Correlation between dental symptoms and functional and clinical manifestations of Crohn's disease and ulcerative colitis

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Introduction

Crohn's disease (CD) and ulcerative colitis (UC) are diseases of immune-inflammatory nature with an incompletely understood etiopathogenesis, representing a significant problem of modern gastroenterology [1]. Crohn's disease is characterized by a chronic continuous course, ulcerative colitis – a chronic relapsing course [2].

According to foreign and Russian researchers, inflammatory bowel diseases (IBD) are inferior in prevalence to other gastroenterological diseases, while at present the incidence of Crohn's disease in populations is significantly higher than UC [3].

Typical clinical symptoms of CD and UC, caused by the development of systemic metabolic disorders, can be combined with extraintestinal manifestations [4].

Typical local and general clinical and functional symptoms of CD and UC include diarrhea, fever, abdominal pain, chest pain, and epigastric pain, discomfort and heaviness in the abdomen, heartburn, regurgitation, vomiting [5], rectal bleeding, and others [6].

The development of extraintestinal manifestations and complications of Crohn's disease and ulcerative colitis directly depends on the frequency of exacerbations and their severity (mild, moderate, or severe). Extraintestinal manifestations of IBD can be observed in patients with an established diagnosis, develop against the background of complex drug treatment, or be the debut symptom of the underlying disease [7]. According to the literature, extraintestinal symptoms of CD and UC reflect damage to the skin and mucous membranes of the oral cavity and eyes, musculoskeletal system, and hepatobiliary system.

There are few studies reflecting the specificity and diversity of oral signs of CD and UC in the form of recurrent aphthous stomatitis, atrophic glossitis, burning mouth syndrome, angular cheilitis, manifested by the symptom of dry mouth, dysgeusia (taste disturbances), halitosis [7]. Thus, according to the results of a clinical examination of 119 (73.9 %) patients with ulcerative colitis and 42 (26.1 %) with Crohn's disease demonstrated [9] that extraintestinal oral manifestations were observed in 29.4 and 40.5 % of cases, respectively, more often (35.6 %) in males and less often (28.4 %) in women.

A. Goldinova et al. (2020), when examining 51 patients with ulcerative colitis, found hyposalivation at rest in 16 %, with stimulation of secretion – in 24 % of cases. The severity of xerostomia symptoms (xerostomia scale) correlated with the activity of simple clinical ulcerative colitis (p = 0.042) and the health-related quality of life index (p = 0.001) [8].

The objective of the study is to analyze the relationship between dental symptoms and clinical and functional manifestations of Crohn's disease and ulcerative colitis.

Materials and methods

The prospective, observational, longitudinal clinical study involved patients with verified inflammatory bowel diseases: Crohn's disease (ICD-10 code K50) – 35 people, including 15 men and 20 women, and ulcerative colitis (ICD-10 code K51) – 35 people, including 19 men and 16 women. The diagnosis of each IBD was confirmed clinically and functionally, in accordance with the clinical recommendations of the Russian Gastroenterological Association and the Association of Proctologists of Russia [7; 8].

A comprehensive dental examination of patients with CD and UC, conducted in accordance with WHO recommendations, included an in-depth assessment of complaints from the oral mucosa and the red lip border (aesthetic defect, tightness and / or peeling of the red lip border, tingling, burning, dryness, pain in the oral mucosa when taking irritating food and / or when talking, during individual oral hygiene) and a clinical examination of the red lip border, oral mucosa, as well as an analysis of anamnesis data. The diagnosis of dental diseases was made taking into account ICD-10. For an objective assessment of the periodontal complex state, the PMA index and the Russell periodontal index PI were calculated (Russell, 1956).

To study the symptoms of gastric and intestinal dyspepsia, a validated questionnaire "7x7" proposed by V.T. Ivashkin et al. (2016) [9] was used. The symptoms of functional gastric dyspepsia were assessed: a feeling of fullness after eating, early satiety, epigastric pain and/or burning. The state of IBD remission in the absence of an active inflammatory process was confirmed endoscopically. Sensory and affective characteristics of pain were assessed using the McGill Pain Questionnaire (Melzack, 1975).

