Recurrent Aphthous Stomatitis Clinical Review

Introduction

Recurrent aphthous stomatitis (RAS), commonly known as canker sores, is among the most prevalent oral mucosal conditions, affecting up to 25% of the general population. It is characterized by recurrent, painful ulcerations of the nonkeratinized oral mucosa that significantly impair nutrition, speech, and quality of life. Despite extensive research, the precise etiology remains multifactorial and incompletely understood. This review synthesizes current evidence on epidemiology, pathogenesis, clinical evaluation, differential diagnosis, and management strategies for optimal patient care.

Epidemiology and Risk Factors

• Prevalence estimates range from 5% to 25% globally, with peak incidence in adolescents and young adults (10–30 years).
• Female predominance (female-to-male ratio ~2:1) suggests hormonal influences.
• Family history confers a 30–90% increased risk, implicating genetic predisposition (HLA-A2, B5, B12, DR4 associations).
• Common triggers and risk factors:
• Nutritional Deficiencies: Iron, folate, vitamin B12, and zinc deficiencies.
• Gastrointestinal Disease: Inflammatory bowel disease (ulcerative colitis, Crohn’s disease), celiac disease.
• Psychological Stress: Type A personality traits, anxiety, and sleep disturbances.
• Hormonal Fluctuations: Pre-menstrual onset and improvement during pregnancy.
• Trauma and Local Irritation: Minor mucosal injury from dental appliances or biting.

Pathogenesis and Etiologic Theories

RAS likely results from an interplay between mucosal immune dysregulation and environmental or systemic factors:
1. Immune-Mediated Injury: T-cell–mediated cytotoxicity against epithelial cells; elevated TNF-α and interleukin-2 in ulcerative lesions.
2. Microbial Factors:
– Viral: DNA fragments of HHV-6, HHV-7, and HPV detected in some patients, though causality remains unproven.
– Bacterial: L-form hemolytic streptococci and Helicobacter pylori have been isolated; eradication may improve symptoms.
3. Gastrointestinal Dysfunction: Malabsorption syndromes and GI inflammation contribute to nutrient deficiencies and systemic inflammation.
4. Endocrine Influences: Sex hormone receptor expression in oral mucosa; estrogen therapy has shown benefit in select premenstrual RAS.
5. Genetic Susceptibility: HLA-linked predisposition and polymorphisms in cytokine genes (IL-1β, TNF-α) modulate ulcer risk.

Clinical Presentation and Classification

• Minor RAS: 80% of cases; small (<1 cm), shallow ulcers on movable mucosa; heal in 7–14 days without scarring.
• Major RAS (Sutton’s Disease): Larger (>1 cm), deeper ulcers that persist >6 weeks; heal with scarring; often more painful.
• Herpetiform RAS: Multiple (10–100), small (1–3 mm) clusters of ulcers that coalesce; mimic herpetic lesions but lack viral etiology.
• Prodrome: Burning or tingling sensation up to 48 hours before lesion appearance; ulcers are round or oval with erythematous halo and yellow–gray fibrinous base.

Diagnostic Evaluation

• Clinical Diagnosis: Based on history of recurrent ulcers, characteristic appearance, and absence of systemic “red flags.”
• Targeted Investigations:
• Complete blood count (CBC) with differential, ferritin, folate, and vitamin B12 levels.
• Celiac serologies (anti–tissue transglutaminase IgA) and inflammatory markers (CRP, ESR) if GI symptoms are present.
• HIV testing in high-risk populations.
• Histopathology: Reserved for atypical or refractory cases; shows superficial ulceration, mixed inflammatory infiltrate, and basilar lymphocytic aggregates.

Differential Diagnosis

• Herpes simplex virus infection (clustered vesicles, positive viral PCR).
• Aphthous-like ulcers in Behçet’s disease (oral plus genital and ocular involvement).
• Erythema multiforme (target lesions on skin, mucosal involvement).
• Neutropenic ulcers, pemphigus vulgaris, lichen planus, and squamous cell carcinoma.

Management Strategies

Acute Ulcer Relief

• Topical Agents:
• Corticosteroids: Triamcinolone acetonide paste; dexamethasone mouthwash.
• Analgesics/Anesthetics: Benzocaine gels; viscous lidocaine for severe pain.
• Antimicrobials: Chlorhexidine gluconate rinse to reduce secondary infection.
• Protective Barriers: Hyaluronic acid gels and bioadhesive pastes to promote healing and reduce irritation.

Prevention and Prophylaxis

• Nutritional Supplementation: Iron, folate, vitamin B12, and zinc in deficient patients.
• Topical Immunomodulators: Low-dose topical tacrolimus or pimecrolimus for refractory lesions.
• Systemic Therapy (Severe or Major RAS):
• Prednisone 20–40 mg/d tapered over 1–2 weeks for extensive ulcers.
• Thalidomide or colchicine in recalcitrant cases under specialist supervision.
• Psychological Interventions: Stress reduction techniques, cognitive behavioral therapy for patients with significant psychosocial triggers.

Patient Education and Follow-Up

• Encourage maintenance of an oral ulcer diary to identify and avoid personal triggers.
• Advise on gentle oral hygiene practices and use of soft-bristled toothbrushes.
• Schedule follow-up visits every 3–6 months for chronic or severe RAS; monitor for evolution of disease pattern or emergence of systemic signs.

Prognosis

• Minor RAS often remits by mid-adulthood; major and herpetiform forms may persist or worsen over decades.
• Long-term complications are rare but include scarring and dysgeusia in severe cases.

Conclusion

Recurrent aphthous stomatitis is a multifactorial condition requiring a tailored approach that addresses underlying deficiencies, immune dysregulation, and psychosocial factors. Clinicians should employ a stepwise management plan—from topical therapies for episodic relief to systemic agents for severe disease—while emphasizing patient education and regular monitoring to optimize outcomes.