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Ulcer, Aphthous
Jay A. Brieler, MD
image BASICS
DESCRIPTION
  • Self-limited, painful ulcerations of the nonkeratinized oral mucosa, which are often recurrent
  • Synonyms: canker sores; aphthae; aphthous stomatitis
    • Comes from aphth meaning “ulcer” in Greek; first used by Hippocrates between 460 and 370 BC to categorize oral disease (1)
  • Categorization
    • Minor aphthous ulcers (2)
      • Usually <10 mm in diameter
      • Self-limited, healing within 4 to 14 days
      • Rarely affect the dorsum of the mouth
      • Nonscarring
    • Major aphthous ulcers (Sutton disease) (2)
      • Usually >10 mm in diameter
      • Can affect the dorsum of the mouth
      • May take weeks to months to heal
      • Generally more painful than minor aphthous ulcers
      • May cause scarring
    • Herpetiform ulcers (2)
      • Usually 2 to 3 mm in diameter, may coalesce to form larger ulcerations
      • Unrelated to viral-caused herpetic stomatitis
      • Occur in small clusters numbering 10s to 100s, lasting 1 to 4 weeks
      • Generally more painful than minor aphthous ulcers
      • May cause scarring
EPIDEMIOLOGY
  • Most frequent chronic disease of the oral cavity, affecting 5-25% of the population (3)
  • More common in patients between 10 and 40 years of age, women, Caucasians, nonsmokers, professional students, and those of higher socioeconomic status (3)
  • Less frequent with advancing age (4)
  • Minor aphthous ulcers
    • Most common: 70-85% of all aphthae
  • Major aphthous ulcers
    • 10-15% of all aphthae
  • Herpetiform
    • Least common: 10% of all aphthae
Prevalence
Lifetime prevalence of 5-60% (3)
ETIOLOGY AND PATHOPHYSIOLOGY
Likely multifactorial; association with stress-induced rise in salivary cortisol, multiple HLA antigens, cellmediated immunity; exact etiology unknown (4)
RISK FACTORS
  • Genetic factors: Offspring of those with recurrent aphthous ulcers have a 90% chance of developing recurrent aphthous stomatitis (RAS) (5)[C].
  • Local trauma: sharp teeth, dental treatments, or mucosal injury secondary to toothbrushing
  • Increased stress and anxiety
  • Nutritional deficiencies: iron, zinc, vitamin B complex, and folate
  • Homocysteinemia (6)[B]
  • Immunodeficiency
  • Recent cessation of tobacco use
  • Food sensitivity: to benzoic acid/cinnamaldehyde
  • Medications
    • NSAIDS
    • &bgr;-Blockers
    • Alendronate
    • Methotrexate
  • Neutropenia
  • Anemia
  • Endocrine alterations (i.e., menstrual cycle) (2)
  • Psychosocial stress
image DIAGNOSIS
Diagnosis is made by history and clinical presentation. Lab work is rarely helpful to diagnose aphthous ulcers (2)[A].
PHYSICAL EXAM
  • Round or ovoid ulcerations generally <10 mm in size. Covered with a grayish-white pseudomembrane surrounded by an erythematous halo (3)[A]
  • Ulcers are typically found in the buccal or lip mucosa, ventral tongue, soft palate, or oral vestibule. Rarely on the dorsum of the mouth/lips
  • Evaluate for signs of secondary infection: elevated temperature, increased surrounding edema, or pus drainage
DIFFERENTIAL DIAGNOSIS
  • Oral trauma
    • Biting
    • Dentures
  • Infection
    • Herpes virus (herpetic stomatitis): vesicular lesions on keratinized tissue (dorsal tongue, vermillion border). Generally not present on mucosa (5)[C]
    • HIV: Ulcerations have lengthened healing time and tend to be more painful (5)[C].
