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  1. Wei, Cheah Chia, Vaithilingam, Rathna Devi, Norazlina Mohammad, Huat, Siar Chong
    Ann Dent, 2019;26(1):30-33.
    MyJurnal
    Desquamative gingivitis (DG) is a manifestation of a number of mucocutanenous disorders, one of it being oral lichen planus (OLP). OLP is an autoimmune disease. The aetiology for this condition is unknown, but there are few factors associated with its occurrence, for example alcohol drinking, smoking, allergic reaction to certain medications or restorative material. DG lesions increase the long-term risk for plaque-induced periodontal disease. At the same time, dental plaque and calculus cause gingival OLP resulting in the erosive disease. This report presents the management of a case of oral lichen planus associated with desquamative gingivitis with periodontitis. The expertise involved are from the oral medicine, periodontic and prosthodontic clinics. The uniqueness of the case management was the introduction of single tufted brush, Tepe® compact tuft toothbrush, to perform “solo brushing technique”. It was able to remove plaque effectively and did not cause irritation to the gingivae. Patients presenting with mucocutaneous disorders which exarcebates other oral conditions requires multidisciplinary management. Proper treatment planning will significantly improve their oral health related quality of life.
  2. Mohamad Hanis Mat Nazri, Mohd Fakhrul Ridwan Mohd Azmi, Nor Adinar Baharuddin, Nur Ayman Abdul Hayei, Roslan Saub, Vaithilingam, Rathna Devi
    Ann Dent, 2018;25(2):36-42.
    MyJurnal
    To evaluate patient’s subjective preferences to scaling with narrow probe-shaped EMS Perio Slim PS tips
    compared to conventional tip based on pain perception using the Visual Analogue Scale (VAS). Ten patients
    were treated using a piezoelectric ultrasonic device (EMS) and two different scaler tips representing a
    conventional scaler tip and a Perio Slim PS scaler tip in a split-mouth design. Pain was evaluated after 2
    minutes scaling using Visual Analogue Scale (VAS). Data obtained was analysed by SPSS version 19.0 using
    Wilcoxon test. Pain assessment after treatment confirmed by the Visual Analogue Scale (VAS) showed that
    the Perio Slim PS scaler tip (maximum pain score: 4, minimum: 2) caused less pain than the conventional
    scaler tip (maximum: 8, minimum: 3) (p-value = 0.007). Using Perio Slim PS scaler tip caused less pain and
    discomfort during scaling treatment when compared with conventional scaler tip.
  3. Aziz J, Rahman MT, Vaithilingam RD
    J Trace Elem Med Biol, 2021 Jul;66:126754.
    PMID: 33831799 DOI: 10.1016/j.jtemb.2021.126754
    BACKGROUND: Periodontitis (PD) is a multifaceted inflammatory disease connected to bacterial infection that results in the destruction of tooth supporting structures and eventually tooth loss. Given their involvement in infection and inflammation, both metallothionein (MT) and zinc (Zn) might play vital roles in the development and progression of PD. More specifically, both MT and Zn are heavily involved in regulating immune functions, controlling bacterial infection, balancing inflammatory responses, and reducing oxidative stress, all of which are associated with the pathogenesis of PD.

    OBJECTIVE: This review paper will explore the physiological functions of MT and Zn and hypothesise how dysregulation could negatively affect periodontal health, leading to PD.

    FINDINGS: Bacterial lipopolysaccharide (LPS) derived from periodontal pathogens, namely P. gingivalis initiates the acute phase response, thus upregulating the expression of MT which leads to the subsequent deficiency of Zn, a hallmark of periodontal disease. This deficiency leads to ineffective NETosis, increases the permeability of the gingival epithelium, and disrupts the humoral immune response, collectively contributing to PD. In addition, the presence of LPS in Zn deficient conditions favours M1 macrophage polarisation and maturation of dendritic cells, and also inhibits the anti-inflammatory activity of regulatory T cells. Collectively, these observations could theoretically give rise to the chronic inflammation seen in PD.

    CONCLUSION: A disrupted MT and Zn homeostasis is expected to exert an adverse impact on periodontal health and contribute to the development and progression of PD.

