Faculty Opinions recommendation of Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis.

AbstractRheumatoid arthritis (RA) is an autoimmune disorder associated with increased periodontal destruction. It is thought that RA increases the risk of periodontal disease; it is not known how it influences the oral microbiota. Our aim was to analyze the impact of RA on subgingival microbiota and its association with periodontal inflammation and RA activity. Forty-two patients with RA were compared to 47 control subjects without RA. Patients were screened for probing depth, clinical attachment level, bleeding on probing and classified as with or without periodontitis. Subgingival plaque was examined by Illumina MiSeq Sequencing of 16S rRNA gene V4 region and inflammatory cytokines were measured in saliva. RA was associated to severe periodontal disease. In addition, the severity of RA, reflected by the number of tender and swollen joints, was significantly correlated with the presence of pathogenic oral bacteria (i.e. Fusobacterium nucleatum and Treponema socransky). Non-periodontitis RA patients compared to healthy controls had increased microbial diversity and bacterial load, higher levels of pathogenic species (Prevotella, Selenomonas, Anaeroglobus geminatus, Parvimonas micra, Aggregatibacter actinomycetemcomitans) and reduction of health-related species (Streptococcus, Rothia aeria, Kingela oralis). Genes involved with bacterial virulence (i.e. lipopolysaccharide biosynthesis, peptidases) were more prevalent in the subgingival metagenome of subjects with RA. In addition, the degree of oral inflammation reflected by IL-2, IL-6, TNF-α, IFN-γ salivary levels was increased in non-periodontitis RA patients in comparison with controls. Our findings support the hypothesis that RA triggers dysbiosis of subgingival microbiota, which may contribute to worsening periodontal status.Author SummaryRheumatoid arthritis (RA) is an autoimmune disease characterized by joints inflammation, swelling, pain and stiffness. Exactly what starts this disease is still unclear. Some recent studies have suggested mucosal surfaces in the body, like those in the gums, could affect the disease process. It has been observed that people with RA have higher risk of periodontitis (a bacterial inflammatory disease of the gums), compared with the general population, and this may be the start of the autoimmune process. Also, periodontitis increases the severity of RA while interventions by treating periodontitis can improve the symptoms of RA. One of the possible mechanisms that link the higher prevalence of periodontitis in RA patients is the dysbiosis of the oral microbiota triggered by the chronic inflammation in RA. Increased levels of molecules of inflammation may affect the oral environment and change the type of bacteria that live there. Here, we examined RA patients and healthy subjects, screening their oral health and inflammatory markers. We collected their saliva and the dental plaque from the space between the teeth and the gum. We found that RA patients exhibited severe periodontitis, increased levels of inflammatory mediators on their saliva and distinct bacterial communities, with higher proportions of bacteria species linked to periodontal disease, even in patients without periodontitis. We also found that the presence of these bacteria species was linked to worse RA conditions. Our study provides new insights to understand the bi-directional mechanisms linking periodontal disease to the development of RA, showing that we need to pay attention to the oral cavity in patients with RA and refer people for dental evaluation. This practice might have a positive impact in the course of RA.

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Oral Health in Rheumatoid Arthritis: Listening to Patients

JDR Clinical & Translational Research ◽

10.1177/23800844211012678 ◽

2021 ◽

pp. 238008442110126

Author(s):

