Introduction

Chronic abdominal pain is prevalent in individuals with inflammatory bowel diseases (IBD). However, the determinants and phenotypes of IBD-associated pain are not well-characterized, frustrating effective pain management and mitigation strategies

Aims & Methods

Aims: This is an ongoing descriptive, cross-sectional study aimed at phenotyping the types of pain experienced by patients with IBD, the impact on health-related quality of life (HRQoL) and psychological health, and relationship to disease activity assessed by clinical metrics and endoscopy. Methods: Fifty-eight adult patients diagnosed with IBD were prospectively enrolled at a single academic medical center between October 17, 2022 and November 7, 2023. Patients completed a set of online patientreported outcome measures (PROM)-based standardized and validated questionnaires (Table 2) just prior to a scheduled colonoscopy. Endoscopically active disease was defined as Mayo Endoscopic Score ≥ 1 for ulcerative colitis (UC) and SES-CD ≥ 3 for Crohn’s Disease.

Results

A total of 58 patients (28 UC/30 Crohn’s, 24 male/34 female, median age 44.5±14.5 years) were included. An initial analysis examined relationships based on endoscopic disease activity. Interestingly, there was no significant difference between those with endoscopically active disease and those without on metrics of pain, HRQoL, or impact on psychological health (p>0.05). However, those with endoscopically inactive disease had significantly higher scores on central sensitization (CS) (31.1±11.5 vs. 23±12.1, p<0.05). Using a validated score threshold of 40 on the central sensitization inventory (CSI), the cohort was then stratified into two new groups (those with and without evidence of CS). Overall, 12/58 patients met diagnostic criteria for CS. Table 1 summarizes the baseline characteristics of the two groups. As detailed in Table 2, those with CS had higher scores on abdominal pain (severity and interference, including catastrophizing), visceral hypersensitivity, lower scores on HRQoL questionnaires, and greater scores on depression and anxiety scales (p<0.05). There was no significant difference in neuropathic pain (p=0.85).

Conclusion

Central sensitization affected at least 20% of this cohort of IBD patients, which is consistent with prior studies. Interestingly, there was a trend towards more central sensitization in those with quiescent disease. CS was associated with worse pain, HRQoL, and psychosocial distress across a broad range of outcomes measured. These data support enhanced attention to contribution of CS to pain in IBD patients, particularly those with persistent pain in remission, as therapies emerge for the treatment of CS.

Introduction

Periodontitis (gum disease) and inflammatory bowel disease (IBD) are both chronic progressive inflammatory diseases with many similarities in their aetiopathogenesis. In addition, patients with IBD are reported to be at increased risk of developing periodontitis, which in turn seems to impact IBD activity and disability as shown in recent studies. However, these findings need to be validated. Thus, we aimed to assess whether the presence of periodontitis is associated with increased IBD activity, disability, and severity, and/or reduced IBD specific quality of life, in a Swedish patient cohort.

Aims & Methods

An on-line questionnaire was distributed to the members of the Swedish patient organisation for gastrointestinal diseases. The survey included questions on social demographics, oral health, as well as IBD-related characteristics. Oral health was assessed by the number of missing teeth, self-reported state of teeth and gums, and the Periodontal Screening Score (PESS), which is a validated instrument to screen for severe periodontitis. Disease activity in patients with Ulcerative Colitis (UC) and Crohn’s disease (CD) was assessed by the Simple Clinical Colitis Index (SCCAI) and the Harvey & Bradshaw’s Activity Index (HBI), respectively. Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI). IBD-specific health-related quality of life measured by the short inflammatory bowel disease questionnaire (sIBDQ).

Results

A total of 786 IBD patients responded to the invitation, including 371 patients with CD and 415 patients with UC. For both CD and UC, self-reported severe periodontitis was significantly associated with a higher level of current disease activity [OR 1.72 (1.86;2.49); p=0.004] based on the HBI (for CD) and the SCCAI (for UC), an increased IBD disability score [Coef. 5.07 (1.86;8.27); p=0.002], and an increased self-reported disease activity in the last 12 months [OR 1.44 (1.05;1.98); p=0.025]. Likewise, number of missing teeth (tooth loss is the ultimate outcome of untreated periodontitis and as such an indirect indicator of its severity), was associated with an increased IBD disability score [Coef. 4.47 (0.71;8.22); p=0.020]. IBD severity (analysed as composite parameter of history of IBD-related surgery and/or treatment with biological therapy) was neither associated with tooth loss [OR 1.57 (0.97;2.52); p=0.065], nor with self-reported severe periodontitis [OR 1.20 (0.80;1.80); p=0.367]. IBD-specific health-related quality of life measured by sIBDQ score showed a tendency to be decreased in the presence of self-reported severe periodontitis [OR -1.45 (-3.01;0.10); p=0.067] but was not associated with tooth loss [Coef. -1.20 (-3.01;0.62); p=0.194].