  4. Eezammuddeen NN, Vaithilingam RD, Hassan NHM
    J Periodontal Res, 2023 Feb;58(1):29-42.
    PMID: 36317493 DOI: 10.1111/jre.13065
    BACKGROUND AND OBJECTIVE: Periodontitis (PD) is a dysbiotic disease of tooth-supporting structures that has been associated with various systemic diseases including rheumatoid arthritis (RA). To date, evidence demonstrated increased prevalence of RA among PD patients and postulated PD to have a role in the development of autoantibodies in RA patients. Therefore, a systematic review was conducted to assess the available evidence to ascertain the effect of PD on levels of autoantibodies in the serum, saliva and gingival crevicular fluid (GCF) of RA patients.

    MATERIAL AND METHODS: The systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Relevant literature was searched from PubMed, Web of Science, Scopus and Ebscohost databases from inception until 31 August 2020. The risk of bias in each study was determined based on the Newcastle-Ottawa Scale tool. Results from random-effect meta-analyses were presented as summary estimates of odds ratios (ORs) for seropositivity and standardised mean difference (SMD) of autoantibody levels with 95% confidence intervals. Sensitivity tests and meta-regression were performed to assess the robustness of the results and potential cause of heterogeneity.

    RESULTS: The electronic and manual searches gathered 932 articles. Following screening and full-text assessment, a total of 29 studies were included in the analysis. Twenty-eight published observational studies were included in the quantitative analysis in the form of random-effect meta-analysis which revealed that PD was associated with anti-citrullinated proteins autoantibodies (ACPAs) and Rheumatoid Factor (RF) seropositive RA patients (OR for ACPA seropositivity: 1.82; 95% CI: 1.13-2.93) (OR for RF seropositivity: 1.53; 95% CI: 1.05-2.24). Also, RA patients with PD had increased serum levels of ACPA and RF. However, high heterogeneity among studies' results, partially ascribed to the unstandardised case definition of PD and laboratory testing of autoantibodies. Apart from ACPA and RF in serum, studies which reported on other RA-related autoantibodies, as well as autoantibody levels in saliva and GCF were scarce.

    CONCLUSION: RA patients with PD tend to have greater ACPA and RF levels in their serum when compared with the RA patients without PD supporting the plausible role of PD in the development of systemic autoimmunity in RA patients.

