eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Aphthous Ulcers: Treatment & Medication

Author: Michael C Plewa, MD, Research Coordinator, Consulting Staff, Department of Emergency Medicine, Lucas County Emergency Physicians, Inc, and Saint Vincent Mercy Medical Center
Contributor Information and Disclosures

Updated: May 12, 2009

Treatment

Medical Care

The primary goals of medical therapy in patients with aphthous ulcers (canker sores) are pain relief, maintenance of fluid and nutrition intake, early resolution, and prevention of recurrence.  Most patients with minor or herpetiform aphthae should be treated empirically before extensive and costly studies are initiated. Treatment of recurrent aphthous ulcers (canker sores) typically includes anti-inflammatory and/or symptomatic therapy, whereas immunomodulators are rarely used, except in severe, refractory cases. Many, if not all, of the therapies listed below have not specifically been studied in children.

Anti-inflammatory agents include corticosteroids, amlexanox and metalloprotease inhibitors. Treatment at onset may reduce symptoms or eliminate ulcer development.

  • High-potency corticosteroids applied locally 2-4 times daily may be successful in promoting healing and shortening the course of recurrent aphthous ulcers (canker sores), especially if applied early in the development of the lesions. Topical preparations such as mouthwash16 or gels are preferred because they limit the amount of medication delivered and thus reduce systemic adverse effects. Remember that corticosteroids increase the risk of candidiasis and other secondary infections.
    • Corticosteroid gels adhere better than creams or ointments, but any of these may be mixed with adhesive bases such as an emollient paste (eg, Orabase) for prolonged contact. The effects of these preparations are limited when lesions are numerous or difficult to reach with the cotton applicator.
    • Isolated severe ulcers may be treated with a one-time local injection of steroid (eg, triamcinolone) in the submucosal tissue after application of a topical anesthetic.
    • When lesions are severe or numerous, local steroid delivery can be achieved with liquid or spray-based (eg, beclomethasone spray) preparations. The liquid is swished around the oral cavity for 2 minutes, then expectorated.  This is repeated 2-4 times a day, with one application always occurring at bedtime, until lesions subside.
    • A short course of pulsed oral prednisone should only be considered for persistent or severe cases. Patients who arrive at this point in the treatment algorithm may require further screening to exclude additional diagnoses. If the patient's condition does not respond to a short burst of corticosteroids, oral prednisone should be continued until the lesions subside and then tapered.
  • Amlexanox paste 5% has been shown to diminish pain as well as hasten resolution of ulcers.17,18,19,20  In patients with recurrent aphthous ulcers (canker sores) who have a good understanding and recognition of their disease, early application at the onset of burning or pricking mucosal sensation 1-2 days before the ulcer appears may significantly reduce the effects of the disease.21
  • Metalloproteinase inhibitors include tetracycline, doxycycline and minocycline. These agents, such as doxycycline in a hydrogel or minocycline 0.2% oral rinse solution,22 demonstrate significant improvement in ulcer healing as well as pain reduction, all at low doses without likelihood of systemic effects or alteration in oral flora.23,24,22 This class of agents should not be used in women who are pregnant or in children.

Symptomatic therapy includes anesthetic and occlusive agents. These agents are commonly used when the ulcers are small and few, to minimize pain and improve oral intake, although some have been found to hasten ulcer healing.

