Practice Based Learning: Gingivostomatitis: To treat with acyclovir or not to treat?

Fahad Malik, MD

Presented by Fahad Malik, MD

Clinical Questions

Should PO acyclovir be used to treat primary HSV gingivostomatitis in immunocompetent patients?

If yes:

  • When?
  • What dose?
  • For how long?

Primary HSV Gingivostomatitis

Clinical features:

  • Prodrome – fever, anorexia, malaise, sleeplessness, etc.
  • Red, edematous gingiva and clusters of small vesicles
  • Vesicle rupture & become surrounded by a red halo
  • Coalesce to form large, painful ulcers
  • Involve: buccal mucosa, tongue, gingiva, hard palate, and pharynx
  • Lips and perioral skin involved in 2/3 of cases
  • Refusal to eat/drink, dehydration


  • Most common between 6mo and 5y
  • No seasonal distribution
  • Rates of diagnosis (retrospective review from 1999-2003 in NY)
    • 1.6 per 10,000 ED visits
    • 5.6 per 10,000 admissions


  • Direct contact with infected oral secretions or lesions
  • Viral shedding for 1wk to several wks (median = 3 wks)
  • Incubation period: 2d – 2wks (mean = 4d)

Amir 1997: Conclusions

  • Acyclovir x 7 days significantly more effective than placebo*
    • Duration of lesions (4.0 to 8.0)
    • Duration of fever (0.8 to 3.2)
    • Eating difficulties (1.31 – 4.69)
    • Drinking difficulties (1.1 to 4.9)
    • Viral shedding (2.9 to 5.1)
  • *Dosing of acyclovir:
    • 15mg/kg, five times daily x 7 days

*(difference in medians in days, 95% CI)

Cochrane Review: Discussion

“Implications for practice”

  • Some “weak evidence” that acyclovir is an effective treatment
  • Reduces # of oral lesions
  • Prevents development of new lesions
  • Decreases PO difficulties
  • Only applicable to children < 6y

“Implications for research”

  • Need larger samples
  • Reduce systematic bias by blinding evaluators of outcomes
  • Standardize evaluators
  • Include patient-reported outcomes (quality of life, satisfaction)

Faden 2006: Conclusions

Current practice:

  • Acyclovir was rarely used despite multiple studies reporting shortened course of illness
  • Most commonly used therapies:
    • Supportive care with IVF
    • Pain management
    • Topical agents:
      • Diphenhydramine + Maalox
      • Viscous lidocaine
        • Swish and spit not possible for younger children
        • Ingested lidocaine can have rare but serious side effects


Should PO acyclovir be used to treat 10 HSV gingivostomatitis in immunocompetent patients?


  • If <72hrs of oral lesions – significantly shortens the duration of illness
  • May shorten hospital course, prevent hospitalization, ↓ cost


  • Need additional studies with larger sample size
    • Significance only shown if oral lesions for <72 hrs
    • Negative effects of PO acyclovir:
      • Side effects: HA, malaise, N/V, diarrhea
      • Development of resistant strains
      • Seen in immunocompromised patients that received multiple courses

If yes:

  • When?
  • What dose?
  • For how long?

When: ideally within 72 hours of oral lesions, to reduce duration of illness

Dosing (further studies needed)

  • Current practice: 40-80 mg/kg/day q6-q8hrs x 7 days
    • Harriett Lane: 12o0mg/day divided q8hrs x 7-10 days
    • Immunocompromised dosing (Lexicomp):
      • 1000 mg/day in 3-5 divided doses x 7-14 days; maximum daily dose should not exceed 80 mg/kg/day (Red Book, 2009; Red Book, 2012)


Amir J, Harel L, Smetana Z, Varsano I. Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. BMJ. 1997 Jun 21;314(7097):1800-3.

Nasser M, Fedorowicz Z, Khoshnevisan MH, Shahiri Tabarestani M. Acyclovir for treating primary herpetic gingivostomatitis. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006700.

Faden H. Management of primary herpetic gingivostomatitis in young children. Pediatr Emerg Care. 2006 Apr;22(4):268-9.

Harriet Lane Handbook, 8th edition.


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