ORIGINAL ARTICLE
Dental Caries and Periodontal Disease in Children and Adolescents with Inflammatory Bowel Disease: A Case–Control Study Vassiliki Koutsochristou, DDS,* Aglaia Zellos, MD,* Konstantina Dimakou, MD,* Ioanna Panayotou, MD,* Sultana Siahanidou, MD,* Eleftheria Roma-Giannikou, MD,* and Alexandra Tsami, DDS†
Background: Previous reports have demonstrated a higher prevalence of dental caries and periodontal disease in adults with inflammatory bowel disease (IBD), but similar data in children and adolescents do not exist. The aim of the study was to evaluate the status of dental caries, oral hygiene, gingival status and periodontal treatment needs of children with IBD.
Methods: In this case–control study, 55 children on remission from a single outpatient IBD clinic, aged 4 to 18 years (12.27 6 3.67 yr) and 55 matched systemically healthy controls of a dental practice were assessed prospectively. The evaluation included medical history, dental questionnaire in both groups, and previous and current medical therapy of children with IBD. Additionally, the decayed, missing, and filled tooth (dmf-t or DMF-T), simplified gingival, plaque control record and community periodontal treatment needs indices were evaluated. Results: Children with IBD compared with controls had a statistically significant (P , 0.001) higher dmf-t (2.95 versus 0.91) or DMF-T (5.81 versus 2.04) index and a higher gingival inflammation (simplified gingival, 40% versus 24%) although the respectively dental plaque index showed no significant difference (plaque control record, 42% versus 41%). Also, the community periodontal treatment needs was significantly higher compared with controls (P , 0.001); most of the patients with IBD needed treatment of gingivitis (47% versus 4%), and none of them had healthy periodontium (0% versus 69%). Conclusions: The results of this case–control study demonstrate a higher frequency of dental caries, more clinical signs of gingival inflammation, and increased periodontal treatment needs in children and adolescents with IBD despite similar oral hygiene status. (Inflamm Bowel Dis 2015;21:1839–1846) Key Words: inflammatory bowel disease, children, adolescents, dental caries, gingival inflammation, periodontal treatment needs
I
nflammatory bowel disease (IBD) comprises 2 major disease entities: Crohn’s disease (CD) and ulcerative colitis (UC); they are characterized by chronic inflammatory involvement of the gastrointestinal tract evolving with a relapsing and remitting course. The etiology of these chronic intestinal disorders is not completely understood, but it is known that distinct immune abnormalities play a major role in the initiation and perpetuation of IBD,1 and that genetic2–4 and environmental factors5–8 are involved in the pathogenesis. About 25% to 35% of patients with both forms of IBD develop at least 1 extraintestinal manifestation usually involving joints, eyes, skin, mouth, and liver.9,10 One or more types of oral
Received for publication March 2, 2015; Accepted March 24, 2015. From the *First Department of Pediatrics, University of Athens School of Medicine, Athens, Greece; and †Department of Periodontology, University of Athens Dental School, Athens, Greece. The authors have no conflicts of interest to disclose. Reprints: Aglaia Zellos, MD, First Department of Pediatrics, University of Athens School of Medicine, Aghia Sofia Children’s Hospital, Thivon and Levadias Street, 11527 Athens, Greece (e-mail: [email protected]). Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000452 Published online 15 May 2015.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
manifestations of IBD can precede, coincide, or follow the onset of the intestinal symptoms11–13 and may occur at any time during disease process and in different forms in the same patient.13–15 Common oral lesions in patients with CD include hypertrophy and nonspecific swellings of the mucosa and lips, gingival soft tissue swelling resembling epulis fissuratum, cobblestone appearance of the buccal mucosa or palate, and aphthous-like ulcerations or deep yellowish white ulcers within the vestibule and on the gingiva.16–21 In patients with UC, pyostomatitis has been described as the main oral manifestation.13,22 Most of these oral lesions are soft and friable and are detached easily from the underlying tissue, leaving an erythematous and ulcerated zone, while some of the smaller may coalesce to form larger ramifying areas of necrosis. Usually these lesions are painful and have been present for a few months, while the patient’s chief complaints are additional bleeding and swelling of gums. In adults with IBD, a higher prevalence of caries has been reported compared with healthy control subjects.23–29 Data about prevalence and severity of periodontal disease in adult patients with IBD are limited.28–33 However, data about prevalence and severity of caries and periodontal disease in children and adolescents with IBD are www.ibdjournal.org |
1839
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Koutsochristou et al
absent. Therefore, the aim of this study was to evaluate the prevalence of dental caries, periodontal disease (gingivitis and periodontitis), and periodontal treatment needs of children and adolescents with IBD by a full-mouth detailed examination, and to compare them with the findings of an age-matched healthy population of a dental practice.
MATERIALS AND METHODS Study Population
The study comprised fifty-five children and adolescents (25 males and 30 females), aged 4 to 18 years (mean age: 12.32 6 3.41 yr) who were followed up in the outpatient IBD clinic of the Gastroenterology Unit at the 1st Department of Pediatrics of University of Athens, “Aghia Sophia” Children’s Hospital. The diagnosis of CD or UC was established according to the Porto criteria.34 Fifty-five systemically healthy children and adolescents (25 males) of a dental practice, aged 4 to 18 years (mean age: 12.21 6 3.96 yr), comprised the control group. Patients with IBD and the controls were matched according to age, sex, and social– economic status (occupation of their father, Registrar-General criteria).35 Both patients and controls were derived from the same geographic area. Patients with IBD or controls were excluded if one or more of the following conditions were observed: smoking, systemic conditions, or medications with impact on periodontal tissues or gingival overgrowth and previous orthodontic or periodontal treatment within the last year. All children with IBD with any medication for their disease were included.
Clinical Examination In patients with IBD, a detailed medical history and review of their records was performed, concerning disease onset, previous and current treatment, followed by oral medical history (by a questionnaire) from each patient and the accompanying parent. A physical examination was performed, and the Pediatric Crohn’s Disease Activity Index36 was used to assess disease activity in patients with CD, whereas the Pediatric Ulcerative Colitis Activity Index37 was used to assess disease activity in patients with UC. Immediately after assessment by the pediatric gastroenterologist, an oral and dental examination was performed in the IBD clinic by the same dentist throughout the study. In the control group, a detailed medical history was obtained, but a physical examination was not performed.
Oral and Dental Questionnaire
A questionnaire was filled out for patients and healthy participants to collect demographic data (age, sex, occupation of their fathers) and dental history including previous oral lesions before disease onset in those with IBD. Closed-ended questions were answered as follows: (1) frequency of toothbrushing (twice per wk, once per d, twice or more per d), (2) method of toothbrushing (horizontal, vertical, circular, other), and duration (,1 min, 1–2 min, .2 min) of toothbrushing, (3) frequency and
1840
Inflamm Bowel Dis Volume 21, Number 8, August 2015
reason of dental visits (only with dental problem, such as dental pain, abscess, or for oral health check-ups every 6 mo or every 12 mo), and (4) gum bleeding on toothbrushing (yes or no), a sign of periodontal disease.
Oral Examination An oral examination in both, patient and control groups, assessed mucosal lesions (number and type of findings) and the decayed, missing, and filled of deciduous (dmf-t) or permanent (DMF-T) tooth index, the simplified gingival index (GI-S) and the plaque control record (PCR) index. Concomitantly, the community periodontal index of treatment needs (CPITN) were performed and evaluated on all present full-erupted deciduous or permanent teeth. The assessment of caries (DMF-T or dmf-t) was determined according to the criteria of the World Health Organization and was calculated as mean value for each patient with IBD or in controls.38 The oral hygiene status was determined with the PCR index in order to assess the presence or absence of marginal plaque.39 The severity of inflammation at the cervical margin was determined by the GI-S, in order to record the gingival units that presented bleeding on gentle probing.40 These evaluations were performed at 4 sites per tooth (disto-buccal, mid-buccal, mesio-buccal and mid-lingual or mid-palatinal) of all existed teeth. The presence or absence of dental plaque (PCR) and of gingival inflammation (GI-S) was recorded as percentage of sites with plaque or bleeding after gentle probing. The prevalence and the severity of periodontal disease were recorded with the CPITN after dividing the oral cavity into sextants.41 For each sextant, the highest index was recorded by applying the following scores: 0 ¼ periodontal health, 1 ¼ gingival bleeding, 2 ¼ calculus and/or overhanging restorations, 3 ¼ probing pocket depth (PPD) of $4 mm but ,6 mm and 4 ¼ PPD $6 mm. Then, the prevalence of the highest CPITN score of each subject was calculated. PPD was recorded as the measurement from the gingival margin to the base of the probe-able pocket reading to the nearest millimeter. All these measurements were taken by the same examiner (V.K.) throughout the study using a conventional periodontal probe (PCP-15; Hu-Friedy, Chicago, IL). The examiner before the initiation of this study had calibrated herself to establish reliability and consistency by 3 repeated examinations of the same 15 children of dental practice in 2-day intervals to reduce intraexaminer error and to provide measurements to within less than 1 mm of error (gold standard). The Kappa scores were greater than 0.80. Additionally, the examiner (V.K.) had calibrated herself in a large number of patients in a previously published study.42
Statistical Analysis For comparison, the distribution of categorical variables, such as oral hygiene habits, symptom of periodontal disease, frequency and reason of dental visits and CPITN among the patients with IBD and a control population, performed the x2 test or Fisher’s exact test for small numbers. Also, for the comparison
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
of existing total or deciduous or permanent teeth or percentages of CPITN-scores, the z-test was used, whereas for the comparison of the average of mean values of each index (GI-S, PCR) Student’s t test was performed. Logistic regression models were used to evaluate the association between personal oral hygiene habits, symptom of periodontal disease as well as frequency and the reason of dental visits (as independent variables) and GI-S index or CPITN separately for each group of subjects. Statistical analysis was conducted using the STATA 9.0 software package, and the results were considered significant at 5% significance level (P ¼ 0.05).
