To Örebro University

Background: Perianal diseases are more common in patients with Crohn's disease (CD) than in the general population, but data are scarce in other inflammatory bowel disease (IBD) subtypes.

Method: Using data from the Swedish National Patient Register (NPR) and SWIBREG, the national quality register for IBD, we estimated the cumulative incidence of perianal fistula/abscess and perianal diseases (fistula, abscess, stenosis, fissure or procedure code for perianal surgery) in relation to diagnosis, and the prevalence in 2023, in individuals with CD, ulcerative colitis (UC) and IBD-unclassified (IBD-U), and in a matched (age, sex, calendar year and region of residence) IBD-free cohort from the general population.

Results: We identified 38,364 patients with incident IBD 2007-2017, and 98,229 patients with prevalent IBD as of 31 December 2022. The cumulative incidence of fistula/abscess was 6.7% at diagnosis, 8.3% at 1 year and 10.4% at 5 years in CD. The corresponding percentages in UC were 0.9%, 1.3% and 2.1%, and in IBD-U 2.4%, 3.1% and 4.5%, respectively. In 2023, 12.8%, 3.1% and 4.1% of patients with prevalent CD, UC and IBD-U had a history of fistula/abscess, compared to 0.8% in the general population. The corresponding numbers for perianal diseases were 19.7%, 7.4%, 8.6% and 2.2%.

Conclusions: The cumulative incidence and prevalence of perianal diseases in Swedish patients with CD was in parity with reports from other countries, and in patients with UC and IBD-U, it was 3-4 times higher than in the population.

BACKGROUND: The Swedish National Patient Register (NPR) is an important source of data for epidemiological research. A review in 2010 described the validity of recorded diagnoses for inpatient care, but did not include specialised outpatient care.

METHOD: Using systematic searches of medical literature databases (Embase, Medline), and reports from members of the Swedish Epidemiological Association, we aimed to identify all studies validating diagnoses and procedure codes in inpatient care since 2010 and all studies validating specialised outpatient care. In addition, we summarize findings from register validation work performed by the National Board of Health and Welfare.

RESULTS: The literature search and personal reports generated 3990 non-duplicate original studies, of which 89 were deemed relevant. Compared to data in patient charts (reference), the median positive predictive value (PPV) for diagnostic codes in the NPR was 84% (interquartile range 72-93%), but with clear differences between types of diagnoses. The median PPV for surgical procedures was 97% (86-99%). The median sensitivity of diagnoses and procedures compared to other registers and cohorts was 73% (45-80%). The completeness of the register has improved over time. Missingness originates mainly from underreporting of procedures performed by private healthcare providers, and for certain variables, e.g. medication codes.

CONCLUSION: The NPR has good diagnostic accuracy for most diagnoses and very good for surgical procedures. The sensitivity is lower. Longitudinal comparisons of incidence or prevalence are affected by changes in completeness. Missingness is low, although it is higher among private healthcare providers and for specific variables such as drug administration.

INTRODUCTION: IgA nephropathy is the most common primary kidney disease in the world and has a highly variable clinical presentation. While studies have indicated a link between glomerular disease and infections, large-scale studies on IgA nephropathy are missing.

METHODS: In our study, IgA nephropathy was defined as having a kidney biopsy record 1997-2011 in Sweden. Each IgA nephropathy patient was matched with five reference individuals based on age, sex, calendar year, and county of residence. We excluded individuals with earlier organ transplants, HIV, immunodeficiency, or end-stage kidney disease. Linear and Cox regressions, adjusted for age, sex, education, and diabetes, were performed to analyze total infections and antimicrobial treatments in both patients and reference individuals. Sibling analyses were also performed.

RESULTS: The linear regression analysis revealed a significant association between IgA nephropathy and the overall frequency of infections compared to the general population (β = 0.44; 95% CI: 0.35-0.53) and siblings (β = 0.36; 95% CI: 0.23-0.49). Similarly, antimicrobial prescriptions, especially antibiotics, were more common in IgA nephropathy compared to the general population and to siblings. Cox regression showed an elevated risk of any infection (adjusted hazard ratio [aHR] = 2.00; 95% CI: 1.84-2.18) and sepsis (aHR = 3.18; 95% CI: 2.17-4.65) corresponding to one extra case of sepsis per 63 patients followed for 10 years. The strongest associations were seen for urinary tract infections; ear, nose, and throat infections; and musculoskeletal and gastrointestinal infections.

