Etiopathogenesis of Behçet's disease: A systematic literature review

Behçet's disease (BD) is a chronic, multisystemic inflammatory vasculitis affecting veins and arteries. Its etiopathogenesis remains unclear but is thought to result from genetic predisposition combined with environmental triggers. Recent genome-wide association studies (GWAS) have linked various genetic polymorphisms (e.g., HLA*B51, ERAP1) to an increased risk of BD, with particular focus on cytokine-related gene variants. Infectious agents, such as Streptococcus species and herpes simplex virus, along with oral and intestinal dysbiosis and molecular mimicry, are key environmental triggers of innate immune inflammation, which is further amplified by adaptive immune responses. The innate immune system's primary cells, including neutrophils and NK cells, are upregulated, leading to an overproduction of proinflammatory cytokines. Additionally, an imbalance in T cell populations, characterized by a decrease in Tregs and expansion of Th1 and Th17 cells, contributes to disease pathogenesis. This review provides an overview of recent advances in understanding BD's etiopathogenesis.