Ethical Considerations Approval of the local ethical committee and parental consent was obtained for all study patients.
RESULTS There were 55 patients with IBD aged 4 to 18 years. Thirtysix patients were diagnosed with CD (18 males) and 19 were diagnosed with UC (7 males). Between patients with UC and CD, there were no statistically significant differences in disease duration (4.4 6 2.3 versus 3.5 6 1.4, Student’s t test ¼ 1.87, P . 0.05). According to Paris classification among the 36 patients with CD, 3 had perianal disease (P), 3 stricturing (B2), 1 stricturing + penetrating (B2B3), and 29 nonstricturing nonpenetrating (B1). Among the 19 patients with UC, 6 had left-sided colitis (E1) and 13 extensive colitis (E2). Patients with IBD were on remission and on treatment with aminosalicylates, corticosteroids, anti-TNF, or immunomodulators. Most patients were taking a combination of 2 medications (46 patients, 83%), while the remaining of them were under treatment with a combination of 3 drugs (9 patients, 16%). On combination therapy were 20 patients on corticosteroids and aminosalicylates, 3 patients on corticosteroids and immunomodulators (azathioprine/6-MP or methotrexate), 16 patients on aminosalicylates and immunomodulators, 5 patients on aminosalicylates and anti-TNF, and finally, 2 patients on immunomodulators and anti-TNF. In total, 28 out of 55 patients with IBD (51%) were taking immunomodulators (23 azathioprine/6-mercaptopurine, 2 methotrexate, and 3 cyclosporine). None of the subjects in the control group received any medication. Oral mucosa history revealed that 13 out of 55 patients with IBD (23%) had oral lesions. The most common oral lesion was aphthae (8 patients) or aphthae in conjunction with swellings of gums, ulcers or candidiasis (5 patients). Children in the control group had no oral mucosa lesions on examination. Regarding personal oral habits, listed in Table 1, there were no statistically significant differences between children and adolescents with or without IBD regarding frequency, duration, method of toothbrushing, or frequency and reason of dental visits. Between patients with IBD and controls as shown in Table 1, there were no statistically significant differences in
Dental and Periodontal Disease in IBD Children
the number of existing total, deciduous, or permanent teeth. However, there was statistically significant difference between the 2 groups in gum bleeding on toothbrushing because bleeding was referred in 30 out of 55 patients with IBD (54%) versus 16 out of 55 controls (29%). As noted in Table 2, the values of dmf-t and DMF-T were significantly higher (P , 0.001) in patients with IBD compared with control subjects. Also, mean value of GI-S was significantly higher (P , 0.001) in patients with IBD. However, there was no statistically significant difference between mean values of PCR in patients with IBD and the control population. Among the total number of patients with IBD, shown in Table 3, more than half (54%) had gingivitis with gingival bleeding, calculus, and/or overhanging restorations (corresponding to CPITN score 2), whereas 36% had only gingival bleeding (corresponding to CPITN score 1), 9% had at least 1 site with PPD values between 4 and 5 mm (corresponding to CPITN score 3), and none of them was found having healthy periodontium. Among the controls, 45% had only gingival bleeding, whereas 40% of subjects had a healthy periodontium (corresponding to CPITN score 0). As noted in Table 4, there was a positive correlation of the mean value of GI-S in patients with IBD (P , 0.001) with the mean value of PCR (r ¼ 0.993) and bleeding of gums on toothbrushing (r ¼ 0.613), whereas there was a negative correlation with duration (r ¼ 20.749) and frequency (r ¼ 20.573) of toothbrushing and the frequency and the reason of dental visits (r ¼ 20.615). Respectively, in the control population, only 1 positive significant correlation between mean values of GI-S and PCR indices (r ¼ 0.622, P , 0.001) was found. Correspondingly, a positive correlation of CPITN in patients with IBD (P , 0.001) with the mean values of GI-S (r ¼ 0.832), PCR (r ¼ 0.814), and bleeding of gums on toothbrushing (r ¼ 0.603) and a negative correlation with the duration of toothbrushing (r ¼ 20.652) was found. In the control population, only 2 significant positive correlations between CPITN and mean value of GI-S (r ¼ 0.650, P , 0.001) and of PCR indices (r ¼ 0.543, P , 0.01 were noticed). A statistically significant difference was found between mean values of GI-S and PCR in patients with IBD on immunomodulators versus those without immunomodulators as shown in Table 5. Additionally, patients with IBD on immunomodulators had more severe periodontal disease and increased periodontal treatment needs than patients with IBD without immunomodulators as shown in Table 6.
DISCUSSION This study examined the status of dental caries, gingival status, oral hygiene, and periodontal treatment needs in children and adolescents with IBD. To our knowledge and according to existing bibliographic data, this is the first case–control study on dental caries and periodontal disease in children and adolescents with IBD. www.ibdjournal.org |
1841
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
Koutsochristou et al
TABLE 1. Comparison Between Children and Adolescents with IBD and Control Population for Factors Related to the Personal Oral Hygiene Habits and Symptom of Periodontal Disease Statistical Analysis Parameters About Oral Health Habits
Patients with IBD (N ¼ 55), n (%)
Frequency of toothbrushing Less than twice per wk Once per d Twice or more per d Duration of toothbrushing ,1 min 1–2 min .2 min Method of toothbrushing Horizontal Vertical Circular Other Frequency and reason of dental visits Only with a problem Every 6 mo Every 12 mo Bleeding gums on toothbrushing Yes No Number of existing teeth Total teeth Deciduous teeth Permanent teeth
Controls (N ¼ 55), n (%)
x Test
Level of Significance (P)
2
12 (21.82) 30 (54.55) 13 (23.63)
12 (21.81) 26 (47.28) 17 (30.91)
0.81a
.0.05
20 (36.37) 22 (40.0) 13 (23.63
17 (30.91) 26 (47.28) 12 (21.81)
0.61a
.0.05
12 14 12 17
10 18 15 12
(18.18) (32.73) (27.27) (21.82)
1.82a
.0.05
17 (30.91) 18 (32.73) 20 (36.37)
18 (32.73) 22 (40.0) 15 (27.27)
1.16a
.0.05
30 (54.55) 25 (45.45)
16 (29.09) 39 (70.91)
6.31b
,0.001
1184 (50.67) 244 (48.51) 940 (51.29)
1152 (49.33) 259 (51.49) 893 (48.71)
0.63c 0.68c 1.13c
0.53 0.50 0.26
(21.82) (25.45) (21.82) (30.91)
x test. x test with Yates correction. z-test.
a 2
b 2 c
TABLE 2. Decayed, Missing, and Filled Tooth (DMF-T or dmf-t) Index, GI-S, and PCR Index in Children and Adolescents with IBD and a Control Population Patients with IBD (55 Subjects) Indices dmf-t index DMF-T index GI-S%a PCR%b
Controls (55 Subjects)
Mean Value
SD
Mean Value
SD
Student’s t Test
P
2.95 5.81 40.24 42.29
1.87 2.05 13.81 14.03
0.91 2.04 24.95 41.96
1.06 0.85 11.52 14.21
4.51 11.86 6.03 0.21
,0.001 ,0.001 ,0.001 .0.05
a
Percentage of sites with bleeding after gentle probing. Percentage of sites with dental plaque.
b
1842
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
Dental and Periodontal Disease in IBD Children
TABLE 3. CPITN in Children and Adolescents with IBD and a Control Population CPITN Index
Score 0 Score 1 Score 2 Score 3
Patients with IBDa (55 subjects) Number of subjects 0 % 0 Controlsa (55 subjects) Number of subjects 22 % 40.00 Statistical analysis Z-test 5.24 P ,0.001
20 36.36
30 54.55
5 9.09
25 45.45
8 14.55
0 0
0.97 0.33
4.41 ,0.001
2.29 0.02
Fisher’s exact test ,0.001.
