Periodontitis and rheumatoid arthritis: Inflammatory relationship

Sir,

Periodontitis and periodontal diseases are true infections of the oral cavity. There is an equilibrium that exists between microbial challenge and host's immune response; any alteration to that with the addition of other modifying factors is responsible for clinical manifestation of periodontal disease. Pathogens of the subgingival microbiota can interact with host tissues even without direct tissue penetration, and the subgingival microbiota accumulate on the oral cavity to form an adherent layer of plaque with the characteristics of a biofilm. The oral cavity works as a continuous source of infectious agents, and its condition often reflects progression of systemic pathologies.[1] Inflamed periodontal tissues produce significant amounts of pro-inflammatory cytokines, mainly interleukin 1-beta (IL-1β), IL-6, prostaglandin E2, and tumor necrosis factor-alpha (TNF-α), which may have systemic effects on the host. Periodontitis initiates systemic inflammation and can be monitored by inflammatory markers, such as C-reactive protein or fibrinogen levels. The host responds to the periodontal infections with an array of events involving both innate and adaptive immunity. Periodontitis has been proposed as having an etiological or modulating role in cardiovascular and cerebrovascular disease, diabetes, respiratory disease, and adverse pregnancy outcome. Recently several mechanisms have been proposed for relationship of periodontitis leading to rheumatoid arthritis (RA). RA is also a chronic destructive inflammatory disease characterized by the accumulation and persistence of an inflammatory infiltrate in the synovial membrane that leads to synovitis and the destruction of the joint architecture resulting in impaired function.[2] The current paradigm for RA includes an initiating event (possibly a microbial exposure or a putative autoantigen) leading to significant synovial inflammation and tissue destruction. As for periodontitis, there is an accumulation of inflammatory cells (T and B lymphocytes, neutrophils, and monocytes), tissue edema, endothelial cell proliferation, and matrix degradation. RA is also modified by systemic, genetic, and environmental variables.[3] Rheumatoid arthritis susceptibility and severity have been associated with genetic markers. The main genetic marker is carried by the highly polymorphic HLA-DRB1 locus. However, as for RA, in the same overall population a similar association was described between the HLA-DRB1 subclasses encoded for the same shared epitope and periodontal disease.[4] Both RA and periodontal disease are associated with an imbalance between pro-inflammatory and anti-inflammatory cytokines. IL1-β and TNF-α are the main proinflammatory cytokines detected in rheumatoid joints and gingival tissues.[5] Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and RA. While this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to experience more significant periodontal problems compared to their non-RA counterparts, and vice versa.[3]