  • Benzocaine is the most commonly used anesthetic agent, applied for temporary relief with cotton-tipped applicator on an as needed basis (usually before meals). Numerous preparations of between 6.4% and 20% benzocaine are available for use over-the-counter, including Anbesol, Hurricaine Liquid and Gel, Kank-A, Orabase B, Oralief, Senso-gard, Tanac, and Zilactin B. Benzocaine has not been studied in clinical trials or shown to improve healing. Excess use can lead to neurotoxicity.
  • Lidocaine 2% gel (by prescription only) can also be used, but can also cause toxicity in children.
  • The antihistamine diphenhydramine used as a swish-and-spit mouth rinse, or applied locally, may provide some pain relief. Diphenhydramine syrup is commonly mixed in a 50:50 dilution with magnesium containing antacid.
  • Local injectable anesthetics (lidocaine, bupivacaine) are discouraged because duration of pain relief is brief.
  • Sucralfate suspension (off-label use) may diminish pain without change in ulcer healing.25  
  • Paste preparations, such as Orabase alone or in combination with 20% benzocaine (Orabase-B) can be temporarily effective for pain relief.
  • Bioadhesive "super-glues", such as 2-octyl cyanoacrylate or isobutyl cyanoacrylate (Iso-Dent) have been studied in children,26 and significantly improves ulcer pain, without measurable difference in ulcer healing.27,28  Orabase Sooth-N-Seal is a cyanoacrylate product available over-the-counter.
  • A mucoadhesive patch which releases citrus oil and magnesium salt (Canker Cover) has been effective in reducing pain and decreasing healing time without adverse effects.29,30 Additional studies are needed to confirm the initial results and to directly correlate the indications and uses.
  • Debacterol Canker Sore Pain Relief (available by prescription only in the United States) or HybenX (over-the-counter in Europe) as a single application to the ulcer, significantly diminishes pain.31  This agent works by disruption (desiccation, denaturation, and coagulation) of the microbial biofilm matrix.32  
  • Over-the-counter glycyrrhiza (licorice) bioadhesive hydrogel patch (CankerMelts GX patches) enhances ulcer healing in addition to reducing pain.33,34,35
  • Polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) is used (off-label) primarily for relief of oral mucositis associated with cancer chemotherapy or irradiation, and may be effective for pain control in severe, refractory recurrent aphthous ulcers (canker sores).36 Available by prescription only, Gelclair is mixed with 15 mL of water, stirred, rinsed around the mouth, gargled, and spit, allowing one hour before eating.

Immunomodulators, including colchicine,37 cyclosporine, interferon, tumor necrosis factor antagonists (infliximab, etanercept, adalimumab), T-cell modulator modifiers (efalizumab, alefacept), antimetabolites (methotrexate), alkylating agents (cyclophosphamide) and thalidomide38 are used in severe, refractory cases, such as in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)39,40 or Behçet syndrome.41,42 However, the indications and uses of such therapy are beyond the scope of this article, and adverse effects can be both problematic and clinically significant. The patient must be closely observed; therefore, use of this therapy stretches beyond the scope of practice of most primary care providers.

Surgical Care

Few patients are unresponsive to the local or systemic therapies described above; however, several other invasive and specialized treatments are available for patients with persistent or severe lesions.

  • Laser therapy is perhaps one of the most intriguing treatments. Studies have shown that laser therapy of most aphthae immediately relieves pain, speeds healing, and reduces recurrences.43,44,45 Limitations include impracticality of the treatment. Lasers are expensive, and specialized training is required to operate them. Patients who have severe disease or frequent recurrences may benefit from referral to a laser treatment center or specialist.
  • Controversy continues to surround the application of silver nitrate. This therapy promotes changing the lesion to a burn. Some studies revealed decreased severity of pain;46 however, none have demonstrated shortened healing time. Additional and large studies are needed before this therapy can be recommended on a routine basis.
  • One of the more controversial therapies involves removing biopsy specimens from lesions as a therapeutic modality. When biopsy is performed, the lesion is changed from an immune-mediated lesion to a traumatic lesion. Some believe that these traumatic lesions are less painful and heal faster than typical aphthous ulcers. Limited data support this practice, and it cannot be recommended.

Consultations

  • Consultation may be necessary if an additional disease is strongly suggested or found.
  • Patients with severe disease may be referred to a laser specialist for evaluation and treatment.

Diet

  • Supplementation with vitamins (especially B12),47,48 zinc, or iron may prevent recurrence in some individuals. Studies of lysine supplementation are preliminary and equivocal.49
  • A gluten-free diet is unlikely to improve recurrent aphthous ulcers (canker sores) unless the patient has celiac disease (gluten-sensitive enteropathy), which may be present in as many as 5% of patients in whom recurrent aphthous ulcers (canker sores) are initially diagnosed.

Medication

Local and systemic medications are used. As a general rule, topical therapy should be initiated first to avoid the adverse effects associated with systemic treatment. Many treatments are controversial, and the clinical data for many treatments are limited. Many treatment modalities are not discussed in this article.

Topical anesthetics

These drugs are used to relieve localized pain.


Benzocaine (Anbesol, Hurricaine Gel, Kank-A, Orabase, Orajel)

PABA derivative ester-type local anesthetic; minimally absorbed. Inhibits neuronal membrane depolarization, blocking nerve impulses. Used to control pain.