a
This study shows that patients with IBD had a significantly worse oral health than age-matched controls. The mean values of dental caries indices at deciduous (dmf-t) and permanent teeth (DMF-T) were more than 2-fold and the value of GI-S was more than 60% higher in patients with IBD compared with controls. In addition, none among patients with IBD had healthy periodontium and more than half of them had gingivitis, while 9% had at least 1 site with pocket probing depth 4 or 5 mm. Accordingly, 40% of the control population had a healthy periodontium, 14% had
gingivitis, and none of the subjects had 1 site with pocket. It is noteworthy that all these clinical findings were recorded despite the lack of significant difference in oral hygiene status between the 2 studied groups. All patients with IBD were on remission and under medical treatment having a mean of 4-year duration of the disease. In 23% of patients with IBD, there was a history of recurrent oral lesions with the majority of them occurring during remission phase than in flare-up of the disease. The prevalence of oral lesions in our study is in agreement with the results of previously published clinical studies and respective case reports in adults with IBD in which it is reported to be about 20%.11,12,16,43–51 However, the prevalence of oral manifestations in our study is lower compared with those by Pittok et al (48%)52 and Harty et al (41%),21 both referring on children with active CD at the time of examination. Finally, in recent studies, oral lesions were not so common as found in older ones and were observed in about 10% of adult patients with active IBD.31 Also, it is of interest to mention that adults with UC but not CD had significantly higher prevalence of deep ulcers in oral soft tissues compared with systemic healthy controls.30 The evaluation of caries revealed that the dmf-t and DMF-T indices had significant differences between patients with IBD and the control population. These results were also in agreement with previous findings in adult subjects with IBD and healthy controls23–27,29,53 showing either an increase in the DMF-S index and the risk of baseline caries23,24 or frequent of dentine caries.25,27–29,53 Yet, it is interesting to refer to the findings of Halme
TABLE 4. Logistic Regression Analysis for Factors Related to Personal Oral Hygiene Habits, Symptoms of Periodontal Disease, Medication Treatment, and Frequency and Reason of Dental Visits in Patients with IBD and a Control Population that Influence the GI-S and CPITN Patients with IBD (55 Subjects) Parameters GI-S Bleeding of gums on toothbrushing Frequency of toothbrushing Duration of toothbrushing Method of toothbrushing Frequency and reason of dental visits PCR index CPITN Bleeding of gums on toothbrushing Frequency of toothbrushing Duration of toothbrushing Method of toothbrushing Frequency and reason of dental visits PCR index GI-S
Controls (55 Subjects)
Correlation Coefficient (r)
P
Correlation Coefficient (r)
P
0.613a 20.573a 20.749a 0.168a 20.615a 0.993b
,0.001 ,0.001 ,0.001 .0.05 ,0.001 ,0.001
0.092a 20.276a 20.025a 0.105a 20.251a 0.622b
.0.05 .0.05 .0.05 .0.05 .0.05 ,0.001
0.603a 20.187a 20.652a 0.015a 20.187a 0.814a 0.832a
,0.001 .0.05 ,0.001 .0.05 .0.05 ,0.001 ,0.001
0.169a 20.155a 20.082a 0.196a 20.264a 0.543b 0.650a
.0.05 .0.05 .0.05 .0.05 .0.05 ,0.001 ,0.01
a
Spearman’s correlation coefficient. Pearson’s correlation coefficient.
b
www.ibdjournal.org |
1843
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
Koutsochristou et al
TABLE 5. GI-S and PCR Index in Children and Adolescents with IBD, Using Medication with or Without Immunomodulators Statistical Analysis Indices GI-S% Without immunomodulators With immunomodulators PCR index% Without immunomodulators With immunomodulators
No. Subjects
Mean Value
SD
Student’s t Test
P
27 28
32.93 47.23
10.98 12.84
4.44
,0.001
27 28
34.95 49.36
10.87 13.19
4.42
,0.001
et al54 who had observed that the adult patients with active IBD had higher number of dental infection foci detected in panoramic radiographs. In most of the above studies, the high risk of dental caries has been hypothesized to occur due to nutritional deficiencies and changes in salivary and microbiologic conditions in the oral cavity.26 Patients with active IBD had more frequently high salivary counts of Streptococci mutans and lactobacilli despite normal salivary flow rate and buffer capacity.27,28 The high count of the acidogenic bacteria may be mainly related to the dietary habits of patients with IBD due to more frequent consumption of refined carbohydrates, mainly during exacerbations, favoring colonization, and growth of these bacteria. A recent article suggests that dysbiosis in the mouth is also linked to the host’s inflammatory response.55 However, we do not know yet if this dysbiosis in saliva has any effect on the incidence of dental caries. In this study, plaque scores in the IBD group were not significantly higher compared with those of controls. The gingival evaluation revealed that the mean value of GI-S in children and adolescents with IBD was much higher compared with the control group despite the absence of significant difference in plaque indices
between the 2 groups. Similarly, the prevalence of marginal bleeding or the mean value of gingival index was greater in adult patients with active CD or UC30 as compared with matched controls56 or to patients with inactive IBD.31 Additionally, a recent prospective study found that gingivitis markers, as papillary bleeding indices, were higher in adults with IBD than in healthy adult controls.33 The increased needs in periodontal treatment in children and adolescents with IBD in this study are in line, as far as we know, with other studies in adults where the majority of patients with CD or UC had a mild or moderate periodontitis, while only smaller percentage had susceptibility for severe periodontitis.28–30,32,33 Correspondent clinical studies about periodontal treatment needs in children and adolescents with CD or UC are absent except for a single case report about a severe rapidly progressive periodontitis occurring in 6-year old boy with CD.57 Finally, it is noteworthy in our study that patients with IBD taking immunomodulators had a higher mean value of GI-S and increased needs of periodontal treatment. To our knowledge, this finding has not been described in adults with IBD. Chronic use of cyclosporine or azathioprine may change periodontal status provoking gingival overgrowth with prevalence rates between 8% and 97%.58–61 The majority of our patients were taking
TABLE 6. Community Periodontal Index Treatment Needs (CPITN) in Children and Adolescents Using Medication with or Without Immunomodulators CPITN Index IBD patients with immunomodulators (28 subjects)a No. subjects % IBD patients without immunomodulators (27 subjects)a No. subjects % Statistical analysis Z-test P
Score 0
Score 1
Score 2
Score 3
0 0
4 7.27
19 34.55
5 9.09
0 0
16 29.09
11 20.0
0 0
0 0
3.46 0.0005
2.02 0.04
2.30 0.02
Fisher’s exact test ,0.001.
a
1844
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
azathioprine/6-mercaptopurine (23 patients), and only 3 were on cyclosporine. There is continued debate over which factors modify the degree of overgrowth, including individual sensitivity, age, or dose and duration of drug therapy. The exact mechanism of gingival overgrowth is not well defined but appears to be caused by the combination of the proliferation of fibroblasts within gingival tissue, the increase in the deposition of collagen and extracellular matrix, and the decrease in phagocytosis resulting in a net gain in gingival tissue mass.58–61 We could hypothesize that the disease itself, medications, different dietary habits, and possibly oral dysbiosis could contribute to dental and periodontal disease in patients with IBD. However, we could speculate that as half of the patients with IBD were on medications known to have periodontal effects, this could be an important risk factor in our patients compared with controls. The strength of this study is that it is the first prospective case–control study dealing with dental caries, oral hygiene, gingival status, and periodontal treatment needs of children and adolescents with IBD. A limitation of this study is that all patients with IBD were on remission (as defined by Pediatric Crohn’s Disease Activity Index and Pediatric Ulcerative Colitis Activity Index ,10) because we included only those attended in the outpatient IBD clinic who were more collaborative. The study did not include inpatients who were in the active phase of the disease because of ethical considerations. Another limitation was that the clinical dental examination of patients with IBD was done without any previous awareness, whereas in controls, the examination was done after an appointment to resolve a new dental problem, reevaluation of a previous one or for oral health checkup. This difference about the type of appointment probably could affect the level of oral hygiene at the time of oral examination, but it had not any effect on the decayed, missing, and filled deciduous or permanent teeth, the gingival status, and periodontal treatment needs. Additionally, the relatively small number of patients (the sample size of patients with IBD) could bring another limitation to infer whether disease characteristics, i.e., disease distribution and extend, complicated disease (i.e., perianal or fistulizing), UC or CD influenced type, or severity of dental manifestations. A bias could also be regarding controls, taken into account that they were on a regular preventing program. However, it did not happen in our case because both groups did not participate in long-term regular oral health checkup program. Additionally, no differences were found between patients with IBD and the control group during regular every 6- to 12-month visits. In conclusion, this study showed that children and adolescents with UC and CD had a significantly worse oral health than age- and sex-matched controls. Overall, patients with IBD had higher prevalence of dentine caries, more clinical signs of gingival inflammation, and increased periodontal treatment needs with distinct differences from the healthy control group. These findings indicate the need for preventive dental and periodontal care of the children and adolescents with IBD and probe for a targeted investigation in the future.
