Inflammatory eye disease is a risk factor for future microscopic colitis: A nationwide population-based matched case control study.

BACKGROUND: Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear. OBJECTIVE: To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC. METHODS: We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables. RESULTS: A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3 years (interquartile range (IQR) = 50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI = 1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI = 1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases. CONCLUSION: Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners.

Comparative risk of serious infection with vedolizumab vs anti-TNF in inflammatory bowel disease: results from nationwide Swedish registers.

OBJECTIVES: We aimed to assess the risk of serious infection in inflammatory bowel disease (IBD) patients treated with vedolizumab, compared to those treated with anti-tumor necrosis factors (TNF) and the general population. METHODS: In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission. RESULTS: During 1376 treatment-episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95%CI=3.98-6.63) with vedolizumab vs 3.54 (95%CI=2.50-4.85) with anti-TNF; HR=1.72 (95%CI=1.12-2.65), partly explained by more gastrointestinal infections. Compared to the rate of 0.75/100 PYs (95%CI=0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR=7.00; 95%CI=5.04-9.72).During 1294 treatment-episodes in ulcerative colitis, the corresponding rates were 3.74/100 PYs (95%CI=2.66-5.11) with vedolizumab vs 3.42/100 PYs (95%CI=2.31-4.89) with anti-TNF; HR=0.80 (95%CI=0.47-1.36) during the initial 1.1 years and HR=2.03 (95%CI=0.65-6.32) after 1.1 years (truncated due to non-proportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF whereas no case was observed among vedolizumab episodes. Compared to the rate of 0.69/100 PYs (95%CI=0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95%CI=3.67-8.11). CONCLUSIONS: Vedolizumab was associated with increased risks of serious infections compared to anti-TNF in Crohn's disease, but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the two therapies.

Psychiatric disorders among 5800 patients with microscopic colitis: A nationwide population-based matched cohort study.

INTRODUCTION: Microscopic colitis (MC) is an inflammatory condition of the large intestine. Primarily diagnosed in middle-aged and older adults, the incidence of the disease has increased markedly during the past decades. While MC is associated with a reduced quality of life, large-scale studies on the association with future psychiatric disorders are lacking. METHODS: We conducted a nationwide matched cohort study in Sweden from 2006 to 2021. Through a nationwide histopathology database (the ESPRESSO study), we identified 5,816 patients with a colorectal biopsy consistent with MC. These patients were matched with 21,509 reference individuals from the general population, all of whom with no previous record of psychiatric disorders. RESULTS: From 2006-2021, 519 patients with MC (median age 64.4 years (interquartile range = 49.5-73.3)) and 1,313 reference individuals were diagnosed with psychiatric disorders (9.9 vs. 6.5 events per 1,000 person-years), corresponding to one extra case of psychiatric disorder in 29 patients with MC over 10 years. After adjustments, the hazard ratio (HR) for psychiatric disorders was 1.57 (95% confidence interval [CI]=1.42-1.74). We found significantly elevated estimates up to 10 years after MC diagnosis and a trend towards higher risk with increasing age. Specifically, we observed increased risks for unipolar depression, anxiety disorders, stress-related disorders, substance abuse, and suicide attempts.In sibling-controlled analysis the aHR was 1.76 (95%CI=1.44-2.15). CONCLUSION: Patients with MC are at increased risk of incident psychiatric disorders compared to the general population.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study.

BACKGROUND: Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. METHODS: This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. RESULTS: During a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. CONCLUSIONS: In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Economic Burden of Eosinophilic Esophagitis: A Nationwide Cost-of-Illness Study.

INTRODUCTION: Despite its increasing prevalence, the economic impact of eosinophilic esophagitis (EoE) is understudied. METHODS: We estimated the societal economic burden of EoE by using real-world data from Swedish health registers. RESULTS: Patients with EoE had 45% higher societal cost ($6,290 vs $4,349) compared with the general population, primarily driven by increased healthcare costs ($2,414 vs $1,022), which accounted for 72% of the excess societal cost in EoE. DISCUSSION: EoE is associated with a considerable economic burden to society. With the prevalence of EoE still rising, the economic burden of EoE is expected to continue to grow.

