Periodontitis and rheumatoid arthritis:A search for causality and role of Porphyromonas gingivalis

There is currently much attention for early detection of rheumatoid arthritis, as early recognition enables timely treatment with a chance of remission of the disease before irreversible damage has occurred. In this respect, important questions are: who will develop rheumatoid arthritis, when and why? The main research question of this thesis was if chronic bacterial infection of oral soft- and hard tissues (periodontitis), in particular with the periodontal pathogen Porphyromonas gingivalis, predisposes to production of auto-antibodies specific for (the onset of) rheumatoid arthritis. Besides periodontitis, chronic inflammation of lung mucosal tissues has also been suggested to predispose to rheumatoid arthritis associated auto-antibody production. Indeed, presence of these auto-antibodies in patients without rheumatoid arthritis was associated with oral- or lung mucosal inflammation, although overall levels were low. Anti-Porphyromonas gingivalis antibody levels were not prognostic for development of rheumatoid arthritis. From this observation however, it cannot be concluded that there is no causal relationship between periodontitis and rheumatoid arthritis. Moreover, animal experiments confirm the suggested role of Porphyromonas gingivalis in development of human rheumatoid arthritis. Periodontitis is more prevalent among patients with rheumatoid arthritis. In addition, severity of periodontitis is correlated with rheumatoid arthritis disease activity. From this thesis is can be concluded that oral health assessment is extremely useful in patients with, or at risk for developing rheumatoid arthritis, given the potential role of chronic bacterial infection of oral tissues in development, progression and disease activity of rheumatoid arthritis

Periodontitis and rheumatoid arthritis:A search for causality and role of Porphyromonas gingivalis

There is currently much attention for early detection of rheumatoid arthritis, as early recognition enables timely treatment with a chance of remission of the disease before irreversible damage has occurred. In this respect, important questions are: who will develop rheumatoid arthritis, when and why? The main research question of this thesis was if chronic bacterial infection of oral soft- and hard tissues (periodontitis), in particular with the periodontal pathogen Porphyromonas gingivalis, predisposes to production of auto-antibodies specific for (the onset of) rheumatoid arthritis. Besides periodontitis, chronic inflammation of lung mucosal tissues has also been suggested to predispose to rheumatoid arthritis associated auto-antibody production. Indeed, presence of these auto-antibodies in patients without rheumatoid arthritis was associated with oral- or lung mucosal inflammation, although overall levels were low. Anti-Porphyromonas gingivalis antibody levels were not prognostic for development of rheumatoid arthritis. From this observation however, it cannot be concluded that there is no causal relationship between periodontitis and rheumatoid arthritis. Moreover, animal experiments confirm the suggested role of Porphyromonas gingivalis in development of human rheumatoid arthritis. Periodontitis is more prevalent among patients with rheumatoid arthritis. In addition, severity of periodontitis is correlated with rheumatoid arthritis disease activity. From this thesis is can be concluded that oral health assessment is extremely useful in patients with, or at risk for developing rheumatoid arthritis, given the potential role of chronic bacterial infection of oral tissues in development, progression and disease activity of rheumatoid arthritis

When should root remnants and unrestorable broken teeth be extracted in frail older adults?

BACKGROUND: Many frail older adults have an unhealthy dentition; unrestorable broken teeth and root remnants with open root canals, commonly accompanied by periapical and periodontal inflammation, are often seen. Improving oral health in the growing group of frail older adults with remaining teeth is a considerable challenge for dental care professionals. Dentists are often uncertain how to deal with root remnants and unrestorable broken teeth in frail older adults. METHODS: The authors aim was to provide recommendations to dentists to help in their clinical decision making about the extraction or retention of roots remnants and broken teeth in frail older adults. CONCLUSIONS: Decisions about the extraction or retention of root remnants should made on the basis of preventing pain and oral discomfort, preventing severe inflammation, and preventing additional decline in oral health. Both root-related and patient-related factors are considered. PRACTICAL IMPLICATIONS: Decision-making trees can help dentists decide whether to extract root remnants and unrestorable broken teeth in frail older adults

Lessons to be learned from periodontitis

Purpose of reviewThis article reviews the link between periodontitis and rheumatoid arthritis (RA) with regard to similarities in genetic risk factors and immunopathogenesis. Emphasis is paid to the potential role of the periodontal pathogen Porphyromonas gingivalis in the etiopathogenesis of both periodontitis and RA, in particular by post-translational modification of arginine into citrulline.Recent findingsP. gingivalis, a major periodontal pathogen, is presently known as the only bacterium in the oral flora which contains a peptidyl arginine deiminase enzyme (PAD). This enzyme is necessary for citrullination. As a result, citrullinated proteins and P. gingivalis PAD, PAD2 and PAD4 (expressed by infiltrating neutrophils) are found in periodontal tissues. Autoantibodies directed to citrullinated proteins, so-called anticitrullinated protein antibodies (ACPAs), are found to be present in gingival crevicular fluid originating from inflamed gingival tissue. Furthermore, treatment studies have revealed that nonsurgical periodontal treatment, that is removal of sub-gingival calculus and biofilm deposits, is accompanied by a reduction in the severity of RA.SummaryIn this study the similarities in immune response and tissue degradation between RA and periodontitis are reviewed. It is shown that the two diseases share the same environmental and genetic risk factors, apart from the fact that there is a link between both diseases via citrullination of proteins by human PAD and P. gingivalis PAD.</p