Dental and Periodontal Disease in IBD Children
REFERENCES
1. MacDonald TT, Monteleone G, Pender SL. Recent developments in the immunology of inflammatory bowel disease. Scand J Immunol. 2000;51: 2–9. 2. Jostins L, Ripke S, Weersma RK. Host- microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491: 119–124. 3. Ponder A, Long MD. A clinical review of recent findings in the epidemiology of inflammatory bowel disease. Clin Epidemiol. 2013;5:237–247. 4. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474:307–317. 5. Soon IS, Molodecky NA, Rabi MD, et al. The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis. BMC Gastroenterol. 2012;12:51. 6. Bernstein CN, Shanahan F Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut. 2008;57:1185–1191. 7. Mahid SS, Minor KS, Soto RE, et al. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006;81:1462–1471. 8. Virta L, Auvinen A, Helenius H, et al. Association of repeated exposure to antibiotics with the development of pediatric Crohn’s disease—a nationwide, register-based Finnish case-control study. Am J Epidemiol. 2012; 175:775–784. 9. Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:235–241. 10. Jiang L, Xia B, Li J, et al. Retrospective survey of 452 patients with inflammatory bowel disease in Wuhan city, Central China. Inflamm Bowel Dis. 2006;12:212–217. 11. Plauth M, Jenss H, Meyle J. Oral manifestations of Crohn’s disease. An analysis of 79 cases. J Clin Gastroenterol. 1991;13:29–37. 12. Williams AJK, Wray D, Ferguson A. The clinical entity of orofacial Crohn’s disease. Q J Med. 1991;79:451–458. 13. Chan SW, Scully C, Prime SS, et al. Pyostomatitis vegetans: oral manifestation of ulcerative colitis. Oral Surg Oral Med Oral Pathol. 1991;72: 689–692. 14. Lisciandrano D, Ranzi T, Carrassi A, et al. Prevalence of oral lesions in inflammatory bowel disease. Am J Gastrenterol. 1996;91:7–10. 15. Dupuy A, Cosnes J, Revuz J, et al. Oral Crohn disease: clinical characteristics and long-term follow-up of 9 cases. Arch Dermatol. 1999;135:439–442. 16. Dudeney TP. Crohn’s disease of the mouth. Proc R Soc Med. 1969;62: 1237. 17. Carr D. Granulomatous cheilitis in Crohn’s disease. Br Med J. 1974;4:636. 18. Snyder MB, Cawson RA. Oral changes in Crohn’s disease. J Oral Surg. 1976;34:594–599. 19. Talbot T, Jewell L, Schloss E, et al. Cheilitis antedating Crohn’s disease: case report and literature update of oral lesions. J Clin Gastroenterol. 1984;6:349–354. 20. Scheper HJ, Brand HS. Oral aspects of Crohn’s disease. Int Dent J. 2002; 52:163–172. 21. Harty S, Fleming P, Rowland M, et al. A prospective study of the oral manifestations of Crohn’s disease. Clin Gastroenterol Hepatol. 2005;3: 886–891. 22. Hansen LS, Silverman S Jr, Daniels TE. The differential diagnosis of pyostomatitis vegetans and its relation to bowel disease. Oral Surg Oral Med Oral Pathol. 1983;55:363–373. 23. Sundh B, Hultén L. Oral status in patients with Crohn’s disease. Acta Chir Scand. 1982;148:531–534. 24. Rooney TP. Dental caries prevalence in patients with Crohn’s disease. Oral Surg Oral Med Oral Pathol. 1984;57:623–624. 25. Bevenius J. Caries risk in patients with Crohn’s disease: a pilot study. Oral Surg Oral Med Oral Pathol. 1988;65:304–307. 26. Sundh B, Emilson CG. Salivary and microbial conditions and dental health in patients with Crohn’s disease: a 3-year study. Oral Surg Oral Med Oral Pathol. 1989;67:286–290. 27. Schütz T, Drude C, Paulisch E, et al. Sugar intake, taste changes and dental health in Crohn’s disease. Dig Dis. 2003;21:252–257. 28. Grössner-Scheiber B, Fetter T, Hedderich J, et al. Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study. J Clin Periodontol. 2006;33:478–484. 29. Brito F, de Barros FC, Zaltman C, et al. Prevalence of periodontitis and DMFT index in patients with Crohn’s disease and ulcerative colitis. J Clin Periodontol. 2008;35:555–560. www.ibdjournal.org |
1845
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Koutsochristou et al
30. Flemmig TF, Shanahan F, Miyasaki KT. Prevalence and severity of periodontal disease in patients with inflammatory bowel disease. J Clin Periodontol. 1991;18:690–697. 31. Meurman JH, Halme L, Laine P, et al. Gingival and dental status, salivary acidogenic bacteria, and yeast counts of patients with active or inactive Crohn’s disease. Oral Surg Oral Med Oral Pathol. 1994;77: 465–468. 32. Habashneh RA, Khader YS, Alhumouz MK, et al. The association between inflammatory bowel disease and periodontitis among Jordanians: a case-control study. J Periodontal Res. 2012;47:293–298. 33. Vavricka SR, Manser CN, Hediger S, et al. Periodontitis and gingivitis in inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2013;19:2768–2777. 34. IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis—the Porto criteria. J Pediatr Gastroenterol Nutr. 2005;41:1–7. 35. Registram-General. Classification of Occupations. London, United Kingdom: HMSP; 1960. 36. Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn’s disease activity index. J Pediatr Gastroenterol Nutr. 1991;12:439–447. 37. Turner D, Hyams J, Markowitz J, et al. Appraisal of the pediatric ulcerative colitis activity index. Inflamm Bowel Dis. 2009;15:1218–1223. 38. World Health Organization. Oral Health Surveys: Basic Methods. 4th ed. Geneva, Switzerland: WHO; 1997. 39. O’Leary TJ, Drake RB, Naylor JE. The plaque control record. J Periodontol. 1972;43:38. 40. Lindhe J. Textbook of Clinical Periodontology. 1st ed. Copenhagen, Denmark: Munksgaard; 1981:327–352. 41. Ainamo J, Barmes D, Beagrie G, et al. Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J. 1982;32:281–291. 42. Tsami A, Pepelassi E, Kontovazenitis G, et al. Frequency and distribution of furcation defects in chronic periodontitis patients. Hellenic Stomatological Rev. 2008;52:25–35. 43. Basu MK, Asquith P, Thompson RA, et al. Proceedings: oral lesions in patients with Crohn’s disease. Gut. 1974;15:346. 44. Taylor VE, Smith CJ. Oral manifestations of Crohn’s disease without demonstrable gastrointestinal lesions. Oral Surg Oral Med Oral Pathol. 1975;39:58–66.
1846
Inflamm Bowel Dis Volume 21, Number 8, August 2015
45. Basu MK. Oral manifestations of Crohn’s disease: studies in the pathogenesis. Proc R Soc Med. 1976;69:765–766. 46. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore). 1976;55:401–412. 47. Wysocki GP, Brooke RI. Oral manifestations of chronic granulomatous disease. Oral Surg Oral Med Oral Pathol. 1978;46:815–819. 48. Basu MK, Asquith P. Oral manifestations of inflammatory bowel disease. Clin Gastroenterol. 1980;9:307–321. 49. Fisher AA. Chronic lip edema with particular reference to the MelkerssonRosenthal syndrome (MRS). Cutis. 1990;45:144–146. 50. Rankin GB. Extraintestinal and systemic manifestations of inflammatory bowel disease. Med Clin North Am. 1990;74:39–50. 51. Rehberger A, Püspök A, Stallmeister T, et al. Crohn’s disease masquerading as aphthous ulcers. Eur J Dermatol. 1998;8:274–276. 52. Pittock S, Drumm B, Fleming P, et al. The oral cavity in Crohn’s disease. J Pediatr. 2001;138:767–771. 53. Vehkalathi M, Paunio I, Nyyssonen V, et al. Oral Health in the Adult Finnish Population and Associated Factors. Helsinki and Turku, Finland: Social Insurance Institution; 1999:237–252. 54. Halme L, Meurman JH, Laine P, et al. Oral findings in patients with active or inactive Crohn’s disease. Oral Surg Oral Med Oral Pathol. 1993;76:175–181. 55. Said HS, Suda W, Nakagome S, et al. Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers. DNA Res. 2014;21:15–25. 56. Van Dyke TE, Dowell VR Jr, Offenbacher S, et al. Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. Infect Immun. 1986;53:671–677. 57. Sigusch BW. Periodontitis as manifestation of Crohn’s disease in primary dentition: a case report. J Dent Child. 2004;71:193–196. 58. Seymour RA, Heasman PA. Drugs and periodontium. J Clin Periodontol. 1988;15:1–16. 59. Santi E, Bral M. Effect of treatment on cyclosporine and nifedipine induced gingival enlargement: clinical and histologic results. Int J Periodontics Restorative Dent. 1998;18:81–86. 60. Seymour RA, Ellis JS, Thomson JM. Risk factors for drug-induced gingival overgrowth. J Clin Periodontol. 2000;27:217–230. 61. Pistorius A, Willershausen B, Callaway A. Effects of selected immunoupressive drugs on prostaglandin release, protein synthesis and cell proliferation in human fibroblasts and on the growth of plaque bacteria. Eur J Med Res. 2003;28:25–32.