J.L.P. Protudjer ◽

C. Billedeau ◽

K. Hurst ◽

R. Schroth ◽

C. Stavropoulou ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Health Care ◽

Oral Health ◽

Periodontal Disease ◽

Health Knowledge ◽

Care Delivery ◽

Oral Care ◽

Oral Health Care ◽

Personal Hygiene ◽

Health Maintenance

Introduction: Rates of periodontal disease and tooth loss are increased in individuals with rheumatoid arthritis (RA). Understanding factors that contribute to the increased burden of periodontal disease in RA is critical to improving oral health and arthritis outcomes. Objectives: To determine the perceptions held by people with RA relating to their oral health, to identify patient-centered priorities for oral health research, and to inform optimal strategies for delivering oral health knowledge. Methods: Semistructured interviews were conducted with patients with RA. Recorded interview transcripts were iteratively reviewed to reveal surface and latent meaning and to code for themes. Constructs were considered saturated when no new themes were identified in subsequent interviews. We report themes with representative quotes. Results: Interviews were conducted with 11 individuals with RA (10 women [91%]; mean age, 68 y), all of whom were taking RA medication. Interviews averaged 19 min (range, 8 to 31 min) and were mostly conducted face-to-face. Three overall themes were identified: 1) knowledge about arthritis and oral health links; 2) oral health care in RA is complicated, both in personal hygiene practices and in professional oral care; and 3) poor oral health is a source of shame. Participants preferred to receive oral health education from their rheumatologists or dentists. Conclusions: People with RA have unique oral health perceptions and experience significant challenges with oral health care due to their arthritis. Adapting oral hygiene recommendations and professional oral care delivery to the needs of those with arthritis are patient priorities and are required to improve satisfaction regarding their oral health. Knowledge Translation Statement: Patients living with long-standing rheumatoid arthritis described poor oral health–related quality of life and multiple challenges with maintaining optimal oral health. Study findings indicate a need for educational materials addressing oral health maintenance for patients with rheumatic diseases and their providers.

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Oral Microbiota Identifies Patients in Early Onset Rheumatoid Arthritis

Microorganisms ◽

10.3390/microorganisms9081657 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1657

Author(s):

Anders Esberg ◽

Linda Johansson ◽

Ingegerd Johansson ◽

Solbritt Rantapää Dahlqvist

Keyword(s):

Rheumatoid Arthritis ◽

Early Onset ◽

Amplicon Sequencing ◽

Oral Bacteria ◽

Oral Microbiome ◽

Rrna Gene ◽

Oral Microbiota ◽

Disease Manifestation ◽

Periodontal Status ◽

Quality Register

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons.

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POS0581 PERIODONTAL DISEASE IN RHEUMATOID ARTHRITIS: RESULTS FROM A COHORT AT TREATMENT WITH BIOLOGICAL, CLASSICAL AND TARGETED SYNTHETIC DMARDs

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3970 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 524.1-524

Author(s):

R. Dos-Santos ◽

F. Otero ◽

E. Perez-Pampín ◽

A. Mera Varela

Keyword(s):

Rheumatoid Arthritis ◽

Oral Health ◽

Periodontal Disease ◽

Disease Activity ◽

Health Problem ◽

Multivariable Analysis ◽

Testing Time ◽

Univariable Analysis ◽

Clinical Attachment Loss ◽

Attachment Loss

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

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POS0068 HIGH LEVELS OF PORPHYROMONAS GINGIVALIS AND PREVOTELLA INTERMEDIA ANTIBODIES IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2222 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 240.2-241

Author(s):

