EENT · PANCE / PANRE

Recurrent Aphthous Stomatitis (Canker Sores)

Recurrent, painful, round, shallow ulcers on non-keratinized oral mucosa — clinical diagnosis; symptomatic care.

Also known as: aphthous ulcers, canker sores, recurrent aphthous stomatitis, RAS, aphthous stomatitis

Overview

A common, idiopathic, recurrent ulcerative disorder of non-keratinized oral mucosa, characterized by painful, round or oval ulcers with a yellowish fibrinous base, erythematous halo, and well-defined margins. Three classic clinical forms: minor, major, and herpetiform.

Epidemiology

Affects 10-25% of the population at some point. Most common cause of recurrent oral ulceration. Onset typically in childhood or adolescence, with decreased frequency after age 40. Female predominance. Tobacco use is paradoxically associated with reduced incidence (hyperkeratosis is protective).

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Risk factors

Family history (positive in 30-40%)
Hematinic deficiencies — iron, vitamin B12, folate
Stress, sleep deprivation
Mechanical trauma (cheek-biting, brushing, dental work)
Food sensitivities (gluten, dairy, nuts, citrus, chocolate)
Sodium lauryl sulfate in toothpaste (controversial)
Hormonal cycles (premenstrual flares)
Smoking cessation may precipitate flares
Systemic conditions: Behcet disease, celiac disease, inflammatory bowel disease, HIV, cyclic neutropenia, PFAPA syndrome (children)

Pathophysiology

Not infectious. Considered a T-cell-mediated mucosal immune response, with focal cytotoxicity to epithelium triggered by various antigens or local trauma. There is increased TNF-alpha and other pro-inflammatory cytokine activity. Genetic susceptibility (HLA associations) and micronutrient deficiencies modulate frequency and severity.

Clinical presentation

Symptoms

Burning or pricking sensation 1-2 days before ulcer appears (prodrome)
Painful, sharply defined ulcer of non-keratinized mucosa (buccal mucosa, lateral/ventral tongue, floor of mouth, soft palate, labial mucosa)
Pain disproportionate to lesion size; worse with food, especially acidic or spicy
Episodes recur every few weeks to months; lesions heal in 7-14 days (minor) or up to 6 weeks (major)

Signs / physical exam

Minor (80%): single or few ulcers, less than 1 cm, shallow, yellow-gray fibrinous base, erythematous halo; heal without scarring
Major (10-15%, Sutton disease): 1-3 cm, deeper, lasts 2-6 weeks, often heals with scarring
Herpetiform (5-10%): clusters of small (1-3 mm) ulcers that coalesce; despite name, NOT viral
Lesions on NON-keratinized mucosa (key distinguishing feature from HSV which prefers keratinized mucosa)
No systemic signs in isolated RAS

Classic findings

Recurrent, painful, round, well-defined ulcer with yellow base and red halo on non-keratinized oral mucosa, sparing the hard palate and gingiva.

Differential diagnosis

Herpes simplex stomatitis — Primary HSV-1 in children — fever, gingivostomatitis, vesicles on keratinized mucosa (hard palate, gingiva, lips); recurrent HSV on lip vermilion; Tzanck or PCR
Behcet disease — Recurrent oral ulcers PLUS genital ulcers, uveitis, skin lesions, pathergy; multisystem; rheumatology referral
Erythema multiforme / Stevens-Johnson syndrome — Targetoid skin lesions plus mucosal involvement, often medication- or HSV-triggered
Pemphigus vulgaris / mucous membrane pemphigoid — Chronic painful erosions of oral and other mucosae, positive Nikolsky sign, biopsy with immunofluorescence
Oral lichen planus (erosive form) — Bilateral chronic erosive lesions with Wickham striae; biopsy
Crohn disease, ulcerative colitis — Cobblestoning, deep linear ulcers in IBD; GI symptoms
Squamous cell carcinoma — Persistent (>2-3 weeks) indurated ulcer in older or high-risk patient; biopsy
Coxsackievirus (hand-foot-mouth, herpangina) — Children; ulcers on soft palate/posterior oropharynx (herpangina) or with hand/foot lesions; viral prodrome

Diagnostic workup

Diagnostic criteria

Clinical: recurrent episodes of round/oval, well-circumscribed ulcers on non-keratinized oral mucosa with no other identified cause.