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Dental Caries and Periodontal Disease in Children and Adolescents with Inflammatory Bowel Disease: A Case–Control Study Vassiliki Koutsochristou, DDS,* Aglaia Zellos, MD,* Konstantina Dimakou, MD,* Ioanna Panayotou, MD,* Sultana Siahanidou, MD,* Eleftheria Roma-Giannikou, MD,* and Alexandra Tsami, DDS†
Background: Previous reports have demonstrated a higher prevalence of dental caries and periodontal disease in adults with inflammatory bowel disease (IBD), but similar data in children and adolescents do not exist. The aim of the study was to evaluate the status of dental caries, oral hygiene, gingival status and periodontal treatment needs of children with IBD.
Methods: In this case–control study, 55 children on remission from a single outpatient IBD clinic, aged 4 to 18 years (12.27 6 3.67 yr) and 55 matched systemically healthy controls of a dental practice were assessed prospectively. The evaluation included medical history, dental questionnaire in both groups, and previous and current medical therapy of children with IBD. Additionally, the decayed, missing, and filled tooth (dmf-t or DMF-T), simplified gingival, plaque control record and community periodontal treatment needs indices were evaluated. Results: Children with IBD compared with controls had a statistically significant (P , 0.001) higher dmf-t (2.95 versus 0.91) or DMF-T (5.81 versus 2.04) index and a higher gingival inflammation (simplified gingival, 40% versus 24%) although the respectively dental plaque index showed no significant difference (plaque control record, 42% versus 41%). Also, the community periodontal treatment needs was significantly higher compared with controls (P , 0.001); most of the patients with IBD needed treatment of gingivitis (47% versus 4%), and none of them had healthy periodontium (0% versus 69%). Conclusions: The results of this case–control study demonstrate a higher frequency of dental caries, more clinical signs of gingival inflammation, and increased periodontal treatment needs in children and adolescents with IBD despite similar oral hygiene status. (Inflamm Bowel Dis 2015;21:1839–1846) Key Words: inflammatory bowel disease, children, adolescents, dental caries, gingival inflammation, periodontal treatment needs
I
nflammatory bowel disease (IBD) comprises 2 major disease entities: Crohn’s disease (CD) and ulcerative colitis (UC); they are characterized by chronic inflammatory involvement of the gastrointestinal tract evolving with a relapsing and remitting course. The etiology of these chronic intestinal disorders is not completely understood, but it is known that distinct immune abnormalities play a major role in the initiation and perpetuation of IBD,1 and that genetic2–4 and environmental factors5–8 are involved in the pathogenesis. About 25% to 35% of patients with both forms of IBD develop at least 1 extraintestinal manifestation usually involving joints, eyes, skin, mouth, and liver.9,10 One or more types of oral
Received for publication March 2, 2015; Accepted March 24, 2015. From the *First Department of Pediatrics, University of Athens School of Medicine, Athens, Greece; and †Department of Periodontology, University of Athens Dental School, Athens, Greece. The authors have no conflicts of interest to disclose. Reprints: Aglaia Zellos, MD, First Department of Pediatrics, University of Athens School of Medicine, Aghia Sofia Children’s Hospital, Thivon and Levadias Street, 11527 Athens, Greece (e-mail: [email protected]). Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000452 Published online 15 May 2015.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
manifestations of IBD can precede, coincide, or follow the onset of the intestinal symptoms11–13 and may occur at any time during disease process and in different forms in the same patient.13–15 Common oral lesions in patients with CD include hypertrophy and nonspecific swellings of the mucosa and lips, gingival soft tissue swelling resembling epulis fissuratum, cobblestone appearance of the buccal mucosa or palate, and aphthous-like ulcerations or deep yellowish white ulcers within the vestibule and on the gingiva.16–21 In patients with UC, pyostomatitis has been described as the main oral manifestation.13,22 Most of these oral lesions are soft and friable and are detached easily from the underlying tissue, leaving an erythematous and ulcerated zone, while some of the smaller may coalesce to form larger ramifying areas of necrosis. Usually these lesions are painful and have been present for a few months, while the patient’s chief complaints are additional bleeding and swelling of gums. In adults with IBD, a higher prevalence of caries has been reported compared with healthy control subjects.23–29 Data about prevalence and severity of periodontal disease in adult patients with IBD are limited.28–33 However, data about prevalence and severity of caries and periodontal disease in children and adolescents with IBD are www.ibdjournal.org |
1839
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Koutsochristou et al
absent. Therefore, the aim of this study was to evaluate the prevalence of dental caries, periodontal disease (gingivitis and periodontitis), and periodontal treatment needs of children and adolescents with IBD by a full-mouth detailed examination, and to compare them with the findings of an age-matched healthy population of a dental practice.
MATERIALS AND METHODS Study Population
The study comprised fifty-five children and adolescents (25 males and 30 females), aged 4 to 18 years (mean age: 12.32 6 3.41 yr) who were followed up in the outpatient IBD clinic of the Gastroenterology Unit at the 1st Department of Pediatrics of University of Athens, “Aghia Sophia” Children’s Hospital. The diagnosis of CD or UC was established according to the Porto criteria.34 Fifty-five systemically healthy children and adolescents (25 males) of a dental practice, aged 4 to 18 years (mean age: 12.21 6 3.96 yr), comprised the control group. Patients with IBD and the controls were matched according to age, sex, and social– economic status (occupation of their father, Registrar-General criteria).35 Both patients and controls were derived from the same geographic area. Patients with IBD or controls were excluded if one or more of the following conditions were observed: smoking, systemic conditions, or medications with impact on periodontal tissues or gingival overgrowth and previous orthodontic or periodontal treatment within the last year. All children with IBD with any medication for their disease were included.
Clinical Examination In patients with IBD, a detailed medical history and review of their records was performed, concerning disease onset, previous and current treatment, followed by oral medical history (by a questionnaire) from each patient and the accompanying parent. A physical examination was performed, and the Pediatric Crohn’s Disease Activity Index36 was used to assess disease activity in patients with CD, whereas the Pediatric Ulcerative Colitis Activity Index37 was used to assess disease activity in patients with UC. Immediately after assessment by the pediatric gastroenterologist, an oral and dental examination was performed in the IBD clinic by the same dentist throughout the study. In the control group, a detailed medical history was obtained, but a physical examination was not performed.
Oral and Dental Questionnaire
A questionnaire was filled out for patients and healthy participants to collect demographic data (age, sex, occupation of their fathers) and dental history including previous oral lesions before disease onset in those with IBD. Closed-ended questions were answered as follows: (1) frequency of toothbrushing (twice per wk, once per d, twice or more per d), (2) method of toothbrushing (horizontal, vertical, circular, other), and duration (,1 min, 1–2 min, .2 min) of toothbrushing, (3) frequency and
1840
Inflamm Bowel Dis Volume 21, Number 8, August 2015
reason of dental visits (only with dental problem, such as dental pain, abscess, or for oral health check-ups every 6 mo or every 12 mo), and (4) gum bleeding on toothbrushing (yes or no), a sign of periodontal disease.
Oral Examination An oral examination in both, patient and control groups, assessed mucosal lesions (number and type of findings) and the decayed, missing, and filled of deciduous (dmf-t) or permanent (DMF-T) tooth index, the simplified gingival index (GI-S) and the plaque control record (PCR) index. Concomitantly, the community periodontal index of treatment needs (CPITN) were performed and evaluated on all present full-erupted deciduous or permanent teeth. The assessment of caries (DMF-T or dmf-t) was determined according to the criteria of the World Health Organization and was calculated as mean value for each patient with IBD or in controls.38 The oral hygiene status was determined with the PCR index in order to assess the presence or absence of marginal plaque.39 The severity of inflammation at the cervical margin was determined by the GI-S, in order to record the gingival units that presented bleeding on gentle probing.40 These evaluations were performed at 4 sites per tooth (disto-buccal, mid-buccal, mesio-buccal and mid-lingual or mid-palatinal) of all existed teeth. The presence or absence of dental plaque (PCR) and of gingival inflammation (GI-S) was recorded as percentage of sites with plaque or bleeding after gentle probing. The prevalence and the severity of periodontal disease were recorded with the CPITN after dividing the oral cavity into sextants.41 For each sextant, the highest index was recorded by applying the following scores: 0 ¼ periodontal health, 1 ¼ gingival bleeding, 2 ¼ calculus and/or overhanging restorations, 3 ¼ probing pocket depth (PPD) of $4 mm but ,6 mm and 4 ¼ PPD $6 mm. Then, the prevalence of the highest CPITN score of each subject was calculated. PPD was recorded as the measurement from the gingival margin to the base of the probe-able pocket reading to the nearest millimeter. All these measurements were taken by the same examiner (V.K.) throughout the study using a conventional periodontal probe (PCP-15; Hu-Friedy, Chicago, IL). The examiner before the initiation of this study had calibrated herself to establish reliability and consistency by 3 repeated examinations of the same 15 children of dental practice in 2-day intervals to reduce intraexaminer error and to provide measurements to within less than 1 mm of error (gold standard). The Kappa scores were greater than 0.80. Additionally, the examiner (V.K.) had calibrated herself in a large number of patients in a previously published study.42
Statistical Analysis For comparison, the distribution of categorical variables, such as oral hygiene habits, symptom of periodontal disease, frequency and reason of dental visits and CPITN among the patients with IBD and a control population, performed the x2 test or Fisher’s exact test for small numbers. Also, for the comparison
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
of existing total or deciduous or permanent teeth or percentages of CPITN-scores, the z-test was used, whereas for the comparison of the average of mean values of each index (GI-S, PCR) Student’s t test was performed. Logistic regression models were used to evaluate the association between personal oral hygiene habits, symptom of periodontal disease as well as frequency and the reason of dental visits (as independent variables) and GI-S index or CPITN separately for each group of subjects. Statistical analysis was conducted using the STATA 9.0 software package, and the results were considered significant at 5% significance level (P ¼ 0.05).