Risk of Kidney Failure in Patients With Inflammatory Bowel Disease Undergoing Colectomy: A Nationwide Cohort Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is frequently accompanied by kidney complications. Potential triggers or subpopulations at high-risk of kidney problems are not well-elucidated. We hypothesized that surgical interventions, specifically colectomy, might in part explain this risk. METHODS: This study was a nationwide Swedish cohort study comprising 82,051 individuals with biopsy-proven IBD diagnosed during 1965 to 2017, with follow-up until 2019. We investigated the association between incident colectomy (time-varying exposure) and future risk of acute kidney injury (AKI) and kidney failure (diagnosis of end-stage kidney disease or death due to chronic kidney disease) using Cox proportional hazard models. We also examined the impact of partial vs total colectomy and the presence/duration of a stoma. Covariates included demographics, education level, and selected comorbidities. RESULTS: Over a median follow-up of 14 years, 16,479 individuals underwent colectomy, and 2556 AKI and 1146 kidney failure events occurred. Colectomy was associated with an increased relative risk of both AKI (adjusted hazard ratio, 2.37; 95% confidence interval, 2.17-2.58) and kidney failure (adjusted hazard ratio, 1.54; 95% confidence interval, 1.34-1.76). Compared with pre-colectomy periods, undergoing total colectomy and colectomy with prolonged stoma showed higher risks of both kidney outcomes versus partial colectomy or colectomy with a temporary stoma, respectively. Subgroup analyses suggested higher risks in patients with ulcerative colitis. CONCLUSIONS: In people with IBD, rates of AKI and kidney failure are higher among those undergoing colectomy, particularly among those following total colectomy, or colectomy with a prolonged stoma. This study identifies a high-risk population that may benefit from established protocols for kidney function monitoring/surveillance and referral to nephrologist care.

Risk of heart failure in inflammatory bowel disease: a Swedish population-based study.

BACKGROUND AND AIMS: Dysregulation of inflammatory and immune responses has been implicated in the pathogenesis of heart failure (HF). But even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD. METHODS: In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 [n = 81,749, Crohn's disease (CD, n = 24,303), ulcerative colitis (UC, n = 45,709), and IBD-unclassified (IBD-U, n = 11,737)]. Each patient was matched with up to five general population reference individuals (n = 382,190) and IBD-free full siblings (n = 95,239) and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals (CI). RESULTS: There were 5,582 incident HF identified in IBD patients (incidence rate [IR]: 50.3/10,000 person-years) and 20,343 in reference individuals (IR: 37.9) during a median follow-up of 12.4 years. IBD patients had a higher risk of HF than reference individuals (aHR 1.19, 95% CI 1.15 to 1.23). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients until then. The increased risk was also observed across IBD subtypes: CD (IR: 46.9 vs. 34.4; aHR 1.28 [1.20 to 1.36]), UC (IR: 50.1 vs. 39.7; aHR 1.14 [1.09 to 1.19]), and IBD-U (IR: 60.9 vs. 39.0; aHR 1.28 [1.16 to 1.42]). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10 [1.03 to 1.19]). CONCLUSIONS: Patients with IBD had a moderately higher risk of developing HF for ≥20 years after IBD diagnosis than the general population.

Coeliac disease and type 2 diabetes risk: a nationwide matched cohort and Mendelian randomisation study.