Labs

Diagnosis is clinical; no testing required for typical, mild recurrent disease
If atypical, severe, or first onset in an adult: CBC (look for cyclic neutropenia), ferritin, vitamin B12, folate, vitamin D
Celiac panel (tissue transglutaminase IgA, total IgA) if GI symptoms or refractory disease
HIV testing if risk factors or severe/persistent ulceration
Inflammatory markers (ESR, CRP) and additional workup for Behcet or IBD when systemic features present

Imaging

Not required
Biopsy reserved for atypical, persistent (>3 weeks), indurated, or non-healing ulcers to exclude malignancy or other specific entities

Diagnostic algorithm

Feature	Minor aphthae	Major aphthae	Herpetiform aphthae	Primary HSV
Frequency	80%	10-15%	5-10%	Separate entity
Size	Less than 1 cm	1-3 cm	1-3 mm (clustered)	1-3 mm vesicles
Site	Non-keratinized mucosa	Non-keratinized; lips, soft palate	Non-keratinized; anywhere	Keratinized (gingiva, hard palate, lip)
Duration	7-14 days	2-6 weeks	1-2 weeks	10-14 days
Scarring	No	Often	Rare	No
Systemic prodrome	No	Sometimes	Sometimes	Fever, malaise (primary)

Differentiating recurrent aphthous stomatitis subtypes from HSV stomatitis.

Treatment

First-line

Topical anesthetics for pain — viscous lidocaine 2%, benzocaine 20% gel, diphenhydramine + Maalox + viscous lidocaine 'magic mouthwash'
Topical corticosteroids — triamcinolone acetonide 0.1% in Orabase, fluocinonide 0.05% gel, clobetasol 0.05% gel; apply 2-4 times daily directly to ulcer
Chlorhexidine 0.12% mouthwash for ulcer cleansing and to reduce secondary infection
Avoidance of identified triggers — acidic/spicy foods, SLS-containing toothpastes, mucosal trauma
Adequate hydration and gentle oral hygiene

Second-line / adjunct

Topical immunomodulators — tacrolimus 0.1% ointment for steroid-refractory cases
Intralesional triamcinolone 10-40 mg/mL for solitary major aphthae
Short courses of systemic corticosteroids (prednisone 0.5-1 mg/kg) for severe or disabling outbreaks
Replace any documented hematinic deficiency
Colchicine 0.6 mg twice daily, pentoxifylline 400 mg three times daily, or dapsone for frequent recurrent disease (specialist care)
Thalidomide for severe HIV-associated or Behcet-related aphthae (specialist, REMS program)
Apremilast (FDA-approved for oral ulcers of Behcet disease)

Complications

Significant pain leading to impaired oral intake, dehydration, and weight loss in major aphthae
Scarring with major form
Secondary bacterial infection (rare)
Missed underlying systemic disease (Behcet, celiac, IBD, HIV) if workup not pursued in atypical cases

PANCE pearls

Aphthous ulcers occur on NON-keratinized mucosa; HSV recurrences appear on keratinized mucosa (hard palate, lip vermilion).
Smoking is paradoxically PROTECTIVE — outbreaks may flare after smoking cessation.
Any non-healing ulcer beyond 2-3 weeks needs a biopsy to exclude malignancy.
Investigate for systemic disease (Behcet, IBD, celiac, HIV) when ulcers are severe, recurrent, or accompanied by extraoral symptoms.
Topical clobetasol 0.05% gel applied at the prodrome can abort an outbreak.

References

AAOM — American Academy of Oral Medicine clinical practice statements on recurrent aphthous stomatitis
AAFP — American Academy of Family Physicians review: Diagnosis and treatment of recurrent aphthous stomatitis
Cochrane — Cochrane Review: Systemic interventions for recurrent aphthous stomatitis

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