Grades of the evidence definitions (I-a, I-b, II-a, II-b, III, IV) and strength of the recommendations (A-E) are repeated at the end of the major recommendations field.
Diagnosis/Evaluation
- Complete comprehensive history of present illness, severity, frequency, duration, associated weight loss or decreased appetite, and past treatments and response.
- Focused exam of lips, mucous membranes and buccal mucosa, dentition, and bite alignment. Sores are typically found in the movable parts of the mouth (i.e., the tongue or the inside linings of the lips and cheeks). Refer to the original guideline document for a table describing classification of ulcers.
- Differential diagnoses include herpetic gingival stomatitis, herpangina, hand foot and mouth disease, bullous diseases, lichen planus, Reiter's syndrome, squamous cell carcinoma, Behcet's disease, adverse drug reactions such as chemotherapy, gold fillings, fixed eruption, immunosuppression, neutropenia, and celiac disease. Complex aphthous and complex aphthous variants associated with systemic disorders should be considered. See the original guideline document for a table with further description of differential diagnosis.
- Diagnostic tests usually are not ordered. If suspected nutritional deficiency, B12, folate/iron levels, and complete blood count (CBC) with differential may be considered. Tzanck smear to rule out herpetic stomatitis, human immunodeficiency virus (HIV) testing for large and slow healing ulcers, and biopsy may be needed for suspected cancer (strength of recommendation A; quality of evidence III & IV).
- Principles of treatment include:
- May need several treatments before they find one that works well for them.
- Initial treatment goals include decreasing the number of ulcers, decreasing pain, and at times reducing frequency.
- In more severe cases, the treatment goal for most people is decreasing pain, trying to make the ulcers more bearable (strength of recommendation B; quality of evidence III).
Treatment/Management
- Lifestyle modifications may aid in prevention, decreased frequency of sores, or minimizing discomfort. Modifications include practicing good oral hygiene, preventing trauma by using adequate sized toothbrush, instituting relaxation techniques to minimize stress, drinking through straw, and avoiding acidic beverages and spicy or sharp/crispy foods, such as chips (strength of recommendation B; quality of evidence III).
- Non-pharmacological treatments include good oral hygiene, prevention of trauma (adequate sized toothbrush), avoidance of spicy foods and acidic fruit juices or carbonated drinks, drinking through a straw to bypass the mouth, avoiding sharp foods such as crisps, avoiding stress if possible which may exacerbate ulcers or trigger a series of ulcers, and orthodontist referral. In addition, if vitamin deficiency has been diagnosed, this should be treated and corrected; if food allergies have been determined, these foods should be avoided (strength of recommendation B; quality of evidence IV)
Pharmacological therapy for minor and major recurrent aphthous stomatitis
- Pharmacological treatment options include vitamins and nutritional supplements, topical glucocorticoids, topical anesthetics, and systemic medications. First line treatment for minor and major recurrent aphthous stomatitis are listed in Table 1.
- Follow up in 1 to 2 days for infants and elderly persons not taking fluids (Strength of recommendation A, quality of evidence III).
Table 1: Treatment regimens minor to major recurrent aphthous ulcers
| Type of treatment |
Preparations |
Particularly suitable for |
| Over-the-counter conservative treatment |
Liquid antacids or 3% hydrogen peroxide/water solution, 1:1 as a gargle
(Strength of recommendation B, quality of evidence IV) |
Minor recurrent apthous ulcer (AU). |
| Covering agents/topical analgesics/anesthetics/numbing agents/anti-inflammatory |
- Orabase, Benzydamine hydrochloride (HCL) mouthwash
- Diphenhydramine EMLA, or mixed 1:1 with Kaopectate or aluminum hydroxide, or Maalox
- Viscous lidocaine 1:1 with Benadryl plus Maalox
- Aphthasol 5%(amlexanox) paste, apply over canker sore, forms a film which protects canker sore and delivers medication, four times daily (QID), after meals and at bedtime (HS).
(Strength of recommendation A, quality of evidence II a) |
Single, sporadic, infrequent minor or major ulcers.