F. Zekre ◽

R. Cimaz ◽

M. Paul ◽

J. L. Stephan ◽

S. Paul ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Juvenile Idiopathic Arthritis ◽

Periodontal Disease ◽

Porphyromonas Gingivalis ◽

Joint Disease ◽

Control Group ◽

Prevotella Intermedia ◽

Igg Antibodies ◽

Idiopathic Juvenile Arthritis ◽

High Level

Background:Idiopathic juvenile arthritis (JIA) is a heterogeneous group of pathologies whose origin remains unknown at present (1). They are characterised by a systemic inflammatory and joint disease affecting children under 16 years of age. The current classification groups the different forms of JIA into 7 distinct entities (systemic forms, polyarticular forms with or without rheumatoid factors, oligoarticular forms, inflammatory arthritis associated with enthesopathies (ERA), arthritis associated with psoriasis and unclassifiable arthritis). Exact etiology of JIA is still unknown. To date, the various hypotheses put forward on the occurrence of JIAs integrate the genetic and environmental framework.The link between periodontal disease and rheumatoid arthritis (RA) is largely reported. Recently, Porphyromonas gingivalis (P. gingivalis) infection explained the occurrence of arthritis in rodent and in RA (2). Several studies mention the beneficial effect of P. gingivalis treatment on disease activity.Currently, there are very few studies on the prevalence of P. gingivalis in patients with JIA and the possible involvement of the germ in the development of inflammatory joint diseases in the pediatric population(3)(4).Objectives:The objective of our study is to determine presence of high IgG antibodies against P. gingivalis and Prevotella Intermedia in a cohort of patients with JIA compared to a control population and to determine variation of level according to sub-classes of JIA.Methods:Sera were obtained from 101 patients satisfying the ILAR classification criteria for JIA and in 25 patients with two other dysimmune disorders (type 1 diabetes and juvenile inflammatory bowel disease). Level of IgG antibodies against P. gingivalis and Prevotella Intermedia were obtained by homemade ELISA already used previously (5).Results:In the JIA group, major children were oligarthritis (47.5%), polyarthritis represents 31.7% of JIAs, ERA and systemic forms of JIA are respectively 9 and 11%. For the control group, 10 (40%) children had diabetes and 15 (60%) had IBD.Levels of anti-P. gingivalis anti-Prevotella Intermedia antibodies were higher in AJI group compared at control groups (P<0.01, P<0.05). Theses difference are mainly related to oligoarthritis and ERA subsets for both P. gingivalis and Prevotella Intermedia.Figure 1.Relative titer of antibodies to P. gingivalis and anti Prevotella intermedia. *: P<0.05; **: P<0.01; ***: P<0.001. P. gingivalis (control vs oligoarthritis p= 0.0032. control vs ERA p= 0.0092). Prevotella intermedia (control vs oligoarthritis p= 0.0194. control vs ERA p= 0.0039).Conclusion:We confirmed high level of anti-P. gingivalis and anti-Prevotella intermedia antibodies in JIA compared to other inflammatory disorders. For the first time, we observed that this high level was mainly in oligoarthritis and ERA. Further investigations are required to investigate involvement of oral dysbiosis in AJI pathogenesis. As observed in RA, it could be a new way to integrate in JIA therapy management.References:[1]Thatayatikom A, De Leucio A. Juvenile Idiopathic Arthritis (JIA). StatPearls Publishing; 2020[2]Cheng Z, Meade J, Mankia K, Emery P, Devine DA. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):19–30.[3]Romero-Sánchez C, Malagón C, Vargas C, Fernanda Torres M, Moreno LC, Rodríguez C, et al. Porphyromonas Gingivalis and IgG1 and IgG2 Subclass Antibodies in Patients with Juvenile Idiopathic Arthritis. J Dent Child Chic Ill. 2017 May 15;84(2):72–9.[4]Lange L, Thiele GM, McCracken C, Wang G, Ponder LA, Angeles-Han ST, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016 Feb 9[5]Rinaudo-Gaujous M, Blasco-Baque V, Miossec P, Gaudin P, Farge P, Roblin X, et al. Infliximab Induced a Dissociated Response of Severe Periodontal Biomarkers in Rheumatoid Arthritis Patients. J Clin Med. 2019 May 26;8(5).Disclosure of Interests:None declared.

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PARE0023 ORAL HEALTH IN RHEUMATOID ARTHRITIS: LISTENING TO PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.612 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1297.2-1297

Author(s):

J. Protudjer ◽

C. Billedeau ◽

C. Stavropoulou ◽

A. Cholakis ◽

R. Schroth ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Oral Health ◽

Periodontal Disease ◽

Oral Care ◽

Structured Interviews ◽

Face To Face ◽

Oral Health Education ◽

To Receive ◽

Latent Content

Background:Rates of periodontal disease and tooth loss are increased in rheumatoid arthritis (RA). Periodontal disease may exacerbate RA inflammation and complicate RA care. Understanding factors that contribute to the increased burden of periodontal disease in RA is critical to improving oral health and possibly arthritis outcomes. People with RA may have unique needs and/or barriers to maintain oral health.Objectives:To determine from people with RA what are their experiences and perceptions about their oral health, their most important questions relating to oral health, and how they wish to receive oral health information.Methods:Semi-structured interviews were conducted with RA patients. Recorded interview transcripts underwent iterative content analysis. Transcripts were initially reviewed to develop a coding guide. Latent content, or larger themes, were then applied to the transcripts. Constructs were considered saturated when no new themes were identified with subsequent interviews. We report identified themes with representative quotes.Results:Interviews with 11 RA (10[91%] female; all on RA medication) averaged 19 minutes (range 8-31 minutes) and were mostly conducted face-to-face. Many believed RA medication contributed to dry mouth. Most participants had not previously considered other links between oral health and RA. Themes identified included the need for complicated oral health routines, barriers of cost and access to dental care, and shame relating to oral health (Table 1). Participants preferred to receive oral health education from their rheumatologists or dentists over printed or online resources.Conclusion:RA patients have unique needs relating to oral health and report poor oral quality of life. Strategies to optimize oral health in RA may include educational tools for optimizing oral self-care appropriate for RA, and improved access to oral care professionals who are aware of the needs of arthritis patients.Disclosure of Interests:Jennifer Protudjer: None declared, Corrie Billedeau: None declared, Chrysi Stavropoulou: None declared, Anastasia Cholakis: None declared, Robert Schroth: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada

