scholarly journals Should We Be Screening for and Treating Periodontal Disease in Individuals Who Are at Risk of Rheumatoid Arthritis?

Healthcare ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1326
Author(s):  
Zhain Mustufvi ◽  
Stefan Serban ◽  
James Chesterman ◽  
Kulveer Mankia

There is increasing evidence supporting an association between periodontal disease (PD) and rheumatoid arthritis (RA), both mechanistically and clinically. Trials have shown that treating PD in people with RA may improve RA disease activity. Patients with musculoskeletal symptoms without arthritis, who test positive for cyclic-citrullinated protein antibodies, are at risk of RA (CCP+ at-risk), with seropositivity preceding arthritis onset by months or years. Importantly, there is evidence to suggest that periodontal inflammation may precede joint inflammation in CCP+ at-risk and, therefore, this could be a trigger for RA. There has been increased research interest in RA prevention and the phenotyping of the pre-RA disease phase. This review will examine the merits of identifying individuals who are CCP+ at-risk and performing screening for PD. In addition, we discuss how PD should be treated once identified. Finally, the review will consider future research needed to advance our understanding of this disease association.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 953-953
Author(s):  
K. Mankia ◽  
Z. Mustufvi ◽  
J. Kang ◽  
A. Tugnait ◽  
R. Letton ◽  
...  

Background:The prevalence of periodontal disease and the citrullinating bacteriumPorphyromonas gingivalisare increased in anti-CCP positive individuals at-risk of rheumatoid arthritis (RA) (1). This suggests periodontal inflammation may have an important role in the initiation and development of RA. Despite significant interest in the role of the periodontium and other mucosal sites in the initiation of RA-related autoimmunity, the influence of mucosal inflammation on progression to inflammatory arthritis (IA) in at-risk individuals remains unclear.Objectives:To investigate the association between periodontitis and progression to inflammatory arthritis in anti-CCP+ at-risk individuals without synovitis.Methods:Anti-CCP positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk) were recruited as part of a national prospective cohort study. Comprehensive periodontal examination was performed at baseline by a dentist; six sites per tooth were assessed for clinical attachment level (CAL), pocket depth (PD) and bleeding on probing (BOP). Periodontal disease sites (PDD) were defined as CAL ≥2mm and PD ≥4mm. The distribution of PDD was classified in line with recent guidelines (2). The severity i.e. total burden of periodontal inflammation, was quantified at patient level using the periodontal inflamed surface area (PISA) index(3). CCP+ at-risk were monitored for progression to IA. Multivariable Cox regression was used to assess the effect of PDD distribution and PISA on progression to IA.Results:126 CCP+ at-risk underwent full periodontal examination and were followed up for median 23.4 months (range 0.6 – 56.8 months). Mean age was 49 years, 86 (68%) were females. At baseline, 42(33%) subjects had no PDD, 51(40%) had localised PDD (<30% teeth with one or more PDD site) and 33 (26%) had generalised PDD (≥ 30% of teeth with one or more PDD site). Mean (SD) PISA for all subjects was 267(319)mm2. 31 subjects (25%) progressed to IA after median of 12.6 months (range 0.6 – 49.5 months). Progression to IA was significantly higher in subjects with localised PDD compared with those without PDD (33% vs 16%, HR (95% CI) 2.45 (1.02, 5.94) p=0.02), figure 1. Interestingly, this association was not seen in subjects with generalised PDD (19% progression, HR 0.68 (0.20, 2.32). In addition, severity (i.e. total burden) of periodontal inflammation (PISA) was not significantly predictive of progression to IA alone (HR 1.001 (0.999-1.002), p=0.08). However, when adjusting for distribution of PDD, PISA was significantly associated with progression to IA (HR 1.0016 (1.0003- 1.003), p=0.00163).Conclusion:Periodontal inflammation predicts progression to IA in CCP+ at-risk individuals without clinical synovitis. The severity (i.e. total burden) of periodontitis appears to be particularly predictive of progression to IA in patients with localised periodontitis. These data suggest periodontitis may be an important factor in the development of RA and provide rationale for periodontal intervention with the aim of arthritis prevention in at-risk individuals.References:[1] Mankia K et al, JAMA Network Open(2019)[2] Caton J et al, J Clin Periodontol(2018)[3] Nesse W et al, J Clin Periodontol(2008)Disclosure of Interests :Kulveer Mankia: None declared, Zhain Mustufvi: None declared, Jing Kang: None declared, Aradhna Tugnait: None declared, Robert Letton: None declared, Laurence Duquenne: None declared, Alastair Speirs: None declared, Val Clerehugh: None declared, Deirdre Devine: None declared, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)