  5. Cheah CW, Vaithilingam RD, Siar CH, Swaminathan D, Hornbuckle GC
    Implant Dent, 2014 Oct;23(5):593-601.
    PMID: 25192162 DOI: 10.1097/ID.0000000000000148
    To assess dimensional changes and histologic/histomorphometric aspects of grafted sockets using either calcium sulfate-platelet-rich plasma (CS-PRP) or CS alone in socket preservation procedure.
  6. Raman RP, Taiyeb-Ali TB, Chan SP, Chinna K, Vaithilingam RD
    BMC Oral Health, 2014;14:79.
    PMID: 24965218 DOI: 10.1186/1472-6831-14-79
    40 subjects with type 2 diabetes and moderate to severe CP were randomly distributed to groups receiving either NSPT or OHI. Periodontal parameters, glycosylated haemoglobin (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) were evaluated at baseline, 2- and 3-months intervals.
  7. Khan S, Saub R, Vaithilingam RD, Safii SH, Vethakkan SR, Baharuddin NA
    BMC Oral Health, 2015;15:114.
    PMID: 26419358 DOI: 10.1186/s12903-015-0098-3
    Chronic periodontitis (CP) is a global public health issue. Studies have suggested CP could be linked to obesity due to their similar pathophysiological pathway. The aim of this study is to determine the prevalence of CP and to assess the predictors for CP among the obese Malaysian population.
    METHODS: This is a cross-sectional study on obese participants. Obesity is defined as an individual who has Body Mass Index (BMI) ≥ 27.5 kg/m(2). A convenience sampling method was used. A total of 165 paricipants were recruited. This study involved answering questionnaires, obtaining biometric and clinical measurements of Visible plaque index (VPI), Gingival bleeding index (GBI), Probing pocket depth (PPD) and Clinical attachment loss (CAL). Data analysis was carried out using SPSS statistical software (SPSS Inc., version 20, US).
    RESULTS: A total of 165 participants; 67 (40.6%) males and 98 (59.4%) females participated in the study. Mean age of the participants was 43.9 (± 8.9). The prevalence of CP among the obese population was found to be 73.9%. Out of this, 43 and 55% were categorised as moderate and severe CP respectively. Around 64% of participants had sites with CAL ≥ 4 mm and participants with sites with PPD ≥ 4 mm were reported to be 25%. Around 83% of the participants had sites with GBI ≥ 30 and 92% of participants had sites with VPI ≥ 20%. GBI and VPI were found to have significantly higher odds for CP.
    CONCLUSION: Prevalence of CP was high among obese Malaysians. GBI and VPI were potential predictors for CP in this obese population.
  8. Akram Z, Safii SH, Vaithilingam RD, Baharuddin NA, Javed F, Vohra F
    Clin Oral Investig, 2016 Jun;20(5):903-14.
    PMID: 27005812 DOI: 10.1007/s00784-016-1793-4
    OBJECTIVE: There is a controversy over the influence of obesity on the periodontal treatment outcome in patients with chronic periodontitis (CP). The aim of the present systematic review was to evaluate the efficacy of non-surgical periodontal therapy (NSPT) in the management of CP among obese and non-obese patients.
    MATERIALS AND METHODS: The addressed focused question was "What is the efficacy, of NSPT with respect to clinical, radiographic, biochemical, microbiological, and patient-centered outcomes in obese as compared to non-obese chronic periodontitis patients?" Databases were searched from 1977 up to and including December 2014 using relevant key indexing terms. Unpublished data, experimental studies, letters to the editor, review articles, case reports, and commentaries were excluded. Meta-analysis of three studies was performed.
    RESULTS: Five clinical studies were included. The total number of patients ranged between 30 and 260 individuals. The mean age of patients was between 42.5 and 48.8 years. In three studies, the clinical periodontal parameters (plaque index (PI), gingival bleeding index (GBI), periodontal pocket depth (PPD), and clinical attachment loss (CAL)) in obese and non-obese patients following NSPT was comparable. Meta-analysis of PPD and CAL among obese and non-obese subjects showed comparable outcomes (PPD P = 0.91, I (2) 67.36 %; CAL P = 0.87, I (2) 77.16 %). However, in three studies, NSPT resulted in a significantly better clinical periodontal outcome among non-obese subjects than obese subjects. The difference in the levels of serum pro-inflammatory cytokine levels (IL-1β, IL-6, TNF-α, IFN-γ, leptin, adiponectin, and CRP) among obese and non-obese patients following treatment for CP was inconsistent.
    CONCLUSION: It remains unclear whether NSPT has a significantly higher impact on the clinical periodontal outcomes in obese patients than in non-obese patients with chronic periodontitis, given that the number of selected studies was relatively low and the reported findings were inconsistent.
    CLINICAL RELEVANCE: Although the effect of obesity on the outcome of NSPT still remains unclear, nevertheless clinicians are prompted to manage obesity prior to and during periodontal treatment.
    KEYWORDS: Cytokines; Inflammatory markers; Obese; Overweight; Periodontal therapy; Periodontitis
  9. Vohra F, Akram Z, Safii SH, Vaithilingam RD, Ghanem A, Sergis K, et al.
    Photodiagnosis Photodyn Ther, 2016 Mar;13:139-147.
    PMID: 26184762 DOI: 10.1016/j.pdpdt.2015.06.010
    BACKGROUND: The aim was to assess the efficacy of antimicrobial photodynamic therapy (aPDT) in the treatment of aggressive periodontitis (AgP).

    METHODS: The addressed focused question was "Is aPDT effective in the treatment of AgP?" MEDLINE/PubMed, EMBASE, Scopus, ISI Web of knowledge and Google-Scholar databases were searched from 1977 till May 2015 using combinations of the following keywords: antimicrobial; photochemotherapy; photodynamic therapy; photosensitizing agents; AgP; scaling and root-planing (SRP). Reviews, case reports, commentaries, and articles published in languages other than English were excluded.

    RESULTS: Seven studies were included. In 5 studies, aPDT was performed as an adjunct to SRP. Laserwavelengths and duration of irradiation ranged between 660-690 nm and 60-120 s, respectively. Laser power output as reported in 2 studies was 75 mW. One study showed significant improvement in periodontal parameters for subjects receiving aPDT as an adjunct to SRP as compared to treatment with SRP alone at follow up. However, comparable periodontal parameters were reported when aPDT as an adjunct to SRP was compared to SRP alone in the treatment of AgP in one study. One study showed comparable outcomes when aPDT was compared to SRP in the treatment of AgP. In two studies, adjunctive antibiotic administration to SRP showed significantly better outcomes when compared to application of adjunctive use of aPDT to SRP.

