Introduction

Systemic diseases can affect oral health and studies have shown that many systemic diseases, including rheumatoid arthritis (RA) are closely associated with dental disorder [1]. RA is a common systemic autoimmune disease characterized by persistent joint inflammation leading to increased mortality. The prevalence of RA was estimated to be between 0.5 and 1.0% with a female to male ratio of approximately 2.5:1 [2]. In Taiwan, the prevalence of RA was reported to be 0.26–0.93% [3]. RA can affect not only the joints, but it can also involve other organ systems, such as the lung, skin vasculitis, and lead to systemic comorbidities [4, 5]. Among these comorbidities or extra-articular manifestations, dental disorders are common in patients with RA, which would increase the need of treatment from dental professionals [6].

Among dental disorders, it is well known that patients with periodontitis have an increased risk of developing RA, and that patients with RA also showed an increased risk of developing periodontitis [7, 8]. Martinez-Martinez et al. reported that the frequency and severity of dental caries were higher in patients with RA compared with controls [9]. In addition, the prevalence of temporomandibular disorders was found to be higher in patients with RA [10, 11]. However, the prevalence and incidence of common dental disorders, such as dental caries, pulpitis, oral ulcer, and stomatitis in patients with RA, was not clear. We hypothesized that the incidence of common dental disorders is higher in patients with RA. In this study, we compared the prevalence of dental conditions and the frequency of dental visits in patients with or without RA. We also performed separate analyses to assess the incidence and incidence rate ratios (IRRs) of common dental disorders.

Materials and methods

Identification of the RA cohort and a comparison cohort

This is a secondary cohort analysis based on the claim data from Taiwan's National Health Insurance Research Database (NHIRD). The study design was based on our previous study with modifications [12]. The study protocol was reviewed and approved by the institutional review board of Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan (No.B10004021). The need for informed consent from individuals was waived because the data in NHIRD were deidentified.

Patients with newly diagnosed RA were identified based on the International Classification of Diseases, Ninth revision, clinical modification (ICD-9-CM) code 714.0 (rheumatoid arthritis) using the 2000–2012 catastrophic illness datafile of the NHIRD. RA is considered a catastrophic illness in Taiwan. Patients with RA can apply for a certificate from the National Health Insurance Administration (NHIA), and their medical records, serological, pathological, and imaging reports will be reviewed by at least two specialists. If approved, holders of a RA catastrophic illness certificate are exempted from copayments for health care expenses related to the treatment of RA. The diagnosed of RA was based on the American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis [13]. The date of application for the catastrophic illness certificate was defined as the index date for RA in this study. Patients whose ages less than 20 years, more than 80 years on the index date or with a diagnosis of primary Sjögren’s syndrome, defined by the catastrophic illness datafile, were excluded from the study. The ending year of the dataset was 2012 because of a change in data protection policy in Taiwan.

A comparison cohort was constructed based on a random sample of the outpatient datafile of the 2000 Longitudinal Health Insurance Database (LHID 2000) of the NHIRD. In this study, 10 patients were selected, based on frequency matching for sex, 5-year age interval, and index year, for each patient with RA to form a comparison cohort. In the comparison cohort, those ages less than 20 years, more than 80 years on the index date, or with a diagnosis of primary Sjögren’s syndrome, defined by the catastrophic illness datafile, were excluded from the study.

A number of diseases were identified as potential confounders, including hypertension, diabetes mellitus, congestive heart failure, chronic pulmonary disease, malignancy, dyslipidemia, coronary artery disease, myocardial infraction, peripheral vascular disease, cerebrovascular disease, dementia, musculoskeletal disorders, peptic ulcer disease, chronic kidney disease, and liver disease. These diseases were identified by their respective ICD-9-CM codes and inclusion criteria as in our previous study [12].

Identification of dental disorders

The RA cohort and the comparison cohort were followed until our outcome of interest had occurred or when the end of the follow-up period had reached. Only dental visits occurred at least 90 days after the index date were included in the analysis. Various dental disorders of patients with RA were reviewed according to ICD-9-CM codes. We selected common or potentially RA-related dental disorders based on the frequency of dental visits and they included: (1) periodontitis (ICD-9 codes: 523.3, 523.4, 523.5, and 523.8) (2) dental caries (ICD-9 code: 521.0), (3) gingivitis (ICD-9 codes: 523.0, 523.1, and 523.2), (4) pulpitis (ICD-9 code: 522.0), (5) oral ulceration (ICD-9 code: 528.2), (6) stomatitis (ICD-9 code: 528.0), and (7) temporomandibular joint disorders (ICD-9 code: 524.6). The incidence and IRRs for each of these dental disorders were separately calculated in the RA cohort and the comparison cohort. The follow-up duration used for the calculation of person-years was obtained by subtracting the date when the outcome of interest occurred from the index date. Patients who were diagnosed with the outcome of interest within 90 days before the index date were excluded from the calculation of the incidence and IRRs.