To determine the differences in the frequencies of the observed features in patients of the observation groups, the c² criterion was used; in cases where the frequency in one of the groups was zero or extremely rare (observed 1–2 times), the Yates correction was used. To compare continuous features (scores) in the compared groups, the nonparametric Mann – Whitney test was used. Differences were considered statistically significant at the p-level of erroneous rejection of the null hypothesis of their absence p < 0.1. Nominal features were presented as absolute and relative (%) observation frequency, continuous features were presented as median and first and third quartiles
(Q₁ and Q₃) or interquartile range IQR, since according to the Shapiro-Wilk criterion there was no compliance with the normal distribution law (p < 0.05). To assess the presence of a relationship between nominal features, a contingency analysis was carried out and Chuprov's mutual contingency coefficient was calculated. Statistical analysis was carried out in the R environment.

The study was carried out in accordance with the principles of the Helsinki Declaration of the World Medical Association, its protocol was approved by the decision of the local ethics committee (protocol No. 11 dated December 16, 2020). Each patient received detailed information about the study and signed an informed consent to participate in it.

Results and discussion

Among patients diagnosed with CD (n = 35) and UC (n = 35), there were 20/15 and 16/19 women and men, respectively (p = 0.339), the median age of patients was 37.5 (Q₁ = 25; Q₃ = 51) and 40.0 (Q₁ = 25; Q₃ = 55) years, respectively, which is statistically indistinguishable (p = 0.457).

The median age of CD onset was 28 years (Q₁ = 18.0; Q₃ = 38.0), with the disease first manifesting itself at the age of under 19 years in 28.6 % of patients (n = 10), in 51.42 % of cases (n = 18) at the age of 20 to 39 years, and in 20 % (n = 7) after 40 years. In the group of patients with UC, the median age of onset was 34 (Q₁ = 24; Q₃ = 42.5) years, with 14.3 % (n = 5) of the disease being diagnosed before the age of 19, 48.6 % (n = 17) – from 20 to 39 years, and 37.1 % (n = 13) – after 40 years. According to the Mann – Whitney criterion, no statistically significant intergroup differences were found regarding the age of primary manifestations of IBD. All (100 %) patients with CD and UC had a chronic, continuously relapsing course of the disease (absence of more than 6-month periods of remission during the therapy).

According to the case histories of patients with CD, terminal ileitis was diagnosed in 20.0 % (n = 7) of cases, colonic lesion in 42.9 % (n = 15), and a combination of small and colonic lesion in 37.14 %. In patients with UC, proctitis was diagnosed in 20.0 % (n = 7), left-sided colonic lesion (colitis) in 37.1 % (n = 13), and total colitis in 42.9 % (n = 15). To analyze the severity of functional and clinical symptoms and syndromes in patients with Crohn's disease and ulcerative colitis, the nature and frequency of the main intestinal and extraintestinal manifestations were analyzed (Table 1).

 

Table 1

 Intestinal and extraintestinal manifestations in patients with inflammatory bowel disease at the onset of the disease according to medical records

Symptom of the disease	Group with CD, n = 35		Group with UC, n = 35		p-level
	abs.	%	abs.	%
Intestinal manifestations
Intestinal bleeding	22	62.9	28	80.0	р = 0.113
Mucus discharge during defecation	22	62.9	32	91.4	р = 0.005**
Diarrhea 4 to 10 times a day	16	45.7	28	80.0	р = 0.003**
Diarrhea 10 to 20 times a day	0	0	1	2.9	р = 1.0#
Abdominal pain	18	51.4	4	11.4	р < 0.001***
Tenesmus	5	14.3	3	8.6	р = 0.453
Anal fissures	2	5.7	0	0	р = 0.474#
Constipation	3	8.6	0	0	р = 0.238#
Extraintestinal manifestations
Arthralgia, arthritis	4	11.4	3	8.6	р = 0.691
Psoriasis	1	2.9	1	2.9	р = 1.0
Erythema nodosum	2	5.7	0	0	р = 0.474#
Anemia	32	91.4	30	85.7	р = 0.453

Note: **, *** – statistically significant differences at p < 0.01, p < 0.001 respectively; # – Yates' correction was used when conducting the chi-square test for differences.

