Pediatric Aphthous Ulcers

Commonly termed canker sores, aphthous ulcers, or aphthous stomatitis, have been the focus of study and research for many years, although the exact etiology of the lesions has yet to be identified. Categorized as an idiopathic disease, aphthous ulcers are frequently misdiagnosed, treated incorrectly, or simply ignored.

Recurrent aphthous ulcer (RAU), or recurrent aphthous stomatitis (RAS), represents a chronic inflammatory disease characterized by painful oral ulcers recurring with varying frequency. Examples of aphthous ulcers are shown in the images below.

Recurrent aphthae in floor of mouth, showing ovoid ulcer with inflammatory halo.

Typical aphthous ulcer in a common site, showing inflammatory halo surrounding a yellowish, round ulcer.

Children with recurrent aphthous ulcers (canker sores) may reduce their oral food and fluid intake because of the associated pain and subsequently become dehydrated; therefore, aggressive therapy for the lesions can be important.

Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. The 3 categories of recurrent aphthous ulcers (canker sores) are as follows:

• Minor aphthous ulcers (80-85% of recurrent aphthous ulcers [canker sores]) are 1-10 mm in diameter and heal spontaneously in 7-10 days.

• Major aphthous ulcers (also called Sutton disease) constitute 10-15% of recurrent aphthous ulcers (canker sores). These lesions are greater than 10 mm in diameter, take 10-30 days or more to heal, and may leave scars.

• Herpetiform ulcers (5-10% of recurrent aphthous ulcers [canker sores]) are multiple, clustered, 1-mm to 3-mm lesions that may coalesce into plaques. These usually heal in 7-10 days.

The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring.

Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8+ cells and decreased numbers of helper CD4+ cells in peripheral blood.[1]  Antithyroid and antigastric antibodies may also play a role[2] since antibodies to gastric parietal cells, thyroglobulin and thyroid microsomes may be present in 13-19% of cases.[3]   Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5;[4] they have a functional deficit of IL-10. Some lesions have also had mast-cell activation and degranulation. In vitro cytotoxicity to oral keratinocyte targets is greater in patients with active recurrent aphthous ulcers (canker sores) than in control subjects or in patients with traumatic ulcers. As expected with this abnormal immunologic activity, corticosteroids are effective therapy.

Aphthous ulcers may have abnormalities in cell communication and epithelial integrity. Lesions have increased expression of an adhesion molecule termed vascular cell adhesion molecule-1 (VCAM-1), E selectin, and keratinocyte intercellular adhesion molecule-1 (ICAM-1).[5] Connexins (markers for the presence of gap junctions) are present in the oral mucosa of patients with recurrent aphthous ulcers (canker sores) in amounts similar to those present in normal mucosal tissue. Experimental treatment with irsogladine maleate, which reinforces gap junctional intercellular communication, is effective.

The oral flora likely plays a role in recurrent aphthous ulcers (canker sores), and a dysbiosis of the microbiota has been suggested.[6]  Helicobacter pylori may or may not be involved in aphthous ulcer formation.[7, 8, 9]

Factors predisposing patients to recurrent aphthous ulcers (canker sores) may include trauma, emotional stress[10] poor nutritional status, thiamine deficiency,[11] vitamin B12 and D deficiency,[12] zinc deficiency,[13]  malabsorption, celiac disease, regional enteropathy, menstruation, food hypersensitivity (eg, cow's milk),[14] allergic reaction, low antioxidant levels,[15, 16] and exposure to toxins (eg, nitrates in drinking water). Aphthous ulcers (canker sores) are more prevalent in nonsmokers and in smokers who quit but are diminished with nicotine replacement therapy.

Frequency

United States

Although recurrent aphthous ulcers (canker sores) are commonly believed to occur in approximately 20% of the general population, a study of medical and dental students revealed a prevalence of 31-66%.

International

The worldwide incidence is similar to that in the United States. Aphthous ulcers (canker sores) are found in all ethnic groups and geographic locations. The prevalence may be increased in affluent countries and socioeconomic classes.

