Aphthous ulcers are very common and easy to recognize Their cause remains uncertain, although an association with human herpesvirus 6 has been suggested Found on freely moving, nonkeratinized mucosa (eg, buccal and labial mucosa and not attached gingiva or palate), they may be single or multiple, are usually recurrent, and appear as painful small round ulcerations with yellow-gray fibrinoid centers surrounded by red halos Minor aphthous ulcers are less than 1 cm in diameter and generally heal in 10–14 days Major aphthous ulcers are greater than 1 cm in diameter and can be disabling due to the degree of associated oral pain Stress seems to be a major predisposing factor to the eruptions of aphthous ulcers A study found that the frequency of viral rhinitis and bedtime after 11 pm were independent predictors of aphthous ulcer frequency and severity in college students Treatment is challenging because no single systemic treatment has proven effective Topical corticosteroids (triamcinolone acetonide, 0 1%, or fluocinonide ointment, 0 05%) in an adhesive base (Orabase Plain) do appear to provide symptomatic relief in many patients Other topical therapies shown to be effective in controlled studies include diclofenac 3% in hyaluronan 2 5%, doxymycine-cyanoacrylate, mouthwashes containing the enzymes amyloglucosidase and glucose oxidase, and amlexanox 5% oral paste A 1-week tapering course of prednisone (40–60 mg/day) has also been used successfully Cimetidine maintenance therapy may be useful in patients with recurrent aphthous ulcers Thalidomide has been used selectively in recurrent aphthous ulcerations in HIV-positive patients Large or persistent areas of ulcerative stomatitis may be secondary to erythema multiforme or drug allergies, acute herpes simplex, pemphigus, pemphigoid, epidermolysis bullosa acquisita, bullous lichen planus, Behçet disease, or inflammatory bowel disease Squamous cell carcinoma may occasionally present in this fashion When the diagno- sis is not clear, incisional biopsy is indicated