| 1. |
- Lebwohl, Benjamin, et al.
(författare)
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Psychiatric disorders in patients with a diagnosis of celiac disease during childhood from 1973 to 2016
- 2021
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:10, s. 2093-2101.e13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood.METHODS: We performed a nationwide study in Sweden using data from the ESPRESSO cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n=94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs).RESULTS: During a median follow-up time of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% Cl, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% Cl, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% Cl, 1.41-2.05). The risk increase persisted into adulthood (older than 18 years: HR, 1.11; 95% Cl, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease was also linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders were also more common prior to diagnosis of celiac disease (odds ratio, 1.56; 95% Cl, 1.39-1.76).CONCLUSIONS: Childhood celiac disease is associated with increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease.
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| 2. |
- Lebwohl, Benjamin, et al.
(författare)
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Cancer Risk in 47,241 Individuals with Celiac Disease : A Nationwide Cohort Study
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:2, s. e111-e131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Celiac disease (CD) is associated with increased mortality, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in CD diagnosis rates and access to gluten-free food. We performed a population-based study of the risk of cancer in CD.METHODS: We identified all patients in Sweden with CD as defined as duodenal villus atrophy, using the ESPRESSO cohort. Each patient was matched to ≤5 controls by age, sex, and county. We used stratified Cox proportional-hazards model, following patients from diagnosis until first cancer, or by December 31, 2016.RESULTS: Among 47,241 patients with CD, 30,080 (64%) were diagnosed since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in CD patients and controls, respectively. The overall risk of cancer was increased (hazard ratio[HR] 1.11; 95%CI 1.07-1.15), but was only significantly elevated in the first year after CD diagnosis (HR 2.47; 95%CI 2.22-2.74), and not subsequently (HR 1.01; 95%CI 0.97-1.05), though the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreas cancers persisted. The overall risk was highest in those diagnosed with CD after age 60 years (HR 1.22; 95%CI 1.16-1.29) and was not increased in those diagnosed before age 40. The cancer risk was similar among those diagnosed with CD before or after the year 2000.CONCLUSIONS: There is an increased risk of cancer in CD, even in recent years, but this risk increase is confined to those diagnosed with CD after age 40, and is primarily present within the first year of diagnosis.
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| 3. |
- Ludvigsson, Jonas F., et al.
(författare)
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Risk of Thyroid Cancer in a Nationwide Cohort of Patients with Biopsy-Verified Celiac Disease
- 2013
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 23:8, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- Background: In earlier studies based on selected populations, the relative risk for thyroid cancer in celiac disease has varied between 0.6 and 22.5. We aimed to test this relationship in a population-based setting. Methods: We collected small intestinal biopsy report data performed in 1969-2008 from all 28 Swedish pathology departments. 29,074 individuals with celiac disease (villous atrophy; Marsh histopathology stage III) were matched for sex, age, calendar year, and county to 144,440 reference individuals from the Swedish general population. Through Cox regression, we then estimated hazard ratios (HRs) and confidence intervals (CIs) for any thyroid cancer and papillary thyroid cancer (defined according to relevant pathology codes in the Swedish Cancer Register) in patients with celiac disease. Results: During follow-up, any thyroid cancer developed in seven patients with celiac disease (expected = 12) and papillary thyroid cancer developed in five patients (expected = 7). Celiac disease was not associated with an increased risk of any thyroid cancer (HR 0.6 [CI 0.3-1.3]) or of papillary thyroid cancer (HR 0.7 [CI 0.3-1.8]). All cases of thyroid cancer in celiac disease occurred in female patients. Risk estimates were similar before and after the year 2000 and independent of age at celiac diagnosis (<= 24 years vs. >= 25 years). Conclusions: We conclude that, in the Swedish population, there is no increased risk of thyroid cancer in patients with celiac disease. This differs from what has been reported in smaller studies in Italy and the United States.
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| 4. |
- Mårild, Karl, et al.