Accelerate resolution of pain and healing, have not been shown to reduce the rate of occurrence |
| Antiseptic mouthwashes |
- Benzydamine hydrochloride (Difflam), at least three times daily (TID)
- Chlorhexadine gluconate (Peridex/Corsodyl) at least TID
- Carboxymethylcellulose paste (Orabase)
(Strength of recommendation A, quality of evidence III). |
Antibacterial mouthwashes.
Primarily for reduction of pain and with wide range of oral sites not accessible to covering pastes, also speed up healing |
| Low potency topical steroid pellets and Ointments |
- Triamcinolone 0.1% in carboxymethylcellulose paste (Adcortyl in Orabase) & Triamcinolone acetonide (Kenalog in Orabase), qid to dried areas around ulcers with moistened finger. Allow film to hydrate before allowing contact with uninvolved mucosa, one application last thing at HS (minor AU).
- Hydrocortisone sodium succinate 2.5mg (Corlan) qid during attack, bid between attacks for at least 6 weeks before reducing to use during attacks only (minor AU) (use of steroids is consensus effective treatment from almost all sources).
(Strength of recommendation A, quality of evidence III, & IV) |
Anti-inflammatory agents.
Frequently recurring mild ulcers or major ulcers. Steroids may be used to reduce the frequency of attacks. Most successful with ulcers located in the sulci where pellet can be left to dissolve. |
| Aerosols |
- Beclomethasone dipropionate aerosol (Beconase spray) 2 puffs (100 micrograms) spray onto affected mucosa to a max of 8 puffs/day. Reduced risks of adverse effects over Betamethasone mouthwash but slightly less effective. Useful if only one or two ulcers are present (moderately severe).
(Strength of recommendation A, quality of evidence IV) |
Most useful when more potent steroid needed and for inaccessible sites (i.e., soft palate or oropharynx). |
| Steroid mouthwashes |
- Betamethasone sodium phosphate (Betnesol mouthwash/Diprolene) one 0.5mg tablet dissolved in 5 to 10 ml of water used as a mouthwash qid during ulcer attack. Must be held in mouth for a minimum of 3 minutes for maximum effectiveness; spit out after use. Can be used 6 times a day under strict supervision (strength of recommendation A, quality evidence III)
- Fluocinonide (Lidex), clobetasol (Temovate) same as Betamethasone (same recommendation & quality)
|
Useful with wide range of ulcer sites and of sufficient severity to merit therapeutic treatment. Monitoring for side effects of steroids is essential as some medication always gets swallowed inadvertently. |
Pharmacological therapy for severe, recurrent aphthous ulcers
- Treatment recommendations for severe recurrent aphthous ulcers are listed in Table 2.
- Follow up in severe cases in 2 to 3 days (strength of evidence A, quality of evidence III).
- Consult specialist if not healed in 2 to 3 weeks.
Table 2: Treatment regimens for severe, recurrent aphthous ulcers
| Type of treatment |
Preparations |
Particularly suitable for |
| Systemic drugs |
- Oral prednisolone 40 mg for 5 days, reduce by 5 mg every 2 days to 5 mg, reduce by 1 mg/day until complete. Monitor severity closely at 15 mg dos; select maintenance dose to maintain remission before ulcers reappear (strength of recommendation B, quality evidence IV)
- Thalidomide 200 mg qd or bid 3 to 8 weeks for HIV or Behcet's disease severe AU (strength of recommendation D, quality of evidence IV – restricted use in U.S.)
- Colchicines 500 micrograms/day or Pentoxifylline 400 mg tid (strength of recommendation C, quality of evidence IV)
- Azathioprine 50 to 100mg daily primarily as a steroid sparing agent during maintenance phase of treatment (strength of recommendation B, quality of evidence III).
|
Reserved for severe recurrent aphthous ulcers interfering with nutrition. |
| Tetracycline |
- Tetracycline 250-mg capsules dissolved in 10 ml of water and used as a mouthwash. Gargle for 3 minutes then spit out (strength of recommendation B, quality of evidence III).