  • Mucocutaneous disease; especially if chronic or nonhealing
    • Lichen planus
    • Pemphigus
  • Malignancy: Investigate and closely monitor nonhealing lesions, especially those with ipsilateral cervical lymphadenopathy.
  • Important to evaluate for underlying systemic disease, causing aphthous-like ulcerations
    • Highest suspicion in adult patients with their initial episode or in individuals with additional lesions elsewhere in the body (3)[A],(4)[C]
    • Behçet syndrome: autoimmune systemic vasculitis usually involving mucous membranes
      • Genital and oral ulceration
      • Uveitis
    • Reiter syndrome: reactive arthritis, preceded by infection, usually of the genital tract (2)[A]
      • Uveitis
      • Urethritis
      • HLA-B27-associated arthritis
    • Sweet syndrome: acute neutrophilic dermatitis (5)[C]
      • Fever, sudden onset
      • Erythematous skin plaques/papules, well-demarcated
      • Leukocytosis
      • 50% of patients have an associated malignancy
      • Most often in middle-aged females
    • Inflammatory bowel disease (IBD): Crohn disease, ulcerative colitis
      • 10% of patients with Crohn disease experience recurrent oral ulcers (5)[C].
      • Bloody or persistent diarrhea
      • Weight loss
    • Cyclic neutropenia (5)[C]
      • Recurrent fevers associated with infections, occasionally occurring intraorally.
      • Begins in childhood
    • Systemic lupus erythematosus (SLE): autoimmune vascular collagen disease
      • Oral lesions have great variability, including recurrent ulceration.
    • Gluten-sensitive enteropathy (celiac disease)
      • Weight loss and signs of malabsorption
      • Bloating and diarrhea
DIAGNOSTIC TESTS & INTERPRETATION
May consider complete blood count, folic acid, ferritin, vitamin B12 to evaluate for systemic causes based on presentation (2)[A]
Follow-Up Tests & Special Considerations
  • HIV is associated with increased amount of ulcers and increased healing time.
  • Biopsy and viral cultures for nonhealing ulcers or atypical presentations
  • Rheumatologic serology if underlying systemic disease is suspected.
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image TREATMENT
GENERAL MEASURES
  • Management is symptomatic. Goal is to reduce inflammation and relieve pain.
  • Avoid potentially irritating food or drink:
    • Spicy
    • Acidic
    • Hot
    • Carbonated beverages.
    • Abrasive/hard foods (i.e., chips, nuts, etc.)
  • Behavior modification to reduce dental trauma with toothbrush or bruxism
MEDICATION
In general, the goals of treatment depend on the extent of ulceration and frequency of outbreaks.
First Line
  • Topical corticosteroids (to improve healing time and symptoms) (2)[A]
    • Adverse effects: may increase risk of oral candidiasis (more likely with higher potency formulations)
    • Preparations
      • Triamcinolone 0.1% dental paste
        • Apply sparingly to ulcers three times daily for up to 2 weeks or until ulcer resolution.
      • Fluocinonide 0.05% gel or ointment
        • Apply sparingly to ulcer four times daily for up to 2 weeks or until ulcer resolution.
      • Dexamethasone 5 mg/5 mL elixir
        • Rinse for 3 minutes and spit four times daily until ulcer resolution.
  • Topical anesthetics (to reduce symptoms only) (2)[A]
    • Adverse effects: may cause initial stinging
    • Preparations
      • Lidocaine 2% gel
        • Apply four times daily or prior to eating as needed for pain, for up to 2 weeks or until ulcer resolution.
  • Antimicrobial mouth rinses (improve healing time, decrease pain, and may prevent recurrence)
    • Preparations
      • Chlorhexidine aqueous mouthwash 0.12% or 0.2%
        • Use four times daily for up to several months.
        • May cause superficial tooth staining
  • Topical immunomodulators (improves healing time, reduces symptoms, and prevents recurrence when used in prodromic phase) (2)[A]
    • Adverse effects: may cause stinging sensation
    • Preparation
      • Amlexanox 5% oral paste
        • Apply to ulcers four times daily for up to 2 weeks or until ulcer resolution.