 

Analysis of intestinal manifestations at the onset of IBD indicated reliable differences in the frequency and structure of the main intestinal symptoms in patients with UC and CD. In the structure of intestinal manifestations of IBD in patients of both groups, the symptoms of "mucus discharge during defecation" and "intestinal bleeding" dominated, and mucus discharge during defecation was detected significantly more often in patients with UC than in CD
(p = 0.005). Diarrhea was observed almost 2 times more often in patients with UC, with a frequency of 4–10 times a day (p = 0.003). In patients with CD, the manifestation of pain symptoms occurred significantly less frequently than in UC (p < 0.001). The spectrum of intestinal manifestations of CD included such as the presence of anal fissures and constipation, which are not typical for UC. Extraintestinal manifestations were detected in 91.4 % of patients with UC and in 100 % of patients with CD (p = 0.077) with absolute dominance of anemic syndrome (respectively, in 91.4 and 85.7 % of cases, which is not statistically distinguishable, p = 0.453).

When assessing the frequency and nature of dyspeptic disorders in patients with IBD during clinical remission, confirmed by the results of control fibrocolonoscopy, a predominance of flatulence symptoms was revealed in both groups (respectively, in 74.3 and 77.1 % of cases). A higher frequency of detection of various dyspeptic disorders and their wider spectrum were noted in patients with CD, with significant differences achieved only at p < 0.1 noted only for the symptom of "'abdominal pain decreasing after bowel emptying".

The results of the assessment of dyspeptic disorders in the study groups according to the questionnaire "7x7" are summarized in Table. 2. In the group of patients with CD, the average score was 7.3 ± 3.1 (median – 6.5, Q₁ = 1; Q₃ = 11.5), in the group with UC, the average score was 5.2 ± 3.5 (median – 4.5, Q₁ = 1; Q₃ = 9), which is not statistically significant (p > 0.2).

 

Table 2

 Severity of functional dyspepsia symptoms in patients with Crohn's disease and ulcerative colitis

Severity of dyspepsia symptoms	Scores on the questionnaire 7x7	Group with CD, n = 35		Group with UC, n = 35		p-уровень
		абс.	%	абс.	%
No dyspepsia symptoms	0–1	9	25.7	12	34.3	р = 0.434
Borderline state	2–6	8	22.9	11	31.4	р = 0.421
Symptoms of bland dyspepsia	7–12	12	34.3	9	25.7	р = 0.434
Symptoms of mild dyspepsia	13–18	4	11.4	3	8.6	р = 0.691
Significant dyspepsia	19–24	2	5.7	0	0	р = 0.474#
Severe dyspepsia	25 and more	0	0	0	0	р = 1.0

Note: # – Yates' correction was used when conducting the chi-square test for differences.

 

As a result of the conducted comprehensive clinical and dental examination, the relationship between functional and clinical symptoms in patients with CD and UC was assessed. When assessing complaints, symptoms, syndromes and anamnesis data, relationships were established between symptoms of CD and UC and the most characteristic features of the clinical condition of the red lip border, the oral mucosa itself in the form of edema, hyperemia, and pitting edema. The results are presented in the form of a table of features contingency (Table 3). No significant differences in the frequency of the main manifestations of dyspeptic disorders in CD and UC were found. Based on the contingency analysis, Chuprov's coefficients (K_Ch) were calculated, assessing the relationship between the frequency of identified dyspeptic disorders and the key objective symptoms of damage to the red border of the lips and the oral mucosa: for patients with CD K_Ch = 0.36 (CI_95%: 0.32–0.40; p = 0.031), for patients with UC K_Ch = 0.28 (CI_95%: 0.24–0.32; p = 0.046). The contingency analysis revealed the presence of a significant relationship between the frequency of identified dyspeptic disorders and the key objective symptoms of damage to the red lip border and oral mucosa, while in CD this relationship is more pronounced.

