1. |
- Lebwohl, Benjamin, et al.
(author)
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Risk of Skin Disorders in Patients with Celiac Disease : A Population-Based Cohort Study
- 2021
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In: The Journal of American Academy of Dermatology. - : Elsevier. - 0190-9622 .- 1097-6787. ; 85:6, s. 1456-1464
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Although dermatitis herpetiformis is closely associated with celiac disease (CD), data on the relationship between CD and other dermatologic disorders have been mixed. We aimed to quantify the risk of skin disorders in patients after CD diagnosis in a population-based setting.METHODS: Using data from all 28 pathology departments in Sweden 1969-2016, we identified patients with CD. Each patient was matched by age, sex, calendar year, and geographic region to up to 5 population controls. We calculated the risk of any skin disease and specific skin diseases using Cox proportional hazards.RESULTS: We identified 43,300 patients with CD and 198,532 matched controls. After a median follow-up time of 11.4 years, the incidences of skin disease in CD patients and controls were 22.6 and 14.8 per 1000 person-years respectively (HR=1.55; 95%CI 1.51-1.58). Increased risks were present for eczema (HR=1.67; 95%CI 1.56-1.79), psoriasis (HR=1.55; 95%CI 1.43-1.68), urticaria (HR=1.52; 95% CI 1.42-1.64), vitiligo (HR=1.90; 95%CI 1.52-2.39), acne (HR=1.39; 95%CI 1.29-1.50), and alopecia areata (HR=1.78; 95%CI 1.43-2.20).CONCLUSIONS: Compared to the general population, patients with CD are at increased risk of multiple common skin disorders, a risk that persists in the long-term.
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2. |
- Alaedini, Armin, et al.
(author)
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Borrelia infection and risk of celiac disease
- 2017
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In: BMC Medicine. - : BioMed Central. - 1741-7015. ; 15
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Journal article (peer-reviewed)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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3. |
- Axelrad, Jordan E., et al.
(author)
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Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study
- 2019
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1311-1322
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Journal article (peer-reviewed)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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4. |
- Bergman, David, et al.
(author)
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Two waves of coeliac disease incidence in Sweden : a nationwide population-based cohort study from 1990 to 2015
- 2022
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 71:6, s. 1088-1094
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Journal article (peer-reviewed)abstract
- Objectives: To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation.Design: Nationwide population-based cohort study 1990-2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum.Results: We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002-2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males). Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa.Conclusions: In Sweden, the incidence of CD increased until 2002-2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.
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5. |
- Bozorg, Soran Rabin, 1993-, et al.
(author)
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Work loss before and after diagnosis in patients with celiac disease
- 2021
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In: European Journal of Immunology. - : John Wiley & Sons. - 0014-2980 .- 1521-4141. ; 51:Suppl. 1, s. 286-286
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Journal article (other academic/artistic)abstract
- 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.
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6. |
- Bozorg, Soran R., 1993-, et al.
(author)
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Work loss in patients with celiac disease : A population-based longitudinal study
- 2022
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:5, s. 1068-1076.e6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Celiac disease (CD) affects around 1% of the population worldwide. Data on work disability in celiac patients remain scarce. We estimated work loss in celiac patients including its temporal relationship to diagnosis.METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 16,005 working-aged patients with prevalent CD (villus atrophy) as of January 1, 2015, and 4,936 incident patients diagnosed with CD in 2008-2015. Each patient was matched to up to 5 general-population comparators. Using nationwide social insurance registers, we retrieved prospectively-recorded data on compensation for sick leave and disability leave to assess work loss in patients and comparators.RESULTS: In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators (mean difference: 14.7, 95%CI: 13.2-16.2), corresponding to a relative increase of 49%. More than half of the work loss (60.1%) in celiac patients was derived from a small subgroup (7%) while 75.4% had no work loss. 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. No difference in work loss was observed between patients with or without mucosal healing at follow-up.CONCLUSIONS: Celiac patients lost more work days than comparators before their diagnosis, and this loss increased after diagnosis. Identifying patients with an increased risk of work loss may serve as a target to mitigate work disability, and thereby reduce work loss, in CD.
