| 1. |
- Ludvigsson, Jonas F., et al.
(author)
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Risk of Thyroid Cancer in a Nationwide Cohort of Patients with Biopsy-Verified Celiac Disease
- 2013
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In: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 23:8, s. 971-976
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Journal article (peer-reviewed)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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| 2. |
- Lebwohl, Benjamin, et al.
(author)
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Season of birth in a nationwide cohort of coeliac disease patients
- 2013
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In: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 98:1, s. 48-51
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Journal article (peer-reviewed)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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| 3. |
- Ludvigsson, Jonas F., 1969-, et al.
(author)
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A large nationwide population-based case-control study of the association between intussusception and later celiac disease
- 2013
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In: BMC Gastroenterology. - : BioMed Central. - 1471-230X. ; 13, s. 89-
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Journal article (peer-reviewed)abstract
- Background: Case reports and case series studies suggest a positive association between intussusception and celiac disease (CD). Methods: We contacted Sweden's 28 pathology departments and obtained data on 29,096 patients with biopsy-verified CD (equal to Marsh stage 3) through biopsy reports. Patients with CD were matched for age, sex, calendar period and county of residence with up to five reference individuals from the general population (n = 144,522). Cases of intussusception were identified from nationwide inpatient, hospital-based outpatient and day-surgery data from the Swedish Patient Register. Odds ratios (ORs) for future CD in patients with intussusception were estimated using conditional logistic regression. Results: 34 (0.12%) individuals with CD had a diagnosis of intussusception vs. 143 (0.10%) reference individuals, suggesting that intussusception was not a risk factor for later CD (OR = 1.17; 95% confidence interval (CI) = 0.82-1.67). The OR for CD in patients with at least two records of intussusception was 0.40 (95% CI = 0.06-2.99). In contrast, a post-hoc analysis showed that CD was associated with a statistically significantly increased risk of intussusception after CD diagnosis (hazard ratio = 1.95; 95% CI = 1.01-3.77); however, this analysis was based on only 12 cases with both CD and intussusception. Conclusion: We found no association between intussusception and future CD; and a mostly modest increased risk of intussusception after a diagnosis of CD.
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| 4. |
- Ludvigsson, Jonas F., et al.
(author)
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Use of computerized algorithm to identify individuals in need of testing for celiac disease
- 2013
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In: JAMIA Journal of the American Medical Informatics Association. - : Oxford University Press (OUP). - 1067-5027 .- 1527-974X. ; 20:E2, s. E306-E310
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Journal article (peer-reviewed)abstract
- Background and aim Celiac disease (CD) is a lifelong immune-mediated disease with excess mortality. Early diagnosis is important to minimize disease symptoms, complications, and consumption of healthcare resources. Most patients remain undiagnosed. We developed two electronic medical record (EMR)-based algorithms to identify patients at high risk of CD and in need of CD screening. Methods (I) Using natural language processing (NLP), we searched EMRs for 16 free text (and related) terms in 216 CD patients and 280 controls. (II) EMRs were also searched for ICD9 (International Classification of Disease) codes suggesting an increased risk of CD in 202 patients with CD and 524 controls. For each approach, we determined the optimal number of hits to be assigned as CD cases. To assess performance of these algorithms, sensitivity and specificity were calculated. Results Using two hits as the cut-off, the NLP algorithm identified 72.9% of all celiac patients (sensitivity), and ruled out CD in 89.9% of the controls (specificity). In a representative US population of individuals without a prior celiac diagnosis (assuming that 0.6% had undiagnosed CD), this NLP algorithm could identify a group of individuals where 4.2% would have CD (positive predictive value). ICD9 code search using three hits as the cut-off had a sensitivity of 17.1% and a specificity of 88.5% (positive predictive value was 0.9%). Discussion and conclusions This study shows that computerized EMR-based algorithms can help identify patients at high risk of CD. NLP-based techniques demonstrate higher sensitivity and positive predictive values than algorithms based on ICD9 code searches.
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| 5. |
- 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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| 6. |
- Bledsoe, Adam C., et al.