    CONCLUSION: aPDT is effective as an adjunct to SRP for the management of AgP, however, further randomized clinical trials with well defined control groups are needed in this regard.

  10. Lee YH, Lew PH, Cheah CW, Rahman MT, Baharuddin NA, Vaithilingam RD
    J Int Acad Periodontol, 2019 07 01;21(3):99-110.
    PMID: 31473702
    Periodontitis (PD), a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and tooth loss, is a major oral health problem. Rheumatoid arthritis (RA), with a global prevalence of 1%, is an autoimmune disease characterized as a chronic inflammatory disorder leading to synovial inflammation and destruction of cartilage and bone. Studies have reported an association between PD and RA whereby PD is reportedly more severe in patients with established RA. Justification for the plausible link between both conditions is based on shared characteristics and pathogenic similarities with regard to risk factors, immunogenetics and tissue destruction pathways. The search for the possible mechanism linking PD to RA continues as it can play an important role in enabling early intervention in the form of prevention and treatment of infection. This will ultimately improve patients' oral health related quality of life and reduce societal burden related to increased patient discomfort and treatment costs. The current review provides an update on the cellular and molecular events that have thus far explained the link.
  11. Sulaiman L, Saub R, Baharuddin NA, Safii SH, Gopal Krishna V, Bartold PM, et al.
    Oral Health Prev Dent, 2019;17(4):365-373.
    PMID: 31093611 DOI: 10.3290/j.ohpd.a42502
    PURPOSE: To assess the impact of extent and severity of chronic periodontitis (CP) on oral health-related quality of life (OHRQoL).

    MATERIALS AND METHODS: A cross-sectional comparative study was performed on subjects from multiple dental centres in Malaysia using a questionnaire covering sociodemographics, OHRQoL using the Malaysian Oral Health Impact Profile questionnaire, OHIP-14(M) and self-reported symptoms. Participants with severe CP were age-and gender-matched with periodontally healthy/mild periodontitis (HMP) participants based on inclusion and exclusion criteria. Full mouth periodontal examination was performed on participants. Outcome measures were OHIP-14(M) prevalence of impact and severity of impact scores.

    RESULTS: One hundred and thirty (130) participants comprising 65 severe CP and 65 HMP participants were included in the study. Prevalence of impact on OHRQoL was significantly higher in the severe CP than HMP group, with an odds ratio of 3. Mean OHIP-14(M) score was significantly higher in the severe CP (18.26 ± 10.22) compared to HMP (11.28± 8.09) group. The dimensions of psychological discomfort and functional limitation, and factors such as 'discomfort due to food stuck' and 'felt shy' were impacted more in severe CP compared to HMP group (p < 0.05). When compared with the HMP group, generalised severe CP participants showed higher prevalence of impact on OHRQoL [OR=5] (p < 0.05) compared to localised severe CP [OR=2] (p = 0.05). Participants who had experienced self-reported symptoms had statistically significant impacts on OHRQoL.

    CONCLUSIONS: Severe CP had a greater impact on OHRQoL compared to HMP. Impacts were mainly for functional limitation and psychological discomfort dimensions. When considering extent of disease, the impact on OHRQoL was mostly in generalised severe CP subgroup.

  12. Abdul Hayei NA, Yahya NA, Safii SH, Saub R, Vaithilingam RD, Baharuddin NA
    BMC Oral Health, 2021 03 31;21(1):169.
    PMID: 33789646 DOI: 10.1186/s12903-021-01540-0
    BACKGROUND: The influence of scaler tip design on root surface roughness, tooth substance loss and patients' pain perception is investigated.

    METHODS: This article was divided into the following parts: Part 1 Surface roughness and substance loss: an in vitro study, which involves intact extracted teeth sectioned and treated using a piezoelectric ultrasonic device (PM200 EMS Piezon, Switzerland) with a conventional scaler tip (FS-407) and a Perio Slim (PS) scaler tip (Perio Slim DS-016A). All sectioned samples for tooth surface roughness (n = 20) and tooth substance loss (n = 46) analyses were measured and compared using a 3D surface texture analyser and scanning electron microscope (SEM) respectively, at baseline and following scaling. Part 2 Pain Perception: a clinical study, which was a split mouth study design including 30 participants with gingivitis and/or mild chronic periodontitis; treated with supra-gingival scaling from teeth #13 to #23. Subjects were randomised to group A or group B. Group A was treated first with PS scaler tips, whereas group B was treated first with conventional scaler tips. Pain perception was recorded using the visual analogue scale (VAS).

