oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Associated disorders in celiac disease
Örebro University, School of Health and Medical Sciences.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Celiac disease (CD) is an autoimmune disorder that affects genetically susceptible individuals and is induced by dietary gluten. Treatment consists of a lifelong gluten-free diet. CD is common and affects about 1% of the general population. The classic symptoms include diarrhea and malabsorption, but many patients have only mild symptoms or no symptoms at all. The proportion of individuals presenting with atypical symptoms or discovered only when investigating an associated condition of CD is increasing.

Aims: The aim of this thesis was to investigate the risk of possible associated disorders through Swedish population-based registers. The objective was to gain more information on the consequences of having CD and to identify high risk groups where screening may be considered.

Materials and methods: We used the Swedish hospital discharge register to examine the risk of liver disease, autoimmune heart disease, Addison’s disease and thyroid disorders in a cohort of about 14,000 individuals with CD and an age and sex matched reference population of 70,000 individuals. In the last study we used all regional pathology registers and the cancer registry to examine the risk of hematopoietic cancer, including lymphoma in three different cohorts: I) 28,810 individuals with CD; II) 12,681 individuals with small intestinal mucosal inflammation but without villous atrophy; and III) 3552 individuals with latent CD (a positive serology test for CD with a normal small intestinal biopsy).

Results: CD is statistically significantly associated with an increased risk of liver disease, Addison’s disease, thyroid disease and lymphoma. We also found an increased risk of lymphoma in individuals with small intestinal mucosal inflammation. There was no statistically significant association between autoimmune heart disease or leukemia and CD. Latent CD was not associated with any hematopoietic cancers.

Conclusion: This thesis found a positive association between CD and a number of autoimmune and inflammatory disorders. Clinicians need to have a high awareness of this association and to test for these conditions when symptoms appear.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2009. , 83 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 27
Keyword [en]
Addison, autoimmune, biopsy, celiac, child, cohort study, cancer, heart, liver, lymphoma, thyroid
National Category
Pediatrics Medical and Health Sciences
Research subject
Pediatrics; Epidemiology; Medicine
Identifiers
URN: urn:nbn:se:oru:diva-5223ISBN: 978-91-7668-649-2 (print)OAI: oai:DiVA.org:oru-5223DiVA: diva2:158229
Public defence
2009-02-27, Wilandersalen, Universitetssjukhuset Örebro, Örebro, 10:00 (English)
Opponent
Supervisors
Available from: 2009-02-06 Created: 2009-01-30 Last updated: 2011-05-02Bibliographically approved
List of papers
1. Celiac disease and risk of liver disease: a general population-based study
Open this publication in new window or tab >>Celiac disease and risk of liver disease: a general population-based study
Show others...
2007 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, Vol. 5, no 1, 63-69 p.Article in journal (Refereed) Published
Abstract [en]

