Is there a relationship between periodontitis and rheumatoid arthritis?

Abstract

Background:

Growth of scientific evidence suggests an exquisite association between oral infection and systemic diseases. Though etiologies of periodontitis and rheumatoid arthritis (RA) are separate, their underlying pathological processes are sufficient to warrant consideration of hypothesis that individuals at risk of developing RA may also be at the risk of developing periodontitis and vice versa.

Materials and Methods:

To test their relationship, a study was carried out on 80 individuals. Part A: Forty subjects having rheumatoid arthritis (RA group) were compared to 40 controls without arthritis (NRA group). Their periodontal indices rheumatoid arthritis clinical laboratory parameters were also correlated with periodontitis in group. Part B: Omplete periodontal treatment was done for 10 patients of group suffering from periodontitis. All parameters of periodontal indices were measured pre-operatively and weeks after completion of periodontal treatment.

Results:

(1) There was high prevalence of mild (12.5%) to moderate (75%) periodontitis in group. (2) Extent severity of periodontal disease rheumatoid arthritis were positively correlated. (3) Statistically significant differences were present in periodontal parameters of RA group compared to NRA group. (4) There was statistically, significant reduction in parameters postoperatively with concomitant decrease in periodontal parameters in RA group.

Conclusion:

Thus, an association exists between periodontal disease with an underlying dysregulation of the molecular pathways in the inflammatory response. Also, there are significant management implications in the future as new host modifying medications are developed.

INTRODUCTION

The notion that oral infection has the ability to cause systemic disease is not a novel concept. Theory of focal infection was first suggested by Hippocrates.[1] Periodontal disease is an all-encompassing term relating to the destructive inflammatory disorders of the hard and soft tissues surrounding the teeth.[2] Traditional paradigms have maintained that periodontitis is an oral disease, and that tissue destructive response remains localized within the periodontium, limiting effects of the disease to the oral tissues supporting the teeth.[3]

However, little attention has been paid to the impact of the periodontal infections on human health.[4] There have been a vast number of reports based on clinical evidence alone, purporting to show that oral infection can either cause or aggravate many diseases. The diseases frequently mentioned are arthritis chiefly of rheumatoid type, valvular heart disease, and skin, ocular and renal disease.[5]

It is an undoubted fact that foci of infections are frequently found in patients suffering from rheumatoid arthritis (RA), but their etiological significance remains obscure. Focus of infection is the means, whereby tissue becomes sensitized to bacterial antigens and that an abnormal immune response follows any further contact with the original antigen. No satisfactory proof is available, that such a sensitizing mechanism is an essential factor underlying the development of RA. If, however, it is shown that a higher incidence of focal infection is present in the RA patients than in a comparable group of controls, it supports the view that focal infection is of etiological importance.[6] The findings of likely relationship between RA and periodontitis require further validation.[7]

Thus, the aims of this study are-

1. To evaluate the periodontal condition of patients with RA

2. To correlate the status of periodontitis to various clinical laboratory parameters of RA

3. To evaluate the condition of RA patients after elimination of oral foci of infection by periodontal therapy.

4. To compare the clinical parameters of arthritis group with non-arthritis group.

MATERIALS AND METHODS

The study was done in parts:

Part A: The study population comprised of 80 individuals between the ages 20-70 years, which were divided into two groups of 40 each.

• Group I: Subjects diagnosed with rheumatoid arthritis (RA group)

• Group II: Subjects in control group without rheumatoid arthritis Non-RA group

Selection criteria for both groups

Subjects having no other systemic disease, no medications to affect the periodontium NRA, no tobacco habit, no dental treatment months prior, no conditions to contraindicate periodontal examination. After obtaining informed consent, the RA group was matched to RA group for age gender.

Part A of the study evaluated and compared the periodontal condition of individuals having RA those who don′t have it.

Phase I: Baseline investigations were done for all subjects: [Figure 1a and b].

Figure 1.

(a) Periodontal condition of rheumatoid Arthritis patient (group 1 - RA group) (b) Intra oral periapical radiograph of rheumatoid arthritis patient (group 1 - RA group) having severe periodontitis (c) Involvement of wrist, metacarpophalangeal and proximal interphalangeal joints of rheumatoid arthritis patients (d) PA hand wristradiograph of rheumatoid arthritis patient showing erosions in metacarpophalangeal and proximal interphalangeal joints

Full mouth intraoral periapical radiographs for RA group, complete hemogram, erythrocyte sedimentation rate (ESR), and blood sugar levels for RA NRA groups.