Adult

Gel, paste, ointment 10-20%: Apply to affected areas qid prn

Pediatric

Administer as in adults

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not for use when infection is present; methemoglobinemia associated with overuse to mouth or throat


Lidocaine (Xylocaine)

Available as gel or viscous PO solution. Decreases permeability of neuronal membranes to sodium ions, inhibiting depolarization and blocking transmission of nerve impulses. Initial treatment of choice for small, sparse ulcers. Does not shorten healing time but may help patient to tolerate eating and drinking. Pain relief may be short, and frequent applications may be necessary.

Adult

Gel or viscous suspension: Apply to affected area prn with cotton-tipped applicator

Pediatric

Administer as in adults

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

External or mucous membrane use only; not for use in eyes; avoid swallowing to minimize potential for systemic toxicity

Antihistamines

These drugs act by competitively inhibiting histamine at the H1 receptor. They prevent histamine responses in sensory nerve endings to relieve symptoms (eg, localized irritation, pain).


Diphenhydramine elixir (Benadryl)

First-line antihistamine for topical treatment of localized skin and mucus-membrane irritation. May be applied directly to ulcerated submucosal tissue. Relieves PO pain in some patients.

Adult

Apply to affected area prn with cotton-tipped applicator or swish in mouth for 2 min and then expectorate

Pediatric

Administer as in adults

None reported with topical application

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer disease, and urinary tract obstruction (less likely with topical application than with PO form)

Topical corticosteroids

These drugs decrease inflammation by suppressing migration of polymorphonuclear (PMN) leukocytes and reversing capillary permeability. Many factors, including the vehicle, the integrity of the mucosal barrier, the amount of friction from adjacent structures, and the amount of salivation determine the extent of mucocutaneous absorption. The medical profile for triamcinolone is outlined below; other medications with the same or similar profiles include betamethasone valerate 0.1% (Valisone), clobetasol propionate 0.05% cream or ointment (Temovate), halobetasol propionate 0.05% ointment (Ultravate), and fluocinonide 0.05% gel (Lidex).

A benzocaine preparation (Orabase) is sometimes added to the corticosteroid, but the practice remains controversial. Data suggest that the benzocaine preparation helps keep the steroid in prolonged contact with the mucosal surface; however, its addition dilutes the mixture, lessening steroid potency. To add the benzocaine preparation to any of these topical steroid prescriptions, simply mix the steroid preparation 1:1 with Orabase.


Triamcinolone (Kenalog in Orabase, Oralone Dental)

Moderate-potency steroid; reduces pain and inflammation at ulcer sites. Close follow-up required to monitor for candidiasis and other secondary infections and adverse effects. Available as dental PO past 0.1%.

Adult

Apply to ulcer area tid; reduce frequency as lesions remit

Pediatric

Administer as in adults

Documented hypersensitivity; fungal, viral, or bacterial skin infections; decreased mucosal circulation; not for use on face

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use causes mucosal atrophy (limit to 2 wk); systemic absorption may cause Cushing syndrome, reversible hypothalamic-pituitary-axis suppression, hyperglycemia, and glycosuria; prolonged use, application over large surface areas, high-potency steroids, and occlusive dressings increase systemic absorption

Local corticosteroid injections

These drugs decrease inflammation by suppressing migration of PMN leukocytes and by reversing capillary permeability.


Triamcinolone diacetate 25 mg/mL (Aristocort-Intralesional) or betamethasone sodium phosphate 3 mg/mL and betamethasone acetate 3 mg/mL (Celestone Soluspan)

Local submucosal injections may substantially reduce pain and inflammation; premedication with topical anesthetic may reduce discomfort.

Adult

0.25-0.5 mL injected into submucosal tissue directly beneath ulcers; increase dose and distribution for large lesions

Pediatric

Administer as in adults

Concurrent estrogens may decrease clearance; may increase digitalis toxicity due to steroid-induced hypokalemia; phenobarbital, phenytoin, or rifampin may increase metabolic rate (may need to increase maintenance dose); monitor patients taking diuretics for hypokalemia

Documented hypersensitivity; active fungal infection

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Risk of candidiasis or other secondary infections lower with injectable preparations than with elixir; although localized injections produce few systemic adverse effects, patients are at risk for multiple complications, including severe infections, especially with HIV infection, AIDS, or other immunocompromised states; closely monitor for candidiasis and other secondary infections; abrupt discontinuation may cause adrenal crisis; other complications include hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, and growth suppression

Topical corticosteroid elixirs

These drugs decrease inflammation by suppressing migration of PMN leukocytes and reversing capillary permeability. Many factors, including the vehicle, the integrity of the mucosal barrier, the amount of friction from adjacent structures, and the amount of salivation determine the extent of mucocutaneous absorption. This type of corticosteroid delivery is indicated when topical or local steroids are not effective, when the lesions are too numerous for practical application, or when the lesions are too difficult to reach with the cotton applicator.