 

Table 3

 Correlation of the frequency of detection of oral mucosa lesions symptoms in various clinical manifestations of functional dyspepsia in patients with Crohn's disease / ulcerative colitis

Main manifestations of dyspeptic disorders (CD / UC)	Pale pink OM	OM hyperemia	OM pitting edema	OM edema	Labial edema	Tongue edema
	abs. (%)	abs. (%)	abs. (%)	abs. (%)	abs. (%)	abs. (%)
Pain in the epigastric area (n = 22 / n = 17, р = 0.229)	0 / 5 (29.4) р = 0.025*. #	4 (18.2) / 2 (11.8) р = 0.582	3 (13.6) / 2 (11.8) р = 0.863	6 (27.3) / 3 (17.7) р = 0.480	4 (18.2) / 2 (11.8) р = 0.582	5 (22.7) / 3 (17.7) р = 0.697
Burning sensation in the epigastric area (n = 16 / n = 14, р = 0.630)	0 / 2 (14.3) р = 0.406#	1 (6.3) / 1 (7.1) р = 0.923	1 (6.3) / 1 (7.1) р = 0.923	6 (37.5) / 4 (28.6) р = 0.605	2 (12.5) / 2 (14.3) р = 0.885	6 (37.5) / 4 (28.6) р = 0.605
Bursting pain in the upper and middle part of the stomach after eating (n = 11 / n = 8, р = 0.421)	0 / 2 (25.0) р = 0.320#	3 (27.3) / 1 (12.5) р = 0.436	0 / 0 р = 1.0	2 (18.2) / 3 (37.5) р = 0.346	4 (36.4) / 1 (12.5) р = 0.244	2 (18.2) / 1 (12.5) р = 0.738
Early satiety (n = 15 / n = 10, р = 0.213)	3 (20.0) / 2 (20.0) р = 1.0	1 (6.67) / 0 р = 0.835#	0 / 0 р = 1.0	4 (26.7) / 6 (60.0) р = 0.096	3 (20.0) / 0 р = 0.380#	4 (26.7) / 2 (20.0) р = 0.723
Pressing pain in the abdomen, decreasing after bowel emptying (n = 16 / n = 9, р = 0.081)	0 / 2 (22.2) р = 0.231#	0 / 0 р = 1.0	6 (37.5) / 2 (22.2) р = 0.432	4 (25.0) / 0 р = 0.046*. #	1 (6.3) / 2 (22.2) р = 0.766#	5 (31.3) / 3 (33.3) р = 0.630
Bloating (n = 14 / n = 19, р = 0.232)	2 (14.3) / 2 (10.5) р = 0.744	9 (64.3) / 7 (36.8) р = 0.119	0 / 3 (15.8) р = 0.344#	3 (21.4) / 3 (15.8) р = 0.674	0 / 0 р = 1.0	0 / 4 (21.1) р = 0.197#
Violation of the consistency and / or frequency of stool (from 1 to 3 times) (n = 11 / n = 8, р = 0.421)	2 (18.2) / 0 р = 0.605#	0 / 0 р = 1.0	0 / 1 (12.5) р = 0.870#	3 (27.3) / 2 (25.0) р = 0.912	0 / 1 (12.5) р = 0.870#	6 (54.5) / 4 (50.0) р = 0.845
Chuprov's contingency coefficients	With CD KCh = 0.36, confidence interval (95 %): 0.32–0.40, p = 0.031, With UC KCh = 0.28, confidence interval (95 %): 0.24–0.32, p = 0.046

Note: * – statistically significant differences at p < 0.05; # – Yates' correction was used when conducting the chi-square test for differences.

