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BASICS

Description

  • Chronic, recurrent HSV type 1 or 2 infection of sacral ganglia-innervated areas.
  • HSV-1 causes anogenital and orolabial lesions; HSV-2 mainly anogenital.
  • Primary episode: no preexisting antibodies; may be asymptomatic.
  • First episode, nonprimary: initial genital eruption with preexisting antibodies.
  • Reactivation: recurrent episodes.
  • Synonym: herpes genitalis.

Epidemiology

  • Most infected age: 15-30 years; prevalence increases with age.
  • Female > male.
  • Higher prevalence in non-Hispanic blacks.
  • Estimated 572,000 to 1.6 million new US cases/year; highest in 18-24 years.
  • HSV-2 prevalence 10-40% in general population; up to 60-95% in HIV-positive.
  • 48% US population HSV-1 seropositive (age 14-49), 12% HSV-2.
  • Up to 90% seropositive unaware of infection.
  • Globally: HSV-1 infects 3.7 billion, HSV-2 infects 140 million.

Etiology and Pathophysiology

  • HSV-1 and HSV-2 are double-stranded DNA viruses, Herpesviridae family.
  • Transmission: genital-genital, oral-genital contact, maternal-fetal.
  • Incubation: 4-7 days.
  • Highest transmission risk with lesions present; asymptomatic shedding also occurs, more with HSV-2.
  • HSV infection increases HIV acquisition risk.

Risk Factors

  • Age, number of sexual partners.
  • History of STIs, especially HIV.
  • Early sexual activity (<17 years).
  • Partner with HSV.
  • Immunosuppression, fever, stress, trauma.

General Prevention

  • Barrier contraception.
  • Avoid sexual contact during symptomatic phases.
  • Abstinence for complete protection.

DIAGNOSIS

History

  • Many asymptomatic (74% HSV-1, 63% HSV-2) or unaware.
  • Primary episode more severe, longer, with constitutional symptoms.
  • Symptoms: multiple genital ulcers, dysuria, pruritus, fever, tender inguinal nodes, malaise, myalgia.
  • Recurrent: prodrome (tingling, burning) 2-24h prior; single/atypical ulcer; dysuria; pruritus lasting ~4-6 days.
  • HSV-2 causes more frequent recurrences, especially first year.
  • Anogenital HSV-1 infections increasing, especially in young women and MSM.
  • Less common: constipation, proctitis, stomatitis, sacral paresthesias.

Physical Exam

  • Lesions: groin, perineum, anus, vagina, cervix.
  • Lesions stages: papular, vesicular, pustular, ulcerated, crusted.
  • Inguinal lymphadenopathy.
  • Extragenital: meningitis, recurrent meningitis (Mollaret), sacral radiculitis, encephalitis, transverse myelitis, hepatitis.

Pediatric Considerations

  • Neonatal infection: 20-50/100,000 live births.
  • 80% from asymptomatic maternal shedding during 3rd trimester.
  • Transmission risk 30-50% if maternal primary infection near delivery; higher with HSV-1.
  • Neonatal HSV high morbidity/mortality.
  • Suspect sexual abuse if genital lesions in children.

Differential Diagnosis

  • HIV, syphilis, chancroid, herpes zoster.
  • Ulcerative balanitis, granuloma inguinale, lymphogranuloma venereum.
  • CMV, EBV.
  • Drug eruption, trauma.
  • Behçet syndrome.
  • Ulcus vulvae acutum (Lipschütz ulcer).
  • Neoplasia.

Diagnostic Tests

  • Laboratory confirmation for atypical/immunocompromised.
  • Viral isolation by culture or PCR (prefer PCR—highest sensitivity/specificity).
  • Use proper swabs (Dacron/polyester, plastic shafts).
  • Culture specificity >99%, sensitivity varies by lesion stage.
  • PCR: 98% sensitivity, >99% specificity; mostly for CSF.
  • Type-specific serology: Western blot (gold standard), type-specific IgG ELISA.
  • IgM testing limited utility.
  • Screening generally not recommended for asymptomatic or discordant couples.

TREATMENT

General Measures

  • Ice packs, sitz baths, topical anesthetics.
  • Analgesics, NSAIDs.

Medications

  • Start antivirals within 72 hours of symptoms.
  • After 3 days, antivirals may help with new lesions or pain.
  • HIV patients require higher/longer dosing.

First Line

Drug Primary Episode Episodic Therapy Suppression Therapy Notes
Acyclovir 400 mg PO TID × 7–10 days 800 mg BID × 5 days / 800 mg TID × 2 days 400 mg BID daily Adjust renal dosing
Valacyclovir 1 g PO BID × 7–10 days 500 mg BID × 3 days / 1 g daily × 5 days 500 mg - 1 g daily Prodrug, better bioavailability
Famciclovir 250 mg PO TID × 7–10 days 125 mg BID × 5 days / 1 g BID × 1 day 250 mg BID daily

Severe/Complicated

  • IV acyclovir 5-10 mg/kg q8h until improvement; total 10–14 days.
  • Immunocompromised may require prolonged/high-dose.

Precautions

  • Renal dose adjustment.
  • Probenecid can increase antiviral levels.
  • Pregnancy: suppression therapy at 36 weeks; C-section if lesions/prodrome at labor.

ISSUES FOR REFERRAL

  • Acyclovir-resistant HSV: consider foscarnet or cidofovir (with infectious disease consult).
  • Neonatal HSV: IV acyclovir urgently.
  • Suspected sexual abuse in children with genital lesions.

ONGOING CARE

Follow-Up

  • Usually not required if treated.
  • Consider suppression for frequent recurrences.
  • Test for HIV/STIs.

Patient Education

  • HSV is lifelong; educate on transmission and symptom recognition.
  • Avoid sexual contact during outbreaks.
  • Viral shedding possible without lesions.
  • Condom use reduces HSV-2 transmission.
  • Inform partners before sexual activity.
  • Notify maternity care providers.

PROGNOSIS

  • Symptoms last 3-21 days.
  • Recurrence 1-4 episodes/year on average.
  • Antivirals reduce shedding, outbreaks, and transmission.
  • Neonates/immunocompromised at highest risk for severe outcomes.

COMPLICATIONS

  • Psychological: stigma, depression, anxiety.
  • Increased HIV risk (2-3 fold with HSV-2).
  • HSV meningitis (rare, more common in women).
  • Disseminated HSV (especially in pregnancy).
  • Hepatitis.

REFERENCES

  1. Nath P, Kabir MA, Doust SK, et al. Diagnosis of herpes simplex virus: laboratory and point-of-care techniques. Infect Dis Rep. 2021;13(2):518-539.

  2. Rogan SC, Beigi RH. Management of viral complications of pregnancy: pharmacotherapy to reduce vertical transmission. Obstet Gynecol Clin North Am. 2021;48(1):53-74.

CLINICAL PEARLS

  • HSV-1 and HSV-2 cause genital herpes; many are unaware of infection.
  • Viral shedding occurs without lesions.
  • Meticulous condom use reduces transmission.
  • Suppressive therapy decreases recurrences and transmission.