Interaction between apical periodontitis and systemic disease (Review)

Abstract

Apical periodontitis is an oral common inflammatory disease initiated by infection of pulp chamber and is characterized by destruction and resorption of the periapical bone. As a local infection, pathogens and their products in periapical tissues, as well as inflammatory cytokines produced in periapical lesions, enter the blood circulation, triggering systemic immune responses and leading to the pathogenesis of various types of systemic disease. Therefore, apical periodontitis might be associated with systemic disease rather than solely simple local oral disease. In addition, the existence of a hyperinflammatory state in certain patients with chronic inflammation‑related disorder may affect the progression or prognosis of apical periodontitis. However, the association and potential mechanisms between apical periodontitis and systemic diseases remain unclear. An in‑depth understanding of the association between apical periodontitis and systemic disease will be useful for both dentists and physicians to eliminate the possible risk factors and promote the healing of apical periodontitis and systemic disease. Thus, the aim of the present review is to introduce the potential relationship between apical periodontitis and systemic disease.

Keywords: apical periodontitis; association; inflammation; microbiota; systemic disease.

Figure 1

AP is associated with systemic disease. AP is a common oral disease associated with a number of systemic diseases, including metabolic (diabetes mellitus and osteoporosis), autoimmune (rheumatoid disease, autoimmune hepatitis/nephritis, inflammatory bowel disease) and cardiovascular diseases, adverse pregnancy outcomes, as well as psychiatric disorders. AP, apical periodontitis.

Figure 2

Bidirectional association between AP and DM. DM may affect the prevalence, progression and prognostic course of AP by elevating the oral susceptibility due to impaired leukocyte function, increasing the systemic inflammatory response (increased secretion of IL-6, IL-17, IL-23 and TNF-α), decreasing bone turnover, altering osteoblast/osteoclast homeostasis, as well as decreasing levels of VEGF and angiogenesis by accumulation of advanced glycation end-products. However, use of metformin can inhibit the negative effects of DM on AP. AP can disrupt the inflammatory response, impair insulin signaling pathways or decrease insulin sensitivity and deplete endogenous antioxidants, leading to increased insulin requirements and blood glucose levels. RCT has been shown to attenuate this adverse effect. AP, apical periodontitis; DM, diabetes mellitus; RCT, root canal treatment; AGE, advanced glycation end-product; DPSC, dental pulp stem cell; PDLSC, periodontal ligament stem cell.

Figure 3

Apical periodontitis accelerates progression of cardiovascular disease. Bacteria and/or their products in the periapical region are transferred to systemic circulation, which can activate the systemic immune response and promote the secretion of pro-inflammatory factors, eventually causing dysbiosis of the intestinal flora, aggregating overloads of ROS and/or developing into hyperlipidemia. Elevated serum inflammatory factors and lipids contribute to plaque/thrombus formation. Excessive ROS and inflammatory mediators directly damage vascular endothelium, impairing FMD and EFR and increase c-IMT and concentration of ADMA. Conversely, root canal treatment improves early endothelial dysfunction. EFR, endothelial flow reserve; ROS, reactive oxygen species; HDL-C, high density lipid-cholesterol; LDL-C, low density lipid-cholesterol; FMD, flow-mediated dilatation; c-IMT, carotid intima-media thickness; ADMA, asymmetrical dimethylarginine.