Risk Factors for the Development of Fistulae and Stenoses in Crohn Disease Patients in the Swiss Inflammatory Bowel Disease Cohort

Zeitz, Jonas; Fournier, Nicolas; Labenz, Christian; Biedermann, Luc; Frei, Pascal; Misselwitz, Benjamin; Scharl, Sylvie; Vavricka, Stephan R.; Sulz, Michael Christian; Fried, Michael; Rogler, Gerhard; Scharl, Michael

doi:10.1159/000458144

Cited by 12 publications

(9 citation statements)

References 43 publications

(41 reference statements)

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“…Previous studies already described a role for a number of SNPs located within the TNFSF15 gene locus as being associated with disease progression in CD patients. 13 , 32 In our paper we identified a further SNP within this gene locus, namely SNP rs4246905, to protect from disease progression, confirming the role of TNFSF15 in this regard. On a functional level, TNFSF15, also known as TL1A, and its receptor DR3 have been shown to be widely expressed in inflamed intestinal tissue of IBD patients.…”

Section: Discussionsupporting

confidence: 69%

“…Clinical parameters, such as the initial CD location at diagnosis, smoking and the age of the patient at diagnosis, have been established as risk factors for a progression to B stage. 3,4,[10][11][12][13][14] Genetic risk factors for the development of penetrating CD include African American origin and family history. 15 In addition, it has been demonstrated that host genetics and particularly the presence of specific single nucleotide polymorphisms (SNPs) within IBD risk genes critically impact the pathogenesis of CD.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic risk factors predict disease progression in Crohn’s disease patients of the Swiss inflammatory bowel disease cohort

Ditrich

Blümel

Biedermann

et al. 2020

Therap Adv Gastroenterol

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Background: Crohn’s disease (CD) may progress from an inflammatory to a stricturing or penetrating disease phenotype. The aim of our study was to identify single nucleotide polymorphisms (SNPs) that predict disease progression in patients of the Swiss IBD Cohort Study (SIBDCS). Methods: We applied a multi-state Markov model for progression behavior of CD with three behavioral states according to the Montreal classification. The model considered transition from B1 to B2/B3 or from B2 to B3 stage. Model dynamics were summarized with transition intensities by including the effect of SNPs and calculating transition intensities for each SNP. Results: We included 1276 CD patients [669 (52.4%) B1, 248 (19.4%) B2, 359 (28.1%) B3 patients] with a median follow-up of 6.8 (interquartile range = 3.6–9.1; range 0–11.6) years. Probability for a B1 patient to develop a stenosis (B1 to B2, q = 0.033) was twice as much as compared to developing a penetrating complication (B3) during the disease course. In contrast, the probability of entering B3 stage was similar regardless of whether antecedent stricture was present (B2 to B3, q = 0.016) or not (B1 to B3, q = 0.016). We identified SNPs within the gene loci encoding ZMIZ1, LOC105373831 and KSR1 as carrying the highest risk for progression to B3, while the presence of SNPs within gene loci TNFSF15 and CEBPB-PTPN1 protected from progression to B2 or B3. Conclusion: We identified new genetic risk factors that can predict disease course in CD patients. A closer understanding on the functional impact of these genetic variations might improve our treatment options finally to prevent disease progression in CD patients.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

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Genetic risk factors predict disease progression in Crohn’s disease patients of the Swiss inflammatory bowel disease cohort

Ditrich

Blümel

Biedermann

et al. 2020

Therap Adv Gastroenterol

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“…With CD, there is a risk of complications such as stenosis or fistulas in the intestine. Perianal disease may be developed with fistulas and/or abscesses (51). Primary sclerosing cholangitis in CD and UC is a chronic cholestatic disease affecting predominantly males with a median age of ~40 years.…”

Section: Disease Severity and Complicationsmentioning

confidence: 99%

Self-care: the way to find balance in life : Development and evaluation of a self-care questionnaire for patients with inflammatory bowel disease