Case history pro-forma for periodontal examination included

Examination of dentition, and gingiva and tooth cleaning habits indices: Laque,[8] ingival leeding,[8] mobility,[9] pocket depth, clinical attachment loss, and bone loss (IOPA).

Rheumatoid arthritis examination: [Figure 1c and d]

1. Morning stiffness

2. Arthritis of three more joint areas

3. Arthritis of hand joints

4. Symmetric arthritis

5. Rheumatoid nodules

6. Serum rheumatoid factor

7. Radiographic changes

For classification purpose, a person was diagnosed for RA if at least out of these seven criteria were met. Criteria one to four must have been present for atleast weeks.

Clinical assessments to determine extent severity of disease of RA

Duration of early morning stiffness:[10] It was measured in minutes from the time of awakening to the time sensation began to wear off.

Grip Strength:[10] It was measured with a mercury sphygmo-manometer.

Walking time:[10] Time in seconds required to walk straight to a distance of 50 feet was taken.

Pain:[11] t was assessed by the patient on visual analog scale (VAS) of 10 cm.

Tender/swollen joint count:[12] It was assessed in 58 joints.

Laboratory parameters: ESR by Wintrobe method, rheumatoid factor by latex agglutination method, white blood cell (WBC) count by Neubaur's chamber, hemoglobin estimation by Sahli's acid hemafin method.

Health assessment questionnaire (Indian HAQ)[11]

Part B – Clinical procedure

1. Baseline examination

   Out of the 40 subjects of RA group diagnosed with rheumatoid arthritis, 10 were evaluated at baseline for all periodontal and RA parameters.

2. Treatment regimen

   After estimating above parameters, 10 patients of RA group were subjected to complete periodontal therapy - scaling and root planning, occlusal adjustment, and instructions for plaque control.

3. Re-evaluation

   All the periodontal indices arthritis parameters were re-evaluated weeks after completion of periodontal therapy. ESR and hemogram were repeated for RA group.

Method of statistical analysis

1. Chi-square test

   Formula X_a,b²=∑(O-E)²/E

2. Unpaired t - test

   Formula t=X₁–X₂√S²(1/n₁+1/n₂)

3. Paired t - test =Mean observed difference/Standard Error (SE) of observed difference

RESULTS

The age sex distribution for both the groups were comparable. The mean duration of rheumatoid arthritis was 2.15 years (±0.43) with a range of 6 months to 30 years. The prevalence of periodontitis in RA group was significantly high (97.5%). Only 1 out of 40 RA patients (2.5%) had no periodontitis, 5 (12.5%) had mild periodontitis, 30 (75%) had moderate periodontitis, 4 (10%) had severe periodontitis. Thus, patients with RA were more likely to have mild to moderate forms of periodontitis [Graph 1].

A comparison of periodontal indices between RA and NRA group showed highly statistically significant scores (P<0.001) for average pocket-depth (4.0295 Vs. 1.57), clinical attachment loss (5.2985 Vs. 1.6648), percentage of bleeding sites (66.2173 Vs. 3.9975), plaque index (3.7448 Vs. 1.1123), and percentage of mobile teeth (32.5657 Vs. 4.4665).

No statistically significant difference (P>0.005) was found in missing teeth (9.6420 Vs. 6.8353). Statistically significant differences (P<0.005) were observed for hemoglobin levels (9.85 Vs. 11.2950) in RA and NRA groups. A highly statistically significant difference was found in total leukocyte cell (TLC) count (8275 Vs. 6269.25), ESR (46.35 Vs. 6.30) in RA NRA groups.

The mean alveolar bone loss in RA group without periodontitis (P0) was 10.9190±19.7973; with mild periodontitis (P1) was 55.0210±24.9072; with moderate periodontitis (P2) was 17.4210±17.2778, in those with severe periodontitis (P3) was 16.7380±29.1977. Thus, there was milder and moderate alveolar bone loss in RA groups than severe bone loss. Thus, the RA group had more mild to moderate type of periodontitis than severe type of periodontitis. The distribution of various RA clinical parameters laboratory values were also compared according to the categories of periodontitis in RA group [Figures 2–5].

Figure 2.

Prevalance of periodontitis in rheumatoid arthritis (RA) group

Figure 5.

Distribution of walking time (sec.), according to clinical attachment loss (mm)

Figure 3.

Distribution of various Rheumatoid Arthritis parameters, according to clinical attachment loss (mm)

Figure 4.