Increased IgA anti-citrullinated protein antibodies in the periodontal inflammatory exudate of healthy individuals compared to rheumatoid arthritis patients

Aim: To assess rheumatoid arthritis (RA)-associated autoantibodies in the gingivocrevicular fluid (GCF) of RA patients and healthy controls with or without periodontal disease, as chronic mucosal inflammation in periodontal disease is hypothesized to contribute to the formation of these autoantibodies. Materials and methods: Anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), and their IgA isotypes were assessed in the serum and GCF of RA patients (n = 72) and healthy controls (HC, n = 151). The presence and levels of these antibodies were studied in relation to interleukin (IL)-8 and periodontal disease. Results: In contrast to the HC, the levels of ACPA and RF in the serum and GCF of the RA patients were strongly correlated (p <.0001). The HC with high levels of IgA-ACPA (n = 27) also had significantly higher levels of total IgG, total IgA, and IL-8 in the GCF than the HC with low levels of IgA-ACPA in the GCF (n = 124). Periodontal inflammation and smoking were seen more frequently in the group with high levels of IgA-ACPA compared to the group with low IgA-ACPA. Conclusion: The IgA-ACPA in the GCF of HC may be associated with periodontal inflammation and smoking, and could be involved in the progression to RA

Levels of Anti-Citrullinated Protein Antibodies and Rheumatoid Factor, Including IgA Isotypes, and Articular Manifestations in Ulcerative Colitis and Crohn's Disease

Systemic presence of arthritis autoantibodies (AAb) is specific for rheumatoid arthritis (RA). AAb initiation might be triggered by chronic mucosal inflammation, such as in inflammatory bowel disease (IBD). We assessed the prevalence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in ulcerative colitis (UC) and Crohn&rsquo;s disease (CD) patients, with regard to the prevalence of joint complaints in AAb+ versus AAb&minus; IBD patients. RA patients and healthy subjects (HC) served as controls. Serum was collected from 226 UC, 165 CD and 86 RA patients, and 36 HCs. One-hundred-and-ten UC (48.7%) and 76 CD (46.1%) patients were seropositive for at least one autoantibody, compared to 4 (13.9%) HCs and 81 (94.2%) RA patients. Eighty-three (37%) UC and 52 (32%) CD patients were seropositive for the anti-cyclic citrullinated protein antibody (anti-CCP2) of the immunoglobulin A type (IgA anti-CCP2), compared to 1 (2.8%) HC and 64 (74%) RA patients. RF of the immunoglobulin G type (IgG RF) and IgA RF seropositivity in UC and CD patients was comparable to HCs and low compared to RA patients. Arthralgia was reported by 34 (18.7%) UC and 50 (33.1%) CD patients, but presence of arthralgia was not increased in AAb+ patients. AAbs are frequently present in IBD patients, supporting the hypothesis that inflammation of intestinal mucosa induces low systemic levels of ACPA

Effect of Anti-Rheumatic Treatment on the Periodontal Condition of Rheumatoid Arthritis Patients

Periodontitis, a bacterial-induced infection of the supporting soft and hard tissues of the teeth (the periodontium), is common in patients with rheumatoid arthritis (RA). As RA and periodontitis underlie common inflammatory pathways, targeting the progression of RA might mediate both periodontitis and RA. On the other hand, patients with RA on immunosuppressive medication have an increased risk of infection. Therefore, the objective of this longitudinal observation study was to assess the effect of methotrexate (MTX) and anti-tumor necrosis factor-alpha (anti-TNF, etanercept) treatment on the periodontal condition of RA patients. Overall, 14 dentate treatment-naive RA patients starting with MTX and 12 dentate RA patients starting with anti-TNF therapy in addition to MTX were included. Follow-up was scheduled matching the routine protocol for the respective treatments. Prior to the anti-rheumatic treatment with MTX or the anti-TNF therapy in addition to MTX, and during follow-up, i.e., 2 months for MTX, and 3 and 6 months for the anti-TNF therapy in addition to MTX, the periodontal inflamed surface area (PISA) was measured. The efficacy of the anti-rheumatic treatment was assessed by determining the change in RA disease activity (DAS28-ESR). Furthermore, the erythrocyte sedimentation rates were determined and the levels of C-reactive protein, IgM-rheumatoid factor, anti-cyclic citrullinated protein antibodies, and antibodies to the periodontal pathogen Porphyromonas gingivalis, were measured. Subgingival sampling and microbiological characterization of the subgingival microflora was done at baseline. MTX or anti-TNF treatment did not result in an improvement of the periodontal condition, while both treatments significantly improved DAS28 scores (both p <0.01), and reduced C-reactive protein levels and erythrocyte sedimentation rates (both p <0.05). It is concluded that anti-rheumatic treatment (MTX and anti-TNF) has negligible influence on the periodontal condition of RA patients