What is the treatment for herpes stomatitis?

Treatment of Herpes Stomatitis

For primary herpetic gingivostomatitis (herpes stomatitis), initiate oral acyclovir 400 mg five times daily for 7-10 days as soon as possible after symptom onset to reduce healing time and symptom duration. 1

Distinguishing Herpes Stomatitis from Other Conditions

Before initiating treatment, it is critical to differentiate herpes stomatitis from other oral conditions:

• Herpes stomatitis presents with clustered vesicles on gingival and adjacent mucosa that rupture to form painful halo-like ulcers, accompanied by fever, lymphadenitis, and severe pain 2
• Recurrent aphthous stomatitis (RAS) does not require antiviral therapy and is treated with topical corticosteroids 3
• Vincent stomatitis requires antibiotics (metronidazole), not antivirals 3

This distinction is essential because misdiagnosis leads to inappropriate treatment and delayed resolution 1

First-Line Treatment Regimens

Primary Herpetic Gingivostomatitis (First Episode)

The CDC guidelines recommend the following oral antiviral regimens for 7-10 days 1:

• Acyclovir 400 mg orally three times daily, OR
• Acyclovir 200 mg orally five times daily, OR
• Famciclovir 250 mg orally three times daily, OR
• Valacyclovir 1 g orally twice daily

Higher doses of acyclovir (400 mg five times daily) were used in treatment studies of first-episode oral infection including stomatitis, though it remains unclear whether these mucosal infections require higher doses than genital herpes. 1

Timing is Critical

• Peak viral titers occur within the first 24 hours after lesion onset 1
• Treatment must be initiated as soon as possible—ideally within 72 hours of symptom onset—to achieve optimal therapeutic benefit 1, 4
• Diagnostic delay beyond 72 hours significantly decreases the effectiveness of antiviral drugs 4
• Oral acyclovir reduces time to healing when given early in the course of primary herpetic gingivostomatitis 1

Topical vs. Systemic Therapy

Oral antiviral therapy is superior to topical treatment:

• Topical acyclovir is substantially less effective than systemic drugs and its use is discouraged 1
• Meta-analysis shows oral antivirals (acyclovir, famciclovir, valacyclovir) decrease outbreak duration and pain by approximately 1 day 1
• Topical antivirals provide only small clinical benefit and require frequent application (5-6 times daily), making them less convenient 1
• Topical agents do not reach the site of viral reactivation and are ineffective for prophylaxis 1

Supportive Care Measures

While antivirals address the viral replication, supportive care is essential 5, 2:

• Maintain hydration and electrolyte balance, especially in children who may refuse oral intake due to pain 2
• Use non-alcoholic mouthwashes containing sodium bicarbonate for oral hygiene 5
• Provide soft, moist, non-irritating foods that are easy to chew and swallow 5
• Consider topical anesthetics such as viscous lidocaine 2% for pain management 5
• Use ice chips or ice pops to numb the mouth as needed 5

Special Populations and Resistant Cases

Immunocompromised Patients

• Acyclovir and famciclovir are beneficial for acute treatment of severe HSV-1 disease in immunocompromised patients 6
• Prophylactic oral acyclovir may reduce frequency and severity of recurrent attacks, though optimal timing and duration are uncertain 6
• Consider prophylactic antiviral therapy for immunocompromised patients with severe symptoms 5

Acyclovir-Resistant Cases

In the rare event of acyclovir-resistant herpes stomatitis (primarily seen in severely immunocompromised patients) 7:

• Test for acyclovir resistance if no response after 1 week of high-dose acyclovir 7
• First-line alternative: Topical cidofovir solution/gel or topical foscarnet cream 7
• Second-line alternative: Intravenous foscarnet 7
• Topical treatment may be sufficient and less toxic than intravenous foscarnet 7

Treatment Duration and Follow-up

• Standard treatment duration is 7-10 days 1
• Extend treatment if healing is incomplete after 10 days 1
• Monitor for resolution of symptoms and lesion healing 5
• Assess for potential complications or recurrence 5

Common Pitfalls to Avoid

• Do not delay treatment waiting for laboratory confirmation in typical presentations—clinical diagnosis based on history and characteristic clustered vesicles is sufficient 2
• Do not use topical acyclovir alone as primary treatment—it is substantially less effective than oral therapy 1
• Do not confuse with MTX-induced mucositis in patients on methotrexate, as HSV reactivation can mimic drug toxicity 8
• Do not assume self-limiting course will be adequate—early antiviral treatment modifies disease course and reduces symptoms 2, 4