(författare)
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Costs and Use of Health Care in Patients With Celiac Disease : A Population-Based Longitudinal Study
- 2020
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Ingår i: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 115:8, s. 1253-1263
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Celiac disease (CD) affects 1% of the population. Its effect on healthcare cost, however, is barely understood. We estimated healthcare use and cost in CD, including their temporal relationship to diagnosis.METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 40,951 prevalent patients with CD (villous atrophy) as of January 1, 2015, and 15,086 incident patients with CD diagnosed in 2008-2015, including 2,663 who underwent a follow-up biopsy to document mucosal healing. Each patient was compared with age- and sex-matched general population comparators (n = 187,542). Using nationwide health registers, we retrieved data on all inpatient and nonprimary outpatient care, prescribed diets, and drugs.RESULTS: Compared with comparators, healthcare costs in 2015 were, on average, $1,075 (95% confidence interval, $864-1,278) higher in prevalent patients with CD aged <18 years, $715 ($632-803) in ages 18-64 years, and $1,010 ($799-1,230) in ages ≥65 years. Half of all costs were attributed to 5% of the prevalent patients. Annual healthcare costs were $391 higher 5 years before diagnosis and increased until 1 year after diagnosis; costs then declined but remained 75% higher than those of comparators 5 years postdiagnosis (annual difference = $1,044). Although hospitalizations, nonprimary outpatient visits, and medication use were all more common with CD, excess costs were largely unrelated to the prescription of gluten-free staples and follow-up visits for CD. Mucosal healing in CD did not reduce the healthcare costs.DISCUSSION: The use and costs of health care are increased in CD, not only before, but for years after diagnosis. Mucosal healing does not seem to lower the healthcare costs.
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| 5. |
- Emilsson, Louise, et al.
(författare)
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Cardiovascular disease in patients with coeliac disease : A systematic review and meta-analysis
- 2015
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 47:10, s. 847-852
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coeliac disease has been associated with an increased risk of cardiovascular disease in some studies, whereas other studies have shown no association. We performed a systematic review and meta-analysis of cardiovascular disease in celiac disease. Methods: Pubmed, Cinahl, EMBASE and Medline via Ovid were searched for relevant articles published until January 5, 2015. English-language articles on studies with more than 20 patients were included, and were quality rated using the GRADE risk of bias tool. We used random-effects models and assessed heterogeneity using the I-2 statistic. Results: Ten studies were relevant, reporting the risk of myocardial infarction, cardiovascular death and stroke in 33,128/32,903/32,466 coeliac disease patients respectively. Only one study examined celiac disease and a composite measure of cardiovascular disease and this study found a hazard ratio of 1.10 (95% CI 1.03-1.28). In a meta-analysis, we observed an increased risk of stroke (OR 1.11; 95% CI 1.02-1.20). The risks of myocardial infarction (OR 1.12; 95% CI 0.83-1.40) and cardiovascular death (OR 1.12; 95% CI 0.96-1.29) were similar but were estimated with less certainty. Heterogeneity was low for all outcomes except for myocardial infarction where it was moderate. Conclusion: Coeliac disease was associated with a modestly increased risk of cardiovascular disease, but the evidence base is limited.
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| 6. |
- Lebwohl, Benjamin, et al.
(författare)
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Mucosal healing and the risk of ischemic heart disease or atrial fibrillation in patients with celiac disease : a population-based study
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF.Methods: We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF.Results: Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were >= 60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73-1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73-1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74-1.30).Conclusions: In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.
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| 7. |
- Lebwohl, Benjamin, et al.
(författare)
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Season of birth in a nationwide cohort of coeliac disease patients
- 2013
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Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 98:1, s. 48-51
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective Genetic factors alone cannot explain the risk of developing coeliac disease (CD). Children born in summer months are likely to be weaned and introduced to gluten during winter when viral infections are more frequent. Earlier studies on birth season and CD are limited in sample size and results are contradictory. Method Case-control study. We used biopsy reports from all 28 Swedish pathology departments to identify individuals with CD, defined as small intestinal villous atrophy (n=29 096). The government agency Statistics Sweden then identified 144 522 controls matched for gender, age, calendar year and county. Through conditional logistic regression we examined the association between summer birth (March-August) and later CD diagnosis (outcome measure). Results Some 54.10% of individuals with CD versus 52.75% of controls were born in the summer months. Summer birth was hence associated with a small increased risk of later CD (OR 1.06; 95% CI 1.03 to 1.08; p<0.0001). Stratifying CD patients according to age at diagnosis, we found the highest OR in those diagnosed before age 2 years (OR 1.17; 95% CI 1.10 to 1.26), while summer birth was not associated with a CD diagnosis in later childhood (age 2-18 years: OR 1.02; 95% CI 0.97 to 1.08), but had a marginal effect on the risk of CD in adulthood (age >= 18 years: OR 1.04; 95% CI 1.01 to 1.07). Conclusions In this study, summer birth was associated with an increased risk of later CD, but the excess risk was small, and general infectious disease exposure early in life is unlikely to be a major cause of CD.