Background & aims: Celiac disease (CD) is an important cause of hypertransaminasemia. CD may also be associated with severe forms of liver disease. We investigated the risk of liver disease in 13,818 patients with CD (1964-2003) and 66,584 age- and sex-matched reference individuals from a general population cohort.Methods: We used Cox regression to estimate hazard ratios (HRs) for later liver disease and conditional logistic regression to estimate the risk of CD in individuals with liver disease prior to study entry.Results: CD was associated with an increased risk of acute hepatitis (HR = 5.21; 95% CI = 1.88-14.40; P = .001), chronic hepatitis (HR = 5.84; 95% CI = 2.89-11.79; P < .001), primary sclerosing cholangitis (PSC)(HR = 4.46; 95% CI = 2.50-7.98; P < .001), fatty liver (HR = 6.06; 95% CI = 1.35-27.16; P = .018), liver failure (HR = 3.30; 95% CI = 2.22-4.88; P < .001), liver cirrhosis or liver fibrosis (HR = 2.23; 95% CI = 1.34-3.72; P < .001) and primary biliary cirrhosis (HR = 10.16; 95% CI = 2.61-39.49; P < .001). There was no increased risk of liver transplantation (HR = 1.07; 95% CI = 0.12-9.62; P = .954). Adjustment for socioeconomic index or diabetes mellitus had no notable effect on the risk estimates.Prior liver disease was associated with a statistically significant 4-6 fold increased risk of later CD.Conclusion: This study suggests that individuals with CD are at increased risk of both prior and subsequent liver disease.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2007
Keyword
autoimmune; celiac; cirrhosis; cohort study; liver and primary sclerosing cholangitis
National Category
Gastroenterology and Hepatology Pediatrics Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:oru:diva-5212 (URN)10.1016/j.cgh.2006.09.034 (DOI)
Note
Part of thesis: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-5223Available from: 2009-01-30 Created: 2009-01-30 Last updated: 2016-12-08Bibliographically approved
2. Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease
Open this publication in new window or tab >>Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease
Show others...
2007 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 5, 545-554 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: We investigated the risk of myocarditis, cardiomyopathy, and pericarditis in patients with celiac disease (CD) from a general population cohort.Subjects and methods: Through the Swedish national registers we identified 9363 children and 4969 adults with a diagnosis of CD (1964–2003). These individuals were matched with upto five reference individuals for age, sex, calendar year and county (n = 69 851). Cox regression estimated hazard ratios (HRs) for later heart disease. Main outcome measures: Myocarditis, cardiomyopathy (any or dilated), and pericarditis defined according torelevant international classification of disease codes in the Swedish national inpatient register.Results: Celiac disease diagnosed in childhood was not associated with later myocarditis (HR = 0.2; 95% CI = 0.0–1.5), cardiomyopathy of any type (HR = 0.8; 95% CI = 0.2–3.7), or pericarditis (HR = 0.4; 95% CI = 0.1–1.9). Restricting our analyses to adulthood CD and heart disease diagnosed from 1987 and onwards in departments of cardiology ⁄ internal medicine, we found no association between CD and later myocarditis (HR = 2.1; 95% CI = 0.4–11.7), dilated cardiomyopathy (HR = 1.7; 95% CI = 0.4– 6.5) or pericarditis (HR = 1.5; 95% CI = 0.5–4.0).Conclusion: This study found no association between CD, later myocarditis, cardiomyopathy or pericarditis

Place, publisher, year, edition, pages
Oxford: Blackwell Publishing, 2007
Keyword
Autoimmunity, cardiology, coeliac disease, pericarditis.
National Category
Pediatrics Gastroenterology and Hepatology Cardiac and Cardiovascular Systems Medical and Health Sciences
Research subject
Pediatrics; Epidemiology
Identifiers
urn:nbn:se:oru:diva-5217 (URN)10.1111/j.1365-2796.2007.01843.x (DOI)
Note
Part of thesis: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-5223Available from: 2009-01-30 Created: 2009-01-30 Last updated: 2016-12-08Bibliographically approved
3. Risk of primary adrenal insufficiency in patients with celiac disease
Open this publication in new window or tab >>Risk of primary adrenal insufficiency in patients with celiac disease
Show others...
2007 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 9, 3595-3598 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.

Place, publisher, year, edition, pages
Chevy Chase, Md.: Endocrine Society, 2007
Keyword
adrenocortical insufficiency, autoimmune; celiac; cohort study; Addison disease
National Category
Pediatrics Gastroenterology and Hepatology Endocrinology and Diabetes Medical and Health Sciences
Research subject
Pediatrics; Epidemiology
Identifiers
urn:nbn:se:oru:diva-5218 (URN)17595243 (PubMedID)
Note
Part of thesis: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-5223Available from: 2009-01-30 Created: 2009-01-30 Last updated: 2016-12-08Bibliographically approved
4. Risk of Thyroid Disease in Individuals with Celiac Disease
Open this publication in new window or tab >>Risk of Thyroid Disease in Individuals with Celiac Disease
Show others...
2008 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, no 10, 3915-3921 p.Article in journal (Refereed) Published
Abstract [en]

Background: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort.Methods: A total of 14,021 individuals with celiac disease (1964–2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up ofmorethan 1 yr and withnothyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease.Results: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR)_4.4;95% confidence interval (CI) _ 3.4 –5.6; P _ 0.001], thyroiditis (HR _ 3.6; 95% CI _1.9–6.7; P _ 0.001) and hyperthyroidism (HR_2.9;95%CI_2.0–4.2; P_0.001). The highest risk estimates were found in children (hypothyroidism, HR _ 6.0 and 95% CI _ 3.4 –10.6; thyroiditis, HR _ 4.7 and 95% CI _ 2.1–10.5; hyperthyroidism, HR _ 4.8 and 95% CI _ 2.5–9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI_2.7– 4.4; P_0.001), 3.3 for thyroiditis(95%CI_1.5–7.7; P_0.001), and 3.1 for hyperthyroidism (95% CI _ 2.0–4.8; P _ 0.001).Conclusion: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.