Ethical Considerations Approval of the local ethical committee and parental consent was obtained for all study patients.
RESULTS There were 55 patients with IBD aged 4 to 18 years. Thirtysix patients were diagnosed with CD (18 males) and 19 were diagnosed with UC (7 males). Between patients with UC and CD, there were no statistically significant differences in disease duration (4.4 6 2.3 versus 3.5 6 1.4, Student’s t test ¼ 1.87, P . 0.05). According to Paris classification among the 36 patients with CD, 3 had perianal disease (P), 3 stricturing (B2), 1 stricturing + penetrating (B2B3), and 29 nonstricturing nonpenetrating (B1). Among the 19 patients with UC, 6 had left-sided colitis (E1) and 13 extensive colitis (E2). Patients with IBD were on remission and on treatment with aminosalicylates, corticosteroids, anti-TNF, or immunomodulators. Most patients were taking a combination of 2 medications (46 patients, 83%), while the remaining of them were under treatment with a combination of 3 drugs (9 patients, 16%). On combination therapy were 20 patients on corticosteroids and aminosalicylates, 3 patients on corticosteroids and immunomodulators (azathioprine/6-MP or methotrexate), 16 patients on aminosalicylates and immunomodulators, 5 patients on aminosalicylates and anti-TNF, and finally, 2 patients on immunomodulators and anti-TNF. In total, 28 out of 55 patients with IBD (51%) were taking immunomodulators (23 azathioprine/6-mercaptopurine, 2 methotrexate, and 3 cyclosporine). None of the subjects in the control group received any medication. Oral mucosa history revealed that 13 out of 55 patients with IBD (23%) had oral lesions. The most common oral lesion was aphthae (8 patients) or aphthae in conjunction with swellings of gums, ulcers or candidiasis (5 patients). Children in the control group had no oral mucosa lesions on examination. Regarding personal oral habits, listed in Table 1, there were no statistically significant differences between children and adolescents with or without IBD regarding frequency, duration, method of toothbrushing, or frequency and reason of dental visits. Between patients with IBD and controls as shown in Table 1, there were no statistically significant differences in
Dental and Periodontal Disease in IBD Children
the number of existing total, deciduous, or permanent teeth. However, there was statistically significant difference between the 2 groups in gum bleeding on toothbrushing because bleeding was referred in 30 out of 55 patients with IBD (54%) versus 16 out of 55 controls (29%). As noted in Table 2, the values of dmf-t and DMF-T were significantly higher (P , 0.001) in patients with IBD compared with control subjects. Also, mean value of GI-S was significantly higher (P , 0.001) in patients with IBD. However, there was no statistically significant difference between mean values of PCR in patients with IBD and the control population. Among the total number of patients with IBD, shown in Table 3, more than half (54%) had gingivitis with gingival bleeding, calculus, and/or overhanging restorations (corresponding to CPITN score 2), whereas 36% had only gingival bleeding (corresponding to CPITN score 1), 9% had at least 1 site with PPD values between 4 and 5 mm (corresponding to CPITN score 3), and none of them was found having healthy periodontium. Among the controls, 45% had only gingival bleeding, whereas 40% of subjects had a healthy periodontium (corresponding to CPITN score 0). As noted in Table 4, there was a positive correlation of the mean value of GI-S in patients with IBD (P , 0.001) with the mean value of PCR (r ¼ 0.993) and bleeding of gums on toothbrushing (r ¼ 0.613), whereas there was a negative correlation with duration (r ¼ 20.749) and frequency (r ¼ 20.573) of toothbrushing and the frequency and the reason of dental visits (r ¼ 20.615). Respectively, in the control population, only 1 positive significant correlation between mean values of GI-S and PCR indices (r ¼ 0.622, P , 0.001) was found. Correspondingly, a positive correlation of CPITN in patients with IBD (P , 0.001) with the mean values of GI-S (r ¼ 0.832), PCR (r ¼ 0.814), and bleeding of gums on toothbrushing (r ¼ 0.603) and a negative correlation with the duration of toothbrushing (r ¼ 20.652) was found. In the control population, only 2 significant positive correlations between CPITN and mean value of GI-S (r ¼ 0.650, P , 0.001) and of PCR indices (r ¼ 0.543, P , 0.01 were noticed). A statistically significant difference was found between mean values of GI-S and PCR in patients with IBD on immunomodulators versus those without immunomodulators as shown in Table 5. Additionally, patients with IBD on immunomodulators had more severe periodontal disease and increased periodontal treatment needs than patients with IBD without immunomodulators as shown in Table 6.
DISCUSSION This study examined the status of dental caries, gingival status, oral hygiene, and periodontal treatment needs in children and adolescents with IBD. To our knowledge and according to existing bibliographic data, this is the first case–control study on dental caries and periodontal disease in children and adolescents with IBD. www.ibdjournal.org |
1841
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
Koutsochristou et al
TABLE 1. Comparison Between Children and Adolescents with IBD and Control Population for Factors Related to the Personal Oral Hygiene Habits and Symptom of Periodontal Disease Statistical Analysis Parameters About Oral Health Habits
Patients with IBD (N ¼ 55), n (%)
Frequency of toothbrushing Less than twice per wk Once per d Twice or more per d Duration of toothbrushing ,1 min 1–2 min .2 min Method of toothbrushing Horizontal Vertical Circular Other Frequency and reason of dental visits Only with a problem Every 6 mo Every 12 mo Bleeding gums on toothbrushing Yes No Number of existing teeth Total teeth Deciduous teeth Permanent teeth
Controls (N ¼ 55), n (%)
x Test
Level of Significance (P)
2
12 (21.82) 30 (54.55) 13 (23.63)
12 (21.81) 26 (47.28) 17 (30.91)
0.81a
.0.05
20 (36.37) 22 (40.0) 13 (23.63
17 (30.91) 26 (47.28) 12 (21.81)
0.61a
.0.05
12 14 12 17
10 18 15 12
(18.18) (32.73) (27.27) (21.82)
1.82a
.0.05
17 (30.91) 18 (32.73) 20 (36.37)
18 (32.73) 22 (40.0) 15 (27.27)
1.16a
.0.05
30 (54.55) 25 (45.45)
16 (29.09) 39 (70.91)
6.31b
,0.001
1184 (50.67) 244 (48.51) 940 (51.29)
1152 (49.33) 259 (51.49) 893 (48.71)
0.63c 0.68c 1.13c
0.53 0.50 0.26
(21.82) (25.45) (21.82) (30.91)
x test. x test with Yates correction. z-test.
a 2
b 2 c
TABLE 2. Decayed, Missing, and Filled Tooth (DMF-T or dmf-t) Index, GI-S, and PCR Index in Children and Adolescents with IBD and a Control Population Patients with IBD (55 Subjects) Indices dmf-t index DMF-T index GI-S%a PCR%b
Controls (55 Subjects)
Mean Value
SD
Mean Value
SD
Student’s t Test
P
2.95 5.81 40.24 42.29
1.87 2.05 13.81 14.03
0.91 2.04 24.95 41.96
1.06 0.85 11.52 14.21
4.51 11.86 6.03 0.21
,0.001 ,0.001 ,0.001 .0.05
a
Percentage of sites with bleeding after gentle probing. Percentage of sites with dental plaque.
b
1842
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
Dental and Periodontal Disease in IBD Children
TABLE 3. CPITN in Children and Adolescents with IBD and a Control Population CPITN Index
Score 0 Score 1 Score 2 Score 3
Patients with IBDa (55 subjects) Number of subjects 0 % 0 Controlsa (55 subjects) Number of subjects 22 % 40.00 Statistical analysis Z-test 5.24 P ,0.001
20 36.36
30 54.55
5 9.09
25 45.45
8 14.55
0 0
0.97 0.33
4.41 ,0.001
2.29 0.02
Fisher’s exact test ,0.001.
