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

Worldwide distribution, and only found in humans
- Most common cause of genital lesions
- Most common cause of acute viral encephalitis in the US, with age peaks at 5 to 30 years and over 50 years
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

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

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 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

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

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

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

Typically localized to a single mucocutaneous area
Symptoms are usually more minor than first-episode or primary infection, and include itching and pain
- Lesions may be atypical, with fissures and unusual ulcers
- May be subclinical, with intermittent viral shedding
- May be preceded by a prodrome of tingling up to 2 days
Average duration of an episode of reactivation orolabial herpes is 5 days
HSV-1 reactivates more frequently around mouth, and HSV-2 in genitals
Frequency
- HSV-2 reactivates on average 4 to 5 times annually, with a gradual decrease over time

HSV infection of the finger, with acute onset swelling, pain, and tenderness with vesicles
Also fever and regional lymphadenopathy
Can be either acquired from parson-to-person exposure or through autoinoculation
Higher rates in healtcare settins

Herpes simplex infection essentially anywhere on the body (chest, ears, face, and hands) associated with wrestling

Keratitis, which presents with pain, blurred vision, chemosis, conjunctivitis, and corneal lesions
May also cause blepharitis and conjunctivitis
May cause chorioretinitis in infants and immunocompromised
Acute necrotizing retinitis
- Presents with painless vision loss in immunocompetent people as well as immunocompromised
- 25% of cases are bilateral

Most commonly caused by HSV-1 (05% of cases)
In children, it is often during primary infection
Less clear in adults, where it may be primary, infection with a new strain, or reactivation of latent infection
Characterized by acute onset fever and neurologic symptoms
- Often affects temporal lobe, with behaviour changes