Mortality/Morbidity

Aphthous ulcers (canker sores) are associated with local pain and discomfort. Symptoms usually last 2-10 days with minor and herpetiform ulcers and as long as 30 days with major ulcers. Most cases are self-limited and heal without sequelae in 7-14 days; however, major ulcers heal slowly (10-30 days or longer).

• Major aphthous ulcers (canker sores) have been known to leave substantial scars.

• The primary morbidity with any type of aphthous ulcer (canker sore) in the pediatric population is dehydration due to poor oral intake.

• Secondary bacterial infections are uncommon.

Race

Race does not appear to influence the frequency or severity of recurrent aphthous ulcers (canker sores).

Sex

Aphthous ulcers (canker sores) may be slightly more common in female individuals than in male individuals. Outbreaks occur most frequently during ovulation or before menstruation, and remissions are common during pregnancy.

Age

Recurrent aphthous ulcers (canker sores) begin in childhood or adolescence, with peak onset in persons aged 10-19 years. Frequency and severity diminish with age. Major aphthous ulcers (canker sores) may begin soon after puberty. Herpetiform recurrent aphthous ulcers (canker sores) tend to affect older persons.

The diagnosis of aphthous ulcers (canker sores) is primarily clinical. Patients typically describe a prodromal stage of a burning or pricking sensation of the oral mucosa 1-2 days before the ulcer appears. Patients with recurrent aphthous ulcers (RAUs), or canker sores, often mention precipitating factors, such as local trauma or food hypersensitivity.

• During the review of systems, infants and small children should be assessed for decreased feeding, weight, and urine output. Associated symptoms, such as those below, suggest other diagnoses and are not associated with recurrent aphthous ulcers (canker sores).

  • Fever

  • Malaise

  • Myalgias

  • Arthralgias

  • Headache

  • Cough

  • Nausea

  • Vomiting

  • Abdominal pain

  • Diarrhea

  • Sore throat

  • Swollen or painful lymphadenopathy

  • Rash

  • Genital or conjunctival lesions

• Inquire about previous ulcers. The natural history of individual lesions is important because it is the benchmark against which treatment benefits are measured.

  • Age at onset should be noted because major recurrent aphthous ulcers (canker sores) begin after puberty, and herpetiform ulcers are uncommon in children.

  • The duration, location, and size of previous lesions should be noted, as well as the therapy received.

  • Having patients keep an ulcer diary for 1-3 months may be useful.

• Ask the patient about medication use, chemotherapy, radiation therapy, vitamin supplementation, and recent dietary changes.

• Assess for a family history of the following:

  • Aphthous ulcers (canker sores)

  • Inflammatory bowel disease

  • Gluten-sensitive enteropathy

  • Behçet disease

  • Systemic lupus erythematosus

• Review the patient's medical history. Consider Behçet disease; human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); cancer; Crohn disease; immunocompromised state; cyclic neutropenia; mouth and genital ulcers with inflamed cartilage (MAGIC syndrome); and systemic lupus erythematosus.

Aphthous ulcers (canker sores) occur on areas of the mouth in which the mucosa is nonkeratinized and loosely attached, particularly the buccal mucosa, the labial mucosa, the floor of the mouth, the ventral surface of the tongue, and the soft palate. Ulcers may appear as single or multiple lesions, and they are easily distinguished from primary or secondary viral infections, bacterial infections (eg, necrotizing ulcerative gingivitis), dermatologic conditions (lichen planus, cicatricial pemphigoid, pemphigus), and traumatic injuries (contusions, lacerations, burns) by the healthy appearance of adjacent tissues and the lack of distinguishing systemic features.

• Minor ulcers are seldom larger than 5 mm but can be as large as 1 cm. They may be single or multiple. The ulcers are round-to-oval, they are covered by a gray or yellowish and fibrinous surface, and they are surrounded by an erythematous border.