Distribution of walking time (sec.), according to clinical attachment loss (mm)

No periodontitis (P0) Vs. mild periodontitis (P1)

There was an increase in mean percentages of tender joints (14.81 Vs. 40.746), percentage of swollen joints (0.00 Vs 12.40), the pain VAS (25 Vs. 47), morning stiffness (15 Vs. 72), HAQ scores (17 Vs. 22.60), TLC counts (6800 Vs. 71), mean ESR rates (22 Vs. 40.80) from no (P0) to mild (P1) periodontitis. The mean grip strength decreased from P0 to P1 group (98.33 Vs. 38.33). The mean walking time (30 Vs 29.80) hemoglobin values (11.20 Vs 11.80) were nearly the same in P0 P1 groups.

Mild periodontitis (P1) Vs. moderate periodontitis (P2)

There was an increase in the mean percentages of tender joints (40.7460 Vs. 47.1883), which was not statistically significant. There was also an increase in mean percentages of swollen joints (12.40 Vs. 13.38), pain scores (47 Vs. 68.5), morning stiffness (72 Vs. 75.07), TLC counts (7100 Vs. 8243.33), ESR (40.80 Vs. 46.03) from mild (P1) to moderate (P2) periodontitis category. Mean HAQ scores were nearly the same (22.60 Vs. 22.30). The mean grip strength (38.33 Vs. 35.44), walking time (29.80 Vs. 27.60), hemoglobin (11.8 Vs. 9.59) decreased from mild (P1) to moderate (P2) periodontitis.

Moderate periodontitis (P2) Vs. severe periodontitis (P3)

There was an increase in the mean percentages of tender joints (47.18 Vs. 69.40), pain VAS (68.5 Vs. 75), walking time (27.6 Vs. 485.5), HAQ scores (20.30 Vs. 25), TLC counts (8243.33 to 10350), mean ESR (46.03 Vs. 60.75) from moderate (P2) to severe (P3) periodontitis. The mean grip strength also increased (35.44 Vs. 36.66), whereas the mean percentage of swollen joints (13.38 Vs. 11.25), morning stiffness (75.07 Vs. 72.5), hemoglobin values (9.59 Vs. 9) decreased from moderate (P2) to severe (P3) periodontitis. Thus, the difference between no (P0) to mild (P1) periodontitis; between mild (P1) to moderate (P2) periodontitis, and between moderate (P2) to severe (P3) periodontitis is positive but not statistically significant (P>0.005), except for walking time (P<0.005), where it is statistically significant.

However, there was a statistically significant reduction in the mean preoperative postoperative periodontal indices RA parameters for rheumatoid arthritis RA group.

Before vs. after periodontal treatment (RA group)

A highly statistically significant reduction (P<0.001) was observed in mean probing depth (4.260 Vs. 1.5920), clinical attachment loss (6.1470 Vs. 2.96), plaque scores (4.2030 Vs. 1.1530), percentage of bleeding sites (89.6290 Vs. 8.61), HAQ scores (2.1470 Vs. 1.6130), ESR (45.90 Vs. 34.1), after completion of periodontal treatment. A highly statistically significant increase in mean grip strength (32.79 Vs. 43.66) hemoglobin (8.50 Vs. 9.90) was also observed after periodontal treatment. A statistically significant reduction (P<0.005) in the mean percentage of mobile teeth (59.09 Vs. 13.84), percentage of tender joints (56.48 Vs. 42.96), percentage of swollen joints (25.18 Vs. 21.11), pain VAS (86 Vs. 56.5), morning stiffness (74 Vs. 57.5), mean TLC (8970 Vs. 7060) was also observed after completion of periodontal treatment in the RA group. However, the difference in the mean walking time preoperatively postoperatively was not statistically significant (P>0.005) [Table 1].

Table 1.

Mean peroperative and post operative periodontal Indices and rheumatoid arthritis paramteres for Rheumatoid arthritis

DISCUSSION

Nested in a complex interaction of different branches of medicine, the management of health disease will require interdisciplinary strategies care.[13] The relationship between dental rheumatoid diseases has long been termed tenous. Hence, to provide a clue about the relationship, the present study was carried out.