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POS0517 A LONGITUDINAL STUDY OF SARCOPENIA, LOCOMOTIVE SYNDROME, AND FRAILTY IN PATIENTS WITH RHEUMATOID ARTHRITIS: FROM THE CHIKARA STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1245 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 492.2-492

Author(s):

K. Mandai ◽

M. Tada ◽

Y. Yamada ◽

T. Koike ◽

T. Okano ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Multivariate Logistic Regression Analysis ◽

Locomotive Syndrome ◽

Chi Squared ◽

Higher Doses ◽

Rheumatoid Arthritis Data ◽

Onset Rate ◽

New Onset

Background:Rheumatoid arthritis (RA) patients have a high frequency of sarcopenia, and they commonly have reduced physical function. We previously reported that the prevalence of sarcopenia was 28%, that of frailty was 18.9%, and that of pre-frailty was 38.9% in RA patients1,2, and 13.2% of RA patients developed sarcopenia within a year 3.Objectives:To investigate the risk factors for new onset of sarcopenia, locomotive syndrome, and frailty in patients with RA and the course of each disease.Methods:Two-year follow-up data from the rural group of the prospective, observational CHIKARA study were used. Sarcopenia was diagnosed using the criteria of the Asian Working Group for Sarcopenia 2014, locomotive syndrome was diagnosed using locomotive 5, and frailty was diagnosed using the basic checklist. New onset of the disease over the 2-year follow-up period was studied, excluding cases that had the disease at baseline. Improvement was defined as cases with disease at baseline that no longer met the diagnostic criteria after 2 years. Differences in the characteristics of each disease were tested using the Chi-squared test and the paired t-test.Results:The 81 patients with RA (82.7% female) had mean age 66.9±11.5 years, mean DAS28-ESR 2.9±1.2, methotrexate use in 81.5% (with a dose of 9.9±2.7 mg/week), and glucocorticoid (GC) use in 22.2% (with a dose of 3.1±1.7 mg/week). The baseline prevalence was 44.4% for sarcopenia, 35.8% for locomotive syndrome, and 25.9% for frailty, and the new onset rate was 4.4% for sarcopenia, 15.4% for locomotive syndrome, and 13.3% for frailty. Of the patients with each disease at baseline, 36.1% had sarcopenia, 20.7% had locomotive syndrome, and 33.3% had frailty, and of those with each disease at 2 years, 36.1% had sarcopenia, 20.7% had locomotive syndrome, and 33.3% had frailty. The new onset sarcopenia and locomotive syndrome groups had significantly higher rates of GC use (p=0.036, p=0.007, paired t-test) and significantly higher doses (p=0.01, p=0.001, paired t-test) than the groups without new onset sarcopenia and locomotive syndrome. High baseline disease activity was an independent predictor of new onset of locomotive syndrome on multivariate logistic regression analysis (OR=3.21, p=0.015).Conclusion:The new onset rates at 2 years were 4.4% for sarcopenia, 15.4% for locomotive syndrome, and 13.3% for frailty. In the new onset sarcopenia and locomotive syndrome groups, both GC use and dosage were significantly higher.References:[1]Tada M, et al. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis. 2018 Nov;21(11):1962-1969.[2]Tada M, et al. Correlation between frailty and disease activity in patients with rheumatoid arthritis: Data from the CHIKARA study. Geriatr Gerontol Int. 2019 Dec;19(12):1220-1225.[3]Yamada Y, et al. Glucocorticoid use is an independent risk factor for developing sarcopenia in patients with rheumatoid arthritis: from the CHIKARA study. Clin Rheumatol. 2020 Jun;39(6):1757-1764.Disclosure of Interests:None declared

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