II. Epidemiology

  1. Prevalence
    1. Worldwide Prevalence: 60-95% (typically acquired by teen years)
    2. Antibody positive: 37% in U.S. college freshman and 46% in college seniors
    3. Cold Sore history: 25-28% of U.S. college students
  2. Age of transmission
    1. Childhood (most common)
    2. Young adults

III. Pathophysiology

  1. Etiology: HSV I (less commonly HSV II)
  2. Transmission via mucous membranes or open skin
    1. Kissing
    2. Fomites (e.g shared towels, utensils)
  3. Incubation: 2-20 days after contact
  4. Shedding: 48-60 hour duration (not longer than 96 hours)
  5. HSV lies dormant after initial infection
    1. Distributed in the trigeminal Ganglion
    2. Periodic reactivation with triggers as described below
    3. Recurrence in 40% of patients
  6. Triggers for recurrence
    1. Fever
    2. Emotional stress
    3. Sun Exposure
    4. Trauma
    5. Immunocompromised state
    6. Menses
    7. Fatigue

IV. Symptoms

  1. Primary (Initial) HSV I: Usually asymptomatic (but first episode is most severe)
    1. Fever
    2. Chills
    3. Malaise
    4. Cervical Lymphadenopathy
    5. Ulcers deep in mouth on Gingival surface
    6. Avoidance of drinking, eating de to pain
  2. Secondary (Later) HSV I (Recurrent labial lesions)
    1. Provocative factors for recurrence: See above
    2. Frequency: Up to 1-6 episodes per year (recurrs in 40% of patients)
    3. Prodrome before lesions (60% of patients)
      1. Itching, burning or Paresthesias for 12 to 36 hours before lesions
    4. Lesions form along vermillion border
      1. Fever Blisters form on outer vermillion border
      2. Cold Sores form on inner lip
    5. Course
      1. Prodrome: Itch, burn, or tingling for 12-36 hours (60% of cases)
      2. Vesicle forms
      3. Vesicle ruptures, ulcerates and crusts in 48 hours
      4. Lesion heals in 10-14 days

V. Signs

  1. Lesion characterictics
    1. Painful grouped Vesicles on erythematous base
    2. Forms on epithelial surface at vermillion border edge
    3. Vesicular lesions rupture to form painful ulceration
    4. Distribution: Lips, Gingiva, Hard Palate, Tongue
  2. Associated findings
    1. Cervical Lymphadenopathy

VI. Complications

  1. Herpes Keratitis (Corneal infection)
  2. Herpetic Whitlow (painful vesicular lesions on fingers)
  3. Herpetic sycosis (beard area vesicular eruption)
  4. Herpes gladiatorum (vesicular lesions typically on torso with history of wrestling exposure)
  5. Erythema Multiforme (HSV is the most common cause)
  6. HSV Encephalitis
    1. Contrast with HSV2 which causes Herpes Meningitis (Mollaret Meningitis) instead of Encephalitis

VIII. Differential Diagnosis: Distinguishing features

  1. Differs from Aphthous Ulcers in that:
    1. Found on keratinized (bound-down) intraoral mucosa
    2. Vesicles rupture into coalescing ulcers
  2. HSV lesions are anterior compared with:
    1. Herpangina
    2. Hand Foot and Mouth Disease

IX. Labs:

  1. Viral culture for HSV
    1. Vesicles are most concentrated with infection within first 48 hours
    2. Unroof Vesicles with scalpel or needle tip and apply viral culture swab
    3. Expect viral growth within 5 days
    4. Test Sensitivity: 50%
  2. HSV PCR
    1. Test Sensitivity: High
  3. HSV Direct Fluorescent Antibody
    1. Test Sensitivity: 80%
  4. HSV IgG
    1. Antibodies form with weeks of primary infection
    2. Does not differentiate acute infection from prior
  5. Rapid Giemsa (Dif-Quik) stain
    1. Multinucleated giant cells
    2. Test Sensitivity: 40-77%

X. Management: General Measures

  1. See Oral Mucositis
  2. Magic Mouthwash
    1. Indicated for analgesia

XI. Management: Antivirals for Primary and Recurrent Outbreaks

  1. Best efficacy when antivirals are started at the first signs of recurrence (e.g. local tingling or Paresthesias)
  2. Systemic antiviral agents for primary outbreaks
    1. Start within 24 hours of lesion onset
    2. Acyclovir (Zovirax)
      1. Child: 15 mg/kg (up to 400 mg) orally 5 times per day for 7 to 10 days
      2. Adult: 400 mg orally 5 times daily for 7 to 10 days
      3. Efficacy
        1. Lesions resolved in 4 versus 10 days, and viral shedding decreased to 1 versus 5 days
        2. Amir (1997) BMJ 314:1800-3 [PubMed]
    3. Famciclovir (Famvir)
      1. Adult: 500 mg orally twice daily for 7 to 10 days
    4. Valacyclovir (Valtrex)
      1. Adult: 1 g orally twice daily for 7 to 10 days
  3. Systemic antvirals for recurrent outbreaks (reduce healing time by up to 2 days)
    1. Acyclovir (Zovirax)
      1. Adult: 400 mg orally 3 to 5 times daily for 5 days
    2. Valacyclovir (Valtrex)
      1. Adult: 2 grams orally twice daily for one day
    3. Famciclovir (Famvir)
      1. Adult: 1500 mg orally for one dose (or 750 mg orally twice daily for one day)
      2. Efficacy
        1. Shortens healing time by 2 days in UV-induced cases
        2. Spruance (1999) J Infect Dis 179:303-10 [PubMed]
  4. Topical antiviral agents (reduce healing time by 0.7 days)
    1. Docosanol (Abreva) cream apply 5 times per day until healed
      1. Least costly topical ($20 in 2014)
    2. Topical Acyclovir
      1. Expensive ($300-600)
      2. Acyclovir (Zovirax) cream apply 5 times per day for 4 days
      3. Acyclovir with Hydrocortisone (Xerese)
    3. Penciclovir (Denavir) 1% cream apply every 2 hours while awake for 4 days
      1. Very expensive ($500/tube in 2014)
    4. Sitavig buccal one tablet per episode placed in upper gum on same side of mouth as symptoms
      1. Very expensive ($300 for 2 tabs in 2014) and only shortens Cold Sore course by <1 day
      2. (2014) Presc Lett 21(9): 53

XII. Prevention: General

  1. Use Sunscreen

XIII. Prevention: Daily Antiviral Suppression

  1. Indications
    1. Recurrence of Herpes Labialis 6 or more times per year
  2. Preparations
    1. Acyclovir (Zovirax) 400 mg orally twice daily
    2. Valacyclovir 500 mg orally once daily to twice daily

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