Statistical analysis

Demographic data, the prevalence and frequency of the visits due to specific dental disorders between the RA cohort and the comparison cohort were compared using the Chi-square test, the t-test, or the non-parametric Mann–Whitney U-test, as appropriate. The incidence per 1000 person-years was calculated separately for the RA cohort and the comparison cohort. Poisson regression models using person-years as the offset variable, with or without adjusting for potential confounding variables were used to calculate IRRs for the outcome variables. All analyses were conducted with IBM SPSS Statistics for Windows, version 24.0 (IBM Corp, Armonk, NY, USA). A p-value less than 0.05 was considered statistically significant.

Results

Basic characteristics and comorbidities of patients in the RA cohort and in the comparison cohort

We selected 1337 newly-diagnosed patients with RA and 13,370 patients without RA in this study. There were no significant differences in sex, age, and geographic region between the two cohorts. In Table 1, the insurance premium levels were significantly higher in the RA cohort. Patients with RA showed a significantly higher proportion of chronic pulmonary diseases (3.0% vs. 2.0%; p = 0.019), musculoskeletal disorders (4.5% vs. 0.4%; p < 0.001), and peptic ulcer diseases (5.1% vs. 2.5%; p < 0.001), but a significantly lower proportion of cancer (1.0% vs. 1.8%; p = 0.033) compared with those in the comparison cohort.

Table 1 Basic characteristics of the rheumatoid arthritis cohort and the comparison cohort (N = 14,707)
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Prevalence, frequency, and common causes of dental visits

Table 2 showed that patients with RA had a higher prevalence (70.3% vs. 66.7%, p = 0.008) and frequency (medium 2.67 vs. 1.78 per year, p < 0.001) of dental visits compared with those without RA. The prevalence and frequency of dental visits for dental caries, pulpitis, gingivitis, periodontitis, and oral ulceration, but not stomatitis were found to be significantly higher in the RA cohort. Moreover, the prevalence and frequency of dental visits for temporomandibular joint disorders were slightly higher in the RA cohort with marginal significance (1.6% vs. 1.0%, p = 0.065).

Table 2 The prevalence and frequency of dental disorders in the rheumatoid arthritis and comparison cohort (N = 14,707)
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Incidence of visits for dental caries and pulpitis in patients with RA

In Table 3, we found that patients with RA had an increased incidence of visits for dental caries (adjusted IRR = 1.16, 95% CI 1.07–1.26, p < 0.001) compared with patients without RA. When stratified by sex, female RA patients had an elevated incidence for dental caries (adjusted IRR = 1.21, 95% CI 1.11–1.33, p < 0.001), but not in male RA patients (adjusted IRR = 0.98, 95% CI 0.81–1.18, p = 0.804). Moreover, compared with patients without RA, those with RA, both the 20–55 years age group (adjusted IRR = 1.18, CI 1.06–1.31; p = 0.002) and > 55 years age group (adjusted IRR = 1.18, CI 1.03–1.34, p = 0.014) showed an increased incidence of dental caries.

Table 3 Incidence and incidence rate ratios of visits for dental caries and pulpitis in the rheumatoid arthritis cohort and the comparison cohort
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Patients with RA also showed an elevated incidence of visits for pulpitis (adjusted IRR = 1.12, 95% CI 1.00–1.24, p = 0.044) compared with those without RA. Female patients with RA had an elevated incidence for pulpitis (adjusted IRR = 1.18, 95% CI 1.05–1.32, p = 0.006), but not in male patients (adjusted IRR = 0.89, 95% CI 0.68–1.15, p = 0.368). The incidence for pulpitis in patients with RA was not significantly higher in different age groups.

Incidence of visits for gingivitis and periodontitis in patients with RA

In Table 4, we found that patients with RA had a significantly higher incidence of visits for gingivitis compared to those without RA (adjusted IRR = 1.13, 95% CI 1.01–1.25, p = 0.027). Female patients with RA showed an increased visits for gingivitis (adjusted IRR = 1.19, 95% CI 1.06–1.34, p = 0.003), but male patients did not (adjusted IRR = 0.86, 95% CI 0.66–1.11, p = 0.241). When stratified by age group, RA patients in the younger age group (20–55 years) had an increased incidence of gingivitis (adjusted IRR = 1.17, 95% CI 1.02–1.33, p = 0.022), but not in the older age group (aged > 55 years; adjusted IRR = 1.09, 95% CI 0.92–1.33, p = 0.330).

Table 4 Incidence and incidence rate ratios of visits for gingivitis and periodontitis in the rheumatoid arthritis cohort and the comparison cohort
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Patients with RA had an elevated incidence of visit for periodontitis compared with patients without RA (adjusted IRR = 1.13, 95% CI 1.04–1.22, p = 0.004). Moreover, female patients with RA showed a significantly increased incidence of periodontitis (adjusted IRR = 1.17, 95% CI 1.07–1.28, p = 0.001), but not in male patients with RA (adjusted IRR = 1.00, 95% CI 0.83–1.19, p = 0.962). Moreover, patients with RA showed an increased incidence of periodontitis in the 20–54 years group (adjusted IRR = 1.15, 95% CI 1.03–1.28, p = 0.013) and the > 55 years group (adjusted IRR = 1.14, 95% CI 1.00–1.29, p = 0.043).

