What are the causes and management options for recurrent aphthous ulcers (canker sores)?

Causes of Recurrent Canker Sores (Recurrent Aphthous Ulcers)

Recurrent aphthous stomatitis (canker sores) is a chronic inflammatory condition affecting over 50% of the population, with an unclear pathogenesis but strong associations with genetic predisposition, immune dysregulation, and various triggering factors including trauma, nutritional deficiencies, hormonal influences, and systemic diseases. 1, 2

Primary Etiologic and Contributing Factors

Genetic and Immunologic Basis

• Strong genetic predisposition exists, with associations to specific interleukin genotypes and frequent family history 2
• The condition involves increased viscosity of oral submucosal extracellular matrix (ECM), which heightens inflammatory response at sites of minor trauma 3
• Immune dysregulation plays a central role, as evidenced by complete suppression with systemic corticosteroids 3

Local Traumatic Factors

• Minor oral trauma is a primary trigger, with lesions localizing clinically and experimentally at sites of mechanical injury 3, 2
• Trauma-induced edema in areas of increased ECM viscosity triggers early cellular inflammation 3

Hormonal Influences

• Sex hormones significantly influence fibroblast activity and concentrate in the buccal mucosa, particularly during early exposure phases 3
• Lesions typically begin in the second decade and peak in the third decade, correlating with hormonal changes 3

Dietary and Food-Related Triggers

• Various foods have been incriminated as trigger agents in individual cases, though specific triggers vary by patient 3
• Gluten sensitivity can cause aphthous ulcers in patients with celiac disease or gluten-sensitive enteropathy 3
• Soluble substances in food or lectins may penetrate the mucosa to influence underlying ECM 3

Nutritional Deficiencies

• Deficiencies in vitamins and minerals can predispose to recurrent ulceration, though specific deficiencies should be evaluated on a case-by-case basis 4

Systemic Disease Associations Requiring Evaluation

Critical pitfall: Failing to recognize that recurrent aphthous ulcers can be the presenting manifestation of serious systemic disease. 1

Autoimmune and Inflammatory Conditions

• Behçet's disease presents with aphthous-like oral ulcers associated with genital ulceration and eye disease (particularly posterior uveitis) 5, 2
• Inflammatory bowel disease (ulcerative colitis and Crohn's disease) occurs in 4.2-7.5% of IBD patients with erythema nodosum, and similar mucosal manifestations can include oral ulceration 5

Infectious Etiologies

• HIV infection can present with recurrent oral ulceration 1
• Other infectious processes may manifest with oral ulcers 1

Hematologic and Oncologic Conditions

• Hematologic malignancies and other oncologic conditions can present with recurrent oral ulceration 1
• These require prompt identification through complete history and physical examination 1

Clinical Evaluation Approach

Essential History Elements

• Age of onset (typically second decade), frequency of recurrence, and family history of similar lesions 3, 2
• Specific trauma history including dental work, accidental biting, or sharp food consumption 3
• Dietary patterns and identification of potential food triggers, including gluten-containing foods 3
• Systemic symptoms: fever, malaise, arthralgias, genital ulcers, eye symptoms, gastrointestinal symptoms, or night sweats 5, 1
• Medication history and immunosuppression status 1

Physical Examination Focus

• Ulcer characteristics: size (typically 1-5 cm), location (commonly anterior tibial areas for associated erythema nodosum; oral mucosa for aphthae), appearance (round or ovoid with circumscribed margins, erythematous haloes, yellow or grey floors) 5, 2
• Examination for systemic disease: genital ulcers, skin lesions, joint inflammation, lymphadenopathy 5, 1, 2
• Assessment for nutritional deficiency signs 4

When to Pursue Systemic Workup

• Presence of systemic symptoms (fever, weight loss, arthralgias, night sweats) 5, 1
• Associated genital ulceration or eye symptoms suggesting Behçet's disease 5, 2
• Gastrointestinal symptoms suggesting inflammatory bowel disease 5
• Atypical presentation requiring biopsy to exclude other diagnoses 2
• Severe, persistent, or unusually large ulcers 1

Management Strategy

First-Line Symptomatic Treatment

• Topical corticosteroids reduce severity but do not prevent recurrence 2
• NSAIDs for pain management during the 7-14 day healing period 5, 1
• Caustic agents (silver nitrate, phenol) can stop lesion growth and pain by breaking ECM viscosity 3

Treatment of Underlying Conditions

• Address identified systemic disease (treat streptococcal infection if present, manage inflammatory bowel disease) 5
• Colchicine is preferred for Behçet's disease-associated ulcers 5
• Systemic corticosteroids reserved for severe cases with significant inflammation or IBD-associated ulceration, used cautiously after excluding infectious causes 5

Refractory or Frequent Recurrence

• Azathioprine for frequent relapses 5
• TNF-alpha inhibitors (infliximab or adalimumab) for resistant cases associated with inflammatory bowel disease 5
• Hydroxychloroquine may be beneficial if associated with sarcoidosis 5

Patient-Specific Preventive Measures

• Identify and eliminate individual food triggers through systematic dietary modification 3, 4
• Gluten-free diet if celiac disease or gluten sensitivity is identified 3
• Avoid oral trauma from sharp foods, aggressive tooth brushing, or ill-fitting dental appliances 3
• Monitor for disease activity in associated systemic conditions 5

Key clinical pitfall: Diagnosis is primarily clinical; biopsy is not usually necessary except in atypical cases to exclude other causes of recurrent ulceration. 2