II. Epidemiology
-
Prevalence
- Worldwide Prevalence: 60-95% (typically acquired by teen years)
- Antibody positive: 37% in U.S. college freshman and 46% in college seniors
- Cold Sore history: 25-28% of U.S. college students
- Age of transmission
- Childhood (most common)
- Young adults
III. Pathophysiology
- Etiology: HSV I (less commonly HSV II)
- Transmission via mucous membranes or open skin
- Kissing
- Fomites (e.g shared towels, utensils)
- Incubation: 2-20 days after contact
- Shedding: 48-60 hour duration (not longer than 96 hours)
- HSV lies dormant after initial infection
- Distributed in the trigeminal Ganglion
- Periodic reactivation with triggers as described below
- Recurrence in 40% of patients
- Triggers for recurrence
- Fever
- Emotional stress
- Sun Exposure
- Trauma
- Immunocompromised state
- Menses
- Fatigue
IV. Symptoms
- Primary (Initial) HSV I: Usually asymptomatic (but first episode is most severe)
- Fever
- Chills
- Malaise
- Cervical Lymphadenopathy
- Ulcers deep in mouth on Gingival surface
- Avoidance of drinking, eating de to pain
- Secondary (Later) HSV I (Recurrent labial lesions)
- Provocative factors for recurrence: See above
- Frequency: Up to 1-6 episodes per year (recurrs in 40% of patients)
- Prodrome before lesions (60% of patients)
- Itching, burning or Paresthesias for 12 to 36 hours before lesions
- Lesions form along vermillion border
- Fever Blisters form on outer vermillion border
- Cold Sores form on inner lip
- Course
V. Signs
- Lesion characterictics
- Painful grouped Vesicles on erythematous base
- Forms on epithelial surface at vermillion border edge
- Vesicular lesions rupture to form painful ulceration
- Distribution: Lips, Gingiva, Hard Palate, Tongue
- Associated findings
VI. Complications
- Herpes Keratitis (Corneal infection)
- Herpetic Whitlow (painful vesicular lesions on fingers)
- Herpetic sycosis (beard area vesicular eruption)
- Herpes gladiatorum (vesicular lesions typically on torso with history of wrestling exposure)
- Erythema Multiforme (HSV is the most common cause)
-
HSV Encephalitis
- Contrast with HSV2 which causes Herpes Meningitis (Mollaret Meningitis) instead of Encephalitis
VII. Differential Diagnosis
- Oral Lesions
- Skin lesions
VIII. Differential Diagnosis: Distinguishing features
- Differs from Aphthous Ulcers in that:
- Found on keratinized (bound-down) intraoral mucosa
- Vesicles rupture into coalescing ulcers
- HSV lesions are anterior compared with:
IX. Labs:
- Viral culture for HSV
- Vesicles are most concentrated with infection within first 48 hours
- Unroof Vesicles with scalpel or needle tip and apply viral culture swab
- Expect viral growth within 5 days
- Test Sensitivity: 50%
-
HSV PCR
- Test Sensitivity: High
- HSV Direct Fluorescent Antibody
- Test Sensitivity: 80%
- HSV IgG
- Antibodies form with weeks of primary infection
- Does not differentiate acute infection from prior
- Rapid Giemsa (Dif-Quik) stain
- Multinucleated giant cells
- Test Sensitivity: 40-77%
X. Management: General Measures
- See Oral Mucositis
-
Magic Mouthwash
- Indicated for analgesia
XI. Management: Antivirals for Primary and Recurrent Outbreaks
- Best efficacy when Antivirals are started at the first signs of recurrence (e.g. local tingling or Paresthesias)
- Systemic Antiviral Agents for primary outbreaks
- Start within 24 hours of lesion onset
- Acyclovir (Zovirax)
- Child: 15 mg/kg (up to 400 mg) orally 5 times per day for 7 to 10 days
- Adult: 400 mg orally 5 times daily for 7 to 10 days
- Efficacy
- Lesions resolved in 4 versus 10 days, and viral shedding decreased to 1 versus 5 days
- Amir (1997) BMJ 314:1800-3 [PubMed]
- Famciclovir (Famvir)
- Adult: 500 mg orally twice daily for 7 to 10 days
- Valacyclovir (Valtrex)
- Adult: 1 g orally twice daily for 7 to 10 days
- Systemic antvirals for recurrent outbreaks (reduce healing time by up to 2 days)
- Acyclovir (Zovirax)
- Adult: 400 mg orally 3 to 5 times daily for 5 days
- Valacyclovir (Valtrex)
- Adult: 2 grams orally twice daily for one day
- Famciclovir (Famvir)
- Adult: 1500 mg orally for one dose (or 750 mg orally twice daily for one day)
- Efficacy
- Shortens healing time by 2 days in UV-induced cases
- Spruance (1999) J Infect Dis 179:303-10 [PubMed]
- Acyclovir (Zovirax)
- Topical Antiviral Agents (reduce healing time by 0.7 days)
- Docosanol (Abreva) cream apply 5 times per day until healed
- Least costly topical ($20 in 2014)
- Topical Acyclovir
- Expensive ($300-600)
- Acyclovir (Zovirax) cream apply 5 times per day for 4 days
- Acyclovir with Hydrocortisone (Xerese)
- Penciclovir (Denavir) 1% cream apply every 2 hours while awake for 4 days
- Very expensive ($500/tube in 2014)
- Sitavig buccal one tablet per episode placed in upper gum on same side of mouth as symptoms
- Very expensive ($300 for 2 tabs in 2014) and only shortens Cold Sore course by <1 day
- (2014) Presc Lett 21(9): 53
- Docosanol (Abreva) cream apply 5 times per day until healed
XII. Prevention: General
- Use Sunscreen
XIII. Prevention: Daily Antiviral Suppression
- Indications
- Recurrence of Herpes Labialis 6 or more times per year
- Preparations
- Acyclovir (Zovirax) 400 mg orally twice daily
- Valacyclovir 500 mg orally once daily to twice daily