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BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear. METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses. RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61). CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD., Funding Agencies:ALF-funding from Region Västra GötalandUniversity of Gothenburg, SwedenBirgitta och Göran Karlssons foundationThe Swedish Society for Medical ResearchThe Swedish Research CouncilThe Swedish Society of MedicineKarolinska InstitutetSwedish Research CouncilThe Swedish Society of MedicineRegion Stockholm (ALF project)Crohn’s and Colitis FoundationJudith Stewart Colton Center for AutoimmunityNIH NIDDK Diseases

BACKGROUND: Birth cohort studies with linked register-based data on inflammatory bowel disease (IBD) provide opportunities to prospectively study early-life determinants of the disease. However, register-based data often lack information on clinical characteristics and rely on diagnostic algorithms. Within the All Babies in Southeast Sweden (ABIS) cohort, we examined the validity of a register-based definition of IBD, its incidence, and clinical and therapeutic characteristics at diagnosis. METHODS: We followed 16,223 children from birth (1997-1999) until the end of 2020 for the diagnosis of IBD as defined by a minimum of two diagnostic codes for IBD in the Swedish National Patient Register (NPR). We described the incidence and cumulative incidence of IBD. Through a medical record review of cases diagnosed by the end of 2017, we examined the positive predictive value (PPV) for IBD and described its clinical characteristics and treatment. RESULTS: By 2020, at an average age of 22.2 years, 113 participants (0.74%, 95% confidence interval [CI] = 0.61-0.89) had a register-based diagnosis of IBD, corresponding to an incidence of 31.3 per 100,000 person-years of follow-up; the incidence for Crohn's disease (CD) was 11.1 per 100,000 person-years and 15.8 for ulcerative colitis (UC). Of 77 participants with a register-based definition of IBD by the end of 2017, medical records were identified for 61 participants, of whom 57 had true IBD (PPV = 93%; 95%CI = 0.87-1.00). While oral 5-aminosalicylic acid treatment was equally common in newly diagnosed CD and UC patients, biologics were more often used for newly diagnosed CD. The median faecal calprotectin levels were 1206 mg/kg at diagnosis and 93 mg/kg at the last follow-up (P < 0.001). CONCLUSIONS: In this population-based sample of Swedish children and young adults the cumulative IBD incidence was 0.74. The validity of register-based definition of IBD was high and supports using such data to identify IBD patients in cohor

Aim: To examine the clinical follow up of paediatric coeliac disease and the rate of loss of follow up during childhood, for which data are scarce. Methods: In a cohort of coeliac children diagnosed in 2013-2018 in Gothenburg, Sweden, we retrospectively explored the follow-up practice of paediatric coeliac disease until June 2021. We used medical records from hospital-based paediatric gastroenterology and general paediatric outpatient clinics, laboratory records, and questionnaires. Loss of follow up was defined no coeliac disease-related follow up or tissue transglutaminase test over the past 2years of study enrolment. Results: We included 162 children (58% girls) aged 7.8-18.2years (average 12.7). Most participants (76%) were followed at general paediatric outpatient clinics rather than hospital-based clinics. After 2.3-8.8 (average 5.3) years since diagnosis, 23 patients (14%; 95% confidence interval, 9%-21%) had been lost to follow up. Patients with loss of follow up were more often boys (61% versus 39%, p = 0.08), with a somewhat longer average disease duration of 5.8 versus 5.2years (p = 0.11). There were no between-group differences in socio-economic characteristics and patient-reported experience measures of coeliac disease care. Conclusion: One in seven coeliac patients may experience loss of follow up during childhood.

Background & aims: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histologic disease activity is unclear. Methods: This was a national population-based study of 55,626 individuals diagnosed with IBD in 1990 to 2016 with longitudinal data on ileocolorectal biopsy specimens followed up through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months after documentation of histologic inflammation (vs histologic remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery, and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses. Results: With histologic inflammation vs remission, there was 4.62 (95% CI, 4.46-4.78) and 2.53 (95% CI, 2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted HR [aHR], 1.59; 95% CI, 1.48-1.72). Histologic inflammation (vs remission) was associated with an increased risk of serious infections in ulcerative colitis (aHR, 1.68; 95% CI, 1.51-1.87) and Crohn's disease (aHR, 1.59; 95% CI, 1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95% CI, 1.28-2.15) and 1.71 (95% CI, 1.22-2.41), respectively. Overall, results were consistent across age groups, sex, and education level, and remained largely unchanged after adjustment for IBD-related medications (aHR, 1.47; 95% CI, 1.34-1.61). Conclusions: Histologic inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histologic remission may reduce infections in IBD. The study was approved by the Stockholm Ethics Review Board (approval numbers 2014/1287-31/4, 2018/972-32, and 2021-06209-01).