a
This study shows that patients with IBD had a significantly worse oral health than age-matched controls. The mean values of dental caries indices at deciduous (dmf-t) and permanent teeth (DMF-T) were more than 2-fold and the value of GI-S was more than 60% higher in patients with IBD compared with controls. In addition, none among patients with IBD had healthy periodontium and more than half of them had gingivitis, while 9% had at least 1 site with pocket probing depth 4 or 5 mm. Accordingly, 40% of the control population had a healthy periodontium, 14% had
gingivitis, and none of the subjects had 1 site with pocket. It is noteworthy that all these clinical findings were recorded despite the lack of significant difference in oral hygiene status between the 2 studied groups. All patients with IBD were on remission and under medical treatment having a mean of 4-year duration of the disease. In 23% of patients with IBD, there was a history of recurrent oral lesions with the majority of them occurring during remission phase than in flare-up of the disease. The prevalence of oral lesions in our study is in agreement with the results of previously published clinical studies and respective case reports in adults with IBD in which it is reported to be about 20%.11,12,16,43–51 However, the prevalence of oral manifestations in our study is lower compared with those by Pittok et al (48%)52 and Harty et al (41%),21 both referring on children with active CD at the time of examination. Finally, in recent studies, oral lesions were not so common as found in older ones and were observed in about 10% of adult patients with active IBD.31 Also, it is of interest to mention that adults with UC but not CD had significantly higher prevalence of deep ulcers in oral soft tissues compared with systemic healthy controls.30 The evaluation of caries revealed that the dmf-t and DMF-T indices had significant differences between patients with IBD and the control population. These results were also in agreement with previous findings in adult subjects with IBD and healthy controls23–27,29,53 showing either an increase in the DMF-S index and the risk of baseline caries23,24 or frequent of dentine caries.25,27–29,53 Yet, it is interesting to refer to the findings of Halme
TABLE 4. Logistic Regression Analysis for Factors Related to Personal Oral Hygiene Habits, Symptoms of Periodontal Disease, Medication Treatment, and Frequency and Reason of Dental Visits in Patients with IBD and a Control Population that Influence the GI-S and CPITN Patients with IBD (55 Subjects) Parameters GI-S Bleeding of gums on toothbrushing Frequency of toothbrushing Duration of toothbrushing Method of toothbrushing Frequency and reason of dental visits PCR index CPITN Bleeding of gums on toothbrushing Frequency of toothbrushing Duration of toothbrushing Method of toothbrushing Frequency and reason of dental visits PCR index GI-S
Controls (55 Subjects)
Correlation Coefficient (r)
P
Correlation Coefficient (r)
P
0.613a 20.573a 20.749a 0.168a 20.615a 0.993b
,0.001 ,0.001 ,0.001 .0.05 ,0.001 ,0.001
0.092a 20.276a 20.025a 0.105a 20.251a 0.622b
.0.05 .0.05 .0.05 .0.05 .0.05 ,0.001
0.603a 20.187a 20.652a 0.015a 20.187a 0.814a 0.832a
,0.001 .0.05 ,0.001 .0.05 .0.05 ,0.001 ,0.001
0.169a 20.155a 20.082a 0.196a 20.264a 0.543b 0.650a
.0.05 .0.05 .0.05 .0.05 .0.05 ,0.001 ,0.01
a
Spearman’s correlation coefficient. Pearson’s correlation coefficient.
b
www.ibdjournal.org |
1843
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
Koutsochristou et al
TABLE 5. GI-S and PCR Index in Children and Adolescents with IBD, Using Medication with or Without Immunomodulators Statistical Analysis Indices GI-S% Without immunomodulators With immunomodulators PCR index% Without immunomodulators With immunomodulators
No. Subjects
Mean Value
SD
Student’s t Test
P
27 28
32.93 47.23
10.98 12.84
4.44
,0.001
27 28
34.95 49.36
10.87 13.19
4.42
,0.001
et al54 who had observed that the adult patients with active IBD had higher number of dental infection foci detected in panoramic radiographs. In most of the above studies, the high risk of dental caries has been hypothesized to occur due to nutritional deficiencies and changes in salivary and microbiologic conditions in the oral cavity.26 Patients with active IBD had more frequently high salivary counts of Streptococci mutans and lactobacilli despite normal salivary flow rate and buffer capacity.27,28 The high count of the acidogenic bacteria may be mainly related to the dietary habits of patients with IBD due to more frequent consumption of refined carbohydrates, mainly during exacerbations, favoring colonization, and growth of these bacteria. A recent article suggests that dysbiosis in the mouth is also linked to the host’s inflammatory response.55 However, we do not know yet if this dysbiosis in saliva has any effect on the incidence of dental caries. In this study, plaque scores in the IBD group were not significantly higher compared with those of controls. The gingival evaluation revealed that the mean value of GI-S in children and adolescents with IBD was much higher compared with the control group despite the absence of significant difference in plaque indices
between the 2 groups. Similarly, the prevalence of marginal bleeding or the mean value of gingival index was greater in adult patients with active CD or UC30 as compared with matched controls56 or to patients with inactive IBD.31 Additionally, a recent prospective study found that gingivitis markers, as papillary bleeding indices, were higher in adults with IBD than in healthy adult controls.33 The increased needs in periodontal treatment in children and adolescents with IBD in this study are in line, as far as we know, with other studies in adults where the majority of patients with CD or UC had a mild or moderate periodontitis, while only smaller percentage had susceptibility for severe periodontitis.28–30,32,33 Correspondent clinical studies about periodontal treatment needs in children and adolescents with CD or UC are absent except for a single case report about a severe rapidly progressive periodontitis occurring in 6-year old boy with CD.57 Finally, it is noteworthy in our study that patients with IBD taking immunomodulators had a higher mean value of GI-S and increased needs of periodontal treatment. To our knowledge, this finding has not been described in adults with IBD. Chronic use of cyclosporine or azathioprine may change periodontal status provoking gingival overgrowth with prevalence rates between 8% and 97%.58–61 The majority of our patients were taking
TABLE 6. Community Periodontal Index Treatment Needs (CPITN) in Children and Adolescents Using Medication with or Without Immunomodulators CPITN Index IBD patients with immunomodulators (28 subjects)a No. subjects % IBD patients without immunomodulators (27 subjects)a No. subjects % Statistical analysis Z-test P
Score 0
Score 1
Score 2
Score 3
0 0
4 7.27
19 34.55
5 9.09
0 0
16 29.09
11 20.0
0 0
0 0
3.46 0.0005
2.02 0.04
2.30 0.02
Fisher’s exact test ,0.001.
a
1844
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Inflamm Bowel Dis Volume 21, Number 8, August 2015
azathioprine/6-mercaptopurine (23 patients), and only 3 were on cyclosporine. There is continued debate over which factors modify the degree of overgrowth, including individual sensitivity, age, or dose and duration of drug therapy. The exact mechanism of gingival overgrowth is not well defined but appears to be caused by the combination of the proliferation of fibroblasts within gingival tissue, the increase in the deposition of collagen and extracellular matrix, and the decrease in phagocytosis resulting in a net gain in gingival tissue mass.58–61 We could hypothesize that the disease itself, medications, different dietary habits, and possibly oral dysbiosis could contribute to dental and periodontal disease in patients with IBD. However, we could speculate that as half of the patients with IBD were on medications known to have periodontal effects, this could be an important risk factor in our patients compared with controls. The strength of this study is that it is the first prospective case–control study dealing with dental caries, oral hygiene, gingival status, and periodontal treatment needs of children and adolescents with IBD. A limitation of this study is that all patients with IBD were on remission (as defined by Pediatric Crohn’s Disease Activity Index and Pediatric Ulcerative Colitis Activity Index ,10) because we included only those attended in the outpatient IBD clinic who were more collaborative. The study did not include inpatients who were in the active phase of the disease because of ethical considerations. Another limitation was that the clinical dental examination of patients with IBD was done without any previous awareness, whereas in controls, the examination was done after an appointment to resolve a new dental problem, reevaluation of a previous one or for oral health checkup. This difference about the type of appointment probably could affect the level of oral hygiene at the time of oral examination, but it had not any effect on the decayed, missing, and filled deciduous or permanent teeth, the gingival status, and periodontal treatment needs. Additionally, the relatively small number of patients (the sample size of patients with IBD) could bring another limitation to infer whether disease characteristics, i.e., disease distribution and extend, complicated disease (i.e., perianal or fistulizing), UC or CD influenced type, or severity of dental manifestations. A bias could also be regarding controls, taken into account that they were on a regular preventing program. However, it did not happen in our case because both groups did not participate in long-term regular oral health checkup program. Additionally, no differences were found between patients with IBD and the control group during regular every 6- to 12-month visits. In conclusion, this study showed that children and adolescents with UC and CD had a significantly worse oral health than age- and sex-matched controls. Overall, patients with IBD had higher prevalence of dentine caries, more clinical signs of gingival inflammation, and increased periodontal treatment needs with distinct differences from the healthy control group. These findings indicate the need for preventive dental and periodontal care of the children and adolescents with IBD and probe for a targeted investigation in the future.