Conclusion

The present study provides further evidence that the presence of periodontitis is associated with an increased disease activity and disability in IBD patients. These results underline that increased attention should be given to the oral health of IBD patients.

Introduction

Up to half of inflammatory bowel disease (IBD) patients experience chronic pain despite disease remission. The factors affecting the development of chronic pain are poorly understood and pain-directed therapies are scarce. Our study aimed to compare the clinical features and psychological characteristics of patients with and without chronic abdominal pain (CAP). The current analysis focuses on patients with IBD in remission and used REDCap to capture electronic data [1].

Aims & Methods

This is a cross-sectional online questionnaire-based study of 2381 IBD patients aged 16 years and above. The Rome IV questionnaire was used to diagnose irritable bowel syndrome (IBS). Remission was defined as Harvey Bradford Index (HBI) < 5 for patients with Crohn’s disease (CD) or Simple Colitis Activity Index (SCAI) < 3 for patients with ulcerative colitis (UC) [2]. Participants in remission with at least weekly abdominal pain for at least three months were defined as the cohort with chronic abdominal pain, and the rest were categorised as the pain-free cohort. The independent samples t-test was used to compare mean Body Mass Index (BMI) and age at diagnosis, and the independent samples Mann Whitney U test to compare the non-parametric scale data of the two cohorts. Spearman’s correlation was used to compare the pain intensity and pain interference scores from the Brief Pain Inventory with scale data from the following scales: Big Five Personality Questionnaire (BFPQ), Highly Sensitive Person Scale (HSPS), General Anxiety Disorder-7 (GAD7), Patient Health Questionnaire 9 (PHQ9), and Cognitive and Behavioural Response Questionnaire (CBRQ). Cronbach’s alpha was used to assess the reliability of these scales.

Results

1191 participants in remission were studied. Their ages ranged from 17 to 92, with a mean age of 51, and 52.6% were male. Eighty-eight percent were of White British ethnic origin and 40% were current or previous smokers.
25.9% (308) of those in remission reported CAP, with a mean age of 47 years, and 41.6% of them were males. The mean age at diagnosis of IBD was 35 years in those with CAP in remission, versus 30 in those without CAP (t= -4.548, p <0.001, 95% CI -6.598 to -2.621). In the CAP group, the prevalence of IBS was 73.1% compared to the total prevalence of 18.9% in the remission cohort. The prevalence of CD and UC were 72.4% and 27.6% respectively in the CAP in remission cohort, compared to 61.3% and 38.7% in all remission participants. 34.4% of people with CAP in remission had previous surgery.
There was a significant difference between the CAP and non-CAP cohort median scores with p values < 0.001 for neuroticism from the BFPQ, Ease of Excitation (EoE) from the HSPS, GAD7, PHQ9. The CBRQ components of fear avoidance, embarrassment avoidance, symptom focusing, all-or-nothing behaviour score, and avoidance/resting behaviour score also showed differences between the CAP and non-CAP groups (p <0.001, 95 % confidence interval). Pain intensity and pain interference scores showed positive correlations significant at the 0.01 level with neuroticism, EoE, GAD7, PHQ9, and all components of the CBRQ except catastrophisation score within the CAP in remission group.

Conclusion

Our results demonstrate that an older age at diagnosis, IBS prevalence, Crohn’s disease, neurotic personality type, and certain behavioural and psychological profiles are significant features of IBD patients with chronic abdominal pain in remission. Further studies will help to develop management strategies and to establish causality.

References

1. Farrokhyar, F., et al., Functional gastrointestinal disorders and mood disorders in patients with inactive inflammatory bowel disease: Prevalence and impact on health. Inflammatory Bowel Diseases, 2006. 12(1): p. 38-46.
2. Srinath, A.I., et al., Predictors of abdominal pain in depressed pediatric inflammatory bowel disease patients. Inflamm Bowel Dis, 2014. 20(8): p. 1329-40.
3. Harris, P.A., et al., Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform, 2009. 42(2): p. 377-81.
4. Teruel, C., E. Garrido, and F. Mesonero, Diagnosis and management of functional symptoms in inflammatory bowel disease in remission. World J Gastrointest Pharmacol Ther, 2016. 7(1): p. 78-90.
*Dr Ruqaya Idrees and Dr Pavit Luthra are joint first authors on this abstract.

Introduction

Inflammatory bowel disease (IBD) is a chronic multi-factorial disease characterized by inflammation of the gastrointestinal tract. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow further insights into the molecular mechanisms underlying IBD.

Aims & Methods

The serum and intestinal mucosa (ileum and left colon) proteomic profiles of patients with Crohn´s disease (CD) and ulcerative colitis (UC) and healthy controls (HC) were analyzed through label-free relative quantitative proteomic profiling using nLC MS/MS. Data mining and pattern recognition techniques were performed to identify hidden relationships that are not detectable using classical linear classifiers, and thus identify potential markers able to discriminate between the different study groups. Six candidate biomarkers were selected for further validation using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in serum and intestinal tissue samples, respectively.