• Major recurrent aphthous ulcers (canker sores) can be 1-3 cm in diameter. They are deeper than minor ulcers and often have a raised, irregular, erythematous border. Patients with a history of major recurrent aphthous ulcers (canker sores) often have residual scarring in the oral mucosa from previous lesions.

• Herpetiform aphthous ulcers appear as small (seldom >3 mm in diameter), tightly clustered lesions. They typically number 2-10 but may number as many as 100. They are not related to herpes simplex infections and do not present as or develop into vesicular lesions. The ulcers appear identical to minor aphthous ulcers with the exception of their small size, proximity to other lesions, and increased numbers. Confusion may arise if the lesions coalesce into a large lesion resembling major aphthous stomatitis.

• The rest of the mouth should appear normal. However, halitosis and necrotic, exudative, or bleeding gums may be present with the following: (1) necrotizing ulcerative gingivostomatitis; (2) erythematous tonsils with periodic fever, aphthous pharyngitis, and adenopathy (PFAPA) syndrome;[17, 18] and (3) vesicular-ulcerative palatal lesions with coxsackieviral infection.

• Vital signs should be normal. Secondary bacterial infection, PFAPA syndrome, primary viral infection, or rheumatologic disorder may cause fever.

• Clinical evidence of dehydration may include decreased weight, tachycardia, hypotension, cool extremities, delayed capillary refill, depressed fontanelle, dry mucus membranes, decreased skin turgor, or decreased axillary moisture. Plotting the weight and height may reveal a trend toward the low percentiles for age; this finding suggests nutritional deficiency or malabsorption syndrome.

• Skin findings should be normal, but rash may be present with Behçet syndrome, erythema multiforme, hand-foot-and-mouth disease, herpes simplex infection, lichen planus, MAGIC syndrome, pemphigus, pemphigoid, Sweet syndrome, syphilis, systemic lupus erythematosus, varicella (chickenpox), or varicella zoster.

• The joints should be normal, but joints may be tender with effusion, erythema, or decreased range of motion in Reiter syndrome, systemic lupus erythematosus, or MAGIC syndrome.

• The eyes should be normal, but examination may reveal conjunctival lesions in patients with Behçet syndrome or cicatricial pemphigoid. Uveitis or iritis may be present with Reiter syndrome or Behçet syndrome.

• Cervical adenopathy should be minimal. Tender or markedly enlarged lymph nodes suggest PFAPA syndrome.

Precipitating factors include trauma, salivary gland dysfunction, stress, depression, genetic predisposition, local infections, nutritional deficiencies, GI disorders, systemic disorders, food allergy or hypersensitivity, hormonal fluctuations, and chemical exposure.

• Trauma: Local injury, such as that caused by an accidental bite, dental injection, toothbrush bristle, or ingestion of sharp food, may precipitate aphthous ulcers in individuals who are susceptible. Traumatic piercing uncommonly occurs in keratinized mucosal epithelium, and recurrent aphthous ulcers (canker sores) are rare in keratinized mucosa.

• Stress: Psychological and physiologic stress and depression may increase the risk of aphthous ulcers.[19, 20, 10] Individuals with aphthous ulcers have had higher-than-average anxiety scores and cortisol levels. Antidepressant therapy may be effective in some patients.

• Genetic predisposition: A family history of recurrent aphthous ulcer (canker sore) is common, though familial penetrance has not been identified as a specific category. Recurrent aphthous ulcers (canker sores) may be associated with human leukocyte antigen (HLA) haplotypes B51 (also common in Behçet syndrome), Cn7, A2, B12, and Dr5. A study by Manthiram et al found a familial tie in some patients with periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. The study found that out of 80 patients, 23% had ≥1 family member with PFAPA.[21]

• Local infection: Several infectious agents have been identified in association with aphthous ulcer lesions, including human herpesvirus (HHV)-6,[22] HHV-8, varicella zoster virus, human papilloma virus (HPV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV)-1, HSV-2, Helicobacter species, and L-forms of streptococci.[23] However, authorities generally agree that aphthous ulcers and RAU do not represent acute infections and are not contagious.

