Summary
Aphthous stomatitis (canker sores) are painful oral ulcers that typically affect nonkeratinized mucosa. They are frequently recurrent and may be primary (i.e., idiopathic recurrent aphthous stomatitis) or secondary to an underlying systemic condition (e.g., Behcet disease, Crohn disease, vitamin deficiencies). Idiopathic recurrent aphthous stomatitis is a clinical diagnosis. Diagnostic testing is usually only required for patients with features of secondary aphthous ulcers to identify the underlying condition or to rule out an alternative diagnosis. Idiopathic recurrent aphthous stomatitis is typically self-limited and usually heals without treatment within 2 weeks. If required, topical corticosteroids and adjunctive pain control (e.g., topical anesthetics, barrier agents, oral analgesics) may be used to alleviate symptoms. Systemic corticosteroids may be required for severe disease, and patients with refractory disease may need specialist-directed therapies. The frequency of recurrence may be reduced by trigger avoidance and optimizing oral hygiene. Treatment of the underlying cause may be curative for patients with secondary aphthous ulcers.
Epidemiology
- Prevalence: 20–50% of the general population [1][2]
- Peak onset: 10–20 years [1][2]
- Frequency of recurrence decreases with age. [1]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
Idiopathic recurrent aphthous stomatitis [2][3]
- Likely multifactorial, with a genetic component
- Often precipitated by triggers, e.g.:
- Minor oral trauma
- Emotional stress, depression, and/or anxiety
- Hormonal fluctuations (e.g., menstruation)
- Toothpaste containing sodium lauryl sulfate
Smoking cessation can trigger idiopathic recurrent aphthous stomatitis, as heavy smoking may play a protective role due to keratization of the oral mucosa. [3]
Secondary aphthous stomatitis
-
Autoimmune and autoinflammatory disorders, e.g.: [2]
- Behcet disease
- Inflammatory bowel disease (e.g., Crohn disease)
- Celiac disease
- Systemic lupus erythematosus
- Fever syndromes (e.g., PFAPA syndrome, cyclic neutropenia)
- Nutritional deficiencies, e.g.:
- Infections, e.g., HIV infection [2]
-
Iatrogenic causes, e.g.: [3]
- Medications (e.g., methotrexate; , NSAIDs)
- Radiation therapy
Clinical features
General features [2]
- Painful round or oval ulcers
- Frequently recurrent
- Solitary or multiple (often clustered in groups) [3]
- Characterized by a gray-white pseudomembrane with a surrounding erythematous halo
- Typically affects soft nonkeratinized surfaces of the oral mucosa
- Keratinized mucosal surfaces overlying bony surfaces are usually spared.
- See "Subtypes and variants" for additional clinical features.
Systemic symptoms are absent in idiopathic aphthous stomatitis, but may occur with secondary aphthous ulcers. [2]
Features suggestive of secondary aphthous ulcers [2][3]
- Age > 40 years with new-onset oral ulcers [2]
- Constitutional symptoms
- Gastrointestinal symptoms
- Linear ulcers and/or cobblestoning of the oral mucosa
- Ocular involvement
- Genital ulcers
- Recurrent infections, suggesting immunosuppression
- Cutaneous manifestations of nutritional deficiencies and/or risk factors for nutritional deficiencies
- Atypical or severe oral ulcers [3]
Subtypes and variants
Idiopathic recurrent aphthous stomatitis is divided into minor, major, and herpetiform subtypes based on lesion characteristics. [2][3]
Minor aphthous ulcers [2][3]
- Most common subtype (∼ 75–85% of cases)
- ≤ 5 small (< 10 mm) ulcers
- Occur on the mucosa of the lips, cheeks, and sides and underside of the tongue
- Heal within 2 weeks without scarring
Major aphthous ulcers [2][3]
- Most severe subtype, occurring in ∼ 10–15% of cases
- ≤ 10 large (> 10 mm) ulcers
- Occur at the same sites as minor aphthous ulcers; may also involve the soft palate, pharynx, and keratinized mucosa
- May be associated with HIV infection [1]
- Prolonged healing (often more than 4–6 weeks), commonly with scarring
Herpetiform aphthous ulcers [2][3]
- Affects ♀ > ♂
- Least common subtype (< 10% of cases)
- 10–100 small (2–3 mm), deep ulcers that often coalesce with irregular borders
- Occur at the same sites as minor aphthous ulcers; may also affect the gingiva
- Heal within 4 weeks, typically without scarring
Diagnosis
General principles [2][3]
- Idiopathic recurrent aphthous stomatitis is a clinical diagnosis based on history and physical examination.
- Indications for diagnostic studies include:
- Features suggestive of secondary aphthous ulcers
- Features of differential diagnoses of aphthous ulcers
- Inadequate response to treatment, persistent lesions, and/or impaired quality of life
Diagnostic studies [2][3]
- CBC and inflammatory markers: to evaluate for infection or fever syndromes (e.g., PFAPA syndrome)
- Vitamin levels (e.g., vitamin D, zinc, folate, B vitamins, iron) and CBC: for suspected nutritional deficiency
- HSV PCR swab: for suspected HSV lesions (e.g., vesicles, gingival involvement)
- HIV testing: for patients with HIV risk factors [1]
- Diagnostics for celiac disease and/or diagnostics for inflammatory bowel disease: for gastrointestinal symptoms
- Diagnostics for Behcet disease: if clinical features of Behcet disease are present
- Biopsy of oral lesion: for atypical or persistent lesions [2]
Differential diagnoses
- Infection, e.g.:
- Trauma (e.g., due to Bednar aphthae, burns, abrasions)
- Cancer of the oral mucosa
- Dermatologic disorders, e.g.:
- See also “Differential diagnoses of oropharyngeal pain.”
The differential diagnoses listed here are not exhaustive.
Treatment
Idiopathic recurrent aphthous stomatitis is typically self-limited. [2]
Approach [1][3]
- Recommend lifestyle modifications.
- Manage underlying conditions (e.g., nutritional deficiencies, Crohn disease, HIV)
- Provide pharmacological symptom relief as needed.
- First line: topical therapy
- Adjunctive: systemic therapy for patients with severe disease or partial treatment response
- Refer to a specialist for additional diagnostic studies and/or advanced therapy for patients with:
- Refractory lesions (e.g., persistent ulcer for > 4 weeks) [3]
- Uncertain diagnosis [2]
- Suspected underlying condition requiring specialist management
Lifestyle modifications [1][3]
- Avoid or minimize triggers, e.g.:
- Optimize oral hygiene and encourage regular preventive dental visits.
Topical therapy [3]
If required, the following medications are suitable initial therapies for symptom relief:
- Topical corticosteroids: e.g., triamcinolone [3]
- Topical anesthetics: e.g., benzocaine (off-label) [3]
- Antiseptic mouthwash: e.g., chlorhexidine (off-label) [3]
- Antibiotic mouthwash (off-label): e.g., minocycline, doxycycline [3]
Consider applying chlorhexidine directly to ulcers (e.g., with a cotton-tipped swab) for individuals who cannot reliably spit (e.g., children aged < 8 years) to prevent accidental ingestion.
Long-term use of chlorhexidine can stain teeth. [1]
Systemic therapy
- Indicated in addition to topical therapy for patients with: [3]
- Partial treatment response
- Numerous ulcers
- Severe disease (e.g., major aphthous ulcers)
- Preferred: prednisone (off-label) [3]
- Alternative: montelukast (off-label) [3]