Dexamethasone elixir (Decadron)

Liquid increases delivery of steroid dose to local area when lesions severe or numerous; typical concentration 0.5 mg/5 mL. Close follow-up required to monitor for candidiasis and other secondary infections and adverse effects.

Adult

Swish 5 mL in mouth for 2 min tid/qid then expectorate; if no improvement, swish 5 mL for 2 min tid/qid then swallow

Pediatric

Young children (unable to swish and expectorate): Not recommended
Older children (able to swish and expectorate): Initially administer as in adults; if no improvement, swish 0.6 mg/kg in mouth for 2 min q6h then swallow

Concurrent estrogens may decrease clearance; may increase digitalis toxicity by inducing hypokalemia, especially in patients taking diuretics; phenobarbital, phenytoin, or rifampin may increase metabolic rate (may need to increase maintenance dose)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increases risk for multiple complications, including severe infections, especially with HIV infection, AIDS, or other immunocompromised states; abrupt discontinuation may cause adrenal crisis; other complications include hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, and growth suppression; monitor patients taking diuretics for hypokalemia

Miscellaneous throat and mouth products

These drugs accelerate aphthous ulcer (canker sore) healing.


Amlexanox oral paste (Aphthasol)

Mechanism of action is unknown, but elicits antiallergic and anti-inflammatory activity. Inhibits inflammatory mediators (ie, histamine, leukotrienes) from mast cells, neutrophils, and mononuclear cells. Available in 5 g tubes. One-fourth inch (about 0.5 cm) is approximately 100 mg of paste and contains 5 mg amlexanox.

Adult

Apply 1/4 inch onto clean fingertip and dap onto each ulcer qid after PO hygiene pc and hs); wash hands after application

Pediatric

Not established; limited data suggests to administer as in adults

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause transient stinging or burning pain at the site of application (2%), or contact mucositis, nausea or diarrhea (<1%)

Systemic corticosteroids

The drugs decrease inflammation by suppressing migration of PMN leukocytes and reversing capillary permeability.


Prednisone (Deltasone)

Systemic corticosteroid for severe aphthae; inactive and must be metabolized to the active metabolite prednisolone. Close follow-up care and monitoring for candidiasis and other secondary infections and adverse reactions required. Available as elixir 5 mg/5 mL.

Adult

40-60 mg/d PO; short course initially, may be extended; taper if >5 d

Pediatric

4-5 mg/m2/d PO or 1-2 mg/kg/d PO; short course initially, may be extended; taper if >5 d

Concurrent estrogens may decrease clearance; may increase digitalis toxicity by inducing hypokalemia, especially in patients taking diuretics; phenobarbital, phenytoin, or rifampin may increase metabolic rate (may need to increase maintenance dose)

Documented hypersensitivity; viral, fungal, or tubercular infections; peptic ulcer disease; hepatic dysfunction; connective tissue infections

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increases risk for multiple complications, including severe infections, especially in patients with HIV infection, AIDS, or other immunocompromised states; abrupt discontinuation may cause adrenal crisis; other complications include hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, and growth suppression; monitor patients taking diuretics for hypokalemia; prolonged use in children can suppress growth

Controversial therapies

Controversial therapies include 5-aminosalicylic acid, levamisole, colchicine, gamma-globulin, dapsone, estrogen replacement, thalidomide, MAOIs, topical penicillin,50 lactic acid mouthwash, topical hyaluronic acid (0.2%), bee propolis,51 Alchemilla vulgaris52 (Lady's Mantle) extract in glycerine (Aphtarine), pentoxifylline,53 botulinum toxin A injection,54 silver nitrate sticks, and tetracycline. A small study suggested topical therapy with 5-aminosalicylic acid diminished symptoms and hastened resolution in recurrent aphthous ulcers (canker sores).55  Of these, only silver nitrate sticks and tetracycline are used with enough frequency and efficacy to be mentioned here.