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7. |
- Dixit, Rohit, et al.
(author)
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Celiac Disease Is Diagnosed Less Frequently in Young Adult Males
- 2014
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In: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 59:7, s. 1509-1512
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Journal article (peer-reviewed)abstract
- The female predominance in celiac disease is difficult to explain because population-based screening studies reveal similar rates for celiac disease-specific autoantibodies in males and females. The aim of this study was to explore the role of age and gender in the presentation of celiac disease. The frequency of presentation according to age, gender and mode of presentation was determined by analysis of a prospectively maintained database of children and adults seen at a tertiary medical center. Of 1,682 patients (68 % female) aged 3 months to 86 years who were diagnosed with celiac disease, age at diagnosis in females peaked at 40-45 years, whereas the age at diagnosis for males had two peaks: 10-15 and 35-40 years. A significantly lower percentage of males in early adulthood were diagnosed compared with males in all other age groups (P < 0.0001). The young and elderly had a more even gender distribution. Based on our analysis, males are diagnosed with celiac disease less frequently than females, especially in early adulthood. There should be more emphasis on the diagnosis of celiac disease among young adult males.
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8. |
- Doyle, John B., et al.
(author)
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Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease : A Population-Based Cohort Study
- 2022
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In: American Journal of Gastroenterology. - : Wolters Kluwer. - 0002-9270 .- 1572-0241. ; 117:12, s. 1971-1981
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort.METHODS: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged ≥18.RESULTS: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged >= 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years.DISCUSSION: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.
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9. |
- Emilsson, Louise, et al.
(author)
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Cardiovascular disease in patients with coeliac disease : A systematic review and meta-analysis
- 2015
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In: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 47:10, s. 847-852
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Journal article (peer-reviewed)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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10. |
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11. |
- Emilsson, Louise, et al.
(author)
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Mucosal healing and the risk of serious infections in patients with celiac disease
- 2018
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In: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 6:1, s. 55-62
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Journal article (peer-reviewed)abstract
- Background: Patients with celiac disease (CD) are at increased risk of certain infections, but it is unknown if mucosal healing influences this risk.Methods: We collected data on 29,096 individuals with CD (equal to villous atrophy) through Sweden's 28 pathology departments undergoing biopsy 1969-2008. Through the Swedish Patient Register we obtained information on any infection and specifically sepsis, streptococcal infection, influenza, Clostridium difficile, herpes zoster and pneumococcal infection up until December 2009. We used Cox regression to calculate hazard ratios (HRs) for the risk of future diagnosis of infection according to mucosal healing on follow-up biopsy (persistent villous atrophy vs mucosal healing).Results: Of 5598 CD individuals with no record of any infections before follow-up biopsy, 45% had persistent villous atrophy, 619 (24%) of them had a later infection, compared to 579 (19%) in those with mucosal healing (p<0.01); the yearly incidence was 2.1% in both groups. Adjusting for age, sex, calendar period, time between biopsies and education, persistent villous atrophy was however not associated with later infection overall (HR=0.99; 95% CI=0.88-1.11) or with any of the specific infections.Conclusions: In CD, mucosal healing does not influence the risk of serious infection requiring hospital-based medical attention.
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12. |
- Emilsson, Louise, 1982-, et al.