(author)
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Mortality and cancer in eosinophilic gastrointestinal disorders distal to the esophagus : nationwide cohort study 1990-2017
- 2022
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In: Journal of gastroenterology. - : Springer. - 0944-1174 .- 1435-5922. ; 57, s. 735-747
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Journal article (peer-reviewed)abstract
- Background: Eosinophilic gastrointestinal disorders (EGIDs) include inflammatory conditions with enteric infiltration of eosinophils and resulting symptoms. This study aims to examine a population-based sample of patients for prevalence, mortality, and cancer risk in EGIDs distal to the esophagus.Methods: Nationwide, population-based cohort study. EGID was identified through relevant biopsy codes from Sweden's all 28 pathology departments through the ESPRESSO cohort. Individuals with EGID were then matched to general population reference individuals with similar age and sex. Study participants were linked to Swedish healthcare registers. Through Cox regression, we calculated adjusted hazard ratios (aHRs) adjusting for sex, age, county, calendar period, and education.Results: In total, 2429 patients (56% female) were found to have EGID distal to the esophagus, representing a prevalence of about 1/4800 in the Swedish population. Mean age was 44 years with 11% children at the time of diagnosis. Mortality was increased 17% in patients with EGIDs compared to reference individuals (aHR = 1.17; 95%CI = 1.04-1.33). Excess mortality was seen in gastric and small bowel eosinophilic disease, but not colonic disease (aHR = 1.81; 95%CI = 1.32-2.48, aHR = 1.50; 95%CI = 1.18-1.89, and aHR = 0.99; 95%CI = 0.85-1.16, respectively). Cause specific mortality was driven by cancer-related death (aHR = 1.33; 95%CI = 1.05-1.69). However, this study failed to show an increase in incident cancers (aHR = 1.14; 95%CI = 0.96-1.35). Comparison of EGID individuals with their siblings yielded similar aHRs.Conclusions: This study found an increased risk of death in patients with EGIDs distal to the esophagus, with cancer death driving the increase. Proximal gut disease seems to confer the greatest risk. There was no increase in incident cancers.
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| 7. |
- Emilsson, Louise, et al.
(author)
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Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease
- 2015
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In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 13:7, s. 1271-1277.e2
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. METHODS: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. RESULTS: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P =.11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. CONCLUSIONS: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.
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| 8. |
- 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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| 9. |
- Lebwohl, Benjamin, et al.
(author)
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Risk of Severe Covid-19 in Patients with Celiac Disease : A Population-Based Cohort Study
- 2021
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In: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 121-130
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Journal article (peer-reviewed)abstract
- Background: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19.Methods: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969-2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome).Results: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80-1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59-1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46-2.02).Conclusion: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.
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| 10. |
- Li, Marcella, et al.
(author)
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A Report on the International Transglutaminase Autoantibody Workshop for Celiac Disease
- 2009
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 104:1, s. 154-163
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Measurement of transglutaminase autoantibodies (TGAA) is considered to be the most efficient single serologic test for celiac disease (CD) by the American Gastroenterological Association Institute. We hypothesized that a large international collaborative effort toward improving and standardizing TGAA measurement is both feasible and necessary. The primary aim of this workshop is to compare TGAA assays among various research and clinical laboratories and examine assay concordance and improve (and eventually standardize) the TGAA assay. METHODS: A total of 20 laboratories (5 commercial laboratories, 15 research and clinical laboratories) participated that included enzyme-linked immunosorbent assay (ELISA) and radiobinding assays. A total of 150 serum samples were distributed to each laboratory, with each laboratory receiving an equal aliquot that was coded and blinded, composed of 100 healthy control sera and 50 CD sera. RESULTS: Laboratory sensitivity ranged from 69% to 93% and specificity ranged from 96% to 100%. By receiver operator characteristic analysis, the area under the curve (C index) ranged from 0.9488 to 0.9904. When analyzing for linear correlation, r-squared was as high as 0.8882 but as low as 0.4244 for the celiac samples between different laboratories performing ELISA. CONCLUSIONS: This transglutaminase autoantibody workshop allows for larger-scale international participation for the purposes of improving and eventually standardizing the TGAA assay with subsequent workshops.
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