 

Extraintestinal (dental) symptoms in patients with both forms of IBD (CD/UC) most often manifested themselves in the form of exfoliative cheilitis (ICD-10 code K13.2) (with CD it was statistically more common (68.6 %) than with UC (54.3 %), p = 0.081), various forms of glossitis (42.9 and 31.4 %, respectively; which is statistically indistinguishable, p = 0.323), primarily diagnosed recurrent aphthous stomatitis (ICD-10 code K12.0) (48.6 and 31.4 %, respectively; statistically indistinguishable, p = 0.144), chronic mechanical trauma of the oral mucosa (ICD-10 code K13.1) (40.0 and 31.4 %, respectively, statistically indistinguishable, p = 0.455), scalloped tongue (ICD-10 code K14.8) (80.0 and 70.0 %, respectively; statistically distinguishable, p = 0.068). At the same time, the total frequency of pathology of the red lip border and the oral mucosa significantly prevails in patients with Crohn's disease (p < 0.05).

The periodontal index PI (Russell, 1956) objectified the presence of inflammatory periodontal diseases in the form of: chronic generalized gingivitis (ICD-10 code K05.10), while significantly less often for patients with Crohn's disease (31.4 %) than for patients with UC (62.9 %), p = 0.002; chronic generalized periodontitis (ICD-10 code K05.3), and, on the contrary, significantly more often with CD (68.6 %) than with UC (37.2 %), p = 0.032. The severity of the inflammatory process according to the PMA index for patients with CD corresponded to a severe degree of severity (Me = 77, IQR: 72–79), for patients with UC – to a moderate degree of severity (Me = 52, IQR: 48–55), which is significantly lower, p < 0.001. The median value of the PI index in patients with CD (Me = 4.5, IQR: 3.5–5.0 points) did not differ significantly from that in UC (Me = 3.75, IQR: 3.5–4.75 points), p = 0.241.

Patients with CD and UC presented many complaints from the oral cavity: a feeling of tightness and peeling, aesthetic defects of the red lip border, a feeling of irritation, soreness of the oral mucosa (mainly in the cheek area) when talking and eating irritating food, an unusual appearance of the tongue surface, an unpleasant odor from the mouth, a burning sensation when eating irritating food (Table 4).

 

Table 4

 Evaluation of the relationship between complaints with extraintestinal manifestations on the red lip border and the oral mucosa itself in CD and UC

Complaints	Group with CD, n = 35		Group with UC, n = 35		p-level
	abs.	%	abs.	%
For a feeling of tightness, dryness, peeling of the red lip border, an aesthetic defect	16	45.7	9	25.7	р = 0.081
For soreness of the lips, making it difficult to talk, eat	6	17.1	4	11.4	р = 0.495
For soreness of the oral cavity	14	40.0	11	31.4	р = 0.455
For soreness when eating	17	48.6	11	31.4	р = 0.144
For "cracks" in the tongue, bad smell, soreness when eating irritating food, dry mouth	7	20.0	5	14.3	р = 0.526
For an unusual appearance of the tongue, burning and pain when eating irritating food	15	42.9	11	31.4	р = 0.323

 

At the same time, no significant differences in such complaints were found in patients with CD and UC, with the exception of a higher frequency of complaints about subjective sensations of changes in the red lip border in CD. Patients with CD more often presented complaints about a feeling of tightness, dryness, peeling of the red lip border, an aesthetic defect (p < 0.1).

