Etiology
The etiology is multifactorial and incompletely understood. Immunological dysregulation is central: T-lymphocyte-mediated cytotoxicity against oral epithelial cells, with elevated TNF-α, IL-2, and IL-12 in lesion tissue.
Genetic predisposition: first-degree relatives of RAS patients have significantly higher prevalence (90% concordance in identical twins in some studies); multiple HLA associations reported.
Precipitating factors: local trauma (cheek biting, sharp foods, dental injections), emotional stress, hormonal changes (menstrual cycle — some women reliably develop ulcers premenstrually), specific foods (nuts, chocolate, tomatoes, citrus — though evidence is limited).
Nutritional deficiencies — particularly iron, folate, zinc, and vitamin B12 — are found in a subset (10-20%) of RAS patients. Correcting these deficiencies may reduce recurrence frequency.
Systemic disease association: Behçet's disease (major criterion: recurrent oral aphthae + genital ulcers + uveitis), celiac disease (gluten sensitivity), IBD (Crohn's disease, ulcerative colitis), HIV infection, MAGIC syndrome.
Sodium lauryl sulfate (SLS) in toothpastes may be a trigger in susceptible individuals.