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Impact of age and inflammation on extraintestinal manifestations of inflammatory bowel disease
Örebro University, School of Medical Sciences.
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is often complicated by extraintestinal manifestations (EIMs) that affect organs beyond the gastrointestinal tract. The EIMs can significantly impair quality of life and complicate disease management in patients with IBD. As the population ages, understanding the interplay between age, chronic inflammation, and EIMs becomes increasingly important for optimizing patient care and outcomes. Thus, the overall aim of the thesis was to assess the impact of age and inflammation on EIM of IBD.

We conducted all studies using Swedish national registers. To evaluate the accuracy of the National patient register (NPR), we compared International classification of diseases (ICD) coded IBD data with clinical records from 1403 IBD patients. For investigating spondyloarthritis (SpA) comorbidity, a cohort of 39,203 IBD patients diagnosed between 2006-2016 and 390,490 matched reference individuals were analyzed. The familial risk of SpA was assessed among 147,080 first-degree relatives (FDRs) and 25,945 spouses of IBD patients. The influence of colectomy on SpA and other EIMs was studied in 3246 ulcerative colitis patients, comparing EIM rates before and after surgery.

The NPR showed high positive predictive values (PPVs) for Crohn's disease (97%) and ulcerative colitis (98%) but a low PPV for IBD-unclassified (8%). Crohn's disease location and behaviour had variable PPVs, indicating frequent misclassification. A high PPV (95%) was observed for age at diagnosis of IBD. Patients with IBD had significantly higher relative risk estimates of SpA both before (odds ratio [OR]: 3.48) and after (hazard ratio [HR]: 7.15) IBD diagnosis compared to the general population. FDRs of IBD patients exhibited a higher risk of SpA (HR: 1.35). Spouses also had an elevated SpA risk, suggesting environmental influences. The highest risks were observed in Crohn's disease and pediatric-onset IBD. Post-colectomy, patients with ulcerative colitis experienced increased EIM rates (rate ratios [RR]: 1.83). In addition, de novo EIMs frequently occurred in patients with no history of EIMs before colectomy.

The NPR is a reliable source for subtype of IBD, although improvements are needed for phenotypic accuracy. IBD significantly increases the risk of SpA. The elevated SpA risk among FDRs and spouses points to shared genetic and environmental factors. Colectomyin patients with ulcerative colitis does not mitigate the risk of EIMs, indicating a need for continued monitoring and management post-surgery. This thesis underscores the importance of comprehensive care approaches that address both gastrointestinal and extraintestinal challenges in IBD.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2024. , p. 99
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 295
Keywords [en]
inflammatory bowel disease, Crohn's disease, ulcerative colitis, ageing, spondyloarthritis, extraintestinal manifestations, colectomy, epidemiology
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-113987ISBN: 9789175295671 (print)ISBN: 9789175295688 (electronic)OAI: oai:DiVA.org:oru-113987DiVA, id: diva2:1863074
Public defence
2024-09-20, Örebro universitet, Campus USÖ, Tidefeltsalen, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2024-05-30 Created: 2024-05-30 Last updated: 2024-08-27Bibliographically approved
List of papers
1. The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
Open this publication in new window or tab >>The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
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2020 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 55, no 4, p. 430-435Article in journal (Refereed) Published
Abstract [en]

Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown.

Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals.

Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis.

Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Crohn’s disease, ICD-codes, Inflammatory bowel disease, Montreal classification, National Patient Register, Swedish Quality Register for IBD, epidemiology, ulcerative colitis, validation
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-81780 (URN)10.1080/00365521.2020.1740778 (DOI)000532826000007 ()32370571 (PubMedID)2-s2.0-85084438205 (Scopus ID)
Available from: 2020-05-11 Created: 2020-05-11 Last updated: 2025-02-11Bibliographically approved
2. Association between inflammatory bowel disease and spondyloarthritis: findings from a nationwide study in Sweden
Open this publication in new window or tab >>Association between inflammatory bowel disease and spondyloarthritis: findings from a nationwide study in Sweden
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2022 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 16, no 1, p. 1540-1550Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been associated with spondyloarthritis (SpA), but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD to the general population, overall and by IBD subtype and age.

METHODS: We used a nationwide register-based cohort study of 39,203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390,490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios (ORs) for a prior (prevalent) SpA diagnosis and conditional Cox regression to calculate hazard ratios (HRs) for a subsequent (incident) SpA diagnosis in IBD patients.

RESULTS: IBD patients were more likely to have prevalent SpA at IBD diagnosis (2.5%) compared to reference individuals (0.7%) with an OR of 3.48 (95%CI:3.23-3.75). They also more often received an incident diagnosis of SpA; during 23,341,934 person-years of follow-up in IBD patients, there were 1,030 SpA events (5.0/1,000 person-years) compared to 1,524 SpA events in the reference group (0.72/1,000 person-years), corresponding to an HR of 7.15 (95%CI:6.60-7.75). In subgroup analyses, associations were most pronounced among patients with Crohn's disease [(OR=5.20; 95%CI:4.59-5.89), and (HR=10.55; 95%CI:9.16-12.15)] and paediatric onset IBD [(OR=3.63; 95%CI:2.35-5.59) and (HR=15.03; 95%CI:11.01-20.53)].

CONCLUSION: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared to the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity across IBD subtypes and age-groups, calls for targeted approaches to facilitate timely diagnosis and intervention.

Place, publisher, year, edition, pages
Oxford University Press, 2022
Keywords
epidemiology, inflammatory bowel diseases, population-based study, spondyloarthritis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-98862 (URN)10.1093/ecco-jcc/jjac065 (DOI)000813274200001 ()35512691 (PubMedID)2-s2.0-85141889167 (Scopus ID)
Funder
European Commission, 754285Swedish Research Council, 2020-02021
Note

Funding agency:

Orebro University Hospital Research Foundation OLL-936004 OLL-890291 OLL-790011 OLL-723021

Available from: 2022-05-06 Created: 2022-05-06 Last updated: 2025-02-11Bibliographically approved
3. Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden
Open this publication in new window or tab >>Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden
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2024 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 18, no 9, p. 1371-1380Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals.

METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA.

RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses.

CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
epidemiology, first-degree relatives, inflammatory bowel diseases, spondyloarthritis, spouses, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-112556 (URN)10.1093/ecco-jcc/jjae041 (DOI)001198352900001 ()38518097 (PubMedID)2-s2.0-85203054672 (Scopus ID)
Funder
EU, Horizon 2020, 754285Region Örebro County, OLL-936004; OLL-890291; OLL-790011; OLL- 723021Swedish Research Council, 2020-02021
Note

Funding agency:

Danish National Research Foundation DNRF148

Available from: 2024-03-25 Created: 2024-03-25 Last updated: 2025-02-11Bibliographically approved
4. The risk of extraintestinal manifestations before and after colectomy in patients with ulcerative colitis
Open this publication in new window or tab >>The risk of extraintestinal manifestations before and after colectomy in patients with ulcerative colitis
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-115586 (URN)
Available from: 2024-08-22 Created: 2024-08-22 Last updated: 2024-08-27Bibliographically approved

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