2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 524.1-524
Author(s):  
R. Dos-Santos ◽  
F. Otero ◽  
E. Perez-Pampín ◽  
A. Mera Varela

Background:Periodontal disease (PD) has been widely studied in the pathogenesis of rheumatoid arthritis (RA). As well, its relationship with severity and disease activity, has also been investigated with ambiguous results. It has been suggested that the improvement of oral health could enhance disease activity scores.1 PD prevalence worldwide stands around 60% in older adults (>65 years) and its frequency increases with aging.2Objectives:To asses oral health in RA patients and to identify predictors of PD in this population.Methods:Patients diagnosed of RA at treatment with biological, classical or targeted synthetic disease modifying anti-rheumatic drugs (b/cs/tsDMARDs) in the aforementioned hospital during 2020 performed a dental review with a specialized periodontal odontologist. Oral health patterns were given for all patients, following criteria of American Academy of Periodontology, and reevaluation of disease activity was made 2 months later.Clinical, demographic and treatment data were collected from participants.Univariable logistic regression was performed to identify predictors of PD. Variables with p<0.20 were selected for multivariable analysis.Stata 15.1 was used to perform statistical analysis.Results:81 patients were recruited. 82.72% were female. Mean age was 56.17 years (SD 14.15) and mean time since diagnosis was 15.58 years (SD 8.17). 25% were current or past smokers. 21 patients had comorbidities (arterial hypertension the most frequent). 66.67% were rheumatoid factor (RF) positive and 72.73% anti-citrullinated peptide autoantibody (ACPA) positive. Median erythrocyte sedimentation rate (ESR) was 12 mm (IQR 6;23) and mean C-reactive protein (CRP) was 0.48 mg/dl (SD 1.18). Mean disease activity score (DAS28-VSG) at the testing time was 2.62 (SD 1.21) and after 2 months was 2.39 (SD 0.97). 96.30% of patients were at treatment with csDMARDs, 64.20% with glucocorticoids, 96.30% with bDMARDs and 6 patients with tsDMARDs.Univariable analysis identified higher age, at least one autoantibody positive and ESR/CRP as potential predictors of medium/severe PD (p<0.20). Multivariable testing including these variables pointed out higher age, lower ESR and at least one autoantibody positive (OR 1.09 [CI95% 1.04-1.14] p=0.001, OR 0.18 [CI95% 0.04-0.95] p=0.044 and OR 0.94 [CI95% 0.88-1.00] p=0.042, respectively) as predictors of medium or severe PD (≥3 mm interdental clinical attachment loss).Univariable analysis identified higher age, the presence of any comorbidity and anti tumour-necrosis factor alpha treatment (anti-TNF) as potential predictors of severe PD (p<0.20). Multivariable testing including these variables pointed out higher age (OR 1.15 [CI95%1.02-1.30] p=0.026) as predictor of severe PD (≥5 mm interdental clinical attachment loss).Conclusion:Periodontal disease is still an extended health problem among the entire population. Its prevalence in RA is increased, therefore higher age and RF or ACPA positive are risk factors for developing severe PD. This analysis might suggest that an aggressive management of PD could implement better responses in DAS28. Also anti-TNF treatment could delimit a “penumbra” group of patients at risk of developing severe PD, where intensive manage could modify the final outcome.References:[1]C O Bingham, M Moni. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Curr Opin Rheumatol. 2013;25(3):345-353.[2]P Carvajal. Periodontal disease as a public health problem: the challenge for primary health care. Rev Clin Periodoncia inplantol. 2016;9(2):177-183.Disclosure of Interests:None declared


2021 ◽  
pp. annrheumdis-2021-220884
Author(s):  
Kulveer Mankia ◽  
Heidi J Siddle ◽  
Andreas Kerschbaumer ◽  
Deshire Alpizar Rodriguez ◽  
Anca Irinel Catrina ◽  
...  