Second Line
  • Systemic corticosteroids—rescue therapy in acute, severe, recurrent outbreaks (2,3)[A]
    • Prednisone 25 mg/day, then tapered over 2 months (3)[A]
  • Colchicine, pentoxifylline, thalidomide, and dapsone have been used with variable success but should be used with caution due to side effects (2,3,4)[A].
ISSUES FOR REFERRAL
Otolaryngology or dental referral if lesions have not resolved as expected.
ADDITIONAL THERAPIES
Vitamin B12 supplementation has been shown to decrease burden of outbreaks and recurrence, independent of preexisting deficiency in one small study (7)[B]. Multivitamins have not been shown to be effective (8)[B].
SURGERY/OTHER PROCEDURES
Chemical cautery with silver nitrate (reduces ulcer pain but not healing time) (9)[B]
COMPLEMENTARY & ALTERNATIVE MEDICINE
Some small cohort studies show clinical improvement with minimal side effects of several herbal and alternative treatments (3)[A].
  • Glycyrrhiza (licorice) (10)[B]
  • Myrtus communis (myrtle) (11)[B]
  • Bee propolis (3)[A]
REFERENCES
1. Preeti L, Magesh K, Rajkumar K, et al. Recurrent aphthous stomatitis. J Oral Maxillofac Pathol. 2011;15(3):252-256.
2. Belenguer-Guallar I, Jiménez-Soriano Y, Claramunt-Lozano A. Treatment of recurrent aphthous stomatitis. A literature review. J Clin Exp Dent. 2014;6(2):e168-e174.
3. Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012;(9):CD005411.
4. Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am. 2014;58(2):281-297.
5. Chavan M, Jain H, Diwan N, et al. Recurrent aphthous stomatitis: a review. J Oral Pathol Med. 2012;41(8):577-583.
6. Sun A, Chen HM, Cheng SJ, et al. Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis. J Oral Pathol Med. 2015;44(4):300-305.
7. Carrozzo M. Vitamin B12 for the treatment of recurrent aphthous stomatitis. Evid Based Dent. 2009;10(4):114-115.
8. Lalla RV, Choquette LE, Feinn RS, et al. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012;143(4):370-376.
9. Soylu Özler G. Silver nitrate cauterization: a treatment option for aphthous stomatitis. J Craniomaxillofac Surg. 2014;42(5):e281-e283.
10. Martin MD, Sherman J, van der Ven P, et al. A controlled trial of a dissolving oral patch concerning glycyrrhiza (licorice) herbal extract for the treatment of aphthous ulcers. Gen Dent. 2008;56(2):206-210; quiz 211-212, 224.
11. Babaee N, Mansourian A, Momen-Heravi F, et al. The efficacy of a paste containing Myrtus communis (myrtle) in the management of recurrent aphthous stomatitis: a randomized controlled trial. Clin Oral Investig. 2010;14(1):65-70.
Additional Reading
&NA;
  • Liu C, Zhou Z, Liu G, et al. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med. 2012;125(3):292-301.
  • Pakfetrat A, Mansourian A, Momen-Heravi F, et al. Comparison of colchicine versus prednisolone in recurrent aphthous stomatitis: a doubleblind randomized clinical trial. Clin Invest Med. 2010;33(3):e189-e195.
Codes
&NA;
ICD10
K12.0 Recurrent oral aphthae
Clinical Pearls
&NA;
  • Aphthous ulcers are the most common chronic disease of the oral cavity.
  • Most cases are mild, self-limited episodes.
  • Appropriate treatment should be aimed at symptom control and promotion of healing.
  • If lesions are nonhealing, simultaneously occur elsewhere in the body, or when patients present with a sudden initial episode in adulthood, it is imperative to rule out secondary causes.