HHV

Question 1

Please explain which HHV is which

Answer 1

HHV1- HSV1
HHV2 - HSV 2
HHV3 - VZV
HHV4 - EBV
HHV5- CMV
HHV6
HHV7
HHV-8 Kaposis

Question 2

Risk factors for genital herpes

Answer 2

• 15-30 years
• Increased number of sexual partners
• Lower levels of income and education
• HIV positivity

Question 3

HSV transmission

Answer 3

• Can be asymptomatic periods of viral shedding
• HSV1: spread primarily through direct contact with contaminated saliva or other infected secretions
• HSV2: primarily by sexual contact

Question 4

Describe what happens to the HSV virus once in the body

Answer 4

Virus replicates at the mucocutaneous site of infection, then travels by retrograde axonal flow to the dorsal root ganglia, where it establishes latency until reactivation
- Latency enables virus to exist in relatively non-infectious state for varying periods of time in its host
HSV-1: intracellular accumulation of CD1d molecules in antigen-presenting cells –> may be how it evades detection and establishes latency

Question 5

How does the immune system respond to HSV

Answer 5

• Limit viral replication
• Recruit other inflammatory cells
• Toll-like receptors are critical for first line of innate immune defense against HSV- functions include priming CD8 T cells
• HSV-specific memory CD8 T cells are selectively activated and retained in latently infected sensory ganglia - have important roles in controlling the infection and preventing recurrences

Question 6

Reactivation triggers for HSV

Answer 6

• Emotional stress
  
  • UV light
  • Fever
  • Menstruation
  • Immunosuppression
  • Surgical or dental proceudres
  • Local tissue damage
• Reactivation can be localized to skin or viraemia in immunocompromised

Question 7

Primary HSV clinical manifestations

Answer 7

• 3-7 days after exposure
• Prodrome: tender lymphadenopathy, malaise, anorexia, fever
• Preceding symptoms: localized pain, tenderness, burning, tingling
• Cutaneous: painful, grouped vesicles on an erythematous base, may be umbilicated, followed by progression to pustules, erosions, and/or ulcerations with a characteristic scalloped border. Crust over and resolve within 2-6 weeks
• Majority of primary orolabial are asymptomatic
• Symptomatic can be gingivostomatitis in children, pharyngitis and a mononucleosis-like syndrome in young adults
• Mouth and lips are the most common sites - oral lesions typically appear on the buccal mucosa and gingivae
• Oedema and painful oropharyngeal ulcerations can lead to dysphagia and drooling

Question 8

Recurrent HSV clinical presentation

Answer 8

• Can still get prodrome, but less common, decreased severity and duration
• 20-40% of those with latent HSV-1 develop recurrent herpes labialis
• Most often on the vermilion border of the lip
• Less common sites: perioral skin, nasal mucosa, cheek, attached oral mucosa overlying bone (gingiva, hard palate)
• Immunocompromised: recurrent herpes infections can involve intraoral movable mucosa not overlying bone

Question 9

Genital HSV clinical presentation

Answer 9

• Frequently asymptomatic, but can also be ++ painful erosive balanitis, vulvitis or vaginitis
• Women: involve cervix, buttocks, perineum, can be associated with inguinal adenopathy and dysuria.
  
  • Systemic complaints more common in women: extragenital lesions (20%), urinary retention (10-15%), aseptic meningitis (10%)
• Men: glans or shaft of the penis, buttocks occasionally affected
  
  • Aseptic meningitis can be a rare complication of primary genital herpes in men
• More extensive local involvement, regional lymphadenopathy and fever generally distinguishes primary herpes from recurrent disease
• Genital HSV infections can result in subclinical viral shedding and clinically evident recurrences - often relatively mild
• Recurrences occur more frequently with HSV2 –> usually limited number of vesicles on the genitalia or buttocks, and resolve within 7-10 days compared to the 20 days for primary infection
• Complications:
  
  • Uncommon
• Frequency of recurrence correlates directly with severity of primary infection, and tends to decrease over the next several years
• Time interval varies greatly - individuals can have an average 4-7 recurrences a year
• Although majority of HSV2 positive people report no genital herpes infection, eventually 50% will develop clinical signs

Question 10

Eczema herpeticum clinical presentation

Answer 10

• Infants/children, associated with mutation in filaggrin mutation
• Can also get in skin barrier impaired conditions: burns, ICD, pemphigus, Darier, Hailey-Hailey, MF, Sezary, Ichthyosis, Grover, PRP, ablative laser, 5-FU
• Due to HSV1
• Rapid, widespread cutaneous dissemination of HSV, monomorphic discrete 2-3 mm punched out erosions with haemorrhagic crusts
• +/- fever, malaise, lymphadenopathy, bacterial infection, systemic dissemination
• Ddx: eczema coxsackium, strep infection

Question 11

Herpetic whitlow clinical presentation

Answer 11

• Young children - often HSV1, increasing in frequency in adults and adolescents –> HSV2 - digital-genital contact
• Historically in dental and medical personnel who did not use gloves
• Pain, swelling and clustered vesicles on a digit, appearance of vesicles may be delayed
• Recurrences in same location
• Often misdiagnosed as blistering dactylitis or paronychia

Question 12

HSV infections in immunosuppressed patients

Answer 12

• Immunocompromised patients - stem cell transplant, organ transplant, HIV, haem malignancy
• Most common presentation: chronic, enlarging ulcerations
• Can affect multiple sites or be disseminated
• Skin findings: often atypical - verrucous, exophytic or pustular
• Recurrences can involve oral mucosa, including the tongue, and movable areas that do not overlie bone
• Can involve resp tract, oesophagus, remainder of GIT

Question 13

Herpes encephalitis clinical presentation

Answer 13

• Most common cause of fatal sporadic viral encephalitis
• Association with mutations in genes encoding TLR 3 or UNC-93B, impair interferon based cellular antiviral responses
• Usually from HSV-1
• Natalizumab, anti-alpha4 integrin monoclonal antibody - which treats MS, Crohn disease –> increases the risk of encephalitis and meningitis due to HSV and VZV
• Systemic and neuro: fever, altered mental status, bizarre behaviour, localized neurologic findings
• Temporal lobe often involved
• Mortality >70% without treatment, residual neurologic defects in most survivors
• Herpes labialis may be a coincidental finding

Question 14

Ocular HSV clinical presentation

Answer 14

• HSV-2 in newborns commonly
• HSV-1 in children and adults
• Primary infection: unilateral or bilateral keratoconjunctivitis, with eyelid oedema, tearing, photophobia, chemosis, pre-auricular lymphadenopathy
• Branching dendritic lesions of the cornea are pathognomonic
• Recurrent episodes are common and typically unilateral
• Cx: corneal ulceration and scarring, globe rupture and blindness

Question 15

Neonatal HSV clinical presentation

Answer 15

• 1/10 000 newborns –> exposure to HSV in vaginal delivery
• Risk of transmission 30-50% in women who acquire a genital HSV infection near the time of delivery
• Risk of transmision is low for recurrent genital herpes - <1-3%
• HSV2 or HSV1 (latter accounts for 30-50% of patients)
• Onset from birth to 2 weeks of age, but usually >-5days of age
• Localized: scalp and trunk, or disseminated
• Can involve the oral mucosa, eye, CNS and multiple internal organs
• Vesicles can progress to bullae and erosions
• Can present with lethargy, irritability, poor feeding, temperature, instability, seizures and a bulging fontanelle
• CNS or disseminated - mortality is >50%, without treatment and ~15% with treatment
• Many survivors have neurologic deficits