Etiology • Unknown—probably represents a focal immunodysfunction;
no viral or other infectious agent identified • Triggers vary from case to case (eg, increased stress/anxiety,
hormonal changes, dietary factors, trauma) • Alterations in barrier permeability may be a factor, as occur with
human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), bone marrow suppression, neutropenia, gluten sensitivity, Crohn’s disease, ulcerative colitis, food allergy, Behçet’s disease, and dietary deficiencies (iron, folate, vitamin B 12
no viral or other infectious agent identified • Triggers vary from case to case (eg, increased stress/anxiety,
hormonal changes, dietary factors, trauma) • Alterations in barrier permeability may be a factor, as occur with
human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), bone marrow suppression, neutropenia, gluten sensitivity, Crohn’s disease, ulcerative colitis, food allergy, Behçet’s disease, and dietary deficiencies (iron, folate, vitamin B 12
, zinc). • Although likely immunologic in nature, the specific mechanism
is undetermined. • Human leukocyte antigen (HLA) subtype susceptibility a
factor in some cases (-B12, -B51, and others) • Affects 18 to 27% of the population; prevalence is approxi-
mately 20%
Clinical Presentation • Recurrent, self-limiting, painful ulcers • Usually restricted to nonkeratinized oral and pharyngeal
mucosa (not hard palate or attached gingiva) • Well-demarcated ulcers with yellow fibrinous base and
erythematous halo • Three clinical forms: minor ulcers, major ulcers, herpetiform
lesions • Minor variant (most common subtype)
• Occasional • Single but more often multiple • Less than 1 cm in diameter • Oval to round shape • Healing within 7 to 14 days
• Major variant (Sutton’s ulcers) • 1 cm or greater in diameter • Single or less commonly several • Deep • To ragged edges with elevated edematous margins• May persist for several weeks to months • Often heal with scarring
• Herpetiform variant (least common variant) • Grouped superficial ulcers 1 to 2 mm in diameter; crops
of 10 to 100 lesions • In nonkeratinized and keratinized tissues • Healing within 7 to 14 days • No etiologic role for herpes simplex virus
• Recurrent aphthous stomatitis occurs as simple (minor) aphthosis (common) and complex (major) aphthosis (uncommon) • Complex aphthosis (severe, almost continuous ulcerations;
disabling, large, or severe lesions) • Simple aphthosis (mild; episodic: 1– 4 episodes/yr; few
lesions, usually minor or herpetiform) • In AIDS patients, lesions are typically more severe and may
occur on any oral surface.
Diagnosis • Usually has diagnostic clinical appearance of focal, well-
defined ulcers involving nonkeratinized mucosa • History helpful; a recurrent process • Positive family history
Differential Diagnosis • Traumatic ulcer • Chancre • Recurrent intraoral herpes simplex stomatitis • Cyclic neutropenia
Treatment • Symptomatic therapy may be adequate. • Systemic causative factors, if present, should be addressed. • Tetracycline-based oral rinses may be helpful. • Corticosteroid therapy is the most rational approach and is a
consistently effective treatment. • Topical corticosteroids as gels, creams, or ointment 4 to
6 times/d to early lesions • Intralesional corticosteroid injections • Short-duration systemic corticosteroids (low to moderate
doses)
• Other immunomodulating drugs may be helpful (dapsone, hydroxychloroquine, topical tacrolimus, amelexanox).
• Colchicine (0.6–1.2 mg/d) is sometimes beneficial. • Thalidomide treatment has shown efficacy in clinical trials. • See “Therapeutics” section for details.
Prognosis • Simple aphthosis
• Excellent • Cannot be cured • Good control with corticosteroids is usually possible. • Typically, severity decreases as patient ages.
• Complex aphthosis • Needs medical evaluation for intercurrent disease • Chronic problem