Silver nitrite sticks cause chemical cauterization. Research findings are split on whether this treatment, which changes the lesion from an ulcer to a burn injury, shortens or prolongs healing. All lesions must be anesthetized before cauterization. This treatment is particularly effective at relieving the pain associated with ulcers.46

Some evidence supports treatment with tetracycline, either as mouthwash or subantimicrobial dose (20 mg orally twice daily). Minocycline 0.2% is more effective than tetracycline 0.25% oral mouth rinse (ie, swish orally and swallow) in decreasing healing time and pain severity and duration.24,22  Benefit is likely due to inhibitory effects on leukocyte function rather than due to a direct antimicrobial effect because effective doses are below those that effect bacterial flora.


Tetracycline syrup (Sumycin)

Decreases healing time and level and duration of discomfort from aphthae; mechanism of action unknown, but attributed to direct antimicrobial effect or inhibitory effect on chemotaxis and chemotoxicity.

Adult

250 mg/10 mL swish in mouth qid, then swallow; treat for 14 d

Pediatric

<11 years: Not established
>11 years: Administer as in adults

Can decrease effects of PO contraceptives, causing breakthrough bleeding and increasing risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants

Documented hypersensitivity; severe hepatic dysfunction

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum-level determinations with prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can permanently discolor teeth; Fanconi-like syndrome may occur with outdated tetracyclines

More on Aphthous Ulcers

Overview: Aphthous Ulcers
Differential Diagnoses & Workup: Aphthous Ulcers
Treatment & Medication: Aphthous Ulcers
Follow-up: Aphthous Ulcers
Multimedia: Aphthous Ulcers
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Bachtiar EW, Cornain S, Siregar B, Raharjo TW. Decreased CD4+/CD8+ ratio in major type of recurrent aphthous ulcers: comparing major to minor types of ulcers. Asian Pac J Allergy Immunol. Jun-Sep 1998;16(2-3):75-9. [Medline].

  2. Buno IJ, Huff JC, Weston WL, et al. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4, and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch Dermatol. Jul 1998;134(7):827-31. [Medline].

  3. Healy CM, Thornhill MH. Induction of adhesion molecule expression on blood vessels and keratinocytes in recurrent oral ulceration. J Oral Pathol Med. Jan 1999;28(1):5-11. [Medline].

  4. Birek C, Grandhi R, McNeill K, et al. Detection of Helicobacter pylori in oral aphthous ulcers. J Oral Pathol Med. May 1999;28(5):197-203. [Medline].

  5. Maleki Z, Sayyari AA, Alavi K, Sayyari L, Baharvand M. A study of the relationship between Helicobacter pylori and recurrent aphthous stomatitis using a urea breath test. J Contemp Dent Pract. Jan 1 2009;10(1):9-16. [Medline].

  6. Haisraeli-Shalish M, Livneh A, Katz J, et al. Recurrent aphthous stomatitis and thiamine deficiency. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Dec 1996;82(6):634-6. [Medline].

  7. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. Jul 1999;135(1):15-21. [Medline].

  8. Padeh S, Brezniak N, Zemer D, et al. Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome. J Pediatr. Jul 1999;135(1):98-101. [Medline].

  9. Ghodratnama F, Wray D, Bagg J. Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis. J Oral Pathol Med. Jan 1999;28(1):12-5. [Medline].

  10. Lin SS, Chou MY, Ho CC, et al. Study of the viral infections and cytokines associated with recurrent aphthous ulceration. Microbes Infect. Apr 2005;7(4):635-44. [Medline].

  11. Gupta SK, Gupta RC, Seth AK, et al. Epidemiological evaluation of recurrent stomatitis, nitrates in drinking water, and cytochrome b5 reductase activity. Am J Gastroenterol. Jul 1999;94(7):1808-12. [Medline].

  12. Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand. Oct 1994;52(5):257-9. [Medline].

  13. Herlofson BB, Barkvoll P. The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers. Acta Odontol Scand. Jun 1996;54(3):150-3. [Medline].

  14. Koridze Kh. Definition of risk of the aphthous stomatitis by hygienic indices [in Russian]. Georgian Med News. Apr 2005;25-8. [Medline].