Incidence of visits for oral ulceration and temporomandibular joint disorder in patients with RA

In Table 5, we found that patients with RA had an elevated incidence of oral ulceration compared with patients without RA (adjusted IRR = 1.24, 95% CI 1.08–1.44, p = 0.003). Female RA patients with RA showed an elevated incidence for having oral ulceration (adjusted IRR = 1.29, 95% CI 1.10–1.51, p = 0.002), but not in male patients with RA (adjusted IRR = 1.05, 95% CI 0.73–1.50, p = 0.804). When stratified by age, the younger group patients with RA showed an elevated incidence of oral ulceration (adjusted IRR = 1.30, 95% CI 1.06–1.58, p = 0.011), but not those with older age group (adjusted IRR = 1.21, CI 0.98–1.50, p = 0.083).

Table 5 Incidence and incidence rate ratios of visits for oral ulceration and temporomandibular joint disorders in the rheumatoid arthritis cohort and the comparison cohort
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Furthermore, no significant differences were observed in developing temporomandibular joint disorders between patients with and without RA either in the overall analysis (adjusted IRR = 1.31, 95% CI 0.77–2.23, p = 0.320) or in the subgroup analyses stratified by sex or age group.

Discussion

In this secondary cohort study, we found the prevalence and frequency of dental visits were increased in patients with RA. The incidence of visits for dental caries, pulpitis, gingivitis, periodontitis and oral ulcer, but not temporomandibular joint disorders was significantly higher in patients with RA especially female patients. For age group, the risks of dental caries and periodontitis were increased in both the younger and older age groups and the risk of gingivitis and oral ulcer were increased in younger age group.

Dental caries is a biofilm-mediated disease with multiple contributing factors that drives net localized demineralization of the teeth [14]. Although RA is considered a risk factor for dental caries, few studies have shown that the frequency and severity of dental caries were also higher in patients with RA [9, 15]. It is interesting to note that RA disease activity could be associated with the severity of dental caries [15]. It should be noted that primary Sjögren's syndrome is a strong risk factor for developing dental caries (aIRR = 1.64) according to our previous study [12]. Therefore, patients with a diagnosis of primary Sjögren's syndrome were excluded from this study. However, patients with RA might still have secondary Sjögren's syndrome. Therefore, it is possible that the developing of dental caries and pulpitis were mediated through hyposalivation in patients with RA [16].

There is a very close and complex relationship between periodontitis and RA. Both periodontitis and RA shared similar pathogenesis, including imbalance between pro- and anti-inflammatory cytokines, the role of smoking, microbial dysbiosis especially Porphyromonas gingivalis, and genetic background [17]. Therefore, our finding was as expected. Periodontitis, a major inflammatory disease of the oral mucosa, is epidemiologically associated with other chronic inflammation-driven disorders, including cardiometabolic, neurodegenerative and autoimmune diseases, and cancer [18]. A recent systematic review analysis of eight articles on nonsurgical treatment of patients with periodontitis found that periodontitis treatment could improve clinical and laboratory test parameters, such as disease activity score by 28 joints [DAS28] and erythrocyte sedimentation rate, of RA [19]. The causal relationship of periodontitis and RA remained to be elucidated. The incidence for oral ulceration was increased in patients with RA, and it could be related to the side effect of common medication methotrexate in the treatment of RA [20]. It is known that RA could destruct the temporomandibular joint [21]. Byun et al. reported a 2.52-fold increased risk of developing temporomandibular joint disorder in patients with RA in a cohort study of 3122 patients with RA and 12,488 matched controls [22]. The sample size of patients with RA was 1337 in the present study, and this smaller sample size might explain why only a trend of increased risk of developing temporomandibular joint disorder was observed in patients with RA.

Overall the findings of this secondary cohort study indicated that patients with had a poor oral health condition, which is similar to a Korean study [23]. Poor oral health might increase personal medical expenses and burden of health insurance. In contrast, good oral health might be a starting point for the general health and well-being of our body [24]. Rheumatologists should be vigilant for the dental condition in their patients with RA [25] and dental professionals should be aware for the potential poor oral health in patients with RA and effect should be made to enhance their oral health.

The strengths of this study is the large number of patients with RA (n = 1337) and a 12-year follow up period. All the diagnoses were made by specialists and the study sample was representative for the whole population in Taiwan. Nevertheless, there are some limitations. First, identification of dental disorders was based on the claim data, some patients with only mild dental disorders might not visit dental professionals. Second, due to the limitation of claim data, we did not have information on the severity of RA and dental disorders. Third, the database used in this study spanned from January 2000 to December 2012, whether the current situation remained the same will require confirmation.

In conclusion, we found an elevated prevalence and frequency of dental visits in patients with RA. In addition, elevated incidence of visits for dental disorders, including dental caries, pulpitis, gingivitis, periodontitis, and oral ulceration, were observed. Both the rheumatologist and dental professionals should accessed the oral health condition regularly in patients with RA.