(author)
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Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease
- 2020
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In: Gastroenterology. - : American Gastroenterology Association Institute. - 0016-5085 .- 1528-0012. ; 159:5, s. 1686-1694
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: The incidence of small bowel cancers is increasing. Associations have been made between celiac disease (CD) and small bowel cancers, but there have been no detailed studies of large cohorts.METHODS: Through the nationwide Epidemiology Strengthened by Histopathology Reports in Sweden cohort study, we retrieved data from Sweden's 28 pathology departments on all individuals who received a diagnosis of CD from 1965 through 2017. Individuals with CD, defined as duodenal or jejunal villous atrophy (stage 3 Marsh score), were matched with as many as 5 randomly selected reference individuals from the general population. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids.RESULTS: During a median follow-up of 11 years, we identified 48,119 individuals with CD (patients) and 239,249 reference individuals. Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%), 7 patients received a diagnosis of carcinoids vs 31 reference individuals, and 48 patients received a diagnosis of adenomas vs 50 reference individuals. Corresponding HRs were small bowel adenocarcinoma 3.05 (95% confidence interval [CI], 1.86-4.99), carcinoids 0.59 (95% CI, 0.16-2.10), and adenomas 5.73 (95% CI, 3.70-8.88). HRs were independent of sex and age. Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years. There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02-1.61), although the HR failed to attain statistical significance.CONCLUSIONS: In an analysis of a nationwide pathology database in Sweden, we found the absolute risk of small bowel adenocarcinoma is low in individuals with CD. However, risks of small bowel adenocarcinoma and adenomas (but not carcinoids) are significantly increased in people with CD compared to people without this disease.
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13. |
- Glimberg, Ida, et al.
(author)
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The prevalence of celiac disease in women with infertility - A systematic review with meta-analysis
- 2021
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In: Reproductive Medicine and Biology. - : Wiley. - 1445-5781 .- 1447-0578. ; 20:2, s. 224-233
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Research review (peer-reviewed)abstract
- Purpose: To determine the prevalence of celiac disease in infertile women.Methods: A systematic search of four databases was conducted up until February 6, 2020. The search terms "c(o)eliac disease", "gluten", "vill(o)us atrophy", "infertility" and "subfertility" yielded 1142 unique hits. Articles in other languages than English, conference abstracts, letters, and publications where relevant information was missing were excluded. In our main analysis, celiac disease had to be verified by duodenal biopsy. The titles and abstracts, and the full-text articles were independently reviewed by two researchers. A fixed-effect model was used to calculate the weighted prevalence.Results: Based on 11 studies (1617 women), the pooled prevalence of biopsy-confirmed celiac disease was 0.7% (95% CI = 0.2%-1.2%) in women with any infertility. Restricting our study population to women with unexplained infertility, the pooled prevalence of biopsy-confirmed celiac disease was 0.6% (95% CI = 0.0%-1.6%). When including studies where celiac disease had been defined per serology (20 studies; 5158 women), the pooled prevalence of celiac disease was 1.1% (95% CI = 0.6%-1.6%) in women with any infertility.Conclusion: Our results indicate that celiac disease is not more common in infertile women than in the general population. Celiac screening in infertile women may have low yield.
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14. |
- Haggård, Linnea, et al.
(author)
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High prevalence of celiac disease in autoimmune hepatitis : Systematic review and meta-analysis
- 2021
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In: Liver international (Print). - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 41:11, s. 2693-2702
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Research review (peer-reviewed)abstract
- BACKGROUND: Previous studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore aimed to examine the prevalence of CD in individuals with AIH.METHODS: Two professional librarians searched PubMed, EMBASE, Cochrane and Web of Science Core Collection up until 7 February 2020. The search terms included 'celiac disease', 'celiac', 'transglutaminases', 'gluten', 'gliadin', 'EMA', 'TTG' and 'villous' combined with 'autoimmune', 'hepatitis', 'ANA', 'SMA' and 'LKM'. This search yielded 2419 unique publications. A systematic review based on the PRISMA guidelines resulted in 31 articles eligible for full text review. Fifteen articles were deemed relevant, with 8 being included in our main analysis. A fixed-effect inverse variance-weighted model was used, and heterogeneity was calculated.RESULTS: Our main analysis included 567 individuals with AIH from eight studies, where biopsy-verified CD (equivalent to Marsh III) was seen in 23 individuals (4.1%). The pooled prevalence of CD in AIH was 3.5% (95% CI = 1.6%-5.3%) (heterogeneity: P = .874; I2 = 0.0%), which is clearly higher than the 1% CD seen in most general populations. When also including studies where CD had been diagnosed through positive serology without biopsy (15 studies: n = 1817 individuals with AIH), the pooled prevalence of CD was 2.9% (95% CI = 2.1%-3.8%) (heterogeneity: P < .001; I2 = 66.8%).CONCLUSION: Our results demonstrate a higher prevalence of CD in individuals with AIH compared to the general population. CD screening may be considered in patients with AIH.