  15. Ficarra G. Oral ulcers in HIV-infected patients: an update on epidemiology and diagnosis. Oral Dis. May 1997;3 Suppl 1:S183-9. [Medline].

  16. Holbrook WP, Kristmundsdottir T, Loftsson T. Aqueous hydrocortisone mouthwash solution: clinical evaluation. Acta Odontol Scand. Jun 1998;56(3):157-60. [Medline].

  17. Bell J. Amlexanox for the treatment of recurrent aphthous ulcers. Clin Drug Investig. 2005;25(9):555-66. [Medline].

  18. Binnie WH, Curro FA, Khandwala A, Van Inwegan RG. Amlexanox oral paste: a novel treatment that accelerates the healing of aphthous ulcers. Compend Contin Educ Dent. Nov 1997;18(11):1116-8, 1120-2, 1124 passim. [Medline].

  19. Greer RO Jr, Lindenmuth JE, Juarez T, Khandwala A. A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers. J Oral Maxillofac Surg. Mar 1993;51(3):243-8; discussion 248-9. [Medline].

  20. Khandwala A, Van Inwegen RG, Alfano MC. 5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: I. Clinical demonstration of acceleration of healing and resolution of pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Feb 1997;83(2):222-30. [Medline].

  21. Murray B, McGuinness N, Biagioni P, et al. A comparative study of the efficacy of Aphtheal in the management of recurrent minor aphthous ulceration. J Oral Pathol Med. Aug 2005;34(7):413-9. [Medline].

  22. Gorsky M, Epstein J, Raviv A, Yaniv R, Truelove E. Topical minocycline for managing symptoms of recurrent aphthous stomatitis. Spec Care Dentist. Jan-Feb 2008;28(1):27-31. [Medline].

  23. Skulason S, Holbrook WP, Kristmundsdottir T. Clinical assessment of the effect of a matrix metalloproteinase inhibitor on aphthous ulcers. Acta Odontol Scand. Feb 2009;67(1):25-9. [Medline].

  24. Gorsky M, Epstein J, Rabenstein S, Elishoov H, Yarom N. Topical minocycline and tetracycline rinses in treatment of recurrent aphthous stomatitis: a randomized cross-over study. Dermatol Online J. 2007;13(2):1. [Medline].

  25. Rattan J, Schneider M, Arber N, et al. Sucralfate suspension as a treatment of recurrent aphthous stomatitis. J Intern Med. Sep 1994;236(3):341-3. [Medline].

  26. Jasmin JR, Muller-Giamarchi M, Jonesco-Benaiche N. Local treatment of minor aphthous ulceration in children. ASDC J Dent Child. Jan-Feb 1993;60(1):26-8. [Medline].

  27. Kutcher M. Evaluating the efficacy of 2-octyl cyanoacrylate bioadhesive for treatment of oral ulcerations. Compend Contin Educ Dent Suppl. 2001;12-6; quiz 22. [Medline].

  28. Kutcher MJ, Ludlow JB, Samuelson AD, Campbell T, Pusek SN. Evaluation of a bioadhesive device for the management of aphthous ulcers. J Am Dent Assoc. Mar 2001;132(3):368-76. [Medline].

  29. Shemer A, Amichai B, Trau H, Nathansohn N, Mizrahi B, Domb AJ. Efficacy of a mucoadhesive patch compared with an oral solution for treatment of aphthous stomatitis. Drugs R D. 2008;9(1):29-35. [Medline].

  30. Mizrahi B, Golenser J, Wolnerman JS, Domb AJ. Adhesive tablet effective for treating canker sores in humans. J Pharm Sci. Dec 2004;93(12):2927-35. [Medline].

  31. Rhodus NL, Bereuter J. An evaluation of a chemical cautery agent and an anti-inflammatory ointment for the treatment of recurrent aphthous stomatitis: a pilot study. Quintessence Int. Dec 1998;29(12):769-73. [Medline].

  32. Porter SR, Al-Johani K, Fedele S, Moles DR. Randomised controlled trial of the efficacy of HybenX in the symptomatic treatment of recurrent aphthous stomatitis. Oral Dis. Mar 2009;15(2):155-61. [Medline].

  33. Moghadamnia AA, Motallebnejad M, Khanian M. The efficacy of the bioadhesive patches containing licorice extract in the management of recurrent aphthous stomatitis. Phytother Res. Feb 2009;23(2):246-50. [Medline].

