Influence of Oral Microbiota on the Presence of IgA Anti-Citrullinated Protein Antibodies in Gingival Crevicular Fluid.

Introduction: The relation between rheumatoid arthritis (RA) and periodontitis (PD) has been investigated ever since the discovery of the citrullinating enzyme peptidyl arginine deaminase presents in the oral bacterium Porphyromonas gingivalis. Recently, we demonstrated the presence of RA autoantibodies, especially of IgA anti-citrullinated protein antibody (ACPA), in gingival crevicular fluid (GCF) of Indonesian patients with and without RA or PD which might indicate the local formation of RA antibodies in the periodontium. Aim: The purpose of this study was to assess whether the subgingival microbiome is related to the presence of IgA ACPA in the GCF of healthy individuals with or without PD. Patients and Methods: Healthy individuals with a known periodontal status and high IgA ACPA (>0.1 U/ml) in GCF (n = 27) were selected and matched for age, gender, periodontal status, and smoking status with 27 healthy individuals without IgA ACPA in their GCF. Taxonomic profiling of the subgingival microbiome was based on bacterial 16S rRNA gene sequencing. Downstream analyses were performed to assess compositional differences between healthy subjects with or without IgA ACPA in GCF and with or without PD. Results: Between groups with or without PD, or with or without IgA ACPA in GCF, no differences in alpha diversity were seen. Beta diversity was different between groups with or without PD (p < 0.0001), and a trend was seen in subjects with PD between subjects with or without IgA ACPA in GCF (p = 0.084). Linear discriminant analysis effect size (LEfSe) revealed no significant differences in the total population between subjects with IgA ACPA compared to subjects without IgA ACPA in GCF. Although Porphyromonas was not identified by LEfSe, its relative abundance was significantly higher in healthy individuals with high IgA ACPA in GCF compared to individuals without IgA ACPA in GCF (p = 0.0363). Zooming in on the subgroup with PD, LEfSe revealed that species Neisseriaceae, Tannerella, and Haemophilus were more abundant in the subjects with IgA ACPA in GCF compared to subjects without IgA ACPA in GCF. Conclusion: Periodontitis and certain taxa, including Porphyromonas, seem to be associated with the local presence of ACPA in the periodontium.

[Why physicians should pay attention to oral health too]. / Kijk ook eens in de mond van uw patiënt.

In literature oral health is broadly described and interrelations between oral health, general health and quality of life have been established. However, oral health is often overlooked by medical professionals, in contrast to veterinarians, who inspect the mouth of their patients as a standard procedure. In this manuscript the authors explain why patients could benefit if medical professionals pay more attention to oral health, by trying to inspire them to assess oral health as part of general health and to cooperate more with dental professionals to safeguard (oral) health.

No Obvious Role for Suspicious Oral Pathogens in Arthritis Development.

A particular role for Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) has been suggested in periodontitis and rheumatoid arthritis (RA), as these bacteria could initiate the formation of rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPA). We assessed whether serum antibodies against Pg and Aa in RA patients and non-RA controls reflect the subgingival presence of Pg and Aa, and evaluated the relationship of these antibodies to the severity of periodontal inflammation and RA-specific serum autoantibodies. In 70 Indonesian RA patients and 70 non-RA controls, the subgingival presence of Pg and Aa was assessed by bacterial 16S rRNA gene sequencing, and serum IgG levels specific for Pg and Aa were determined. In parallel, serum levels of ACPA (ACPA:IgG,IgA) and RF (RF:IgM,IgA) were measured. The extent of periodontal inflammation was assessed by the periodontal inflamed surface area. In both RA patients and the controls, the presence of subgingival Pg and Aa was comparable, anti-Pg and anti-Aa antibody levels were associated with the subgingival presence of Pg and Aa, and anti-Pg did not correlate with ACPA or RF levels. The subgingival Pg and Aa were not related to RA. No noteworthy correlation was detected between the antibodies against Pg and Aa, and RA-specific autoantibodies.

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.

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-α (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.

Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines).

OBJECTIVES: To assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA. METHODS: In the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up. RESULTS: Of 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia. CONCLUSIONS: ACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.

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's disease (CD) patients, with regard to the prevalence of joint complaints in AAb+ versus AAb- 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.

