TRANSLATIONAL AND CLINICAL MEDICINE - Georgian Medical Journal

Background: Recurrent aphthous stomatitis is one of the most common diseases affecting the oral mucosa, and one of its variants is the most painful affliction of the oral mucosa.

Aim: To search for new immunologic pathways of the disease for the purpose of developing an accurate treatment and simplifying diagnostic procedures.

Methods: A literature search was made of the PubMed, Cochrane, and Scopus databases, limited to articles published between 2020 and 2026, with scientific levels of evidence 1 and 2 (meta-analyses, systematic reviews, phase I and II randomized clinical trials, cohort studies, and case-control studies), and conducted in humans.

Results: The present article provides a detailed review of the current knowledge of the etiology and pathogenesis of recurrent aphthous stomatitis.

Conclusions: Recurrent aphthous stomatitis (RAS) is a complex condition with no single identifiable cause. It is considered multifactorial, involving interactions between genetic predisposition, immune dysregulation, environmental triggers, and systemic factors. Genetic factors, particularly HLA variants and cytokine polymorphisms, influence disease susceptibility and severity, while immune mechanisms—such as increased pro-inflammatory cytokines and abnormal T-cell responses—play a key role in mucosal damage.

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