Prevalence of periodontitis in RA

The present study showed that the prevalence of periodontitis in RA was 97.5%. The prevalence of mild (12.5%) to moderate (75%) periodontitis was significantly elevated in RA patients. This is in accordance with that reported by Mercado F. 62.5%.[2]

Possible link between periodontitis and RA

In accordance with the present study, Mercado F.[2] also correlated the extent of periodontitis to the severity of arthritis and identified a possible relationship between the two. However, in two studies by Stoiber E. and Helminen–Pakkala E., no relationship between RA and periodontal diseases could be demonstrated.[14] Reich H. Von and Shimizu K. have put forth the hypothesis that infections in the marginal periodontium and periapical region function as source of infection for arthritis.[15] The above results, though in line with the work of Mc. Dougall, Tolo K. and Lens JW.,[15] cannot be compared directly with the present study, as the study designs are different.

Evaluation of periodontal condition of patients with RA group and comparison of various periodontal indices with the NRA group

In the present study, the age and gender range of individuals in RA group reflected the epidemiology of the disease, i.e. more female (80%) which is consistent with the findings by Mercado F.;[7] in which 74.6% female were affected. Similar findings were reported by Arnett F. and Albander E.[7] The age range of the present study (20-70 years) is also consistent with the study by Mercado F. (50-70 years).[7]

Periodontal conditions of RA group compared to non-RA group

A statistically highly significant difference (P<0.001) was observed in the plaque index and gingival bleeding index of RA group compared to NRA group. Bozkurt also reported similar findings.[16] The probing pocket depth and clinical attachment loss was statistically significantly higher (P<0.001) in RA group than NRA group. This is also in accordance with the studies of Bozkurt[16] and Mercado F.[7] However, Mercado F.[7] have used only radiographic bone loss to correlate periodontitis to RA. The present study does not include radiographs due to lack of standardized techniques for radiographs; instead clinical attachment loss has been chosen to judge the past and present periodontitis activity for both the groups.

In contrast to the present study, Sjostrom L.[17] reported better periodontal status among arthritis patients than controls. They attributed this difference to the long term administration of non-steroidal anti-inflammatory drugs.[17] In the present study, no significant difference was found in missing teeth in both groups, which is in accordance with Sjostrom L.[17] However, Mercado[7] showed that RA group had more missing teeth than NRA group. In the present study, the percentage of mobile teeth was statistically and significantly higher (P<0.001) in the RA group than NRA group. This parameter has not been assessed in other studies.

Comparison of laboratory parameters in the RA and NRA group

In the present study, hemoglobin levels were statistically and significantly lower (P<0.005); the TLC and ESR parameters were statistically and significantly higher (P<0.001) in the RA group as compared to NRA group. This indicates that periodontitis could contribute to the severity of arthritis by lowering hemoglobin and increasing TLC and ESR.

Correlation between clinical and laboratory parameters of rheumatoid arthritis with clinical attachment loss i.e. periodontitis in the RA group

In the present study, a significant association between the degree of functional debilitation due to RA and severity of periodontal disease was observed. These results are in conformity with those of Mercado F.[7] However, statistical evaluation did not reveal any significant difference (P>0.005).

Evaluation of RA severity pre-operatively and post-operatively i.e. after periodontal treatment

An association between the degree of arthritis and severity of periodontitis is evident in this study. Thus, treatment of periodontitis can reduce or eliminate the focus of infection play a pivotal role in reducing the risk and severity of RA. This is in accordance with the study by Ortiz P. in which non-surgical periodontal surgery had a beneficial effect on signs and symptoms of RA, regardless of the medications used to treat this condition.[18] Results demonstrated a highly statistically significant reduction (P<0.001) in mean plaque scores, percentage of bleeding sites, probing pocket depth, clinical attachment, health assessment scores, and ESR after completion of periodontal treatment in the RA group. Also, a highly statistically significant increase (P<0.001) was observed in the mean grip strength and hemoglobin values, after periodontal treatment, in the RA group. However, no significant difference (P<0.005) was observed in the walking time after periodontal treatment.

Likewise, a statistically significant reduction (P<0.005) was also noted in the mean percentages of mobile teeth, tender joints, swollen joints, pain scores, morning stiffness, and TLC after completion of periodontal treatment in the RA group. The American Academy of Periodontology[19] reported a case of rheumatoid arthritis caused by focal infection from periodontal issues in which ESR dropped from 62-27 mm after the treatment of periodontal infection. However, this study design being different from present study, not all the results can be compared.

Limitations

Large sample size long term clinical observations are required. Alveolar bone loss has not been assessed and a prospective study must be done to check for the relationship vice-versa.

CONCLUSION

The present study stresses that association between periodontitis and RA exists. Interventions to prevent, minimize, or treat periodontitis in arthritis patient will definitely promise a better future for these patients.