Keyword
autoimmune; celiac; coeliac; child; cohort study; hypothyroidism; hyperthyroidism; thyroiditis.
National Category
Pediatrics Gastroenterology and Hepatology Endocrinology and Diabetes
Research subject
Pediatrics; Epidemiology
Identifiers
urn:nbn:se:oru:diva-5219 (URN)10.1210/jc.2008-0798 (DOI)
Note
Part of thesis: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-5223Available from: 2009-01-30 Created: 2009-01-30 Last updated: 2016-12-08Bibliographically approved
5. Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3
Open this publication in new window or tab >>Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3
Show others...
(English)Manuscript (Other academic)
Abstract [en]

Background: Celiac disease (CD) is associated with an increased risk of lymphoma, but it is unknown if borderline mucosal damage and latent CD are risk factors for lymphoma.Methods: We examined the risk of hematopoietic cancer in a nationwide population–based cohort of 28,800 individuals with biopsy-verified CD (villous atrophy, Marsh 3), 12,663 individuals with small intestinal inflammation (Marsh 1+2), and 3,551 with latent CD (positive antiendomysial, tissue transglutaminase or antigliadin test but normal mucosa on biopsy). The study participants were identified through all pathology departments (n=28) in Sweden and were biopsied in 1969-2006 (median: 1998). Cox regression estimated the hazard ratio (HR) for hematopoietic malignancies.Results: While biopsy-verified CD and intestinal inflammation were both statistically significantly associated with lymphoma (CD: HR = 3.18; 95% CI = 2.63-3.83; inflammation: 1.66; 1.28-2.17), latent CD was not (1.04; 0.44-2.43). CD was associated with both non-Hodgkin’s (NHL) and Hodgkin’s lymphoma (HL) (4.81; 3.81-6.07 and 4.39; 2.59-7.45 respectively). Risk estimates for NHL and HL were lower in inflammation (1.65; 1.15-2.38 and 1.48; 0.60-3.62 respectively) and latent CD (1.79; 0.74-4.34 and 1.08; 0.13-9.00 respectively). No increased risk of lymphoma was seen in children with a small intestinal biopsy. This study found no association between leukemia and small intestinal pathology.Conclusion: CD is associated with an increased risk of lymphoma. This risk increase was also seen in individuals with small intestinal inflammation. Latent CD is not associated with lymphoma of any kind, and positive CD serology alone cannot be used to predict future risk of lymphoma.

Keyword
autoimmune, biopsy, celiac, coeliac, child, cohort study, cancer, hematopoietic, leukemia, lymphoma, pathology
National Category
Pediatrics Gastroenterology and Hepatology Medical and Health Sciences
Research subject
Pediatrics; Epidemiology; Medicine
Identifiers
urn:nbn:se:oru:diva-5222 (URN)
Available from: 2009-01-30 Created: 2009-01-30 Last updated: 2016-12-08Bibliographically approved

Open Access in DiVA

cover(374 kB)94 downloads
File information
File name COVER01.pdfFile size 374 kBChecksum SHA-512
fbeb55ab2e25c14e3f20a20d6e8453bc320c317712a21c8d89e4cf12538266470dd5ef79ccbfcdcccffcc07fccb8300fdc4635489be840b69c105a141b497e10
Type coverMimetype application/pdf
kappa(1931 kB)927 downloads
File information
File name FULLTEXT02.pdfFile size 1931 kBChecksum SHA-512
fc184fe22749435aae79fca66cb718d6ccb066c9399da0f779f50c51504172047dcca1d4eeedb6ef7d2e63a70a1691b93bd0ff916f9261485e0eb4227c3f0edd
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Elfström, Peter
By organisation
School of Health and Medical Sciences
PediatricsMedical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 927 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 388 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf