Oral health in Behçet's disease and its association with disease severity: cross-sectional and case- control study

Abstract

Background: Behçet's disease is a chronic autoimmune disorder that affects various organs, including oral aphte, genital ulceration, cutaneous manifestation, ocular involvement, and positive pathergy test according to International Study Group for Behçet’s Disease criteria. This study aimed to investigate the oral health condition of patients with Behçet's disease and to assess how it correlates with the patients' gender, clinical symptoms, and severity of the disease.
Methods: A total of 92 participants, including 42 patients with Behçet's disease and 50 healthy controls, were enrolled in this cross-sectional study. The periodontal indices were measured and compared between the two groups. Logistic regression analysis was used to identify potential risk factors for disease severity.
Results: This study assessed the periodontal health of patients with Behçet's disease and found that they had significantly higher plaque, gingival, bleeding, and probing depth scores compared to healthy controls (P<0.05). Logistic regression analysis revealed that plaque accumulation was a significant risk factor for higher severity scores in Behçet's disease. Gender-specific approaches may be necessary in the management and treatment of periodontal disease in Behçet's disease patients.
Conclusions: The findings of this study suggest that patients with Behçet's disease are at increased risk for periodontal disease and its associated symptoms. Specifically, plaque accumulation appears to be a significant risk factor for more severe periodontal health issues in these patients. Therefore, it is important for clinicians to be aware of this increased risk and to develop tailored treatment plans that address both the underlying Behçet's disease and the associated periodontal disease.

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Oral health in Behçet's disease and its association
with disease severity: cross-sectional and case-
control study
Naram Khalayli
Damascus University
Jawdat Ataya (  dr.jawdat.ataya@gmail.com )
Damascus University
Lama Al Darwish
Syrian Private University
Nour Rabah
Syrian Private University
Karam Rabah
Syrian Private University
Ghina Haidar
Syrian Private University
Jamal Ataya
Syrian Private University
Maysoun Kudsi
Damascus University
Research Article
Keywords: Behçet's disease, Periodontal disease, Plaque accumulation, Gingival health, Bleeding
Posted Date: July 18th, 2023
DOI: https://doi.org/10.21203/rs.3.rs-3173934/v1
License:   This work is licensed under a Creative Commons Attribution 4.0 International License. 
Read Full License

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Abstract
Background: Behçet's disease is a chronic autoimmune disorder that affects various organs, including
oral aphte, genital ulceration, cutaneous manifestation, ocular involvement, and positive pathergy test
according to International Study Group for Behçet’s Disease criteria. This study aimed to investigate the
oral health condition of patients with Behçet's disease and to assess how it correlates with the patients'
gender, clinical symptoms, and severity of the disease.
Methods: A total of 92 participants, including 42 patients with Behçet's disease and 50 healthy controls,
were enrolled in this cross-sectional study. The periodontal indices were measured and compared
between the two groups. Logistic regression analysis was used to identify potential risk factors for
disease severity.
Results: This study assessed the periodontal health of patients with Behçet's disease and found that they
had signicantly higher plaque, gingival, bleeding, and probing depth scores compared to healthy
controls (P<0.05). Logistic regression analysis revealed that plaque accumulation was a signicant risk
factor for higher severity scores in Behçet's disease. Gender-specic approaches may be necessary in the
management and treatment of periodontal disease in Behçet's disease patients.
Conclusions: The ndings of this study suggest that patients with Behçet's disease are at increased risk
for periodontal disease and its associated symptoms. Specically, plaque accumulation appears to be a
signicant risk factor for more severe periodontal health issues in these patients. Therefore, it is
important for clinicians to be aware of this increased risk and to develop tailored treatment plans that
address both the underlying Behçet's disease and the associated periodontal disease.
Introduction
Behçet's disease (BD) is a systemic disorder (1) characterized by various clinical manifestations,
including oral aphte, genital ulceration, cutaneous manifestation, ocular involvement, and positive
pathergy test according to International Study Group for Behçet’s Disease criteria (2, 3)BD is prevalent in
areas along the ancient Silk Road, such as the Mediterranean region and other countries (4), and its
pathogenesis will be affected and involved both genetic and microbial factors (5).
Streptococcal infections and the oral microbial ora have been implicated in the pathogenesis, as
evidenced by increased oral manifestations after dental treatments, benecial antibacterial therapy, and
elevated pro-inammatory cytokine responses to streptococcal antigens (6–8).
Poor oral hygiene is a major issue in patients with BD, with painful oral ulcers being the rst
manifestation in 70% of patients and leading to a restriction in regular oral hygiene habits (9, 10). Studies
have shown that having poor oral health is linked to a higher number of teeth that need to be extracted as
a result of decay and uctuations in oral pH levels (11, 12). However, the relationship between oral health

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and the clinical course of BD remains unclear, with some reports showing a correlation between poor oral
hygiene and disease activity, clinical manifestations, and male gender (13–15).
This study aimed to investigate the oral health condition of patients with Behçet's disease and to assess
how it correlates with the patients' gender, clinical symptoms, and severity of the disease.
Methods
This study has a cross-sectional and case control study design. 92 participants were enrolled in this
study after providing informed consent. The study included 42 patients with Behçet's disease who were
diagnosed according to International Study Group for Behçet's Disease criteria (3). The patients were
recruited from the outpatient clinic of Al-Moussat University Hospital between January 2019 and January
2022. The control group comprised 50 age-matched healthy individuals without any symptoms or signs
of autoimmune disorders and who were not closely related to the patients' family.
Damascus University ethics approval committee examined and authorized this study (number 1688; date:
April 18, 2019). All prospective participants provided their informed consent, during which they were
made aware that the information they submitted would be kept private and used only for this research.
To determine the severity of Behçet's disease, a scoring system was used (16) where each symptom was
assigned a certain number of points. Oral aphthae, genital ulcers, cutaneous lesions, and arthralgia were
assigned 1 point each, which indicated mild disease. Arthritis, anterior uveitis, deep vein thrombosis in the
legs, and gastrointestinal involvement were assigned 2 points each, indicating moderate disease.
Neurological manifestation, posterior/ panuveitis, retinal vasculitis, arterial thrombosis, and bowel
perforation were assigned 3 points each, indicating severe disease.
The total score was calculated by adding up the points for each symptom. Patients were then classied
into three groups based on their score: severe group (≥ 7 points), moderate group (a score between 4 and
6 points), and mild group (< 4 points).
Patients were examined monthly for 3 months, registering the number of the healing time of ulcers and
erythema nodosum per month.
The same dentist (GM) examined all participants each visit, using the plaque index to assess the
thickness of plaque at the gingival area, the gingival index to evaluate the severity of gingivitis, the sulcus
bleeding index to record the presence of initial inammatory gingival disease, probing depth assesses the
state of periodontal health and the decayed/missing/lled/teeth (DMFT) score to determine the total
dental caries experience (17–19).
Statistical analysis
Statistical analysis was performed using SPSS version 23. A P-value of less than 0.05 was considered
statistically signicant. The unpaired t-test, Mann-Whitney U-test, and multiple variant ANOVA were used

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to analyse the data.
Results
92 participants were enrolled in this study, including 42 patients with Behçet's disease (mean age 32.8 ±
9.9 years, 24 males and 16 females) who were diagnosed according to the International Study Group
criteria (3) and were recruited from the outpatient clinic of Al-Moussat University Hospital between
January 2019 and January 2022. The control group comprised 50 age-matched healthy individuals
(mean age 33.3 ± 8.7 years, 26 males and 24 females).
The clinical manifestations of Behçet's disease in the patients were as follows: oral ulcers (78.5%),
genital ulcers (71.4%), cutaneous manifestations (66.6%), arthritis (52.3%), ocular manifestations
(28.5%), and neurological manifestations (4.7%). None of the patients had a positive pathergy reaction.
Colchicine (1–2 mg/day) was used to treat 78.5% of the patients, mainly those with active oral ulcers,
while azathioprine (1–2 mg/kg) was used by 45% of the patients. Corticosteroids were administered to
20 patients with arthritis, 11 patients with ocular manifestations, and 2 patients with neurological
involvement.
The results presented in Table1 indicate that patients with Behçet's disease had signicantly higher
mean scores for plaque index, sulcus bleeding index, gingival index, and probing depth compared to the
control group (P < 0.05).
Table 1
Oral health of patients with Behçet's disease, and healthy controls
Behçet's disease
(n= 42)
Mean ± SD
Healthy controls
(n= 50)
Mean ± SD
Plaque index 1.8 ± 1.05 1.1 ± 1.89
Gingival index 2.1 ± 1.1 1.3 ± 1.2
Sulcus bleeding index 1.9 ± 1.03 1.3 ± 1.3
Probing depth (mm) 2.7 ± 1.03 2.1 ± 1.2
DMFT 7.2 ± 5.9 6.6 ± 4.9
Number of carious teeth 2.6 ± 2.4 2.8 ± 2.5
Number of extracted teeth 3.6 ± 5.2 0.8 ± 1.5
Tooth brushing (number/day) 1.1 ± 0.5 1.4 ± 0.8
Cigarette consumption (number/day) 3.3 ± 6.5 15.2 ± 12.2

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The DMFT score, count of decayed teeth, frequency of oral ulcers per month, duration of time required for
healing of oral ulcers, and the duration of the disease showed no signicant differences between the two
groups. The daily frequency of tooth brushing was higher in the control group (1.4 ± 0.8) compared to the
Behçet's disease group (P = 0.008), while the mean number of cigarettes consumed was higher in the
control group (n = 16, 15.2 ± 12.2/day) than in the Behçet's disease group (n = 29, 3.3 ± 6.5/day) (P <
0.0001).
The mean severity score for the entire study population was 4.9 ± 2.6. Patients were classied into three
groups based on their disease severity score: mild group (score < 4, n = 22), moderate group (score
between 4 and 6, n = 12), and severe group (score ≥ 7, n = 8). The mean severity score was 3.06 ± 0.1 in
the mild group, 4.9 ± 0.4 in the moderate group, and 8.1 ± 1.5 in the severe group.
Total clinical severity scores and periodontal indices were higher in males (P = 0.018 and P < 0.05,
respectively). However, females had a longer disease duration than males (P < 0.0001). No signicant
differences were observed between the two groups in terms of the number of oral ulcerations per month,
healing time of oral ulcerations, DMFT scores, numbers of extracted teeth, or carious teeth. According to
the ndings presented in Table2, the average number of cigarettes smoked per day was 1.6 ± 3.1 among
female participants (n = 9) and 6.2 ± 8.6 among male participants (n = 20).

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Table 2
Oral health and related factors in patients and controls according to gender
Bechet disease Healthy control
Male
(n=24) Female
(n=16) Male
(n=
26)
Female
(n= 24) 
Mean ±
SD Mean ± SD P-
value Mean
± SD Mean ± SD P-value
Plaque index 2.4 ± 0.7 1.9 ± 0.8 0.008* 1.9 ±
1.5 1.6 ± 0.5 0.036*
Gingival index 2.6 ± 0.3 2.1 ± 0.7 0.043* 2.4 ±
0.9 1.3 ± 1.6 0.028*
Sulcus bleeding index 2.2 ± 0.8 1.8 ± 1.1 0.045* 2.5 ±
0.9 1.5 ± 1.2 0.0093*
Probing depth (mm) 3.2 ± 0.6 2.7 ± 0.7 0.006* 3.5 ±
0.5 2.7 ± 0.6 0.004*
DMFT 6.91 ±
5.3 7.1 ± 5.1 0.951 7.9 ±
7.8 7.8 ± 4.3 0.678
Extracted teeth 3.5 ± 4.4 3.5 ± 5.4 0.349 5.2 ±
7.4 4.6 ± 4.9 0.807
Carious teeth 2.4 ± 2.3 2.2 ± 2.5 0.614 0.8 ±
1.4 2.9 ± 2.4 0.002*
Oral ulcers
(number/month) 5.7 ± 6.1 7.4 ± 7.6 0.198 6.01 ±
5.9 4.7 ± 3.8 0.473
Healing time (days) 8.8 ± 4.0 9.2 ± 3.1 0.849 9.5 ±
4.7 9.8 ± 4.2 0.887
Disease duration (yr) 5.9 ± 4.8 11.9 ± 9.0 0.000* 11.4 ±
8.6 7.4 ± 4.6 0.201
Tooth brushing
(number/day) 1.1 ± 0.9 1.1 ± 0.8 0.875 0.6 ±
0.7 1.4 ± 0.8 0.003*
Cigarette consumption
(number/day) 6.2 ± 8.2 1.6 ± 3.1 0.021* 0 ± 0 0.4 ± 1.2 -
*Statistically signicant.
The results of this study demonstrate that periodontal scores were signicantly higher in patients with
active oral ulcers, as well as those with severe and moderate Behçet's disease (BD) (P < 0.05). Although
the oral ulcers score/month was higher in patients with moderate symptoms than those with severe
symptoms (P = 0.0003), no signicant differences were observed between these groups. Furthermore,

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cigarette consumption was found to be higher in patients with severe symptoms compared to those with
moderate (P = 0.037) and milder symptoms (P = 0.04). Logistic regression analysis, as presented in
Table3, revealed that an increased plaque index was a signicant risk factor for higher severity scores in
BD (P = 0.033). Therefore, it is suggested that efforts aimed at reducing plaque accumulation may help to
prevent or mitigate the severity of BD.
Table 3
Logistic regression analysis for increased severity score φ in BD
     95% C.I. for OR
B S.E. P OR Lower–upper
Plaque index score 0.838 0.395 0.033* 2.311 1.065–5.012
Probing depth (mm) 0.430 0.383 0.261 1.537 0.726–3.255
Gender (male) 0.912 0.604 0.131 2.489 0.763–8.123
Number of oral ulcers (month) −0.022 0.036 0.536 0.978 0.912–1.049
Disease duration (yr) −0.013 0.036 0.726 0.987 0.919–1.060
Constant −3.054 1.213 0.013 0.047 
φ: Increased severity score = 1 (severity score ≥ 4), severity score < 4 = 0.
B, the partial regression coecient for each variable in the regression equation.
*Statistically signicant.
The study also conducted a gender-based analysis of periodontal indices in patients with BD. The results
indicated that periodontal index scores were signicantly higher in male patients with active oral ulcers
compared to ulcer-free patients, as well as in patients with severe or moderate symptoms compared to
mild ones (P < 0.05). Logistic regression analysis showed that probing depth in males (odds ratio [OR] =
4.05, P = 0.04) and plaque index score in females (OR = 6.07, P = 0.04) were signicant risk factors for
increased severity scores in BD. Although an increased risk associated with plaque index was also
observed in male BD patients (OR = 1.8), it did not reach statistical signicance. These ndings suggest
that gender-specic approaches may be necessary in the management and treatment of periodontal
disease in patients with BD.
Discussion
Numerous studies have underscored the crucial role of immune responses against oral streptococci in the
pathogenesis of BD, emphasizing the signicance of oral health as a key factor in the development of the
disease(20–22). In addition, suboptimal oral hygiene can result in an increase in oral microbes, which
can trigger the formation of oral ulcers(23,24).

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Our research demonstrates that oral health was compromised in BD patients compared to healthy
controls, and higher indices were associated with active oral ulcers and a moderate to severe disease
course. These ndings are in line with the study by Çelengil-Nazlıel et al., where higher scores were
reported in BD patients than in healthy controls, and the plaque index was identied as a signicant risk
factor for disease activity, as well as the sulcus bleeding index and probing depth(25). Similarly, Nakae et
al. found a higher prevalence of decayed, extracted teeth, and multiple carious lesions in BD patients
compared to the healthy population(26–28).
Our study further identied signicant risk factors for oral health parameters in BD patients. For instance,
the accumulation of plaque in females and probing depth in males were found to be independent risk
factors for increased severity scores (23,29,30). Moreover, male gender was identied as an independent
risk factor for oral health in healthy controls. Immunosuppressive therapy was found to be effective in
reducing the number of oral ulcers in severe BD patients compared to those with moderate and milder
symptoms, which may help improve oral health (7,30,31).
Conclusion
The ndings of this study suggest that patients with Behçet's disease are at increased risk for periodontal
disease and its associated symptoms. Specically, plaque accumulation appears to be a signicant risk
factor for more severe periodontal health issues in these patients. Therefore, it is important for clinicians
to be aware of this increased risk and to develop tailored treatment plans that address both the
underlying Behçet's disease and the associated periodontal disease.
Declarations
Ethics approval and consent to participate.
Damascus University ethics approval committee examined and authorized this study (number 1688; date:
April 18, 2019).
Consent for publication
The consent will be available on request.
Availability of data and materials
All the necessary data are presented herewith. However, if needed, raw data on excel format can be
available on request from the corresponding author.
Competing interests
The authors declare that they have no competing interests.

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Funding
There has been no funding for this study. However, this study supported by Damascus University.
Authors' contributions
All authors contributed to conception and design of the study, collecting and data analysis and
interpretation. All authors read and approved the nal manuscript.
Acknowledgements
A very big thank you for Damascus University, Syrian Virtual University and Syrian Private University for
their support.
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