Table 1: Summary of papers relating to the relationship between periodontitis and rheumatoid arthritis.

AuthorsStudy
population
Demographic
characteristics
Exclusion
criteria
Periodontal disease
evaluation
RA
treatment
ResultsAssociation of PD × RA

Ishida et al., 2012 [34]30 RA patients;
30 patients with PD;
30 healthy volunteers
RA (27 females and 3 males; 66 ± 2 years; 3 smokers);
PD (20 females and
10 males; 62.3 ± 1.5 years;
1 smoker and 2 former smokers);
healthy (20 females and 10 males; 53.4 ± 2.7 years; nonsmokers)
Periodontal therapy 6 months prior to examination
Less than 15 teeth
Diabetes mellitus and pregnancy
CAL, PPD, and missing teethAnti-TNF-αThe hypomethylated status, a single region of the IL-6, may contribute to elevated serum levels of this cytokine, implying a role in the pathogenesis of PD and RA

Mikuls et al., 2012 [35]Patients: 171 autoantibody negative;
75 autoantibody positive; 38 high risk based on the presence of a positive ACPA or positivity to 2 or more RF assays
Negative antibody (69% female; 44 ± 14 years; 37% smokers; 5% with DM);
positive antibody (73% female; 48 ± 15 years; 31% smokers; 4% with DM);
high risk (76% female; 51 ± 16 years; 29% smokers; 5% with DM)
Age < 18 yearsNot analyzedNot
informed
Anti-P. gingivalis concentrations were higher in high-risk, with autoantibody (anti-CCP and RF), positive group than in the autoantibody negative group

Nesse et al., 2012 [36]15 patients with PD; 6 healthy volunteers;
4 RA patients
PD and Ab5612+ (63% female; 48.9 ± 11.4 years;
50% smokers); PD and Ab5612− (71% female; 53.6 ± 17.9 years; 29% smokers);
PD and F95+ (50% female; 55 ± 12.4 years; 40% smokers); PD and F95− (100% female; 43.2 ± 16.3 years; 40% smokers); PD either+ (58% female; 52.3 ± 14 years; 42% smokers); PD both− (100% female; 46.2 ± 18.5 years; 33% smokers); controls either+ (100% female; age: 28.5 ± 5.5 years;
50% smokers); controls either− (50% female;
28 ± 8.6 years; 25% smokers)
Other systemic conditions
(excluding RA)
PPDNot
informed
Formation of citrullinated proteins in periodontal tissues was shown,
which appear to be a variety similar to those observed
in RA synovial tissue affected by RA

Ranade and Doiphode, 2012 [37]40 RA patients;
40 healthy volunteers
80% female
20–70 years
Systemic diseases;
medications that affect the periodontium; tobacco habit
Dental treatment
(a month before)
ABL, CAL, PPD, GI, and PINot
informed
High prevalence of mild to moderate PD in patients with RA presenting significantly higher GI, PI, PPD, and CAL, when compared to healthy volunteers

Scher et al., 2012 [38]31 patients with new-onset RA;
34 chronic RA patients; 18 healthy volunteers
New-onset RA (68% female; 42.2 years; 16% smokers, 16% former smokers, and 68% nonsmokers); chronic RA (79% female; 47.7 years; 6% smokers; 24 former smokers; 70% nonsmokers); healthy (65% female; age: 42.2 years; 6% smokers; 16% former smokers; 78% nonsmokers)Recent use of any antibiotic therapy;
current extreme diet;
inflammatory bowel disease
Malignancy;
consumption of probiotics;
tract surgery leaving permanent residua;
liver, renal, or peptic ulcer diseases
CAL, PPD, and BOPCorticoids, DMARDs, and biologic therapyNew-onset RA patients exhibit a high prevalence of PD at disease onset; the colonization with P. gingivalis correlates with PD severity; overall exposure was similar among groups

Smit et al., 2012 [39]95 RA patients; 44 non-RA controls;
36 healthy volunteers
RA (68% female; 56 ± 11 years; 23% current smokers;
40% former smokers);
non-RA controls (57% female; 54 ± 9.7 years;
27% current smokers; 43% former smokers); healthy (56% female; 34 ± 15 years;
14% current smokers)
Age < 18 years;
edentulism;
diabetes mellitus;
active thyroid disease;
nonoral infections
Malignancy; myocardial infarction or stroke; pregnancy
Antibiotic use
BOP, PPD, and CALDMARDs and anti-TNF-αAssociation between PD and RA and the increased prevalence of PD in patients with RA
Anti-P. gingivalis titers were higher in RA patients with severe PD compared with non-RA patients  