BackgroundDespite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).MethodsAn European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC.ResultsEpidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.ConclusionThese consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1115.1-1115
Author(s):  
F. Rahal ◽  
N. Brahumi ◽  
A. Ladjouze-Rezig ◽  
S. Lefkir

Background:Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). There are also suggested to have a more severe rheumatoid arthritis.Objectives:The aim of this study was to assess the influence of ACPA on disease activity, radiological severity, and functional disability in Algerian patient with early rheumatoid arthritis (RA).Methods:Consecutive early RA patients (symptom duration ≤24 months) recruited were included in the descriptive, longitudinal, prospective study. Demographic, biological, immunological and radiographic data were collected at the time of inclusion in the study. Disease activity as determined by the Disease Activity Score 28-CPR (DAS28- CPR: 4 variables), functional handicap as calculated by Heath Assessment Score (HAQ), and bone and joint damage as evaluated by Sharp-Van der Heijde (SVDH) erosion and narrowing score.Results:One hundred and sixty-one patients with RA were recruited. Patients mean age 43.71±14 years and mean symptom duration at inclusion was 10.48±7 months. Small and larges were affected in 64,3%. The mean ESR was 23,53±15,2 mm/1st hour, and the mean CRP level was 19,42±39.8 mg/l. Rheumatoid Factors (RFs) and Anti-Citrullinated Protein Antibodies (ACPAs) were present in 74% and 88% of patients, respectively. The presence of ACPAs was significantly associated with DAS28 (p=0,004) and HAQ (p=0,002). There was no significant difference in inflammatory markers and radiographic SVDH score between patients with and without ACPAs. Stepwise regression analysis showed that the presence of ACPAs was independently associated with localization when RA affected smalls and larges joint in the same time (OR=5,24; IC 95% 1,224-22,483; p=0,026).Conclusion:These data show that in patients with early RA, ACPAs positivity was significantly associated with articular manifestations, activity disease and functional handicap, but not with structural damage.References:[1]Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis. 2016;75(12):2080-2086. doi:10.1136/annrheumdis-2015-208669.[2]Karimifar M, Salesi M, Farajzadegan Z. The association of anti-CCP1 antibodies with disease activity score 28 (DAS-28) in rheumatoid arthritis. Adv Biomed Res. 2012;1:30. doi:10.4103/2277-9175.98156.[3]Boman A, Brink M, Lundquist A, et al. Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study. RMD Open. 2019;5(2):e000946. Published 2019 Sep 3. doi:10.1136/rmdopen-2019-000946.Disclosure of Interests:None declared


2014 ◽  
Vol 41 (11) ◽  
pp. 2153-2160 ◽  
Author(s):  
Allen Anandarajah ◽  
Ralf Thiele ◽  
Ellen Giampoli ◽  
Johnny Monu ◽  
Gwy-Suk Seo ◽  
...  

Objective.The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology.Methods.We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined.Results.Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US.Conclusion.Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 522.3-523
Author(s):  
R. Shumnalieva ◽  
D. Kachakova ◽  
R. Kaneva ◽  
Z. Kolarov ◽  
S. Monov

Background:MicroRNAs (miRNAs) are a class of small, non-coding RNAs that negatively regulate gene expression at posttranscriptional level. In rheumatoid arthritis studies have shown that miRNA are differentially expressed systemically as well as locally in the inflamed joints [1,2]. The correlation between their systemic or local expression levels and scores for disease activity and progression in RA make them possible candidate for biomarkers in the clinical practice.Objectives:To analyze the expression levels of miR-155 and miR-223 in synovial fluid (SF) from RA patients in regard to the ultrasound scores for disease activity.Methods:A total number of 48 RA patients according to the 1987 ACR criteria were included in the study. Expression levels of miR-155 and miR-223 SF were determined by qPCR (SybrGreen technology) and compared to healthy controls (HCs). Relative changes of gene expression levels of the studied miRNAs were calculated by 2-ΔΔCt method. Musculoskeletal ultrasound (MSUS) examination was performed by two independent examiners on ESAOTE, MyLab60 using both grey scale and power Doppler technic. A semi-quantitative assessment of the peripheral joints was performed for detecting joint inflammation and determining the grade of synovial thickening and the degree of vascularization. Ultrasound features for active disease were correlated to the local expression of the studied miRNAs. SPSS was used for statistical analysis.Results:RA SF showed overexpression of miR-155 (in 79.17%, p=1.63x10-4) and of miR-223 (in 79.17%, p=1.64x10-3) when compared to HCs and both miRNAs could be used to differentiate RA patients from HCs (р=8.0х10-5 and р=2.8х10-4, respectively). When we analyzed the correlation between the diagnosis, the expression of miRNAs and the changes on the musculoskeletal ultrasound examination we found a statistically significant correlation between the presence of synovitis and the degree of the power Doppler signal on MSUS and the local expression of miR-223 (p=6.19 x 10-4 and p=0.003, respectively). SF levels of miR-223 correlated also with the degree of synovial hypertrophy on MSUS (p=0.013). The results for miRNA-155 were not statistically significant.Conclusion:The correlation between the local expression of miR-223 and the ultrasound features of active joint inflammation shows that this miRNA might be a better candidate for local disease biomarker than miR-155. Further analysis with larger sets is needed to confirm if altered local miRNA expression could be used in the clinical practice as biomarker for disease activity especially in cases with subclinical synovitis.References:[1]Filková M, Aradi B, Šenolt L, et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. ARD, 2014; 73: 1898-1904.[2]Kriegsmann, M., Randau, T.M., Gravius, S. et al. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch, 2016; 469, 93–100.Acknowledgements:The study was supported by Grant 14-D/2012 and Grant 60/2013 funded by Medical University-Sofia.Disclosure of Interests:Russka Shumnalieva: None declared, Darina Kachakova: None declared, Radka Kaneva: None declared, Zlatimir Kolarov Speakers bureau: Amgen, Pfizer, Novartis, Abbvie, Roche, Astra-Zeneka, Simeon Monov Speakers bureau: Amgen, Pfizer, Novartis, Abbvie, Roche, Astra-Zeneka