  34. Burgess JA, van der Ven PF, Martin M, Sherman J, Haley J. Review of over-the-counter treatments for aphthous ulceration and results from use of a dissolving oral patch containing glycyrrhiza complex herbal extract. J Contemp Dent Pract. Mar 1 2008;9(3):88-98. [Medline].

  35. Martin MD, Sherman J, van der Ven P, Burgess J. A controlled trial of a dissolving oral patch concerning glycyrrhiza (licorice) herbal extract for the treatment of aphthous ulcers. Gen Dent. Mar-Apr 2008;56(2):206-10; quiz 211-2, 224. [Medline].

  36. Buchsel PC. Polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair): a bioadherent oral gel for the treatment of oral mucositis and other painful oral lesions. Expert Opin Drug Metab Toxicol. Nov 2008;4(11):1449-54. [Medline].

  37. Katz J, Langevitz P, Shemer J, et al. Prevention of recurrent aphthous stomatitis with colchicine: an open trial. J Am Acad Dermatol. Sep 1994;31(3 Pt 1):459-61. [Medline].

  38. Revuz J, Guillaume JC, Janier M, et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol. Jul 1990;126(7):923-7. [Medline].

  39. Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. May 22 1997;336(21):1487-93. [Medline].

  40. Wu JJ, Huang DB, Pang KR, et al. Thalidomide: dermatological indications, mechanisms of action and side-effects. Br J Dermatol. Aug 2005;153(2):254-73. [Medline].

  41. Altenburg A, Zouboulis CC. Current concepts in the treatment of recurrent aphthous stomatitis. Skin Therapy Lett. Sep 2008;13(7):1-4. [Medline].

  42. O'Neill ID. Off-label use of biologicals in the management of inflammatory oral mucosal disease. J Oral Pathol Med. Nov 2008;37(10):575-81. [Medline].

  43. Tezel A, Kara C, Balkaya V, Orbak R. An Evaluation of Different Treatments for Recurrent Aphthous Stomatitis and Patient Perceptions: Nd:YAG Laser versus Medication. Photomed Laser Surg. Feb 2009;27(1):101-6. [Medline].

  44. Zand N, Ataie-Fashtami L, Djavid GE, Fateh M, Alinaghizadeh MR, Fatemi SM, et al. Relieving pain in minor aphthous stomatitis by a single session of non-thermal carbon dioxide laser irradiation. Lasers Med Sci. Apr 12 2008;[Medline].

  45. Sharon-Buller A, Sela M. CO2-laser treatment of ulcerative lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 2004;97(3):332-4. [Medline].

  46. Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol. Sep 2005;153(3):521-5. [Medline].

  47. Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med. Jan-Feb 2009;22(1):9-16. [Medline].

  48. Gulcan E, Toker S, Hatipoglu H, Gulcan A, Toker A. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sci. Nov 2008;336(5):379-82. [Medline].

  49. Wright EF. Clinical effectiveness of lysine in treating recurrent aphthous ulcers and herpes labialis. Gen Dent. Jan-Feb 1994;42(1):40-2; quiz 51-2. [Medline].

  50. Kerr AR, Drexel CA, Spielman AI. The efficacy and safety of 50 mg penicillin G potassium troches for recurrent aphthous ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Dec 2003;96(6):685-94. [Medline].

  51. Samet N, Laurent C, Susarla SM, Samet-Rubinsteen N. The effect of bee propolis on recurrent aphthous stomatitis: a pilot study. Clin Oral Investig. Jun 2007;11(2):143-7. [Medline].

  52. Shrivastava R, John GW. Treatment of Aphthous Stomatitis with topical Alchemilla vulgaris in glycerine. Clin Drug Investig. 2006;26(10):567-73.

  53. Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol. Apr 2007;143(4):463-70. [Medline].

  54. Yang TY, Jang TY. The value of local botulinum toxin A injection in the treatment of the pain of aphthous ulcer. Eur Arch Otorhinolaryngol. Mar 2009;266(3):445-8. [Medline].

  55. Collier PM, Neill SM, Copeman PW. Topical 5-aminosalicylic acid: a treatment for aphthous ulcers. Br J Dermatol. Feb 1992;126(2):185-8. [Medline].

