Herpes simplex virus

• Comprises herpes simplex virus 1 (HSV-1) and HSV-2, which are members of the Human herpesvirus family
• Cause typical painful vesicular lesions on labia or external genitals
• Occasionally cause a viral encephalitis

Background

Microbiology

• Enveloped, double-stranded DNA virus
• HSV-1 and HSV-2 are morphologically and genetically distinct viruses
• Can be infected with both

Epidemiology

• Worldwide distribution, and only found in humans
• Most common cause of genital lesions
• Spread through person-to-person contact with skin or mucosa; not spread via fomits
• HSV-1 is more common, with 90% of adults having antibodies by age 40
  • Often acquired in childhood in Asia and Africa
  • More common in lower SES populations
• HSV-2 has seroprevalence of 15-20% in US
  • More common in women than men, in HIV-infected people, and in MSM
  • May be subclinical if already infected with HSV-1

Pathophysiology

• Fusion of envelope and cell membrane is mediated by viral glycoproteins B, C, and D and host cell proteins cellular heparin sulfate, TNF receptors, and immunoglobulins
• Internal capsid is released, which makes its way to the nucleus
• Viral DNA polymerase enzyme and viral DNA helicase are targets of antivirals
• Viral DNA may remain latent in about 10% of nearby neurons, characterized by latency-associated transcripts (LATs)
  • Despite being latent, virus can still be shed in mucosa anywhere from 1/10 to 3/4 of days
• HSV-1 prefers trigeminal ganglia as well as cervical ganglia, or sacral nerve root ganglia if genital

Clinical Presentation

• Incubation period usually within 5 days for primary infection
• Mucocutaneous lesiosn may become secondarily infected

Orofacial infection

• Most common sites of primary infection are gingivostomatitis and pharyngitis
  • Includes lesions on hard and soft palate, gingiva, tongue, lips, and face
  • Pharyngeal lesions may be exudative or ulcerative
• May also have malaise, myalgias, anorexia or odynophagia, and cervical lymphadenopathy
• Self-resolving after 3 to 14 days
• Can cause a Bell palsy

Genital infection

• Genital lesions typically last 10 to 12 days, especially with first episode
  • Often widely spaced bilateral lesions
  • First episode often also involves fever, headache, malaise, and myalgias
  • May have pain, itching, dysuria, genital discharge, and inguinal lymphadenopathy
• May develop extragenital sites of infection, including buttock, groin, and thigh with HSV-2 and perioral area with HSV-1
  • Rarely fingers and eyes
  • Develop around 14 days into the disease, likely from autoinoculation
• HSV-2 genital infections are less severe if the person has had HSV-1
• 12-month recurrence rate is up to 90% for HSV-2 and 55% for HSV-1

Neurological complications

• These can include aseptic meningitis, transverse myelitis, and sacral radiculopathy
• Typically occur in conjunction with first episode of genital HSV-2 infection

Meningitis

• Mengitis is more common with HSV-2 than HSV-1
• Often concurrent with primary genital infection, typically 3 to 12 days after start of symptoms
• HSV-2 may also cause Mollaret's meningitis (benign recurrent lymphocytic meningitis)

Autonomic dysfunction

• May have hyperesthesia or anaesthesia of perineum, lumbar or sacrum, as well as urinary retention and constipation
• Resolves over 4 to 8 weeks

Transverse myelitis

• Decreased strength and deep tendon reflexes in lower extremities in conjunction with autonomic dysfunction (as above)

Pelvic inflammatory disease

• Rare cause of PID, possibly representing dual infection with a typical bacterial copathogen

Disseminated disease

• Rarely can disseminate
• Can be cutaneous, with concurrent meningitis, hepatitis, and pneumonitis
• Can also involve monocular arthritis, thrombocytopenia, adrenal necrosis, and myoglobinuria
• Patient factors include primary genital HSV in pregnancy, reactivation of genital HSV in a patient with cellular immunocompromise