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.

Autoantibodies against citrullinated histone H3 in rheumatoid arthritis and periodontitis patients.

AIM: To determine the presence of citrullinated histones in inflamed periodontal tissue and to determine the presence of anti-citrullinated histone autoantibodies in sera from patients with rheumatoid arthritis (RA) and periodontitis (PD) patients. METHODS: The presence of citrullinated histone H3, PAD4 and CD68 was determined in 15 periodontal tissue biopsies from PD patients by immunohistochemistry. Sera from 36 healthy controls (HC), 113 PD patients and 84 patients with RA were assessed on presence of autoantibodies against citrullinated histones by Western blot and against citrullinated histone H3 by ELISA. RESULTS: Citrullinated histone H3, PAD4 and CD68 were present in periodontal tissue from nine (60%), 14 (93%) and 13 (87%) PD patients, respectively. Anti-citrullinated histone H3 autoantibodies were found in 33 (39%) patients with RA compared to three (8%) HC and 11 (10%) PD patients. Anti-citrullinated histone H3 levels were higher in anti-cyclic citrullinated peptide (anti-CCP)-positive compared to anti-CCP-negative patients with RA (p = .0008) and correlated moderately with anti-CCP levels (ρ = .22). No associations were found between anti-citrullinated histone H3 levels and periodontal status or smoking behaviour of patients with RA. CONCLUSION: PD patients are exposed to citrullinated histone H3 in inflamed periodontal tissue. Citrullinated histone H3 is targeted by autoantibodies present in RA sera. This supports a role for periodontitis in generation of antigens targeted by autoantibodies directed against citrullinated proteins.

Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis.

Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is a post-translational modification of arginine residues, leading to a change in structure and function of the respective protein. This modification, which is catalyzed by peptidylarginine deiminases (PADs), plays a role in several physiological processes in the human body. Interestingly, P. gingivalis secretes a citrullinating enzyme, known as P. gingivalis PAD (PPAD), which targets bacterial and human proteins. Because the extent of P. gingivalis protein citrullination by PPAD was not yet known, the present study was aimed at identifying the extracellular proteome and citrullinome of P. gingivalis. To this end, extracellular proteins of two reference strains, two PPAD-deficient mutants, and three clinical isolates of P. gingivalis were analyzed by mass spectrometry. The results uncovered substantial heterogeneity in the extracellular proteome and citrullinome of P. gingivalis, especially in relation to the extracellular detection of typical cytoplasmic proteins. In contrast, the major virulence factors of P. gingivalis were identified in all investigated isolates, although their citrullination was shown to vary. This may be related to post-translational processing of the PPAD enzyme. Altogether, our findings focus attention on the possible roles of 6 to 25 potentially citrullinated proteins, especially the gingipain RgpA, in periodontitis and rheumatoid arthritis.

Regulatory CD4+ T-Cell Subsets and Anti-Citrullinated Protein Antibody Repertoire: Potential Biomarkers for Arthritis Development in Seropositive Arthralgia Patients?

OBJECTIVE: Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP. METHODS: Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12). SAP that developed RA were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin. RESULTS: Treg numbers were similar between HC, SAP and RA patients. Although the bonafide Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p = 0.01). Fourteen (41%) SAP developed RA during follow-up. Their Treg numbers and subsets were comparable to non-switched SAP. At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Switched SAP displayed a more diverse IgG ACPA repertoire compared to non-switched SAP (p = 0.046) and showed more IgA reactivity than non-switched SAP reaching significance for Fib1 only (p = 0.047). CONCLUSION: Numbers of Total Treg and bonafide Treg subsets are not indicative for RA development in SAP, opposed to the ACPA repertoire.

The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis.