• Nutritional deficiencies: Deficiencies of iron (in 20%);[3] folic acid; zinc; and vitamins B-1, B-2, B-6, B-12, C and D have all been implicated in recurrent aphthous ulcers (canker sores). Oxidative stress and diminished antioxidant activity (vitamin E and selenium) may also predispose individuals to recurrent aphthous ulcers (canker sores).[24, 16]

• GI disorders, such as regional enteropathy (Crohn disease), ulcerative colitis, and celiac disease (gluten-sensitive enteropathy), may result in aphthous ulcers. The ulcers may be the only presenting symptom or the only symptom that is evident for a number of years in patients with GI disorders; therefore, a high degree of suspicion should be maintained when patients present with recurrent aphthous ulcers (canker sores).

• Systemic disorders: Disorders such as cyclic neutropenia, Reiter syndrome, Behçet disease, or HIV infection may result in aphthous ulcers (canker sores).

• Food allergy and hypersensitivity: Flavoring agents, essential oils, benzoic acid, cinnamon, gluten, cow's milk,[14] coffee, chocolate, potatoes, cheese, figs, nuts, citrus fruits, and certain spices have been implicated in some individuals with recurrent aphthous ulcers (canker sores).

• Hormonal fluctuations: In some women, recurrent aphthous ulcers (canker sores) are associated with the menstrual cycle, with outbreaks most commonly occurring during ovulation or before menstruation. A diminished incidence of recurrent aphthous ulcers (canker sores) during pregnancy has been reported.

• Chemical exposures: High levels of nitrates in drinking water have been associated with aphthous ulcers.[25] The nitrates may induce cytochrome b5 reductase activity. Sodium lauryl sulfate (SLS), a detergent commonly used in toothpaste, may be a trigger of aphthous ulceration in some individuals.[26, 27] Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with aphthous ulcers.[28] Smoking and nicotine exposure do not increase, and may actually decrease, the risk of aphthous ulcers.

• Significant correlations have been shown between the severity of aphthous stomatitis and hygiene of the oral cavity.[29] Good hygiene reduces not only the number of outbreaks but also the severity.[30]

See the list below:

• The diagnosis of aphthous ulcers (canker sores) is usually based on the history and clinical presentation. No laboratory procedures are available for definitive diagnosis.

  • In patients with severe recurrent aphthous ulcers (RAUs), or canker sores, the clinical picture should guide laboratory testing. CBC count, a chemistry panel, and nutritional workup may be necessary.

  • Patients with suspected malabsorption or a nutritional deficiency should undergo immediate screening. Consider screening in patients presenting with a history of recurrent aphthous ulcers (canker sores) lasting 6 months or longer.

• CBC counts may be within the reference range in patients with recurrent aphthous ulcers (canker sores), although some have found anemia in 21%.[3] Findings of neutropenia suggest Sweet syndrome or cyclic neutropenia; findings of leukocytosis suggest periodic fever, aphthous pharyngitis, and adenopathy (PFAPA) syndrome.

• Serum iron levels may be low in 20% of those with recurrent aphthous ulcers (canker sores).[3]

• If a patient is dehydrated and catabolic, urinalysis may reveal an elevated specific gravity and ketone levels. In small children, serum chemistry testing may be performed to exclude hypoglycemia and metabolic acidosis (low serum bicarbonate levels and elevated anion gap [see the Anion Gap calculator]).

See the list below:

• No imaging studies are indicated.

See the list below:

• Histopathologic examination of biopsy specimens does not reveal unique findings and is rarely indicated, except to exclude other diagnoses, such as pemphigus, cicatricial pemphigoid, carcinoma, and Behçet disease.