AIMS/HYPOTHESIS: While the association between coeliac disease and type 1 diabetes is well documented, the association of coeliac disease with type 2 diabetes risk remains undetermined. We conducted a nationwide cohort and Mendelian randomisation analysis to investigate this link. METHODS: This nationwide matched cohort used data from the Swedish ESPRESSO cohort including 46,150 individuals with coeliac disease and 219,763 matched individuals in the comparator group selected from the general population, followed up from 1969 to 2021. Data from 9053 individuals with coeliac disease who underwent a second biopsy were used to examine the association between persistent villous atrophy and type 2 diabetes. Multivariable Cox regression was employed to estimate the associations. In Mendelian randomisation analysis, 37 independent genetic variants associated with clinically diagnosed coeliac disease at p<5×10-8 were used to proxy genetic liability to coeliac disease. Summary-level data for type 2 diabetes were obtained from the DIAGRAM consortium (80,154 cases) and the FinnGen study (42,593 cases). RESULTS: Over a median 15.7 years' follow-up, there were 6132 (13.3%) and 30,138 (13.7%) incident cases of type 2 diabetes in people with coeliac disease and comparator individuals, respectively. Those with coeliac disease were not at increased risk of incident type 2 diabetes with an HR of 1.00 (95% CI 0.97, 1.03) compared with comparator individuals. Persistent villous atrophy was not associated with an increased risk of type 2 diabetes compared with mucosal healing among participants with coeliac disease (HR 1.02, 95% CI 0.90, 1.16). Genetic liability to coeliac disease was not associated with type 2 diabetes in DIAGRAM (OR 1.01, 95% CI 0.99, 1.03) or in FinnGen (OR 1.01, 95% CI 0.99-1.04). CONCLUSIONS/INTERPRETATION: Coeliac disease was not associated with type 2 diabetes risk.

Association of celiac disease with eosinophilic esophagitis: Nationwide register-based cohort study with sibling analyses.

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.

Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort study.

Background: Roughly more than one in six adults worldwide suffer from psychiatric conditions. Sporadic studies have associated parental psychiatric disorders with autism spectrum disorder in offspring. Comprehensively examining the association between parental psychiatric disorders and offspring autism spectrum disorder is needed to guide health policies, and to inform etiologic studies. Methods: We included all children born in Sweden and Finland 1997-2016. Diagnoses were clinically ascertained from National Registers through 2017. We calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for autism spectrum disorder in offspring of fathers and mothers with psychiatric disorders, in both parents jointly and across co-occurring conditions. Findings: Among 2,505,842 children, 33,612 were diagnosed with autism spectrum disorder, of which 20% had a parent with psychiatric disorders. The risk of autism spectrum disorder was increased across all psychiatric disorders in fathers (Sweden: aHR = 2.02, 95% CI = 1.92-2.12; Finland: aHR = 1.63, 95% CI = 1.50-1.77), mothers (Sweden: aHR = 2.34, 95% CI = 2.24-2.43; Finland aHR = 2.12, 95% CI = 1.92-2.28), or both parents (Sweden: aHR = 3.76, 95% CI = 3.48-4.07; Finland aHR = 3.61, 95% CI = 3.20-4.07), compared to neither parents. Co-occurrence of parental psychiatric disorders further increased risk (e.g., Sweden: for one, two or ≥three different diagnostic categories compared to no diagnosis, in fathers aHR = 1.81, 2.07, 2.52; in mothers aHR = 2.05, 2.63, 3.57). Interpretation: Psychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Funding: Swedish-Research-Council-2021-0214.

Microscopic Colitis and Risk of Incident Psoriasis: A Nationwide Population-Based Matched Cohort Study.

Background: Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking. Objective: To examine the association between MC and psoriasis. Methods: In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021. Results: During a median follow-up of 9.2 years (interquartile range = 6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53-2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36-2.51). Conclusion: Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.

Celiac Disease-Related Conditions: Who to Test?

Celiac disease (CeD) is a chronic immune-mediated condition triggered by gluten consumption in genetically predisposed individuals. Approximately 1% of the general population is affected by the disorder. Disease presentation is heterogeneous and, despite growing awareness among physicians and the public, it continues to be underestimated. The most effective strategy for identifying undiagnosed CeD is proactive case finding through serologic testing in high-risk groups. We reviewed the most recent evidence on the association between CeD and more than 20 conditions. In light of this review, CeD screening is recommended in individuals with (1) autoimmune disease and accompanying symptoms suggestive of CeD; (2) diseases that may mimic CeD (eg, irritable bowel syndrome [IBS], inflammatory bowel disease [IBD], and microscopic colitis); and (3) among patients with conditions with a high CeD prevalence: first-degree relatives, idiopathic pancreatitis, unexplained liver enzyme abnormalities, autoimmune hepatitis, primary biliary cholangitis, hyposplenism or functional asplenia with severe bacterial infection, type 1 diabetes mellitus, Hashimoto's thyroiditis and Graves' disease, Sjögren's syndrome, dermatitis herpetiformis, recurrent aphthous syndrome and enamel defects, unexplained ataxia, peripheral neuropathy, delayed menarche or premature menopause, Down syndrome, Turner syndrome, Williams syndrome, chronic fatigue syndrome, IgA nephropathy, and IgA deficiency. CeD serology should be the initial step in the screening process. However, for patients with any of the aforementioned disorders who are undergoing upper endoscopy, biopsies should be performed to rule out CeD.

Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide Cohort Study.

BACKGROUND: There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD). Only a few previous reports include patients diagnosed during the last decade. AIM: To assess and compare the risk of ACS between patients with IBD and the general population. METHODS: In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year and area of residence with up to 10 general population comparators. The primary outcome was incident ACS. We used semi-parametric Cox proportional hazard models to estimate hazard ratios (HRs). RESULTS: We identified 76,517 patients with IBD (Crohn's disease [CD], N = 22,732; ulcerative colitis [UC], N = 42,194 and IBD-unclassified, N = 11,591) and 757,141 comparators. During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS compared with 19,598 (28.0/10,000 person-years) among comparators (HR 1.30; 95% confidence interval 1.24-1.35) after adjustments for confounding factors, and approximately one extra case of ACS in 100 IBD patients followed for 10 years. The highest HRs for ACS were in patients with elderly onset IBD (≥60 years) and among patients with CD or UC with extra-intestinal manifestations. No increased HRs were observed in patients diagnosed with IBD before the age of 40. CONCLUSION: In this contemporary cohort of patients with IBD, exposed to modern IBD care, there was an increased risk for ACS compared with individuals from the general population.

Validation of IgA nephropathy diagnosis in the Swedish Renal Registry.

AIM: The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis. METHODS: In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015-2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis. RESULTS: A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90-98%). Median age was 46 years (range: 18-85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m2. Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases. CONCLUSION: Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research.

Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. METHODS: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990-2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006-2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). RESULTS: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98-6.73) and 7.09 (95% CI, 6.48-7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81-1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78-1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72-0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70-0.81]) and CD (aFRR, 0.76 [95% CI, 0.70-0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73-0.98]). CONCLUSIONS: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD.

Association Between Celiac Disease and Irritable Bowel Syndrome: A Nationwide Cohort Study.

BACKGROUND & AIMS: The aim of this study was to determine the risk of irritable bowel syndrome (IBS) diagnosis in patients with celiac disease (CD) compared with general population comparators. METHODS: Using Swedish histopathology and register-based data, we identified 27,262 patients with CD diagnosed in 2002-2017 and 132,922 age- and sex-matched general population comparators. Diagnoses of IBS were obtained from nationwide inpatient and non-primary outpatient records. Cox regression estimated hazard ratios (aHRs) for IBS adjusted for education level and Charlson Comorbidity Index. To reduce potential surveillance bias our analyses considered incident IBS diagnosis ≥1 year after CD diagnosis. Using conditional logistic regression, secondary analyses were calculated to estimate odds ratios (ORs) for IBS diagnosis ≥1 year before CD diagnosis. RESULTS: During an average of 11.1 years of follow-up, 732 celiac patients (2.7%) were diagnosed with IBS vs 1131 matched general population comparators (0.9%). Overall (≥1-year of follow-up), the aHR for IBS was 3.11 (95% confidence interval [CI], 2.83-3.42), with aHR of 2.00 (95% CI, 1.63-2.45) after ≥10 years of follow-up. Compared with siblings (n = 32,010), celiac patients (n = 19,211) had ≥2-fold risk of later IBS (aHR, 2.42; 95% CI, 2.08-2.82). Compared with celiac patients with mucosal healing, those with persistent villus atrophy on follow-up biopsy were less likely to be diagnosed with IBS (aHR, 0.66; 95% CI, 0.46-0.95). CD was also associated with having an earlier IBS diagnosis (OR, 3.62; 95% CI, 3.03-4.34). CONCLUSIONS: In patients with CD, the risk of IBS is increased long before and after diagnosis. Clinicians should be aware of these long-term associations and their implications on patient management.