Periodontitis is an infective process that ultimately leads to destruction of the soft and hard tissues that support the teeth (the periodontium). Periodontitis has been proposed as a candidate risk factor for development of the autoimmune disease rheumatoid arthritis (RA). Porphyromonas gingivalis, a major periodontal pathogen, is the only known prokaryote expressing a peptidyl arginine deiminase (PAD) enzyme necessary for protein citrullination. Antibodies to citrullinated proteins (anti-citrullinated protein antibodies, ACPA) are highly specific for RA and precede disease onset. Objective of this study was to assess P. gingivalis PAD (PPAD) gene expression and citrullination patterns in representative samples of P. gingivalis clinical isolates derived from periodontitis patients with and without RA and in related microbes of the Porphyromonas genus. Our findings indicate that PPAD is omnipresent in P. gingivalis, but absent in related species. No significant differences were found in the composition and expression of the PPAD gene of P. gingivalis regardless of the presence of RA or periodontal disease phenotypes. From this study it can be concluded that if P. gingivalis plays a role in RA, it is unlikely to originate from a variation in PPAD gene expression.

Rheumatoid arthritis-associated autoantibodies in non-rheumatoid arthritis patients with mucosal inflammation: a case-control study.

INTRODUCTION: Rheumatoid arthritis-associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation. METHODS: The presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking. RESULTS: Logistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides. CONCLUSION: Although overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA-AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates.

Periodontitis and Rheumatoid Arthritis: What Do We Know?

BACKGROUND: Currently, in the field of rheumatology, there is much attention given towards the possible causality between periodontitis and rheumatoid arthritis (RA), specifically regarding the role of Porphyromonas gingivalis (Pg). This bacterium is unique, having a citrullinating enzyme. Antibodies against citrullinated proteins are rather specific for RA. METHODS: Because causality is ultimately tested in longitudinal cohort studies which currently do not exist for periodontitis and RA, this commentary applied Bradford Hill criteria on the existing literature to assess causality as the most likely interpretation of this association. CONCLUSIONS: From an epidemiologic point of view, patients with RA have a higher incidence of periodontal disease than individuals without RA. In addition, there is a dose-response pattern in the association between the severity of periodontitis and RA disease activity. There are indications that periodontitis precedes RA, but there is no evidence yet available to show that Pg plays a direct role in this temporal relationship. The role of the unique characteristic of citrullination by Pg remains unexplained. However, in animal models, citrullination by Pg plays a distinct role in the development and aggravation of experimental arthritis. Although the role of Pg in RA remains speculative, a causative role for periodontitis as a chronic inflammatory disease caused by infectious agents in RA seems biologically plausible.

The proportion of cancellous bone as predictive factor for early marginal bone loss around implants in the posterior part of the mandible.

AIM: This study envisaged to explain early marginal bone loss (first years of function) around implants in the posterior area of the mandible by the local bone quality (ratio cortical vs. cancellous bone). MATERIAL AND METHODS: Four hundred and twenty-three Brånemark MKIII implants inserted in the posterior region of the mandible were examined, retrospectively, on intra-oral radiographs taken at abutment connection, and 1 and 3-4 years after loading. The quality of the bone was assessed on cone beam or multi-slice CTs. The bone quality was determined by the relative proportions of cortical and trabecular bone at the insertion site. Cortical bone was defined as a clearly white structure without a trabecular pattern. Trabecular bone was defined as the structure between the two cortical plates. The width of both structures was measured at 1, 3, 5, and 7 mm away from the crest of the alveolar bone and converted in to relative proportions. Other parameters (smoking, history of periodontitis, dehiscence, pre-tapping, submerged healing, etc.) were retrieved from the patients record. RESULTS: At abutment connection, the mesial and distal marginal bone level was located 0.7 (±0.7) and 0.8 (±0.7) mm apically to the implant-abutment junction. At 1 year and 3-4 years of loading implants placed in a mandible consisting of <30% of cancellous bone had lost 1.49 and 1.83 mm, respectively. Implants placed in jawbone consisting of more than 60% of cancellous bone lost 0.74 and 0.91 mm after 1 year and 3-4 years of loading. The bone-level changes (both first year as well as after 3-4 years) were significantly less when the implant was placed in sites with a higher proportion of cancellous bone. Other parameters were significantly less important. CONCLUSIONS: Very cortical bone could jeopardize the long-term stability of the marginal bone surrounding implants placed in the posterior region of the mandible. A correlation between marginal bone loss and the proportion of cortical bone was demonstrated around Brånemark implants. At present, no comparable studies are available, and therefore, it cannot be excluded that similar events take place around other implant systems.

Lessons to be learned from periodontitis.