• Persistent ulceration in a patient with human immunodeficiency virus (HIV) should be biopsied to exclude carcinoma.[31]

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.[32, 33] Topical preparations such as mouthwash, [34]  mucoadhesive paste,[35]  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.[36] 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% (available as an oral adhesive tablet in some countries) has been shown to diminish pain as well as hasten resolution of ulcers.[37, 38, 39, 40, 41] 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.[42]

• Metalloproteinase inhibitors include tetracycline, doxycycline and minocycline. These agents, such as doxycycline in a hydrogel or minocycline 0.2% oral rinse solution,[43] 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.[44, 45, 43] 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.[46]

• 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,[47] and significantly improves ulcer pain, without measurable difference in ulcer healing.[48, 49] Orabase Sooth-N-Seal is a cyanoacrylate product available over-the-counter.

• 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.[50] This agent works by disruption (desiccation, denaturation, and coagulation) of the microbial biofilm matrix.[51]

• Over-the-counter glycyrrhiza (licorice) bioadhesive hydrogel patch (CankerMelts GX patches) enhances ulcer healing in addition to reducing pain.[52, 53, 54]

• An oral bioadherent containing polyvinylpyrrolidone and sodium hyaluronate gel (Gelclair) is used primarily for relief of oral mucositis associated with cancer chemotherapy or irradiation and is also indicated for pain control in severe, refractory, recurrent aphthous ulcers (canker sores).[55] Available by prescription only, Gelclair is mixed with 15 mL of water, stirred, rinsed around the mouth, gargled, and expectorated. At least 30-60 minutes must elapse after use before eating.

Many natural therapies have been suggested in the treatment of aphthous ulcers. El-Haddad et al noted reductions in ulcer pain, size and erythema with topical honey in a Saudi cohort of 94 subjects with minor aphthous ulcers.[56]  Adhesive patches with 7% alum used three times daily significantly decreased aphthous ulcer size and pain, hastening recovery in subjects with recurrent aphthous ulcers.[57]  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.[58, 59] Similarly, adhesive films with extract of Propolis entrapped in niosomes may decrease pain and hasten healing.[60]   Regular use of a chitosan 0.5% mouthwash may decrease ulcer size and pain.[61]   Chronic use of Echinacea tablets may decrease the recurrence, pain and number of lesions.[62]   Ozone in air and ozonated oil have also been shown to be effective in relieving recurrent aphthous ulcer pain and size.[63, 64]  Additional studies are needed to confirm these promising results.

Immunomodulators, including colchicine,[65, 36] dapsone,[66] clofazimine,[67] cyclosporine, interferon, tumor necrosis factor antagonists (infliximab, etanercept, adalimumab, pentoxifylline),[66, 68] T-cell modulator modifiers (efalizumab, alefacept), antimetabolites (methotrexate), alkylating agents (cyclophosphamide) and thalidomide[69] are used in severe, refractory cases, such as in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)[70, 20] or Behçet syndrome.[71, 72] 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.

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.[73, 74, 75, 76, 77] 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 pain severity[78] ; 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.

See the list below:

• 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.

See the list below:

• Supplementation with vitamins (especially B12 and C),[79, 80, 81, 82] zinc, or iron may prevent recurrence in some individuals. Studies of lysine supplementation are preliminary and equivocal.[83]  A randomized, double-blind study on 42 patients reported data showing that vitamin B12 can be an effective analgesic treatment for aphthous ulcers.[84]

• 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.

Use of a mouthguard while sleeping may decrease the incidence of recurrent aphthous ulcers (canker sores).[85]  

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.

Class Summary

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.

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.

Class Summary

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.

Class Summary

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), dexamethasone (Decadron), halobetasol propionate 0.05% ointment (Ultravate), and fluocinonide 0.05% gel (Lidex).

A benzocaine preparation (Orabase B) 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 topical (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 paste 0.1%.

Class Summary

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.

Class Summary

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.

Class Summary

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.

Class Summary

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.

