HSV clinically and initiate antiviral therapy. Refer for: frequent/severe recurrences (suppressive therapy optimization), atypical presentations, immunocompromised patients with HSV, or adverse effects from antivirals. Coordinate with obstetrics in pregnant HSV+ women.

Frequently Asked Questions

Q: Can I transmit herpes without visible sores?
A: Yes. Asymptomatic viral shedding occurs 10-15% of days in HSV-positive individuals. Transmission risk reduced 50% with suppressive acyclovir therapy and condom use. Transmission risk highest during prodromal/active lesion phases.

Q: Will antiviral therapy cure my herpes?
A: No cure exists; virus remains latent in nerve cells lifelong. Antivirals reduce recurrence frequency (by 70% with suppressive therapy) and accelerate healing of active lesions (by 1-3 days). Recurrences resume upon discontinuation in most patients.

Q: When can I have sex after herpes?
A: Avoid all sexual contact during active lesions/prodromal phase. After healing (full epithelialization), transmission risk low with barrier protection. Risk further reduced with suppressive therapy. Discuss timeline with partner; many resume relations within 1-2 weeks of healing.

Q: Will I pass herpes to my baby?
A: If HSV+ with planned vaginal delivery: discuss with obstetrician. Suppressive acyclovir 36 weeks onward significantly reduces risk. Cesarean section recommended if active lesions/prodrome at labor onset. Neonatal herpes preventable with delivery planning.

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