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15. |
- King, James A., et al.
(author)
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Incidence of Celiac Disease Is Increasing Over Time : A Systematic Review and Meta-analysis
- 2020
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In: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 115:4, s. 507-525
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Research review (peer-reviewed)abstract
- OBJECTIVES: To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends.METHODS: MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time.RESULTS: Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I-2= 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I-2= 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I-2= 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I-2= 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I-2= 79.6%) per year over the past several decades.DISCUSSION: Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.
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16. |
- Kuja-Halkola, Ralf, et al.
(author)
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Birth weight, sex, and celiac disease : a nationwide twin study
- 2017
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In: Clinical Epidemiology. - : DOVE Medical Press Ltd.. - 1179-1349. ; 9, s. 567-577
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Journal article (peer-reviewed)abstract
- Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.Materials and methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD-non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97-1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11-2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.
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17. |
- Kuja-Halkola, Ralf, et al.
(author)
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Heritability of non-HLA genetics in coeliac disease : a population-based study in 107 000 twins
- 2016
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In: Gut. - London, United Kingdom : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 65:11, s. 1793-1798
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Journal article (peer-reviewed)abstract
- Background and objective: Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA.Design: In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions.Results: We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and non-shared (15%) environmental factors explaining the remaining variability of CD.Conclusions: CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.
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18. |
- Kurien, Matthew, et al.
(author)
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Persistent mucosal damage and the risk of epilepsy in people with celiac disease
- 2018
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In: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 25:3, s. 592-e38
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Journal article (peer-reviewed)abstract
- BACKGROUND: Celiac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of CD patients have persistent villous atrophy (VA) on follow-up biopsy. This study's objective was to determine whether persistent VA on follow-up biopsy affects long-term epilepsy risk and epilepsy-related hospital emergency admissions.METHODS: Nationwide Cohort Study. We identified all people in Sweden with histological evidence of CD who underwent a follow-up small intestinal biopsy (1969-2008). We compared those with persistent VA to those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant ICD codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures.RESULTS: Of 7590 people with CD who had a follow-up biopsy, VA was present in 43%. The presence of persistent VA was significantly associated with a reduced risk of developing newly-diagnosed epilepsy (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.38-0.98). On stratified analysis this effect was primarily amongst males (HR 0.35; 95 CI 0.15-0.80). Among the 58 CD patients with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (HR 0.37; 95%CI 0.09-1.09).CONCLUSIONS: In a population-based study of CD individuals, persisting VA on follow up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy-related hospital admissions. Mechanisms as to why persistent VA confers this benefit requires further exploration. This article is protected by copyright. All rights reserved.
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19. |
- Laszkowska, Monika, et al.
(author)
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Nationwide population-based cohort study of celiac disease and risk of Ehlers-Danlos syndrome and joint hypermobility syndrome
- 2016
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In: Digestive and Liver Disease. - : Elsevier. - 1590-8658 .- 1878-3562. ; 48:9, s. 1030-1034
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Journal article (peer-reviewed)abstract
- Background: Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS). Aims: This study examines the risks of EDS/JHS in patients with CD. Methods: This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969-2008 (n = 28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD (n = 16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression. Results: There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95% CI = 1.07-2.07). The HR for EDS was 2.43 (95% CI = 1.20-4.91) and for JHS 1.34 (95% CI = 0.93-1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio = 2.29; 95% CI = 1.21-4.34). Conclusions: Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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20. |
- Laszkowska, Monika, et al.
(author)
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Socioeconomic vs Health-related Factors Associated With Google Searches for Gluten-Free Diet
- 2018
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In: Clinical Gastroenterology and Hepatology. - : Saunders Elsevier. - 1542-3565 .- 1542-7714. ; 16:2, s. 295-297
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Research review (peer-reviewed)abstract
- In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs.