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| 8. |
- Thawani, Sujata, et al.
(författare)
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Type 1 Diabetes, Celiac Disease, and Neuropathy - A Nationwide Cohort Study
- 2017
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Ingår i: Journal of Clinical Neuromuscular Disease. - : Lippincott Williams & Wilkins. - 1522-0443 .- 1537-1611. ; 19:1, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both type 1 diabetes (T1D) and celiac disease (CD) have been linked to an increased risk of neuropathy. This study examined the risk of neuropathy in patients with T1D compared with patients with both T1D and CD.METHODS: In a nationwide population-based cohort, T1D was defined as having a diagnosis of diabetes between 1964 and 2009 recorded in the Swedish National Patient Register in individuals ≤30 years of age. CD was defined as having villous atrophy (Marsh histopathology stage III) on small intestinal biopsy. CD cases were identified through biopsies examined between 1969 and 2008 at any of Sweden's 28 pathology departments. Nine hundred fifty-eight patients had both T1D and CD and were matched for sex, age, and calendar period with 4590 controls who only had T1D. Through Cox regression analysis, with CD as the time-dependent covariate, we estimated the risk of neuropathy in T1D patients with CD.RESULTS: Fifty-four individuals with T1D and CD had later neuropathy (expected: n = 42). This corresponded to an adjusted hazard ratio of 1.27 (95% confidence interval = 0.95-1.71) compared with those who had T1D alone. The hazard ratio was statistically significant in the first 5 years with CD (1.67; 95% confidence interval = 1.13-2.47) but decreased to neutrality thereafter. Risk estimates were similar in men and women, and did not differ by age at CD onset.CONCLUSIONS: CD does not seem to influence the risk of neuropathy in individuals with T1D, although a small excess risk cannot be ruled out.
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| 9. |
- Alaedini, Armin, et al.
(författare)
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Borrelia infection and risk of celiac disease
- 2017
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.Methods: Biopsy reports from all of Sweden's pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease.Results: Twenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06-2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40-2.35), with the risk of disease being highest in the first year of follow-up.Conclusions: Only a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.
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| 10. |
- Axelrad, Jordan E., et al.
(författare)
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Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1311-1322
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case-control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC).METHODS: Using the Swedish National Patient Register, we identified 44,214 patients with IBD (26,450 with UC; 13,387 with CD; and 4377 with IBD-unclassified) from 2002 to 2014 and matched them with 436,507 individuals in the general population (control subjects). We then identified patients and control subjects with reported episodes of gastroenteritis (from 1964 to 2014) and type of pathogen associated. We collected medical and demographic data and used logistic regression to estimate odds ratios (ORs) for IBD associated with enteric infection.RESULTS: Of the patients with IBD, 3105 (7.0%) (1672 with UC, 1050 with CD, and 383 with IBD-unclassified) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR, 1.64; 1.57-1.71), bacterial gastrointestinal infection (aOR, 2.02; 1.82-2.24), parasitic gastrointestinal infection (aOR, 1.55; 1.03-2.33), and viral gastrointestinal infection (aOR, 1.55; 1.34-1.79). Patients with UC had higher odds of previous infection with Salmonella, Escherichia coli, Campylobacter, or Clostridium difficile compared to control subjects. Patients with CD had higher odds of previous infection with Salmonella, Campylobacter, Yersinia enterocolitica, C difficile, amoeba, or norovirus compared to control subjects. Increasing numbers of gastroenteritis episodes were associated with increased odds of IBD, and a previous episode of gastroenteritis remained associated with odds for IBD more than 10 years later (aOR, 1.26; 1.19-1.33).CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found previous episodes of gastroenteritis to increase odds of later development of IBD. Although we cannot formally exclude misclassification bias, enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals.
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