INTRODUCTION: Patients with celiac disease (CD) have an increased risk of encapsulated bacterial infections. Less is known about other serious infections in CD, especially in patients diagnosed in the 21st century. METHODS: We contacted all 28 pathology departments in Sweden through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort study and identified 20,088 individuals with CD (defined as villous atrophy) diagnosed in 2002-2017. Patients were matched for sex, age, and calendar year to 80,152 general population comparators and followed up until December 31, 2019. Serious infections were defined as having a hospital-based (inpatient and outpatient) diagnosis in the National Patient Register. Cox regression yielded adjusted hazard ratios (aHR) controlling for education, country of birth, and comorbidities. RESULTS: During 173,695 person-years of follow-up, 6,167 individuals with CD (35.5/1,000 person-years) had a serious infection. This was compared with 19,131 infections during 743,260 person-years (25.7/1,000 person-years) in matched comparators, corresponding to an aHR of 1.29 (95% confidence interval [CI] = 1.25-1.33). aHR were similar when restricted to infection requiring hospital admission (1.23; 95% CI = 1.17-1.29). The excess risk of serious infections also persisted beyond the first year after CD diagnosis (aHR = 1.24; 95% CI = 1.20-1.29). Patients with CD were at risk of sepsis (aHR = 1.26; 95% CI = 1.09-1.45) and gastrointestinal infections (1.60; 95% CI = 1.47-1.74). Mucosal healing during CD follow-up did not influence the risk of subsequent serious infections. DISCUSSION: This nationwide study of patients with celiac disease diagnosed in the 21st century revealed a significantly increased risk of serious infections. While absolute risks were modest, vaccinations should be considered during CD follow-up care.

OBJECTIVES: To determine the risk of inflammatory bowel disease (IBD) in patients with celiac disease (CeD) (and vice versa) compared to general-population comparators. METHODS: Using Swedish histopathology and healthcare register data, we identified 48,551 patients with CeD and 83,529 with IBD diagnosed in 1969-2016. Each patient was compared to age- and sex-matched general-population comparators (CeD: n=240,136; IBD: n=408,195). Cox regression estimated hazard ratios (HRs) for IBD in CeD patients and vice versa. Our main analyses were limited to events beyond the first year of follow-up to reduce potential surveillance bias. RESULTS: During follow-up, 784 (1.6%) CeD patients were diagnosed with IBD compared to 1015 (0.4%) matched comparators. In CeD patients the HR for IBD was 3.91 (95%CI 3.56-4.31), with largely similar HRs for Crohn's disease (4.36; 3.72-5.11) and ulcerative colitis (3.40; 3.00-3.85). During follow-up, 644 (0.8%) IBD patients and 597 (0.1%) comparators were diagnosed with CeD. The HR for CeD in IBD patients was 5.49 (95%CI 4.90-6.16), with the highest risk estimates seen in ulcerative colitis (HR=6.99; 6.07-8.05), the HR for Crohn's disease was 3.31 (2.69-4.06).In patients with CeD and IBD the diagnostic interval was usually <1 year; however, HRs of 3-4 were seen even after 10 years of follow-up. During 20 years of follow-up, 2.5% of CeD patients developed incident IBD and 1.3% of IBD patients developed CeD. CONCLUSIONS: The bidirectional association between CeD diagnosis and IBD warrants attention in the initial assessment and follow-up of these conditions. Their co-occurrence, independent of temporal sequence, suggests shared etiology., Funding agencySwedish government ALFGBG-771121

Celiac disease (CD) is an immune‐mediated disease triggered by gluten intake and affects around 1% of the population worldwide. Although patients with CD have an increased use of healthcare, data on work disability remains scarce. To estimate work loss in patients with CD before and after diagnosis. We identified 16,005 working‐age patients with prevalent CD, and 4,936 incident working‐age patients diagnosed in 2008‐2015 through biopsy reports from Sweden’s 28 pathology departments. CD was defined by presence of villus atrophy (Marsh 3) on biopsy (gold standard). Each patient was compared to up to 5 matched general‐population comparators. Using nationwide social insurance registers, we retrieved prospectively‐recorded data on compensation for sick leave and disability. In 2015, patients with prevalent CD had a mean of 42.5 (95%CI: 40.9‐44.1) lost work days as compared with 28.6 (27.9‐29.2) in the general‐population comparators, corresponding to a relative difference of 49%. Among incident patients, the annual mean difference between patients and comparators was 8.0 (5.4‐10.6) lost work days 5 years before CD diagnosis, which grew to 13.7 (9.1‐18.3) days 5 years after diagnosis. In addition to the continuously increasing mean difference in lost work days over time, there was also a transient increase in work loss in patients with CD during the year of diagnosis (mean difference: 15.6 days, 95%CI: 13.1‐18.0). Patients with CD miss more work days than comparators before their diagnosis, and this loss increases and persists after diagnosis despite presumed installation of treatment with gluten‐free diet.