Témoin et al., 2012 [40]11 RA patients; 25 patients with OARA (100% female; 45–70 years); OA (9 males and 16 females; 50–80 years)Antibiotic use
Edentulism
Not analyzedNot
informed
Bacterial DNA was detected in 13.9% of RA patients; F. nucleatum consisted in the pathogen most prevalent

Torkzaban et al., 2012 [41]53 RA patients; 53 healthy volunteersRA (41.5 years);
healthy (43.5 years);
58 females and 48 males
<7 teeth; systemic diseases such as diabetes or Sjögren’s disease; antibiotics use; treatment for PD; immunosuppressive drugs; smokersPI, BOP, and CALNot
informed
Patients with RA had a higher percentage of sites presenting plaque, BOP, and CAL

Bıyıkoğlu et al., 2013 [42]10 patients with
PD and RA;
15 patients with PD
PD and RA (9 females; 46.6 ± 8 years; 8 smokers); PD (6 females; 46.73 ± 7 years; 9 smokers)Systemic disease or infection other than RA; history of antibiotic therapy
Periodontal treatment
<10 teeth
PPD, CAL, BOP, and PIMTX, leflunomide, prednisolone, chloroquine, sulfasalazine, anti-CD20, and anti-TNF-αThe nonsurgical periodontal treatment reduced the clinical periodontal parameters and promoted an improvement in the scores of RA

Cetinkaya et al., 2013 [43]17 RA patients; 16 patients with PD; 16 healthy volunteersRA (14 females and 3 males; 47.82 years)
PD (6 females and 10 males; 44 years); healthy (8 females and 8 males; 28 years)
Conservative or prosthetic restorations;
caries at the anterior region; systemic or local disease with an influence on the immune system (cancer and cardiovascular and respiratory diseases); history of hepatitis or HIV infection; immunosuppressive chemotherapy;
current pregnancy or lactation; antibiotic prophylaxis; history of antibiotic therapy
Periodontal treatment
<18 years; smokers
PI, GI, PPD, and CALMTX, sulfasalazine, leflunomide, NSAIDs, and corticoidsNo significant differences in the levels of pro- and anticytokine between PD and RA were observed

Chen et al., 2013 [44]13779 RA patients; 137790 non-RA patientsRA (77.4% female; 52.6 ± 14.4 years); controls (77.4% female; 52.4 ± 15.4 years); comorbidities: diabetes mellitus and Sjögren’s syndromeAge < 16 yearsPeriodontal surgery, number of PD-related visitsNot
informed
PD severity was related to a history of periodontal surgery, more PD-related visits, and higher costs of medical care; an association between periodontitis and incident RA was demonstrated

Dev et al., 2013 [45]852 patients with PD; 668 healthy volunteers52.8% female
and 47.2% male
30–70 years
Smokers; diabetes mellitus; periodontal therapy (3 months before); antibiotic use (3 months before); systemic disease and osteoporosis;
antibiotic prophylaxis;
pregnancy; lactation
PPD, BOP, and CALNot
informed
Moderate to severe periodontitis is an independent risk factor for RA

Erciyas et al., 2013 [46]30 RA patients with moderate to high disease activity and chronic PD (LDA); 30 RA patients with low disease activity and chronic PD (MHDA)LDA (25 females; 42.6 ± 10.05 years); MHDA (22 females; 43.83 ± 10.97 years)Periodontal therapy (6 months); presence of any other systemic diseases;
smokers; <18 teeth
Antibiotic therapy
PI, PPD, CAL, and BOPDMARDs
Corticoids
NSAIDs or anti-TNF-α
SRP might prove beneficial in reducing RA severity as measured by ESR, CRP, TNF-α levels in serum, and DAS28 in RA patients with chronic periodontitis
related to TNF-α

Gümüş et al., 2013 [47]17 RA patients; 19 patients with OPR; 13 healthy volunteersRA (17 females; 44 years)
OPR (19 females; 58 years)
Healthy (13 females; 54 years)
Systemic disease;
antibiotic use (6 months); corticosteroids; β-blockers use; diabetes mellitus; periodontal therapy (6 months)
<10 teeth; smokers
PPD, CAL, and BOPNSAIDsConcentrations in serum and GCF of RANKL and OPG were significantly higher and lower, respectively, in patients with RA when compared to individuals with OPR and healthy volunteers; the total counts of the IL-17 and IL-17F were significantly higher in patients with RA compared to the control group