CONCLUSION: Conclusively, our study demonstrates an increased prevalence of infections and antibiotic prescriptions in IgA nephropathy patients. The increased risk of sepsis warrants clinical awareness and prevention.

INTRODUCTION: It is uncertain whether the risk of major congenital anomalies (mCAs) is increased in children of women with inflammatory bowel disease (IBD).

METHODS: We aimed to determine the risk of mCAs in a Swedish nationwide cohort of 13,131 singleton live births from 1997 to 2020 to women with IBD and 61,909 matched children to women without IBD from the general population. We additionally examined mCAs according to periconceptional histological inflammation (vs remission: 1,124 and 646 births, respectively) or clinically active IBD (vs quiescent: 3,380 and 6,603 births, respectively). Adjusted risk ratios (aRRs) for overall and organ-specific mCAs were estimated using generalized linear models. These models adjusted for maternal sociodemographics, comorbidities, body mass index, and smoking.

RESULTS: There were 38.0 (n = 499) mCAs per 1,000 births to women with IBD vs 33.9 (n = 2,101) in matched comparators and a risk difference of 1 extra mCA per 246 births to women with IBD (aRR 1.11; 95% confidence interval [CI] 1.01-1.23). Risks of heart defects and mCAs of the urinary system partly drove estimates. The risk of mCAs was similar in children of women with ulcerative colitis and Crohn's disease. Periconceptional histological inflammation (vs remission) or clinically active (vs quiescent) IBD did not further influence the risk of mCA in the child (aRR 0.87 [95% CI 0.55-1.40] and aRR 1.04 [95% CI 0.85-1.27], respectively).

DISCUSSION: Children of women with IBD had a heightened susceptibility to mCAs, although absolute and relative risks were lower than previously reported. IBD activity was not linked to mCA risks, but those analyses included relatively few events.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to pancreatic diseases, but evidence from population-based studies with liver histology is lacking.

Aims and methods: In this population-based cohort including all Swedish adults (n = 8563) with biopsy-proven MASLD, we aimed to investigate incidences of pancreatic diseases compared with matched reference individuals from the general population (n = 38,858) and full siblings (n = 6696). Using Cox proportional hazard models, we calculated multivariable adjusted hazard ratios (aHRs) and confidence intervals (CIs).

Results: We documented 359 incidents of pancreatic diseases in MASLD patients and 880 events in matched reference individuals, resulting in an incidence rate difference of 1.54 (95% CI, 1.25-1.84). The relative risk of pancreatic disease was highest in the first two years after MASLD diagnosis (aHR, 2.19 [95% CI, 1.92-2.50), but remained statistically significant increased even up to ten years [aHR, 1.60 (95% CI, 1.38-1.85)]. The most common pancreatic disease in individuals with MASLD was acute non-biliary pancreatitis (1.44 vs. 0.44 events/1000 PY), followed by chronic pancreatitis (0.54 vs. 0.12/1000 PY) and pancreatic cancer (0.88 vs. 0.47/1000 PY). We documented 130 versus 344 pancreas-related deaths among individuals with MASLD and their matched comparators, yielding an absolute risk difference of 0.51/1000 PY and an aHR of 2.41 (95%CI = 1.95-2.97). The findings were consistent in sibling-controlled analyses with an aHR of 2.21 (95%CI = 1.69-2.90).

Conclusions: MASLD was associated with significantly higher rates of acute and chronic pancreatitis of predominantly non-biliary origin, as well as an increased risk of pancreatic cancer and pancreas-related mortality.

INTRODUCTION: Inflammatory diseases have been associated with increased risk of venous thromboembolism (VTE). However, data on VTE is lacking in large population-based cohorts of microscopic colitis (MC).

METHODS: This study included all Swedish adults with incident MC without prior VTE (1990-2017; n=12,489; follow-up until 2021). MC and subtypes (collagenous colitis and lymphocytic colitis) were defined from prospectively recorded colorectal histopathology reports from all 28 pathology departments in Sweden. Individuals with MC were matched for birth year, sex, calendar year and county with up to five general population reference individuals (n=55,809) without prior MC. Sensitivity analyses included full sibling comparisons and stricter definitions of VTE requiring a primary diagnosis of VTE and a prescription of anticoagulant medication. Incidence rates and multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) for VTE events were calculated using Cox proportional hazards modelling.