- Topical tetracycline (aureomycin, chlortetracycline, and tetracycline) (strength of recommendation B, quality of evidence IIII & IV)
|
Herpetiform ulcers. Often unresponsive to steroids, which form a second line of treatment if tetracyclines fail. |
| Topical immunomodulatory agents |
Azelastine, human alpha-2 interferon cream, topical cyclosporine, deglycyrrhizinated licorice, topical 5-aminosalicylic acid (5-ASA), amlexanox 5% paste, and prostaglandin E2 (PGE2) gel. (Strength of recommendation C, quality of evidence IV). |
Suggested to be of some benefit in the management of recurrent aphthous stomatitis (RAS); may significantly reduce the pain and healing time to RAS ulceration. |
Pharmacological Therapy for children under age 12
- Children may experience weight loss, time off of school, difficulty in speaking and eating, and dehydration
- Principles of treatment:
- Ensure correct diagnosis
- Ensure underlying conditions are detected and effectively treated
- Reassure parents and child and explain limitations of treatment
- Avoid "over-medicalizing" condition (consider no intervention)
- Teach parents to monitor child's eating and dehydration
- Nutritional support may be considered in children who refuse to eat during the entire duration of the attack
- Children under 6 cannot rinse and expectorate effectively; avoid preparations that cannot be swallowed by young children
- Avoid tetracycline preparations, even as a mouthwash, in children under 12
- Refer to Table 3 for preparation recommendations for children
Table 3: Recommendations for Recurrent Aphthous Stomatitis in children under age 12
| First Line |
- Benzydamine and local anesthetics
- Lidocaine gel preps (Calgel teething gel) may be applied several times a day in small quantities and before meals to improve eating (strength of recommendation A; quality of evidence II-b, III, & IV).
|
| In more severe cases |
- Triamcinolone 0.1% in carboxymethylcellulose paste (Adcortyl in Orabase) can be managed only by older children.
- Hydrocortisone sodium succinate 2.5mg tablets (Corlan) are safe in children because of their low steroid potency (strength of recommendation A; quality of evidence II-b, III, & IV).
|
Principles of treatment for HIV-associated ulcers
- Antifungal treatment may be required in conjunction with steroids.
- Biopsy may be indicated to ensure treatable infection (i.e., herpes simplex, cytomegalovirus [CMV]).
- A further immunosuppression with new infections may arise.
- Steroids should be used with caution: prednisolone 40 mg for 4 days, reducing by 5 mg every 2 days until 5 mg, then reducing by 1 mg per day to 0 mg provide rapid relief.
- Intralesional injection delivers high doses of steroids directly to the lesion and avoids long-term systemic adverse effects.
Definitions:
Strength of the Recommendation
- There is good evidence to support the recommendation that the treatment be specifically considered in the management of recurrent aphthous stomatitis.
- There is fair evidence to support the recommendation that the treatment be specifically considered in the management of recurrent aphthous stomatitis.
- There is insufficient evidence to recommend for or against the inclusion of the treatment in the management of recurrent aphthous stomatitis, but recommendations may be made on other grounds.
- There is fair evidence to support the recommendation that the treatment be excluded from consideration in the management of recurrent aphthous stomatitis.
- There is good evidence to support the recommendation that the treatment be excluded from consideration in the management of recurrent aphthous stomatitis.
Quality of Evidence
- Category Ia. Evidence is obtained from meta-analysis of randomized controlled trials.
- Category Ib. Evidence is obtained from at least one randomized controlled trial.
- Category IIa. Evidence is obtained from at least one well-designed controlled study without randomization.
- Category IIb. Evidence is obtained from at least one other type of well-designed quasi-experimental study.
- Category III. Evidence is obtained from well-designed non-experimental descriptive studies such as comparative studies, correlational studies, and case control studies.
- Category IV. Evidence is obtained from expert committee reports or opinions and/or clinical experience of respected authorities.
Adapted from: United Stated Department of Health and Human Services (U.S. DHHS), Office of Public Health & Science. U.S. Preventive Services Task Force, (1996). Guideline to Clinical Preventive Services, (2nd ed.), Alexandria, VA: International Medical Publishing, Inc.
