Aphthous stomatitis is a common inflammatory condition characterized by clinically characteristic ulcerations of the oral mucosa. The associated pain may be severe, leading the patient to experience difficulty with eating and speaking. Ulceration typically occurs in a periodic fashion, which has led to the frequent use of the term recurrent aphthous stomatitis (RAS). The lifetime incidence of this disease is estimated at 20%, with a slight female predominance. The peak age of onset occurs in the second decade, with a higher prevalence and disease severity seen in children of higher socioeconomic status. With age, the frequency of recurrences and overall disease severity tend to diminish. While the etiology remains largely unknown, it is thought to involve a complex interplay between genetic predisposition, environmental factors, and immune dysregulation. Although conflicting data exist and anecdotal claims are rarely substantiated with controlled studies, several factors have been reported to precipitate disease expression in some individuals (Table 4-1).

The classification of RAS includes an assessment of lesion morphology, severity, and systemic involvement. The three morphologic variants include minor, major, and herpetiform aphthae. The designation of simple aphthosis applies to cases with a limited frequency of recurrence (∽2 to 4 episodes per year) and no associated systemic findings. In contrast, complex aphthosis features genital involvement, continuous disease activity, and/or systemic symptoms. Systemic disease entities that may present with aphthous-like lesions include Behçet’s disease, reactive arthritis, gastrointestinal diseases (e.g., gluten-sensitivity enteropathy, inflammatory bowel disease), PFAPA syndrome, MAGIC syndrome, Sweet syndrome, and immunodepressed states [e.g., HIV (human immunodeficiency virus) infection, leukemia, and cyclic neutropenia] (Table 4-2). Of note, the oral ulcers of Behçet’s disease may precede systemic involvement for 7 to 8 years. Several medications have been implicated in producing aphthous-like lesions, including nonsteroidal anti-inflammatory drugs, activator of ATP-sensitive potassium (nicorandil), angiotensin-converting enzyme inhibitors, β-blockers, and alendronate.

All varieties of aphthae are painful and prone to recurrence. They may present as solitary or multiple lesions. In one individual, a combination of aphthae variants may occur over the course of their disease. The recurrent aphthous-like lesions seen in the setting of systemic disease may be indistinguishable from those of the primary type. Nearly all patients (99%) with Behçet’s disease present with oral lesions, which tend to follow a more severe course than idiopathic aphthae, but otherwise display no distinguishable clinical features.

Minor aphthae are the most common variant, comprising ∽80% of all cases. They present as small (<10 mm diameter), round- or oval-shaped, shallow ulcers. In well-developed lesions, a gray-white pseudomembrane and surrounding erythematous halo may be seen (Fig. 4-1). Nonkeratinizing mucosa (e.g., labial mucosa, buccal mucosa, and floor of the mouth) is most commonly involved; minor aphthae only rarely occur on keratinized sites (e.g., palate and dorsal tongue). They may occur at any frequency and heal without scarring in 10 to 14 days.

Major aphthae (periadenitis mucosa necrotica recurrens or Sutton disease) occur far less frequently (∽10% of cases). Their clinical appearance differs from that of minor aphthae in that they are larger (>10 mm diameter), are deeper, and have a higher propensity to involve keratinizing sites (Fig. 4-2). They may persist for over 6 weeks and often heal with scarring. If a single lesion is longstanding and recalcitrant to treatment, the possibility of malignancy must be considered.

Herpetiform aphthae are the least common variant and most closely resemble ulceration secondary to herpes simplex infection. Herpetiform aphthae typically present as widely distributed, small (2 to 3 mm) ulcerations in the oral cavity. They often can be found to coalesce into large, irregularly shaped ulcers. They heal relatively quickly (7 to 10 days) and usually heal without scarring. This type often appears later in onset than the minor and major variants, and occurs more commonly in women. In contrast to herpes simplex virus-related ulcers, herpetiform aphthae do not start as a vesicle.