Results

Comparison of serum proteins between UC patients and HC revealed statistically lower levels of protein 1 and 2 and higher levels of protein 3. The comparison of potential biomarkers between CD and HC group showed lower levels of protein 1 and higher levels of protein 3. In addition, protein 4 was differentially upregulated in CD patients compared to UC. Regarding the intestinal biopsies, protein 5 showed higher intensity in the IHC staining of ileum from CD patients compared to HC, whereas protein 6 was significantly decreased in left colon and ileum from CD and UC patients compared to HC. These proteins are involved in thyroxine transport, regulation of chemotactic chemokine activity, inflammatory processes, triglyceride homeostasis, oxidative stress and regulation of NF-kappa-B activation in the cytosol.

Conclusion

In this study, we have identified a panel of six potential biomarkers that could help to elucidate mechanisms involved in IBD pathogenesis. Their roles in the pathophysiology need to be clarified in further experiments.

Introduction

20-50% of patients with inflammatory bowel disease (IBD) experience chronic pain during remission (1-5). The clinical features of IBD patients with and without abdominal pain during remission remain unknown.

Aims & Methods

In a cross-sectional pilot study of IBD patients in remission, our aims were to assess patient recruitment, compliance, feedback to optimise the questionnaires for future use and to determine clinical features that distinguish patients with and without abdominal pain. Online validated questionnaires about disease activity, symptoms and psychological assessment were sent to participants of the UK IBD BioResource (total sample 30,000 patients). Inclusion and exclusion criteria of the IBD BioResource main cohort were applied. Descriptive statistics were used in all participants to assess disease status. Descriptive and inferential statistics were applied to all participants in remission.

Results

​2,050 patients were approached and 291 (14.2%) participated. 249 completed the study and 244 patients were included in the analysis. Technical problems, lack of understanding of the relevance of some questionnaires and their length were identified as factors which affected completion in 35 participants. 244 patients were full responders with 122 (50%) participants in remission, out of which 33 (27%) experienced chronic abdominal pain. Comparison of the remission groups with (N=33) versus without (N=89) chronic abdominal pain yielded higher scores in patients with pain for the following: use of azathioprine (p=0.021); patient health questionnaire 15 score (p<0.001); gastrointestinal symptoms rating scale total score (p<0.001); coping resources inventory health in general ((p=0.046); big five questionnaire neuroticism (p=0.019); highly sensitive person scale- short form total score (p=0.007); cognitive and behaviour responses questionnaire catastrophizing score (p=0.010); Pittsburgh sleep quality index poor sleeper (global score > 5, p=0.03).

Conclusion

Rectifiable factors affecting recruitment and compliance were identified. Differences in symptoms and psychological characteristics exist in patients with IBD in remission with and without chronic abdominal pain. Further research is warranted to translate these preliminary findings into meaningful and personalised holistic treatment options for IBD patients with chronic pain.

References

1. Zeitz J, Ak M, Müller-Mottet S, Scharl S, Biedermann L, Fournier N, et al. Pain in IBD Patients: Very Frequent and Frequently Insufficiently Taken into Account. PLoS One. 2016;11(6):e0156666.
2. Sweeney L, Moss-Morris R, Czuber-Dochan W, Meade L, Chumbley G, Norton C. Systematic review: psychosocial factors associated with pain in inflammatory bowel disease. Aliment Pharmacol Ther. 2018;47(6):715-29.
3. Schirbel A, Reichert A, Roll S, Baumgart DC, Büning C, Wittig B, et al. Impact of pain on health-related quality of life in patients with inflammatory bowel disease. World J Gastroenterol. 2010;16(25):3168-77.
4. Norton C, Czuber-Dochan W, Artom M, Sweeney L, Hart A. Systematic review: interventions for abdominal pain management in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;46(2):115-25.
5. Farrokhyar F, Marshall JK, Easterbrook B, Irvine EJ. Functional gastrointestinal disorders and mood disorders in patients with inactive inflammatory bowel disease: prevalence and impact on health. Inflamm Bowel Dis. 2006;12(1):38-46.

Disclosure

Maike Engelmann-Kewitz: No conflict of interest.
Iman Khwaja: No conflict of interest.
Kazuya Takahashi: No conflict of interest.
Dr. Miles Parkes: No conflict of interest.
Prof. Christine Norton: Consultancy: Pfizer; Lecture fees: Merck, Takeda, Tillotts, Janssen.
Prof. Ailsa Hart: No conflict of interest.
Dr. David Bulmer: No conflict of interest.
Prof. Qasim Aziz: Takeda pharmaceuticals and Classado pharmaceuticals.