    RESULTS: In vitro study: both scaler tips caused significant reduction in root substance roughness after scaling (p  0.05) was observed. The PS scaler tip caused statistically significantly less root substance loss (p 

  13. Sultan T, Cheah CW, Ibrahim NB, Asif MK, Vaithilingam RD
    J Dent, 2020 Oct;101:103455.
    PMID: 32828845 DOI: 10.1016/j.jdent.2020.103455
    OBJECTIVES: This clinical study assessed and compared the linear and volumetric changes of extraction sockets grafted with a combination of Platelet-Rich Fibrin (PRF) and Calcium Sulfate (CS) (PRF-CS), and extraction sockets grafted with a combination of PRF and xenograft (X) (PRF-X).

    METHODS: Five single maxillary premolar extraction sockets received PRF-CS grafts and five single maxillary premolar sockets received PRF-X grafts. Linear (horizontal and vertical) measurements were accomplished using Cone Beam Computed Tomography (CBCT) images and volumetric changes were assessed using MIMICS software. Soft tissue level changes were measured using Stonecast models. All measurements were recorded at baseline (before extraction) and at 5-months post-extraction.

    RESULTS: Significant reduction in vertical and horizontal dimensions were observed in both groups except for distal bone height (DBH = 0.44 ± 0.45 mm, p = 0.09) and palatal bone height (PBH = 0.39 ± 0.34 mm, p = 0.06) in PRF-X group. PRF-CS group demonstrated mean horizontal shrinkage of 1.27 ± 0.82 mm (p = 0.02), when compared with PRF-X group (1.40 ± 0.85 mm, p = 0.02). Vertical resorption for mesial bone height (MBH = 0.56 ± 0.25 mm, p = 0.008), buccal bone height (BBH = 1.62 ± 0.91 mm, p = 0.01) and palatal bone height (PBH = 1.39 ± 0.87 mm, p = 0.02) in PRF-CS group was more than resorption in PRF-X group (MBH = 0.28 ± 0.14 mm, p = 0.01, BBH = 0.63 ± 0.39 mm, p = 0.02 and PBH = 0.39 ± 0.34 mm, p = 0.06). Volumetric bone resorption was significant within both groups (PRF-CS = 168.33 ± 63.68 mm3, p = 0.004; PRF-X = 102.88 ± 32.93 mm3, p = 0.002), though not significant (p = 0.08) when compared between groups. In PRF-X group, the distal soft tissue level (DSH = 1.00 ± 0.50 mm, p = 0.03) demonstrated almost 2 times more reduction when compared with PRF-CS group (DSH = 1.00 ± 1.00 mm, 0.08). The reduction of the buccal soft tissue level was pronounced in PRF-CS group (BSH = 2.00 ± 2.00 mm, p = 0.06) when compared with PRF-X group (BSH = 1.00 ± 1.50 mm, p = 0.05).

    CONCLUSIONS: PRF-CS grafted sites showed no significant difference with PRF-X grafted sites in linear and volumetric dimensional changes and might show clinical benefits for socket augmentation. The study is officially registered with ClinicalTrials.gov Registration (NCT03851289).

  14. Lee YH, Baharuddin NA, Chan SW, Rahman MT, Bartold PM, Sockalingam S, et al.
    Clin Oral Investig, 2021 Mar;25(3):1441-1450.
    PMID: 32656595 DOI: 10.1007/s00784-020-03452-9
    OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA.

    MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 μm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups.

    RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls.

    CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation.

    CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.

  15. Han PSH, Saub R, Baharuddin NA, Sockalingam S, Bartold PM, Vaithilingam RD
    BMC Oral Health, 2020 11 23;20(1):332.
    PMID: 33225923 DOI: 10.1186/s12903-020-01275-4
    BACKGROUND: This study aimed to assess the impact of periodontitis (PD) on the health related quality of life (HRQoL) and oral health related QoL (OHRQoL) of subjects with rheumatoid arthritis (RA) and PD.