The demographic data of the patients we selected for an in-depth study of the clinical and functional characteristics of CD and UC correspond to similar results of population studies. The median age of onset for CD was 28 years (IQR: 18–38 years), for UC – 34 years (IQR: 24–42.5 years), which is consistent with a similar population study, for example, in B. Kochar (2018), the median onset for CD was 30 years (IQR: 21–32), for UC – 33 years (IQR: 28–38). Also in our study, the average age of patients in the groups with CD and UC was 37.5 (IQR: 25–51) and 40.0 (IQR: 25–55) years, and in the study of B. Kochar (2018), where similar indicators were studied in 2378 patients with CD and in 1455 patients with UC, the average age for the groups was 41 years with IQR: 29–54 years IQR: 31–53 years, respectively [10].

In the group of patients with CD, women predominated (57 %), which is also consistent with the data of B. Kochar [10].

According to the results of our study, extraintestinal dental manifestations were more common and in a wider range in patients with CD compared to the corresponding parameters in UC, which is consistent with the results obtained by B. Kochar (2018) [10].

In the study of T. Sahin et al. (2017), it was shown that 45 % of patients with CD have extraintestinal manifestations in the form of ulcerative defects of the oral mucosa [11], according to other authors, aphthous lesions recur in the active phase of UC [12; 13]. A. Goldinova et al. (2020) showed that sensory-paresthetic phenomena from the OM (burning syndrome, paresthesia) in patients with CD and UC manifest themselves both in the active and inactive phases of the diseases – in 14.3 and 8.1 % of cases, respectively [8].

Conclusions

The conducted comprehensive study has shown that in patients with CD and UC, there is a correlation between functional and clinical symptoms and syndromes in manifestations of pathology of the red lip border and oral mucosa, and in CD this relationship is more pronounced.

Manifestations of UC in the oral cavity can be the most intuitive evidence of the underlying systemic disease: oral lesions can accompany or precede the diagnosis of UC.

Pain syndromes were more common in CD (p < 0.1). The main sensory characteristics of pain were distension, constriction, burning, soreness and a feeling of pressure.

In clinical support of extraintestinal manifestations of CD and UC with abdominal pain, diarrhea, rectal bleeding and other intestinal symptoms, dentists should cooperate with gastroenterologists and neurologists. The results of the study indicate the need for close interaction between gastroenterologists, neurologists and dentists in the dynamic monitoring of patients with CD and UC, and emphasize the need to develop and implement effective programs for interdisciplinary support of patients with chronic IBD.

About the authors

R. D. Yunusova

Bashkir State Medical University; Premier Dental Clinic

Email: irinausma@mail.ru
ORCID iD: 0000-0003-4556-0864

Postgraduate Student of the Department of Therapeutic Dentistry, Dental Therapist

Russian Federation, Ufa; Ufa

I. N. Usmanova

Bashkir State Medical University

Email: irinausma@mail.ru
ORCID iD: 0000-0002-1781-0291

DSc (Medicine), Associate Professor, Professor of the Department of Therapeutic Dentistry

Russian Federation, Ufa

I. A. Lakman

Bashkir State Medical University; Ufa University of Science and Technology

Email: irinausma@mail.ru
ORCID iD: 0000-0001-9876-9202

PhD (Technical Sciences), Leading Researcher of the Central Scientific Research Laboratory, Head of the Scientific Laboratory for the Research of Social and Economic Problems of the Regions

Russian Federation, Ufa; Ufa

A. N. Ishmukhametova

Bashkir State Medical University

Email: irinausma@mail.ru
ORCID iD: 0000-0003-0892-0058

PhD (Medicine), Associate Professor, Associate Professor of the Department of Internal Medicine and Clinical Psychology

Russian Federation, Ufa

A. P. Akopyan

Bashkir State Medical University

Email: irinausma@mail.ru
ORCID iD: 0000-0001-8436-5610

PhD (Medicine), Associate Professor of the Department of Neurology and Neurorehabilitation

Russian Federation, Ufa

E. A. Gaisina

Republican Clinical Hospital named after G.G. Kuvatov

Author for correspondence.
Email: irinausma@mail.ru

Chief Freelance Specialist in Gastroenterology, Head of the Gastroenterological Department, Gastroenterologist

Russian Federation, Ufa

References

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