Gümüş et al., 2013 [48]17 RA patients; 19 patients with OPR; 13 healthy volunteersRA (17 females; 44 years)
OPR (19 females; 58 years)
Healthy (13 females; 54 years)
Systemic disease
Antibiotic use (6 months); corticosteroids; β-blocker use; diabetes mellitus; periodontal therapy (6 months);
<10 teeth; smokers
PPD, CAL, BOP, and PINSAIDsDespite the long-term use of various anti-inflammatory drugs in RA and osteoporosis, patients involved in this study showed an increase in gingival crevicular and serum levels of TNF-α

Joseph et al., 2013 [49]100 RA patients;
112 healthy volunteers
RA (76 females and 24 males; 46.54 ± 8.5 years) Healthy (86 females and 26 males; 45.91 ± 9.76 years)Systemic diseases;
smokers; conditions that may alter the serum CRP and blood ESR levels; antibiotic use; periodontal therapy
GI, PPD, CAL, missing teeth, and OHI-SNot
informed
Patients with RA, compared to healthy volunteers, showed a significant difference in PPD and CAL, and 58% of patients with RA had moderate to severe PD

Lappin et al., 2013 [50]38 RA patients;
36 healthy volunteers
RA (17 females and 21 males; 31–70 years; 24 nonsmokers and 16 smokers); healthy (16 females and 20 males; 30–65 years; 20 nonsmokers and 16 smokers)Systemic disease;
previous antibiotic use
(3 months)
PPD, CAL, BOP, and missing teethNot
informed
Although smokers have shown lower antibody titers, individuals with periodontitis showed higher levels of anti-CCP antibodies

Okada et al., 2013 [51]55 RA patientsTreatment group (84.6% female; 60.7 years; 9 former smokers and 17 nonsmokers); control group (82.8% female; 62.7 years; 11 former smokers and 18 nonsmokers)Diabetes mellitus;
pregnancy;
antibiotic use (3 months);
periodontal therapy
(3 months)
GI, PI, CAL, BOP, and PPDCorticoids, DMARDs, and NSAIDsSRP decreased RA parameters and serum levels of IgG to P. gingivalis
Citrulline in patients with RA

Reichert et al., 2013 [52]42 RA patients;
114 healthy volunteers
Healthy (40.4% female; 53.8 ± 16.7 years; 10.7% smokers, 14.3% former smokers, and 75% nonsmokers); RA (52.4% female; 56.1 ± 15.2 years; 14.3% smokers, 11.9% former smokers, and 73.8% nonsmokers)Pregnancy;
antibiotic use;
periodontal therapy
BOP, CAL, and PINot
informed
There was a significant amount of P. gingivalis DNA in synovial fluid and in subgingival plaque from patients with RA

De Pablo et al., 2014 [53]96 patients with PD; 98 without PDPD (62% female; 46 ± 8.9 years; 24% smokers)
Without PD (59% female; 29 ± 7.3 years; 22% smokers)
Pregnancy; lactation;
antibiotic and NSAIDs use (3 months before); vitamin supplementation
(3 months before);
regular mouthwash;
dietary requirements (celiac disease)
Not analyzedNot
informed
Serum antibodies were significantly higher in patients with PD compared with those without PD for antibodies against CEP-1, REP-1, vimentin, and fibrinogen
Cit-vim

Khantisopon et al., 2014 [54]196 RA patients87% female; 51.7 ± 9.7 years; 78% nonsmokers, 30.69% with hypertension; 34.16% with dyslipidemia; 2.97% with DM; 2.47% with chronic kidney disease; 58.97% with osteoporosis; and 23.08% with osteopenia.Pregnancy; lactation;
systemic conditions that could affect the progression of periodontal disease, such as uncontrolled diabetes mellitus, severe hypertension, severe renal insufficiency, or malignancies; antibiotic uses
GI, PI, CAL, PPD, and gingival recessionMTX, prednisolone, DMARDs, and diclofenacRA Patients had a high prevalence of moderate or severe periodontitis  — 
Increasing age, the male sex, history of previous or current smoking, and high PI were associated with the severity of periodontal disease

Mikuls et al., 2014 [55]287 RA patients;
330 healthy volunteers
RA (63% male; 59 years; 19% smokers, 43% former smokers; 38% nonsmokers); healthy (60% male; 59 years; 11% smokers, 35% former smokers, and 54% nonsmokers)Tetracycline or antibiotic use (6 months);
cyclosporine or dilantin; antibiotic prophylaxis prior to dental probing
PPD, BOP, PI, and gingival recessionNot
informed
Periodontitis was more common in patients with RA positive for anticyclic citrullinated peptide; there was an association between periodontitis and the number of inflamed joints and RF Antibodies specific for anticyclic citrullinated peptide were higher in patients with P. gingivalis subgingival plaque