    METHODS: Subjects from dental and RA clinics were screened. Complete periodontal examinations were performed. Subjects were divided into 4 groups: RA-PD, RA, PD and healthy controls (HC). Questionnaires on characteristics and Malaysian versions of Oral Health Impact Profile (OHIP-14(M)) and Health Assessment Questionnaire (HAQ-DI)) were answered.

    RESULTS: A total of 187 subjects were included (29 RA-PD, 58 RA, 43 PD and 57 HC). OHIP-14(M) severity score was highest in the PD group (17.23 ± 10.36) but only significantly higher than the HC group (p 

  16. Tengku H TNN, Peh WY, Shoaib LA, Baharuddin NA, Vaithilingam RD, Saub R
    Children (Basel), 2021 May 22;8(6).
    PMID: 34067484 DOI: 10.3390/children8060435
    This study aimed to investigate the association between oral disease burden and oral health related quality of life (OHRQoL) among overweight/obese (OW/OB) and normal weight (NW) Malaysian adolescents. A total of 397 adolescents were involved in the two-year prospective observational cohort study. OHRQOL was measured through a self-administered questionnaire containing the short version of the Malaysian Oral Health Impact Profile (OHIP[M]). Body mass index (BMI) was used for anthropometric measurement. Whilst, decayed, missing, and filled teeth (DMFT) index, Significant Caries Index (SiC), simplified basic periodontal examination (S-BPE), and gingival bleeding index (GBI) were used for clinical assessment tools. Higher dental caries prevalence was observed in the NW group while higher SiC was reported in the OW/OB group. Regardless of the obesity status, the prevalence of gingivitis (BPE code 1 and 2) was high in this study. A reduction of GBI prevalence was observed in the two-year follow-up results with an increased prevalence of OHRQoL impact in the OW/OB group compared to the NW group (p > 0.05). The findings from this study suggested that obesity status did not have influence over the burden of oral diseases and OHRQoL. It offers insights referring to the changes in adolescents' oral diseases burden and OHRQoL.
  17. Cheah CW, Al-Maleki AR, Vadivelu J, Danaee M, Sockalingam S, Baharuddin NA, et al.
    Int J Rheum Dis, 2020 Oct;23(10):1344-1352.
    PMID: 32743970 DOI: 10.1111/1756-185X.13919
    INTRODUCTION: Rheumatoid arthritis (RA) is associated with chronic periodontitis (CP) due to shared risk factors, immuno-genetics and tissue destruction pathways. Human cathelicidin LL-37 has been suggested as a possible mechanistic link for these diseases. This study investigated the levels of salivary and serum LL-37 in subjects with RA and CP and their correlation with disease parameters.

    METHOD: Subjects were allocated into RA (n = 49) or non-RA (NRA) (n = 55) groups, where 3 subgroups were further established; chronic periodontitis (CP), gingivitis (G) and periodontal health (H). Demographic and periodontal parameters were collected. Rheumatology data were obtained from hospital records. Serum and salivary LL-37 levels were measured using enzyme-linked immunosorbent assay and compared for all groups.

    RESULTS: For salivary LL-37, RA-CP was significantly higher than NRA-G and NRA-H (P = .047). For serum LL-37, all RA and NRA-CP were significantly higher than NRA-G and NRA-H (P = .024). Salivary LL-37 correlated negatively with clinical attachment loss (CAL) (P = .048), but positively with erythrocyte sedimentation rate (ESR) in RA-H (P = .045). Serum LL-37 showed positive correlation with ESR (P = .037) in RA-G, with C-reactive protein (P = .017) in RA-H, but negative correlation with number of teeth (P = .002) in NRA-CP. Rheumatology data correlated positively with periodontal parameters in RA-CP group.

    CONCLUSION: NRA-CP subjects with high serum LL-37 should receive comprehensive periodontal therapy. Positive correlation between rheumatology data and periodontal parameters showed that RA disease stability may be obtained by assessing the periodontal condition. Periodontal therapy is necessary to compliment RA treatment to achieve optimum outcome for RA patients with concurrent CP.

  18. Batool A, Vaithilingam RD, Mohamad Hassan NH, Safii SH, Saub R
    Medicine (Baltimore), 2023 Oct 13;102(41):e35340.
    PMID: 37832126 DOI: 10.1097/MD.0000000000035340
    BACKGROUND: Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA patients with periodontitis (RA-PD) are associated with elevated inflammatory burden due to increased production of proinflammatory cytokines. Controlling upregulated MMPs activity in these patients may have potential therapeutic effects. Therefore, aim of this study is to address the focused question: "Do RA subjects with concurrent PD have different levels of MMPs in comparison to RA alone, PD alone and HC subjects?"

