What causes frequent canker sores?

Common Causes of Frequent Canker Sores

Frequent canker sores (recurrent aphthous stomatitis) result from a multifactorial process involving immune dysregulation, nutritional deficiencies (particularly vitamin B12 and folate), mechanical trauma, stress, hormonal factors, food sensitivities, and underlying systemic diseases—though the exact cause remains unknown in many cases. 1

Primary Etiologic Factors

Nutritional Deficiencies

• Vitamin B12 and folate deficiencies are significantly associated with recurrent canker sores, with affected patients demonstrating measurably lower dietary intake of these nutrients compared to controls 2
• Iron deficiency can contribute to oral ulceration and should be evaluated 3
• Hematinic deficiencies represent "correctable causes" that, when treated appropriately, can result in remission or substantial reduction in disease activity 4

Immune System Disturbances

• Genetically mediated disturbances of innate and acquired immunity play a central role in disease development 5
• The immune response is modified by various factors including food allergies, hormonal changes, and stress 5
• Increased viscosity of oral submucosal extracellular matrix may trigger inflammatory responses at sites of minor trauma 6

Mechanical Trauma

• Sharp food edges, dental appliances, or accidental biting create ulcers that correspond in location and shape to the inciting factor 7
• Trauma sites are particularly vulnerable in individuals predisposed to canker sores 1, 6

Associated Systemic Conditions to Exclude

Gastrointestinal Disorders

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) commonly causes recurrent oral ulceration and requires specific investigation 3, 7, 5
• Celiac disease (gluten sensitivity) can manifest with oral ulcers, and gluten has been identified as a trigger agent in susceptible individuals 5, 6

Hematologic Disorders

• Anemia and leukemia can present with oral ulcers, requiring full blood count and potentially bone marrow biopsy 3
• Neutropenia may cause widespread necrotic ulcers with yellowish-white pseudomembrane 3
• Cyclic neutropenia should be considered in patients with periodic recurrences 4

Autoimmune and Rheumatologic Conditions

• Behçet's disease manifests as recurrent bipolar aphthosis (oral and genital ulcers) and significantly impacts quality of life 7, 4
• Bullous diseases (pemphigus, pemphigoid) require evaluation for serum-specific antibodies 3

Infectious Causes

• HIV infection can manifest with oral ulcers and should be tested for in persistent cases 3, 7
• Syphilis can present with oral ulceration, necessitating serology examination 3, 7
• Deep fungal infections occur particularly in immunosuppressed or hyperglycemic patients 3, 7

Modifying Factors

Hormonal Influences

• Sex hormones significantly influence fibroblast activity and concentrate in the oral mucosa 6
• Lesions typically begin in the second decade and peak in the third decade, correlating with hormonal changes 6
• Hormonal state is an important element in the multifactorial process leading to lesion development 4

Lifestyle and Environmental Factors

• Stress is a recognized trigger for recurrent episodes 5, 4
• Smoking status affects disease presentation, with smokers reporting fewer outbreaks 1
• Food hypersensitivity can trigger lesions in individual cases 5, 4

Medication-Related Causes

• NSAIDs can cause oral ulceration as part of gastrointestinal complications 7
• Medication review is essential in evaluating recurrent ulcers 7

Essential Diagnostic Workup

When to Investigate Further

• Any ulcer persisting beyond 2 weeks or not responding to 1-2 weeks of treatment requires specialist referral and comprehensive testing 8, 3, 7
• Solitary chronic ulcers >2 weeks must be biopsied to exclude malignancy 7

Recommended Laboratory Tests

• Full blood count to evaluate for anemia, leukemia, or neutropenia 3, 7
• Fasting blood glucose level to assess for hyperglycemia 3, 7
• HIV antibody testing in persistent cases 3, 7
• Syphilis serology examination 3, 7
• Nutritional markers including vitamin B12, folate, and iron levels 7, 2
• Coagulation studies before biopsy 8

When Biopsy is Indicated

• Ulcers lasting over 2 weeks despite appropriate treatment 8, 3
• Atypical features suggesting malignancy 7
• Multiple biopsies may be necessary if ulcers involve different sites with varying characteristics 3

Critical Pitfalls to Avoid

• Relying solely on topical treatments without establishing a definitive diagnosis for persistent ulcers delays identification of malignancy or systemic disease 3, 7
• Inadequate biopsy (small or superficial) may miss important diagnostic features 3
• Overlooking systemic causes leads to delayed diagnosis and inappropriate management 3
• Failing to test for nutritional deficiencies misses easily correctable causes 4, 2