PURPOSE OF REVIEW: This 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 FINDINGS: P. 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. SUMMARY: In 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.

Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study.

INTRODUCTION: The association between rheumatoid arthritis (RA) and periodontitis is suggested to be linked to the periodontal pathogen Porphyromonas gingivalis. Colonization of P. gingivalis in the oral cavity of RA patients has been scarcely considered. To further explore whether the association between periodontitis and RA is dependent on P. gingivalis, we compared host immune responses in RA patients with and without periodontitis in relation to presence of cultivable P. gingivalis in subgingival plaque. METHODS: In 95 RA patients, the periodontal condition was examined using the Dutch Periodontal Screening Index for treatment needs. Subgingival plaque samples were tested for presence of P. gingivalis by anaerobic culture technique. IgA, IgG and IgM antibody titers to P. gingivalis were measured by ELISA. Serum and subgingival plaque measures were compared to a matched control group of non-RA subjects. RESULTS: A higher prevalence of severe periodontitis was observed in RA patients in comparison to matched non-RA controls (27% versus 12%, p < 0.001). RA patients with severe periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis (p < 0.001), while no differences were seen in IgM-RF or ACPA reactivity. Furthermore, RA patients with severe periodontitis had higher IgG- and IgM-anti P. gingivalis titers than non-RA controls with severe periodontitis (p < 0.01 resp. p < 0.05), although subgingival occurrence of P. gingivalis was not different. CONCLUSIONS: Severity of periodontitis is related to severity of RA. RA patients with severe periodontitis have a more robust antibody response against P. gingivalis than non-RA controls, but not all RA patients have cultivable P. gingivalis.

Clinical reliability of non-organoleptic oral malodour measurements.

AIM: Measurement of volatile sulphur compounds (VSC) by portable sulphur monitors (Halimeter, OralChroma) is a common practice for diagnosis of oral malodour. In this study, the clinical value of these devices was examined. MATERIALS AND METHODS: Two hundred and eighty patients with bad breath complaints attending a halitosis consultation were enrolled. Organoleptic scores were given by a trained and calibrated judge, before measurement of the VSC levels (Halimeter, OralChroma), to avoid any bias. RESULTS: Significant correlations were found between the organoleptic assessment, the Halimeter, and the OralChroma (R=0.74 for organoleptic versus Halimeter; 0.66 for organoleptic versus OralChroma; 0.63 for Halimeterversus OralChroma). The sensitivity and specificity (with regard to the organoleptic score) to detect patients with/without oral malodour for the Halimeter were 63% and 98%, respectively, and for the OralChroma 69% and 100% when using the cutoffs suggested by the manufacturer. By lowering these values, sensitivity could be improved without a significant decrease in specificity (both devices). CONCLUSIONS: We concluded that the measurement of the VSC levels can be used as an adjunct to the organoleptic assessment. Thresholds should be revisited in order to improve their clinical utility. These devices can prove the absence of malodour in case of pseudo-halitosis.

Characteristics of 2000 patients who visited a halitosis clinic.

AIMS: The aim of this paper was to analyse the aetiology and characteristics of 2000 patients who visited a multidisciplinary bad breath clinic in Leuven, Belgium and to correlate organoleptic ratings with portable device measurements. MATERIALS AND METHODS: The characteristics and aetiology of breath malodour of two thousand consecutive patients who visited a halitosis consultation were explored by means of a standard questionnaire and a clinical examination, including organoleptic scores provided by a trained and calibrated judge, and a portable bad breath detector (Halimeter). RESULTS: Most patients came without referral and had complaints for several years (mean: 7 years, SD: 8 years). For 76% of the patients, an oral cause was found [tongue coating (43%), gingivitis/periodontitis (11%) or a combination of the two (18%)]. Pseudo-halitosis/halitophobia was diagnosed in 16% of the cases; and ear, nose and throat/extra-oral causes were found in 4% of the patients. Most patients had an organoleptic score <3 and a Halimeter value <240 p.p.b. CONCLUSIONS: Even though it was observed that halitosis has a predominantly oral origin, a multidisciplinary approach remains necessary to identify ear, nose and throat or extra-oral pathologies and/or pseudo-halitosis/halitophobia.