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21. |
- Lebwohl, Benjamin, et al.
(author)
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Association Between Celiac Disease and Mortality Risk in a Swedish Population
- 2020
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In: Journal of the American Medical Association (JAMA). - : American Medical Association. - 0098-7484 .- 1538-3598. ; 323:13, s. 1277-1285
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Journal article (peer-reviewed)abstract
- Question: Is celiac disease associated with increased mortality?Findings: In this population-based cohort study of 49 & x202f;829 patients in Sweden with celiac disease followed up for a median of 12.5 years, the mortality rate compared with general population controls was 9.7 vs 8.6 deaths per 1000 person-years, a difference that was statistically significant.Meaning: In a Swedish population, celiac disease was associated with a small but statistically significant increased mortality risk.Importance: Celiac disease may be associated with a modest but persistent increased long-term mortality risk. It is uncertain whether this risk has changed in the era of wider diagnosis rates, less severe clinical disease, and more widespread availability of gluten-free food.Objective: To evaluate the association between celiac disease and mortality risk in a population-based cohort in Sweden.Design, Setting, and Participants: All individuals in Sweden with celiac disease diagnosed between 1969 and 2017 were identified through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort. Participants (n = 49 & x202f;829) were observed starting on the day of the biopsy. The final date of follow-up was December 31, 2017.Exposures: Celiac disease was defined by the presence of small intestinal villus atrophy on histopathology specimens during the years 1969-2017 from Sweden's 28 pathology departments. Each individual was matched with as many as 5 control participants in the general population by age, sex, county, and calendar period.Main Outcomes and Measures: The primary outcome was all-cause mortality, and the secondary outcome was cause-specific mortality. Patients with celiac disease were compared with controls using stratified Cox proportional modeling, stratifying by year of diagnosis.Results: There were 49 & x202f;829 patients with celiac disease, including 24% who were diagnosed between the years 2010 and 2017. The mean (SD) age at diagnosis was 32.2 (25.2) years and 62.4% were women. During a median follow-up time of 12.5 years, 13.2% (n = 6596) died. Compared with controls (n = 246 & x202f;426), overall mortality was increased in those with celiac disease (9.7 vs 8.6 deaths per 1000 person-years; absolute difference, 1.2 per 1000 person-years; hazard ratio [HR], 1.21 [95% CI, 1.17-1.25]). The relative increase in mortality risk was present in all age groups and was greatest in those diagnosed in the age range of 18 to 39 years (1.9 vs 1.1 per 1000 person-years; HR, 1.69 [95% CI, 1.47-1.94]; P values for heterogeneity comparing 18-39 years with 40-59 years and with >= 60 years were both <.001). Individuals with celiac disease were at increased risk of death from cardiovascular disease (3.5 vs 3.4 per 1000 person-years; HR, 1.08 [95% CI, 1.02-1.13]), cancer (2.7 vs 2.2 per 1000 person-years; HR, 1.29 [95% CI, 1.22-1.36]), and respiratory disease (0.6 vs 0.5 per 1000 person-years; HR, 1.21 [95% CI, 1.08-1.37]). When compared with controls, the overall mortality risk was greatest in the first year after diagnosis (15.3 vs 6.5 per 1000 person-years; HR, 2.34 [95% CI, 2.14-2.55]) but persisted beyond 10 years after diagnosis (10.5 vs 10.1 per 1000 person-years; HR, 1.15 [95% CI, 1.10-1.20]). The mortality risk was likewise present for patients diagnosed during the years 2010-2017 (7.5 vs 5.5 per 1000 person-years; HR, 1.35 [95% CI, 1.21-1.51]).Conclusions and Relevance: In a Swedish population studied between 1969 and 2017, a diagnosis of celiac disease compared with the general population was associated with a small but statistically significant increased mortality risk. This population epidemiology study used Swedish histopathology registry data to estimate mortality risk in patients with vs without celiac disease.
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22. |
- Lebwohl, Benjamin, et al.