    METHODS: The systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search from 4 electronic databases (EMBASE, Medline, Web of Science, and Cochrane library) and manual search was performed from inception to July 2023. Quality assessment of each article was done using Newcastle-Ottawa Scale. Meta-analyses derived results were summarized as standardized mean difference (SMD) with 95% confidence intervals.

    RESULTS: A total of 879 articles were extracted. Following screening and full text assessment, 9 studies were included. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 were consistently elevated in RA-PD subjects. MMP-8 levels were found to be higher in RA-PD subjects compared with RA alone, PD alone, and HC in 3 studies reporting GCF levels (SMD = 1.2; Z = 2.07; P = .04) and 2 studies reporting serum levels (SMD = 0.87; Z = 4.53; P < .00001).

    CONCLUSION: RA-PD group showed significantly higher MMP levels in their serum and GCF compared with HC, RA, and PD alone individuals. MMP-8 may serve as a reliable biomarker in the diagnosis and management of RA-PD subjects.

  19. Shahbaz M, Al-Maleki AR, Cheah CW, Aziz J, Bartold PM, Vaithilingam RD
    Int J Rheum Dis, 2024 Nov;27(11):e15415.
    PMID: 39526323 DOI: 10.1111/1756-185X.15415
    Periodontitis (PD) is characterized by the host's inflammatory responses to microbial dental biofilm dysbiosis, potentially resulting in tooth loss if left untreated. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease leading to synovial inflammation and destruction of joint cartilage and bone. The suggested association between PD and RA is based on the potential of chronic inflammation present in periodontitis, which could induce alterations in proteins through post-translational modifications, leading to the formation of citrullinated and carbamylated protein antigens. Antibodies directed against these antigens can serve as biomarkers for the underlying immunological processes in RA. Recent studies have also focused on bacterial proteolytic enzymes released from PD-associated bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which are also sources of these antibodies. Chronic inflammation in PD causes increased levels of inflammatory cytokines (interferon-α, interleukins-6 and 8, tumor necrosis factor-α) and neutrophil extracellular traps (NETs). The oral microbiota in PD is also associated with the release of NETs (a process known as NETosis). Elevated NET levels are a source of citrullinated and carbamylated proteins which highlights their role in an individual's risk of developing RA (pre-RA individuals) and the progression of chronic RA. This narrative review describes periodontitis and the dysbiotic subgingival microbiota and its role in NETosis as risk factors for inducing early RA and the prospects of identifying pre-RA individuals and seronegative RA patients with these risk factors.
  20. Lew PH, Rahman MT, Safii SH, Baharuddin NA, Bartold PM, Sockalingam S, et al.
    BMC Oral Health, 2021 07 20;21(1):360.
    PMID: 34284769 DOI: 10.1186/s12903-021-01712-y
    BACKGROUND: Previous studies have reported conflicting findings between serum anti-citrullinated protein antibodies (ACPA) levels in rheumatoid arthritis (RA) participants with and without periodontitis (Pd). This study aimed to analyse possible correlations between serum ACPA levels and clinical parameters in Pd and RA participants.

    METHODS: Full mouth periodontal examination (probing pocket depth, clinical attachment levels, gingival bleeding index, visual plaque index) was conducted and serum samples obtained from 80 participants comprising RA, Pd, both RA and Pd (RAPd) and healthy individuals (HC). Erythrocyte sedimentation rates (ESR) and periodontal inflamed surface area (PISA) were obtained. Serum samples were analysed for ACPA quantification using enzyme-linked immunosorbent assay (ELISA).

    RESULTS: Median levels (IU/mL) of ACPA (interquartile range, IQR) in RAPd, RA, Pd and HC groups were 118.58(274.51), 102.02(252.89), 78.48(132.6) and 51.67(91.31) respectively. ACPA levels were significantly higher in RAPd and RA as compared to HC group (p  RA > Pd > HC. However, lack of any significant correlation between the serum ACPA levels with the clinical Pd and RA parameters warrants further studies to investigate the causal link between RA and Pd for such a trend. Further studies involving more inflammatory biomarkers might be useful to establish the causal link between Pd in the development and progression of RA or vice versa.

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