Class Summary

Controversial therapies include 5-aminosalicylic acid, levamisole, colchicine,[36] gamma-globulin, dapsone,[66] estrogen replacement, thalidomide, clofazimine,[67] MAOIs, topical penicillin,[86] topical quercetin,[87] lactic acid mouthwash, topical hyaluronic acid (0.2%), bee propolis,[88] Alchemilla vulgaris[19] (Lady's Mantle) extract in glycerine (Aphtarine), pentoxifylline,[89] botulinum toxin A injection,[90] silver nitrate sticks, tincture of benzoin, and tetracycline. A small study suggested topical therapy with 5-aminosalicylic acid diminished symptoms and hastened resolution in recurrent aphthous ulcers (canker sores).[91] Of these, only silver nitrate sticks, tincture of benzoin 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.[78]

Similarly, tincture of benzoin applied after use of local anesthesia has been used to coat the surface of the ulcer. Few studies have addressed this method,[58] and although it may diminish pain, it may have little effect of ulcer resolution.

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.[45, 43] 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.

Class Summary

Mucoadhesive action reduces pain by adhering to the mucosal surface of the mouth.

Bioadherent oral (Gelclair)

This agent adheres to the mucosal surface of mouth and forms a protective coating that shields exposed and overstimulated nerve endings. Ingredients include water, maltodextrin, propylene glycol, polyvinylpyrrolidone (PVP), sodium hyaluronate, potassium sorbate, sodium benzoate, hydroxy ethylcellulose, polyethylene glycol (PEG)–40, hydrogenated castor oil, disodium edetate, benzalkonium chloride, flavoring, saccharin sodium, and glycyrrhetinic acid.

See the list below:

• Dietary supplementation with vitamins, zinc,[92] or iron may prevent recurrence of aphthous ulcers (canker sores) in some individuals. Studies of lysine supplementation are preliminary and equivocal.[83]

• Vitamin B12 supplementation may prevent ulcer recurrence even when B12 values are normal.[79, 80, 81]

• A gluten-free diet is unlikely to improve recurrent aphthous ulcers (RAUs), or canker sores,[93] 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.

• Susceptible patients may benefit from avoiding toothpaste or mouthwash products containing sodium lauryl sulfate (SLS).[26, 27]

• Use of a low-intensity ultrasound toothbrush may decrease recurrent aphthous ulcers (canker sores) activity.[94]

• Regular use of a mouthguard while sleeping may also decrease recurrent aphthous ulcers (canker sores).[85]

• Use of mouthwash or toothpaste with triclosan[95] or amyloglucosidase and glucose oxidase (Zendium) may decrease recurrent aphthous ulcers (canker sores).[96]

• Stress reduction may be useful, although evidence for this intervention is lacking.

• Although numerous reasons abound for convincing a pediatric patient to quit smoking or chewing tobacco, cessation does not have a beneficial effect on recurrent aphthous ulcers (canker sores), which nicotine appears to prevent.

See the list below:

• Secondary bacterial infection is rare.

• Patients with major recurrent aphthous ulcers (canker sores) can have clinically significant oral scarring.

• Painful lesions can cause interruption in eating and drinking, leading to dehydration and perhaps nutritional deficiencies.

• Patients with acquired immunodeficiency syndrome (AIDS) may have ulcerations that are resistant to topical steroid therapy. However, systemic steroids must be administered only with caution because of the possibility of adverse effects, especially the development of opportunistic infections.

See the list below:

• Herpetiform and minor recurrent aphthous ulcers (canker sores) have a self-limited course and tend to have few or no sequelae.

• Major recurrent aphthous ulcers (canker sores) can cause scarring, dehydration, and malnutrition; however, if recognized early and treated effectively, major recurrent aphthous ulcers (canker sores) can be well controlled, with minimal sequelae.

See the list below:

• General therapeutic measures for active ulcers include good oral hygiene, nonirritating gargles, and increased fluid intake.

• Cool bland beverages, such as milkshakes, are well tolerated. Patients should be advised to avoid salty or spicy foods.

• Although efficacy for recurrent aphthous ulcers (canker sores) is unproven, stress control may benefit some patients.

• For patient education resources, see the Teeth and Mouth Center, as well as Canker Sores.