What is the best course of treatment for a patient presenting with intraoral mouth sores, considering potential underlying conditions and medications?

Treatment of Intraoral Mouth Sores

For patients presenting with intraoral mouth sores, initiate treatment with topical high-potency corticosteroids (betamethasone sodium phosphate 0.5 mg in 10 mL water as a rinse-and-spit solution 1-4 times daily, or clobetasol 0.05% ointment mixed with Orabase applied twice daily to localized lesions) combined with supportive oral care including non-alcoholic sodium bicarbonate mouthwashes 4-6 times daily and topical anesthetics for pain control. 1, 2

Initial Assessment and Diagnostic Considerations

Before initiating treatment, identify the underlying etiology by examining:

• Location and distribution of lesions - diffuse versus localized ulcerations help differentiate between conditions like aphthous stomatitis (typically on non-keratinized mucosa) versus herpes simplex (typically on keratinized mucosa and lips) 3, 4
• Timing and pattern - acute onset suggests trauma, infection, or drug reaction; recurrent episodes suggest aphthous stomatitis or herpes simplex; chronic solitary ulcers require biopsy to exclude malignancy 5
• Associated symptoms - burning sensation suggests burning mouth syndrome or oral dysesthesia; severe pain with eating suggests Stevens-Johnson syndrome/TEN 3
• Nutritional deficiencies - check iron, vitamin B12, folate, and ferritin levels before diagnosing idiopathic recurrent aphthous stomatitis, as deficiencies are strongly associated (OR 2.62-7.55) 1, 6
• Candidal infection - take oral swabs if secondary infection is suspected, as concurrent candidiasis requires antifungal therapy rather than corticosteroids alone 3, 2

First-Line Treatment Algorithm

Mild Stomatitis (Grade 1-2)

Topical corticosteroids are the cornerstone of therapy:

• Betamethasone sodium phosphate 0.5 mg dissolved in 10 mL water as a 2-3 minute rinse-and-spit solution 1-4 times daily for widespread lesions 2
• Clobetasol 0.05% ointment mixed in equal amounts with Orabase applied twice daily to localized, easily accessible ulcers on dried mucosa 3, 2
• Dexamethasone mouth rinse (0.1 mg/mL) 10 mL swish for 2 minutes then spit, four times daily for multiple or difficult-to-reach ulcerations 1

Supportive oral care measures:

• Sodium bicarbonate rinses (1 teaspoon salt with three-quarter teaspoon baking soda in 500 mL water) 4-6 times daily to maintain oral pH and reduce inflammation 1, 7
• White soft paraffin ointment to lips immediately and every 2 hours if lip involvement is present 3
• Mucoprotectant mouthwash (e.g., Gelclair) three times daily to protect ulcerated surfaces 3, 2
• Gentle oral hygiene with soft toothbrush, mild toothpaste, and non-alcoholic mouthwashes 1

Pain management:

• Benzydamine hydrochloride oral rinse or spray every 3 hours, particularly before eating 3
• Viscous lidocaine 2% (15 mL per application) as topical anesthetic if benzydamine is insufficient 3, 1
• Barrier preparations such as Gengigel mouth rinse/gel for additional pain control 2

Moderate to Severe Stomatitis (Grade 2-3)

Escalate therapy when first-line measures fail:

• Increase corticosteroid potency or frequency - use clobetasol 0.05% if betamethasone was ineffective, or increase rinse frequency up to hourly 1
• Tacrolimus 0.1% ointment applied twice daily for 4 weeks for recalcitrant ulcers not responding to topical corticosteroids 2
• Intralesional triamcinolone (weekly, total dose 28 mg) in conjunction with topical clobetasol for persistent ulcers 1, 2

Systemic corticosteroids for highly symptomatic or recurrent ulcers:

• Prednisone 30-60 mg (or 1 mg/kg) daily for 1 week, followed by dose tapering over the second week 1, 2
• This approach is reserved for severe cases with significant functional impairment 1

Antiseptic measures to prevent secondary infection:

• 0.2% chlorhexidine digluconate mouthwash (10 mL twice daily), diluted by up to 50% if soreness occurs 3
• 1.5% hydrogen peroxide mouthwash (10 mL twice daily) as alternative antiseptic 3

Treatment of Concurrent Candidal Infection

If oral swabs confirm candidiasis, initiate antifungal therapy:

• Nystatin oral suspension 100,000 units four times daily for 1 week 3, 2, 7
• Miconazole oral gel 5-10 mL held in mouth after food four times daily for 1 week 3, 2, 7
• Fluconazole 200 mg on first day, then 100 mg once daily for oropharyngeal candidiasis, treating for at least 2 weeks to decrease relapse 8

Critical caveat: Do not use corticosteroids alone if herpes simplex virus is suspected, as this requires antiviral therapy instead 1

Dietary and Lifestyle Modifications

Implement supportive measures to facilitate healing:

• Soft, moist, non-irritating foods that are easy to chew and swallow; avoid crunchy, spicy, acidic, or hot foods 3, 1
• Adequate hydration with frequent water sips; limit caffeine intake which can worsen dry mouth 3
• Sugarless chewing gum, lozenges, or candy to stimulate saliva production if dry mouth is present 3, 1
• Salivary substitutes or moisture-preserving mouth rinses for patients with sicca syndrome 3

Special Considerations

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

If severe mucosal involvement with systemic symptoms is present:

• Daily oral examination is necessary during acute illness 3
• Clean mouth daily with warm saline mouthwashes or oral sponge, sweeping gently in labial and buccal sulci to reduce fibrotic scarring 3
• Cocaine mouthwashes 2%-5% can be used three times daily for severe oral discomfort 3
• Intravenous fluids and nasogastric feeding may be required if oral intake is severely compromised 3

Immunotherapy-Related Oral Toxicity

For patients on immune checkpoint inhibitors:

• Hold immunotherapy for moderate (Grade 2) or severe (Grade 3) oral toxicity 3
• Gabapentin can be considered for oral dysesthesia (burning sensation without visible lesions) 3
• Systemic sialagogues (cevimeline or pilocarpine) for persistent dry mouth 3
• Rechallenge can be considered after symptoms become Grade 1, with careful risk-benefit discussion 3

Common Pitfalls to Avoid

• Do not use alcoholic mouthwashes, as they aggravate mucosal irritation and worsen symptoms 1, 7
• Do not assume all oral ulcers are benign - any solitary chronic ulcer lasting >3 weeks requires biopsy to exclude squamous cell carcinoma 5
• Do not overlook systemic associations - recurrent aphthous stomatitis can be associated with celiac disease (OR 3.79), inflammatory bowel disease, or Behçet's disease 6, 5
• Do not use topical corticosteroids for suspected herpes simplex - this requires antiviral therapy and corticosteroids may worsen viral infections 1, 9
• Do not discontinue treatment prematurely - inadequate treatment duration leads to recurrence of active infection 8