  56. Sharquie KE, Najim RA, Al-Hayani RK, Al-Nuaimy AA, Maroof DM. The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis (ras) in comparison with dapsone. Saudi Med J. May 2008;29(5):734-8. [Medline].

  57. Hunter IP, Ferguson MM, Scully C, et al. Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy. Oral Surg Oral Med Oral Pathol. May 1993;75(5):595-8. [Medline].

  58. Brice SL. Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Jan 1997;83(1):14-20. [Medline].

  59. Skaare AB, Herlofson BB, Barkvoll P. Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU). J Clin Periodontol. Aug 1996;23(8):778-81. [Medline].

  60. Fridh G, Koch G. Effect of a mouth rinse containing amyloglucosidase and glucose oxidase on recurrent aphthous ulcers in children and adolescents. Swed Dent J. 1999;23(2-3):49-57. [Medline].

  61. Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children--a review. Int J Paediatr Dent. Apr 1992;2(1):1-10. [Medline].

  62. Hodosh M, Hodosh SH, Hodosh AJ. Treatment of aphthous stomatitis with saturated potassium nitrate/dimethyl isosorbide. Quintessence Int. Feb 2004;35(2):137-41. [Medline].

  63. Mahdi AB, Coulter WA, Woolfson AD, Lamey PJ. Efficacy of bioadhesive patches in the treatment of recurrent aphthous stomatitis. J Oral Pathol Med. Sep 1996;25(8):416-9. [Medline].

  64. Rogers RS. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg. Dec 1997;16(4):278-83. [Medline].

  65. Saxen MA, Ambrosius WT, Rehemtula al-KF AL, et al. Sustained relief of oral aphthous ulcer pain from topical diclofenac in hyaluronan: a randomized, double-blind clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Oct 1997;84(4):356-61. [Medline].

  66. Scully C. Clinical practice. Aphthous ulceration. N Engl J Med. Jul 13 2006;355(2):165-72. [Medline].

  67. Ueta E, Osaki T, Yoneda K, et al. A clinical trial of Azelastine in recurrent aphthous ulceration, with an analysis of its actions on leukocytes. J Oral Pathol Med. Mar 1994;23(3):123-9. [Medline].

  68. Victoria JM, Correia-Silva Jde F, Pimenta FJ, et al. Serotonin transporter gene polymorphism (5-HTTLPR) in patients with recurrent aphthous stomatitis. J Oral Pathol Med. Sep 2005;34(8):494-7. [Medline].

  69. Vincent SD, Lilly GE. Clinical, historic, and therapeutic features of aphthous stomatitis. Literature review and open clinical trial employing steroids. Oral Surg Oral Med Oral Pathol. Jul 1992;74(1):79-86. [Medline].

  70. Wormser GP, Mack L, Lenox T, et al. Lack of effect of oral acyclovir on prevention of aphthous stomatitis. Otolaryngol Head Neck Surg. Jan 1988;98(1):14-7. [Medline].

  71. Ylikontiola L, Sorsa T, Hayrinen-Immonen R, Salo T. Doxymycine-cyanoacrylate treatment of recurrent aphthous ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 1997;83(3):329-33. [Medline].

[ CLOSE WINDOW ]

Keywords

aphthous ulcers, aphthous stomatitis, canker sores, mouth sores, mouth ulcers, recurrent aphthous ulcers, RAU, recurrent aphthous stomatitis, RAS, aphthae minor, ulcerative stomatitis, Sutton disease, Sutton's disease, minor aphthous ulcers, major aphthous ulcers, herpetiform ulcers, Helicobacter pylori, malabsorption, celiac disease, regional enteropathy, myalgia, arthralgia, inflammatory bowel disease, gluten-sensitive enteropathy, Behçet disease, systemic lupus erythematosus, HIV, AIDS, Crohn disease, cyclic neutropenia, mouth and genital ulcers with inflamed cartilage, MAGIC syndrome, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Michael C Plewa, MD, Research Coordinator, Consulting Staff, Department of Emergency Medicine, Lucas County Emergency Physicians, Inc, and Saint Vincent Mercy Medical Center
Michael C Plewa, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Physicians for Social Responsibility, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Halim Hennes, MD, MS, Pediatric Emergency Medicine Research Director, Professor, Departments of Pediatrics and Emergency Medicine, Medical College of Wisconsin
Halim Hennes, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati
Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.