2009 ◽  
Vol 36 (12) ◽  
pp. 2635-2641 ◽  
Author(s):  
JENNIFER L. BARTON ◽  
LINDSEY A. CRISWELL ◽  
RACHEL KAISER ◽  
YEA-HUNG CHEN ◽  
DEAN SCHILLINGER

Objective.Patient self-report outcomes and physician-performed joint counts are important measures of disease activity and treatment response. This metaanalysis examines the degree of concordance in joint counts between trained assessors and patients with rheumatoid arthritis (RA).Methods.Studies eligible for inclusion met the following criteria: English language; compared patient with trained assessor joint counts; peer-reviewed; and RA diagnosis determined by board-certified or board-eligible specialist or met 1987 American College of Rheumatology criteria. We searched PubMed and Embase to identify articles between 1966 and January 1, 2008. We compared measures of correlation between patients and assessors for either tender/painful or swollen joint counts. We used metaanalysis methods to calculate summary correlation estimates.Results.We retrieved 462 articles and 18 were included. Self-report joint counts were obtained by a text and/or mannequin (picture) format. The summary estimates for the Pearson correlation coefficients for tender joint counts were 0.61 (0.47 lower, 0.75 upper) and for swollen joint counts 0.44 (0.15, 0.73). Summary results for the Spearman correlation coefficients were 0.60 (0.30, 0.90) for tender joint counts and 0.54 (0.35, 0.73) for swollen joint counts.Conclusion.A self-report tender joint count has moderate to marked correlation with those performed by a trained assessor. In contrast, swollen joint counts demonstrate lower levels of correlation. Future research should explore whether integrating self-report tender joint counts into routine care can improve efficiency and quality of care, while directly involving patients in assessment of RA disease activity.


2021 ◽  
Author(s):  
Mihnea R. Mangalea ◽  
David Paez-Espino ◽  
Kristopher Kieft ◽  
Anushila Chatterjee ◽  
Jennifer A. Seifert ◽  
...  

SUMMARYRheumatoid arthritis (RA) is an autoimmune disease characterized in seropositive individuals by the presence of anti-cyclic citrullinated protein (CCP) antibodies. RA is linked to the intestinal microbiota, yet the association of microbes with CCP serology and their contribution to RA is unclear. We describe intestinal phage communities of individuals at risk for developing RA, with or without anti-CCP antibodies, whose first degree relatives have been diagnosed with RA. We show that at-risk individuals harbor intestinal phage compositions that diverge based on CCP serology, are dominated by Lachnospiraceae phages, and originate from disparate ecosystems. These phages encode unique repertoires of auxiliary metabolic genes (AMGs) which associate with anti-CCP status, suggesting that these phages directly influence the metabolic and immunomodulatory capability of the microbiota. This work sets the stage for the use of phages as preclinical biomarkers and provides insight into a possible microbial-based causation of RA disease development.


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