Wickman

2019

Linköping University Medical Dissertations

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Introduction: Inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) occur worldwide and are lifelong chronic conditions. The symptoms, which include abdominal pain and frequent diarrhea, cause limitations in life. Thus, patients with IBD need self-care in accordance with their symptoms, their own commitment to maintaining health, and decisions on symptom management. To strengthen self-care, there is a need for a tool that assesses self-care in patients with IBD, which aims to support the patient dialogue about self-care. The overall aim of this thesis was to develop and evaluate a questionnaire for the clinical assessment of self-care, and to explore self-care in relation to disease activity and to health-related quality of life (HRQOL) in patients with IBD. Design and method: The thesis includes four studies, where studies I, II and IV were conducted in Sweden, and study III was conducted in the United States (U.S.). In study I, a descriptive design, interviews were conducted with twenty adult patients, in order to explore self-care in patients with IBD. In study II, the self-care questionnaire was developed and tested with 193 patients with IBD in Sweden. In study III, a cross-sectional descriptive design, the self-care questionnaire was translated into English, and the responses of 67 patients in the U.S. were evaluated. Finally, in study IV, a cross-sectional exploratory design was used to explore self-care in relation to patient characteristics, disease activity, and HRQOL among 234 patients. For a total of 421 patients, the data was analyzed using content analysis, and descriptive and analytic statistics (studies I, II, III and IV). Results: Among patients with IBD, self-care relates to symptom recognition, handling symptoms, planning life, and seeking new options. Self-care varied according to how the patient managed daily life with regard to the symptoms of the disease (study I). Based on the results from study I, the self-care questionnaire was developed in Swedish, resulting in a valid and reliable questionnaire comprising 22 items (study II). The questionnaire was translated to English, and performed self-care activities were associated with a lower degree of well-being in relation to age and gender (study III). The patients were taking medication for IBD, paying attention to their Abstract intestinal symptoms, adapting their diet, managing their stress, planning their day and avoiding activities (studies III and IV). Self-care was more frequent in patients with CD when it came to paying attention to psychological symptoms; diet adaption; avoiding various activities including sex; and looking for new approaches to living with IBD. A greater degree of selfcare activities was associated with a lower degree of HRQOL (IV). Conclusion: The results indicate the importance of identifying the total symptom experience, and of the patient's need to discuss self-care, in order to strengthen self-care and achieve better treatment. The self-care questionnaire can be a useful tool to be...

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“…In general, the behavior of CD can be categorized into three phenotypes including inflammatory (non-stricturing, non-penetrating), stricturing and penetrating (fistulizing) disease[ 4 ]. Strictures consist of inflammatory, fibrotic or mixed processes leading to acute abdominal pain or obstruction and are a risk factor for developing internal fistulae and cancer[ 5 , 6 ]. At diagnosis, only a tenth of CD patients will present with a stricture however, up to one third of patients will ultimately develop stricturing within ten years of diagnosis, predominantly in the ileum[ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Crohn’s strictures open with anti-mycobacterial antibiotic therapy: A retrospective review

Collyer¹,

Clancy²,

Agrawal³

et al. 2020

WJGE

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BACKGROUND Medical therapy for strictures is limited and first-line treatment consists of endoscopic balloon dilatation, strictureplasty or surgical resection. Mycobacterium tuberculosis , Helicobacter pylori and Streptococcus can all cause stenosis, for which antibiotic treatment achieves stricture resolution. Mycobacterium avium ssp. paratuberculosis is a suspected causative agent in Crohn’s disease (CD). Thus, specialized antimicrobial treatment, in particular, anti-mycobacterial antibiotic therapy (AMAT) has been proposed as a potential treatment option. To our knowledge, the opening of CD strictures has not been recorded using any form of antibiotic therapy. We hypothesized that AMAT would resolve strictures in patients with CD. AIM To investigate the effect and outcomes of AMAT in a cohort of CD patients with an ileal stricture. METHODS A single center, retrospective, medical record case review was conducted on an observational cohort of patients with CD who had an ileal stricture on colonoscopy and were treated with AMAT. Forty patients meeting the inclusion criteria were identified from the internal medical database. Thirty (75%) patients had follow-up colonoscopy and clinical data available. The AMAT regimen was prescribed after the initial colonoscopy for a duration of at least six months until follow-up colonoscopy with the attending gastroenterologist. Patient demographics, symptoms, colonoscopy reports, inflammatory serum markers and concurrent medications were recorded at pre-treatment and follow-up between January 1995 and June 2018. RESULTS Of the patients that returned for follow-up after > 24 mo of AMAT, twenty (67%) had complete resolution (CR) of their ileal strictures, three (10%) had partial resolution and seven (23%) had no resolution. Irrespective of stricture outcome, 21 patients (70%) demonstrated clinical response to AMAT and there was a statistically significant reduction in inflammatory serum markers C-reactive protein ( P < 0.0001) and erythrocyte sedimentation rate ( P = 0.04) from pre-treatment to follow-up. It was observed that 11 (37%) patients experienced side effects, but no serious adverse effects were attributable to AMAT. At follow-up there were 26 (87%) patients on concomitant medication for CD and a statistically significant association between CR and AMAT with a concomitant immunomodulator ( P = 0.02). CONCLUSION This study demonstrated a high rate of stricture resolution (67%) similar to that seen in tuberculosis strictures (70%), suggesting a shared mycobacterial origin of strictures, and perhaps disease.

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Risk Factors for the Development of Fistulae and Stenoses in Crohn Disease Patients in the Swiss Inflammatory Bowel Disease Cohort

Cited by 12 publications

References 43 publications

Genetic risk factors predict disease progression in Crohn’s disease patients of the Swiss inflammatory bowel disease cohort

Genetic risk factors predict disease progression in Crohn’s disease patients of the Swiss inflammatory bowel disease cohort

Self-care: the way to find balance in life : Development and evaluation of a self-care questionnaire for patients with inflammatory bowel disease

Crohn’s strictures open with anti-mycobacterial antibiotic therapy: A retrospective review

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