Recurrent Aphthous Ulcer (Recurrent Aphthous Stomatitis - RAS)

Definition and Epidemiology

• Most common lesion of oral mucosa; affects 10-40% of the population
• Greater prevalence among professionals, higher socioeconomic groups, and non-smokers (tobacco use appears protective)
• Familial clustering noted (HLA B51 association)
• Onset typically in 2nd-3rd decade; patients may experience recurrences several times yearly for decades

Etiology and Pathogenesis

• Immune-mediated: T-cell and antibody-mediated keratinocyte lysis; TNF-α and other cytokines/chemokines are upregulated
• Early lesion: lymphocytic infiltrate at the future ulcer site (preulcerative phase)
• The specific triggering antigen remains unidentified
• Histology: lymphocytic infiltrate with occasional plasma cells and eosinophils (delayed hypersensitivity pattern); no pathognomonic features

Trigger Factors

Clinical Types

1. Minor Aphthous Ulcers (85% of all cases)

• Size: up to 10 mm
• Location: nonkeratinized movable mucosa (labial, buccal, ventral/lateral tongue, floor of mouth, soft palate, tonsillar pillars) - anterior oral cavity predominantly
• Duration: 7-10 days
• Healing: without scarring
• Absence of vesicular phase (key distinction from herpes)

2. Major Aphthous Ulcers (~10% of cases)

• Size: >1 cm
• Location: posterior oral cavity, oropharynx
• Deeply cratered, sharply marginated, painful
• Duration: up to 6 weeks (longer in immunocompromised)
• Heals with scarring
• May cause odynophagia

3. Herpetiform Aphthous Ulcers (least common)

• Multiple pinhead-sized to 2-mm shallow craterform ulcers
• Widespread distribution over movable mucosa
• No vesicular phase (unlike herpes simplex)
• Pain disproportionately greater than lesion size
• Adult onset

Differential Diagnosis

Key point from Andrews' Dermatology: "History, physical examination, complete blood count, and long-term follow-up documenting the recurrent course, in the absence of other symptoms, will secure the diagnosis."

Workup for RAU Without Associated Symptoms

• CBC (rule out cyclic neutropenia, anemia)
• Serum ferritin, vitamin B12, folate (deficiency found in ~20% of patients; correction clears or improves aphthosis)
• Consider anti-tissue transglutaminase (anti-tTG) if celiac disease suspected
• Long-term follow-up to document recurrent course

Treatment

Symptomatic / Pain Relief

• Diphenhydramine (Benadryl) + Maalox mixture (1:1) - hold in mouth 5 min before meals
• Lidocaine 2% viscous solution (1 tsp held for several minutes)
• Dyclonine hydrochloride 0.5% topical
• OTC topical anesthetics/protectants

Topical Agents (Shorten Duration + Aid Healing)

• Topical corticosteroids (mainstay): fluocinonide gel or fluocinolone in Orabase 3-4x/day; clobetasol ointment
• Chlorhexidine mouthwash 0.12-0.2% twice daily (reduces secondary bacterial colonization)
• Amlexanox 5% oral paste (Aphthasol) - promotes healing and relieves pain
• Tetracycline suspension 250 mg/5 mL, hold 2 min then swallow, 4x/day for 1 week
• Sucralfate suspension (alone or with topical steroid)

Systemic Agents (Severe or Continuous Outbreaks)

• Short course oral corticosteroids (3-4 days) - for severe/indolent lesions
• Intralesional steroid injection - for major aphthae
• Colchicine 0.6 mg/day, increasing to 1.2-1.8 mg/day - for prevention
• Dapsone (if colchicine fails/not tolerated) - start 25 mg, titrate up to 100-150 mg/day
• Thalidomide 100-300 mg/day - highly effective but reserved for severe refractory cases (risk: teratogenicity, peripheral neuropathy); lenalidomide is an alternative
• Nutritional supplementation: correct B12, folate, or iron if deficient - often clears condition

Trigger Avoidance

Key Points for RAU Without Systemic Symptoms

1. True idiopathic RAS is a diagnosis of exclusion - rule out systemic associations first
2. NSAIDs, beta-blockers, and K-channel blockers can mimic RAU - withdrawal resolves lesions
3. Smoking cessation may worsen RAU (tobacco appears to be protective)
4. If lesions number 3 or more and involve both oral AND genital mucosa, the term complex aphthosis applies and Behçet disease workup is warranted
5. PFAPA syndrome should be considered in children with striking 4-week periodicity
6. No permanent cure exists; treatment is aimed at reducing frequency, duration, and pain