Dental and Periodontal Disease in IBD Children
REFERENCES
1. MacDonald TT, Monteleone G, Pender SL. Recent developments in the immunology of inflammatory bowel disease. Scand J Immunol. 2000;51: 2–9. 2. Jostins L, Ripke S, Weersma RK. Host- microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491: 119–124. 3. Ponder A, Long MD. A clinical review of recent findings in the epidemiology of inflammatory bowel disease. Clin Epidemiol. 2013;5:237–247. 4. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474:307–317. 5. Soon IS, Molodecky NA, Rabi MD, et al. The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis. BMC Gastroenterol. 2012;12:51. 6. Bernstein CN, Shanahan F Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut. 2008;57:1185–1191. 7. Mahid SS, Minor KS, Soto RE, et al. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006;81:1462–1471. 8. Virta L, Auvinen A, Helenius H, et al. Association of repeated exposure to antibiotics with the development of pediatric Crohn’s disease—a nationwide, register-based Finnish case-control study. Am J Epidemiol. 2012; 175:775–784. 9. Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:235–241. 10. Jiang L, Xia B, Li J, et al. Retrospective survey of 452 patients with inflammatory bowel disease in Wuhan city, Central China. Inflamm Bowel Dis. 2006;12:212–217. 11. Plauth M, Jenss H, Meyle J. Oral manifestations of Crohn’s disease. An analysis of 79 cases. J Clin Gastroenterol. 1991;13:29–37. 12. Williams AJK, Wray D, Ferguson A. The clinical entity of orofacial Crohn’s disease. Q J Med. 1991;79:451–458. 13. Chan SW, Scully C, Prime SS, et al. Pyostomatitis vegetans: oral manifestation of ulcerative colitis. Oral Surg Oral Med Oral Pathol. 1991;72: 689–692. 14. Lisciandrano D, Ranzi T, Carrassi A, et al. Prevalence of oral lesions in inflammatory bowel disease. Am J Gastrenterol. 1996;91:7–10. 15. Dupuy A, Cosnes J, Revuz J, et al. Oral Crohn disease: clinical characteristics and long-term follow-up of 9 cases. Arch Dermatol. 1999;135:439–442. 16. Dudeney TP. Crohn’s disease of the mouth. Proc R Soc Med. 1969;62: 1237. 17. Carr D. Granulomatous cheilitis in Crohn’s disease. Br Med J. 1974;4:636. 18. Snyder MB, Cawson RA. Oral changes in Crohn’s disease. J Oral Surg. 1976;34:594–599. 19. Talbot T, Jewell L, Schloss E, et al. Cheilitis antedating Crohn’s disease: case report and literature update of oral lesions. J Clin Gastroenterol. 1984;6:349–354. 20. Scheper HJ, Brand HS. Oral aspects of Crohn’s disease. Int Dent J. 2002; 52:163–172. 21. Harty S, Fleming P, Rowland M, et al. A prospective study of the oral manifestations of Crohn’s disease. Clin Gastroenterol Hepatol. 2005;3: 886–891. 22. Hansen LS, Silverman S Jr, Daniels TE. The differential diagnosis of pyostomatitis vegetans and its relation to bowel disease. Oral Surg Oral Med Oral Pathol. 1983;55:363–373. 23. Sundh B, Hultén L. Oral status in patients with Crohn’s disease. Acta Chir Scand. 1982;148:531–534. 24. Rooney TP. Dental caries prevalence in patients with Crohn’s disease. Oral Surg Oral Med Oral Pathol. 1984;57:623–624. 25. Bevenius J. Caries risk in patients with Crohn’s disease: a pilot study. Oral Surg Oral Med Oral Pathol. 1988;65:304–307. 26. Sundh B, Emilson CG. Salivary and microbial conditions and dental health in patients with Crohn’s disease: a 3-year study. Oral Surg Oral Med Oral Pathol. 1989;67:286–290. 27. Schütz T, Drude C, Paulisch E, et al. Sugar intake, taste changes and dental health in Crohn’s disease. Dig Dis. 2003;21:252–257. 28. Grössner-Scheiber B, Fetter T, Hedderich J, et al. Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study. J Clin Periodontol. 2006;33:478–484. 29. Brito F, de Barros FC, Zaltman C, et al. Prevalence of periodontitis and DMFT index in patients with Crohn’s disease and ulcerative colitis. J Clin Periodontol. 2008;35:555–560. www.ibdjournal.org |
1845
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
Koutsochristou et al
30. Flemmig TF, Shanahan F, Miyasaki KT. Prevalence and severity of periodontal disease in patients with inflammatory bowel disease. J Clin Periodontol. 1991;18:690–697. 31. Meurman JH, Halme L, Laine P, et al. Gingival and dental status, salivary acidogenic bacteria, and yeast counts of patients with active or inactive Crohn’s disease. Oral Surg Oral Med Oral Pathol. 1994;77: 465–468. 32. Habashneh RA, Khader YS, Alhumouz MK, et al. The association between inflammatory bowel disease and periodontitis among Jordanians: a case-control study. J Periodontal Res. 2012;47:293–298. 33. Vavricka SR, Manser CN, Hediger S, et al. Periodontitis and gingivitis in inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2013;19:2768–2777. 34. IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis—the Porto criteria. J Pediatr Gastroenterol Nutr. 2005;41:1–7. 35. Registram-General. Classification of Occupations. London, United Kingdom: HMSP; 1960. 36. Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn’s disease activity index. J Pediatr Gastroenterol Nutr. 1991;12:439–447. 37. Turner D, Hyams J, Markowitz J, et al. Appraisal of the pediatric ulcerative colitis activity index. Inflamm Bowel Dis. 2009;15:1218–1223. 38. World Health Organization. Oral Health Surveys: Basic Methods. 4th ed. Geneva, Switzerland: WHO; 1997. 39. O’Leary TJ, Drake RB, Naylor JE. The plaque control record. J Periodontol. 1972;43:38. 40. Lindhe J. Textbook of Clinical Periodontology. 1st ed. Copenhagen, Denmark: Munksgaard; 1981:327–352. 41. Ainamo J, Barmes D, Beagrie G, et al. Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J. 1982;32:281–291. 42. Tsami A, Pepelassi E, Kontovazenitis G, et al. Frequency and distribution of furcation defects in chronic periodontitis patients. Hellenic Stomatological Rev. 2008;52:25–35. 43. Basu MK, Asquith P, Thompson RA, et al. Proceedings: oral lesions in patients with Crohn’s disease. Gut. 1974;15:346. 44. Taylor VE, Smith CJ. Oral manifestations of Crohn’s disease without demonstrable gastrointestinal lesions. Oral Surg Oral Med Oral Pathol. 1975;39:58–66.
1846
Inflamm Bowel Dis Volume 21, Number 8, August 2015
45. Basu MK. Oral manifestations of Crohn’s disease: studies in the pathogenesis. Proc R Soc Med. 1976;69:765–766. 46. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore). 1976;55:401–412. 47. Wysocki GP, Brooke RI. Oral manifestations of chronic granulomatous disease. Oral Surg Oral Med Oral Pathol. 1978;46:815–819. 48. Basu MK, Asquith P. Oral manifestations of inflammatory bowel disease. Clin Gastroenterol. 1980;9:307–321. 49. Fisher AA. Chronic lip edema with particular reference to the MelkerssonRosenthal syndrome (MRS). Cutis. 1990;45:144–146. 50. Rankin GB. Extraintestinal and systemic manifestations of inflammatory bowel disease. Med Clin North Am. 1990;74:39–50. 51. Rehberger A, Püspök A, Stallmeister T, et al. Crohn’s disease masquerading as aphthous ulcers. Eur J Dermatol. 1998;8:274–276. 52. Pittock S, Drumm B, Fleming P, et al. The oral cavity in Crohn’s disease. J Pediatr. 2001;138:767–771. 53. Vehkalathi M, Paunio I, Nyyssonen V, et al. Oral Health in the Adult Finnish Population and Associated Factors. Helsinki and Turku, Finland: Social Insurance Institution; 1999:237–252. 54. Halme L, Meurman JH, Laine P, et al. Oral findings in patients with active or inactive Crohn’s disease. Oral Surg Oral Med Oral Pathol. 1993;76:175–181. 55. Said HS, Suda W, Nakagome S, et al. Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers. DNA Res. 2014;21:15–25. 56. Van Dyke TE, Dowell VR Jr, Offenbacher S, et al. Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. Infect Immun. 1986;53:671–677. 57. Sigusch BW. Periodontitis as manifestation of Crohn’s disease in primary dentition: a case report. J Dent Child. 2004;71:193–196. 58. Seymour RA, Heasman PA. Drugs and periodontium. J Clin Periodontol. 1988;15:1–16. 59. Santi E, Bral M. Effect of treatment on cyclosporine and nifedipine induced gingival enlargement: clinical and histologic results. Int J Periodontics Restorative Dent. 1998;18:81–86. 60. Seymour RA, Ellis JS, Thomson JM. Risk factors for drug-induced gingival overgrowth. J Clin Periodontol. 2000;27:217–230. 61. Pistorius A, Willershausen B, Callaway A. Effects of selected immunoupressive drugs on prostaglandin release, protein synthesis and cell proliferation in human fibroblasts and on the growth of plaque bacteria. Eur J Med Res. 2003;28:25–32.
| www.ibdjournal.org
Copyright © 2015 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.
