• Clinical science

Herpes simplex virus infections

Abstract

Herpes simplex virus infections may be caused by two virus genotypes: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Worldwide seroprevalence is high, with antibodies detectable in over 90% of the population. Of these cases, approx. 60% are caused by HSV-1. The most common infections are labial and genital herpes, which present with painful ulcerations. Two further conditions, seen especially in children, are herpetic gingivostomatitis and herpetic whitlow. While herpetic gingivostomatitis is characterized by painful lesions of the oral and pharyngeal mucosa, herpetic whitlow causes blisters on the fingers with pronounced regional lymphadenopathy. In individuals with underlying dermatological conditions, infection with HSV can cause eczema herpeticum, resulting in painful erosions spread diffusely over the head and upper body. However, the majority of primary infections remain asymptomatic, while recurrent infections present with the typical manifestations. The diagnosis of HSV infections is usually confirmed through viral cultures, but may also be based on detection of HSV DNA in PCR, or multinucleated giant cells in Tzanck smears. Treatment consists mainly of topical or oral acyclovir; IV administration may be needed in critical cases, such as HSV infection in immunocompromised patients.

General information

  • Prevalence: More than 90% of the world's population over the age of 40 carries HSV.
  • Types
  • Transmission
    • Direct contact with mucosal tissue or secretions of another infected person
    • Infection with HSV-1 usually acquired in childhood via saliva
  • Type of infection
    • Primary infection
      • Mostly asymptomatic (up to 80% of cases, but virus is still shed)
      • If symptomatic, the infection is often sudden and severe
    • Reactivation of infection
      • Frequency and severity vary individually; symptoms are usually less severe than in primary infection.
      • Often at the same site as primary infection

Pathophysiology

  • Inoculation: The virus enters the body through mucosal surfaces or small dermal lesions.
  • Neurovirulence: The virus invades, spreads, and replicates in nerve cells.
  • Latency: After primary infection, the virus remains dormant in the ganglion neurons (e.g., trigeminal, sacral ganglion)
  • Reactivation: triggered by various factors (e.g., immunodeficiency, stress, trauma) → clinical manifestations
  • Dissemination: infection spreads to unusual sites (e.g., lungs, gastrointestinal tract, eyes)
    • May occur in pregnant patients or patients with severe immunodeficiency (e.g., malnutrition, recipients of organ transplants, patients with AIDS)

Labial herpes (herpes labialis)

Genital herpes (herpes genitalis)

Herpetic gingivostomatitis

Eczema herpeticum

Eczema herpeticum is considered a dermatological emergency and treatment with oral or IV acyclovir must be initiated quickly!

Herpetic whitlow

  • Pathogen: HSV-1 in 60% of cases; HSV-2 in 40% of cases (in the adult population)
  • Etiology
    • Direct contact with infected secretions through a break in the skin, e.g., torn cuticle
    • Main groups:
      • Children; (via sucking of thumb/fingers (may have a history of labial herpes)
      • Health care workers exposed to oral secretions (e.g., dentists)
  • Incubation period: 2–20 days
  • Clinical features
  • Differential diagnoses: paronychia, cellulitis, felon
  • See “Diagnostics” and "Treatment" below.

Surgical treatment is not indicated because it may cause severe complications (e.g., bacterial superinfection, systemic spread, herpes encephalitis)!

Other HSV infections

Diagnostics

Diagnosis is primarily based on clinical features, with confirmation through the following tests:

  • Light microscopy findings on a Tzanck smear
    • Multinucleated giant cells (non-specific)
    • Eosinophilic intranuclear Cowdry A inclusion bodies (non-specific)
    • Results available within 1 hour
    • Unable to differentiate between HSV-1 and HSV-2
  • Viral culture: gold standard for definitive diagnosis; results available in 48 hours
  • PCR: detects HSV RNA; identification of virus genotype
  • Direct fluorescent antibody test : identification of the virus genotype
  • Serum antibody testing: shows primary seroconversion
  • Bacterial culture: confirmation of bacterial superinfection

Treatment

Depending on the site, type, and severity of HSV-1 infection, antiviral drugs are administered either topically or systemically. In most cases of recurrent infection, topical and/or symptomatic treatment is sufficient.

Antiviral treatment

  • Effect
    • Decrease in duration and severity of infection; (most effective if therapy is initiated within 72 hours of onset of infection)
    • Reduction of viral shedding
    • However, recurrence cannot be prevented.
  • Agents
  • Duration: 7–10 days
  • Prophylaxis: indicated in the case of frequent (more than 6 recurrent infections per year) or severe relapses; in patients with prodromal symptoms
    • Long-term suppressive therapy with (val)acyclovir
    • Variable results in studies
    • Costly

Early treatment of herpes infections is essential to prevent complications because antiviral drugs only inhibit the virus during its replication phase!

Symptomatic treatment

Prevention

  • Use of condoms, gloves
  • Consider isolation of hospitalized patients with shedding lesions