Wolff et al., 2014 [56]22 RA patients; 22 healthy volunteers68% female;
51.7 ± 9.7;
14% smokers
Current therapy with biological DMARDs;
poor oral hygiene or disabilities that interfere with adequate oral hygiene;
periodontitis as a manifestation of systemic disease; periodontal therapy within the past 5 years;
professional to antibiotics use; pregnancy or nursing during the past 6 months
PPD, BOP, GI, PI, and CALDMARDs and corticoidsPPD, BOP, and CAL
were increased in RA patients when compared to healthy volunteers

Seror et al., 2015 [57]694 early-RA patients; 79 healthy controls; 61 patients with PD; 54 patients with siccaRA (78.2% female; 48.5 ± 12.3 years; 48% ever smokers); healthy (84.6% female; 47.6 ± 11.9 years; 16.2% ever smokers); sicca (85.2% female; 48.9 ± 11.5 years; 37.3% ever smokers); PD (41% female; 50.7 ± 8.3 years; 65.6% ever smokers)DMARDs (except within the 15 days before inclusion) or steroids use; inflammatory rheumatic disease other than RANot analyzed NSAIDs and DMARDsAnti-P. gingivalis antibody titres did not significantly differ between early-RA patients and
healthy controls,
sicca controls,
or PD controls



Silosi et al., 2015 [58]21 healthy controls, 16 with active RA, 14 with PC, and 12 RA-CP associationControls (7 males and 14 females; 35–58 years) RA (4 males and 12 females; 38–62 years); PC (6 males and 8 females; 39–68 years)
RA-PC (3 males and 9 females; 38–62 years)
History of medication other than NSAIDs
Drugs (6 months);
periodontal
treatment;
pregnancy;
hormonal or vitamin therapy
PI, BOP, and PPDNot informedDifferences of serum MMP-9 between RA and CP groups and control
Serum levels of MMP-9 were similar in RA and RA-CP
Increased MMP-9 CGF levels in RA-CP subjects as compared to CP

Gonzales et al., 2015 [59]287 with RA and
330 controls with OA
RA (63% male; 59 ± 12 years; 38% never smokers; 43% former smokers; 19% current smokers; 18% with DM; 45% hypertension; 13% cardiovascular disease; 11% osteoporosis); OA (60% male; 59 ± 11 years; 54% never smokers; 35% former smokers; 11% current smokers; 25% with DM; 57% hypertension; 10% cardiovascular disease; 15% osteoporosis)Tetracycline or related antibiotic use (6 months);
antibiotic premedication
Pregnancy or breastfeeding;
prior use of cyclosporine or phenytoin;
systemic inflammatory disease
ABLMTX, prednisolone, and biologic therapyACPA-positive patients with RA had a statistically significantly higher mean percentage of sites with ABL >20% than patients with OA
After multivariate adjustment, greater ABL was significantly associated with higher serum ACPA concentration,
DAS28, health assessment questionnaire disability,
tender joint count,
and joint space
narrowing scores among patients with RA

ABL, alveolar bone loss; anti-CCP, anticyclic citrullinated peptide; anti-TNF-α, tumor necrosis factor-alpha antagonists; BI, bleeding index; BOP, bleeding on probing; CAL, clinical attachment level; CI, calculus index; DAS28, disease activity score in 28 joints; DM, diabetes mellitus; DMARDs, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; GAP, generalized aggressive periodontitis; GBI, gingival bleeding index; GBTI, gingival bleeding time index; GCF, gingival crevicular fluid; GI, gingival index; HCQ, hydroxychloroquine; IL, interleukin; JIA, juvenile idiopathic arthritis; LAP, localized aggressive periodontitis; MMP, matrix metalloproteinase; MTX, methotrexate; NSAIDs, nonsteroidal anti-inflammatory drugs; OA, osteoarthritis; OHI-S, oral hygiene index-simplified; OPR, osteoporosis; PBI, papillary bleeding index; PD, periodontitis; PI, plaque index; PPD, probing pockets depths; PsA, psoriatic arthritis; PSI, periodontal screening index; RA, rheumatoid arthritis; RANK, Receptor Activator of Nuclear Factor κB; RANKL, Receptor Activator of Nuclear Factor κB Ligand; RF, rheumatoid factor; SRP, scaling and root planning; TNF-α, tumor necrosis factor alpha; VPI, visible plaque index. was considered significant.