RESULTS: Over a median of 10.0 years of follow-up, 755 (6.0%; 11.3/1000 person-years) incident VTE events occured in individuals with MC and 2674 (4.8%; 8.6/1000 person-years) in reference individuals. Individuals with MC had a higher overall relative risk of any VTE event compared with reference individuals (aHR=1.21, 95%CI=1.11-1.32) including higher risk of pulmonary embolism (aHR=1.23, 95%CI=1.08-1.40), deep vein thrombosis of the legs (aHR=1.16, 95%CI=1.03-1.32), and other VTE events (aHR=1.31, 95%CI=1.08-1.58). The results remained robust in sensitivity analyses.

DISCUSSION: In this population-based study, individuals with MC had a 21% higher risk of VTE compared with reference individuals, equivalent to one extra VTE event for every 37 MC individuals followed for ten years.

OBJECTIVES: Celiac disease (CeD) has been associated with a low response to hepatitis B (HBV) vaccination, but guidelines for testing and revaccination among individuals with CeD are sparse. We examined the risk of future HBV among individuals with CeD in a population-based Swedish cohort. Furthermore, we examined the rate of prior HBV infection in CeD patients.

METHODS: All individuals in Sweden diagnosed with biopsy-verified CeD between 1990 and 2017 were identified through the ESPRESSO cohort. Each individual with CeD was matched by age, sex, calendar year, and birth country (Nordic vs. other) with up to 5 reference individuals.

RESULTS: We identified 44,721 CeD and 222,238 reference individuals. The incidence rates of diagnosed HBV were 2.3 and 2.9 per 100,000 person-years, respectively. This represented no association with CeD (HR 0.77 (0.45-1.30)). This null association was similar for those with a Nordic (HR 0.80 (0.40-1.60)) and non-Nordic ((HR 0.31 (0.09-1.08)) country of birth. Rates of prior HBV infection were low (CeD 0.08%, controls 0.06%). This corresponded to a small but insignificant increase among individuals with CeD (odds ratio, OR 1.41 (0.97-2.05).

CONCLUSION: In a population-based Swedish cohort, there was no increased risk of developing HBV in individuals with CeD. This finding does not support current practices of testing and revaccination for HBV. Additional studies should be completed in areas with higher endemic rates of HBV. Slightly higher rates of prior HBV infection in CeD may be secondary to increased testing in those seeking medical care for another disease process.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) are at increased risk of fracture. It is unclear if this risk varies by recent histological activity. AIMS: To determine the fracture risk in IBD during periods with and without histological inflammation.

METHODS: We studied a nationwide cohort of 54,591 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies. Fractures were identified by inpatient and hospital-based outpatient diagnoses. We derived Cox regression estimated hazard ratios (HRs) for fracture during 12 months following a histological inflammation (vs. histological remission) record after adjusting for socio-demographics, comorbidities, IBD duration, IBD-related surgery and hospitalization. We adjusted sensitivity analyses for medical IBD treatment including corticosteroids.

RESULTS: Mean age of patients was 44.0 (SD = 18.3) and 45.5 (SD = 17.1) years at biopsy with histological inflammation and remission, respectively. For histological inflammation, there were 1.37 (95% CI 1.29-1.46) fractures per 100 years' follow-up versus 1.31 (95% CI 1.19-1.44) for remission (adjusted [a]HR 1.12; 95% CI 1.00-1.26; p = 0.04). HRs were similar with histological inflammation of Crohn's disease (1.11; 95% CI 0.91-1.36) and ulcerative colitis (1.18; 95% CI 1.02-1.36). Estimates were consistent across age groups. An overall small excess risk of any fracture remained after accounting for corticosteroids. A more prominently raised fracture risk was observed in corticosteroid-naïve IBD patients with histological inflammation versus histological remission (aHR 1.41; 95% CI 1.07-1.85). The aHR of hip fracture following histological inflammation was 1.29 (95% CI 0.87-1.92).

CONCLUSIONS: Histological inflammation in IBD predicted a small increase in short-term fracture risk. Measures to reduce disease activity may reduce fracture risk in IBD.

BACKGROUND: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE).

OBJECTIVE: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings.

METHODS: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding.

RESULTS: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51).

CONCLUSIONS: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.