(author)
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Cancer Risk in 47,241 Individuals with Celiac Disease : A Nationwide Cohort Study
- 2022
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:2, s. e111-e131
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Journal article (peer-reviewed)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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23. |
- Lebwohl, Benjamin, et al.
(author)
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Celiac disease and non-celiac gluten sensitivity
- 2015
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In: BMJ-BRITISH MEDICAL JOURNAL. - : B M J Group. - 1756-1833. ; 351
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Research review (peer-reviewed)abstract
- Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.
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24. |
- Lebwohl, Benjamin, et al.
(author)
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Decreased Risk of Celiac Disease in Patients With Helicobacter pylori Colonization
- 2013
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 178:12, s. 1721-1730
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Journal article (peer-reviewed)abstract
- The prevalence of celiac disease (CD) has increased in recent decades without a clear explanation. The hygiene hypothesis theorizes that decreased exposure to bacterial antigens may trigger autoimmunity. We aimed to determine whether Helicobacter pylori infection and CD were associated among patients undergoing upper gastrointestinal endoscopy. We performed a cross-sectional study of patients who underwent esophagogastroduodenoscopy with submission of gastric and duodenal biopsies to Miraca Life Sciences, Inc. (Irving, Texas), a US commercial pathology laboratory, during a 4.5-year period (January 2008June 2012). We compared the prevalence of H. pylori in CD patients with that in persons without CD. We performed multiple logistic regression analysis, adjusting odds ratios for patient age, gender, and racial, ethnic, and socioeconomic factors. Among 136,179 patients, a total of 2,689 (2.0) had CD. H. pylori prevalence was significantly lower in patients with CD (4.4) than in those without CD (8.8; P 0.0001). After adjustment for the above covariates, this inverse relationship remained strong (adjusted odds ratio (OR) 0.48, 95 confidence interval (CI): 0.40, 0.58). The relationships were similar in men (unadjusted OR 0.51, 95 CI: 0.38, 0.69) and women (unadjusted OR 0.46, 95 CI: 0.36, 0.58) and in all age groups. We conclude that H. pylori presence and CD are inversely associated, a relationship that persists after adjustment for socioeconomic factors. Future studies should address whether H. pylori modulates immune responses to ingested gluten.
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25. |
- Lebwohl, Benjamin, et al.
(author)
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Isotretinoin Use and Celiac Disease : A Population-Based Cross-Sectional Study
- 2014
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In: American Journal of Clinical Dermatology. - : Springer. - 1175-0561 .- 1179-1888. ; 15:6, s. 537-542
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Journal article (peer-reviewed)abstract
- Background and aim: Isotretinoin, a vitamin A analogue, can promote a pro-inflammatory milieu in the small intestine in response to dietary antigens. We hypothesized that oral isotretinoin exposure would increase the risk of celiac disease (CD).Methods: We contacted all 28 pathology departments in Sweden, and through biopsy reports identified 26,739 individuals with CD. We then compared the prevalence of ever using oral isotretinoin to the prevalence in 134,277 matched controls through conditional logistic regression. Data on isotretinoin exposure were obtained from the national Swedish Prescribed Drug Registry. As the only indication for isotretinoin use in Sweden is acne, we also examined its relationship to CD. Data on acne were obtained from the Swedish Patient Registry.Results: Ninety-three individuals with CD (0.35 %) and 378 matched controls (0.28 %) had a prescription of isotretinoin. This corresponded to an odds ratio (OR) of 1.22 [95 % confidence interval (CI) 0.97-1.54]. Risk estimates were similar in men and women, and when we restricted our data to individuals diagnosed after the start of the Prescribed Drug Registry. Restricting our analyses to individuals diagnosed aged 12-45 years did not influence the risk estimates (OR 1.38, 95 % CI 0.97-1.97). Meanwhile, having a diagnosis of acne was positively associated with CD (OR 1.34, 95 % CI 1.20-1.51).Conclusions: This study found no association between isotretinoin use and CD, but a small excess risk of CD in patients with a diagnosis of acne.
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