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  • 1. Elfstrom, Peter
    et al.
    Granath, Fredrik
    Smedby, Karin Ekstrom
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Askling, Johan
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease2011In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 103, no 5, p. 436-444Article in journal (Refereed)
    Abstract [en]

    Background Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown. Methods We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28 989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13 140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227 911 age-and sex-matched reference individuals. Results Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100 000 person-years, 83.4 per 100 000 person-years, and 28.0 per 100 000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas. Conclusion The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.

  • 2.
    Elfström, Peter
    Örebro University, School of Health and Medical Sciences.
    Associated disorders in celiac disease2009Doctoral 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.

    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
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    2007 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 5, no 1, p. 63-69Article 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
    Keywords
    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: 2017-12-14Bibliographically 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, p. 545-554Article 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
    Keywords
    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: 2017-12-14Bibliographically 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, p. 3595-3598Article 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
    Keywords
    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: 2017-12-14Bibliographically 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, p. 3915-3921Article 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.

    Keywords
    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: 2017-12-14Bibliographically 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
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    (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.

    Keywords
    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: 2017-10-18Bibliographically approved
  • 3.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Granath, Fredrik
    Ekström Smedby, Karin
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Askling, Johan
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences.
    Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3Manuscript (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.

  • 4.
    Elfström, Peter
    et al.
    Department of Neonatology, Astrid Lindgren Children's Hospital-Danderyd, Karolinska University Hospital, Stockholm, Sweden.
    Granath, Fredrik
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ye, Weimin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Low Risk of Gastrointestinal Cancer Among Patients With Celiac Disease, Inflammation, or Latent Celiac Disease2012In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 10, no 1, p. 30-36Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Celiac disease has been associated with gastrointestinal (GI) cancers in small studies; risks have not been estimated from large populations or based on histopathology analyses.

    METHODS: We examined the risk of GI cancers by using data from cohorts of patients with celiac disease (villous atrophy, Marsh score of 3; n = 28,882) or inflammation (Marsh score of 1-2; n = 12,860); biopsy samples were evaluated at 28 pathology centers. A third cohort included 3705 individuals with latent celiac disease (normal mucosa, but positive serology results). Data were compared with those from an age-and sex-matched population.

    RESULTS: Of patients with celiac disease, 372 developed incident GI cancers; 347 patients with inflammation and 38 with latent celiac disease developed GI cancers. In the first year after diagnosis and initial biopsy, celiac disease was associated with 5.95-fold increase in risk of incident GI cancer (95% confidence interval [ CI], 4.64-7.64); the hazard ratio [HR] for inflammation was 9.13 (95% CI, 7.19-11.6) and for latent celiac disease was 8.10 (95% CI, 4.69-14.0). After the first year, patients were at no significant increase in risk for GI cancers; the HR for celiac disease was 1.07 (95% CI, 0.93-1.23), for inflammation it was 1.16 (95% CI, 0.98-1.37), and for latent celiac disease it was 0.96 (95% CI, 0.56-1.66). The absolute risk for any GI cancer in patients with celiac disease was 101/100,000 person-years, with an excess risk of 2/100,000 person-years.

    CONCLUSIONS: Although celiac disease, inflammation, and latent disease all increase risk for GI cancers in the first year after diagnosis, there is no increase in risk thereafter.

  • 5.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hamsten, Anders
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 5, p. 545-554Article in journal (Refereed)
    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

  • 6.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Kämpe, Olle
    Uppsala Universitet.
    Ekbom, Anders
    Karolinska Institutet.
    Ludvigsson, Jonas F.
    Risk of primary adrenal insufficiency in patients with celiac disease2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 9, p. 3595-3598Article in journal (Refereed)
    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.

  • 7.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Kämpe, Olle
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Risk of Thyroid Disease in Individuals with Celiac Disease2008In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, no 10, p. 3915-3921Article in journal (Refereed)
    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.

  • 8.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Värmland County, Sweden; Department of Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Bert
    Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Elfström, Peter
    Department of Neonatology, Astrid Lindgren Children's Hospital Danderyd, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Green, Peter H. R.
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Sweden; the Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease2012In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 3, article id e001594Article in journal (Refereed)
    Abstract [en]

    Background: Dilated cardiomyopathy (DCM) is a rare disease of largely unknown origin. Previous studies have suggested an increased prevalence of celiac disease (CD) in patients with DCM. These studies, however, were based on a maximum of 5 patients with both CD and DCM. In the present large Swedish population-based cohort study, we examined the risk of idiopathic DCM in patients with CD determined by small-intestinal histopathology.

    Methods and Results: From 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy, Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments in Sweden. These individuals were compared with 144 429 reference individuals matched for age, sex, calendar year, and county. Data on DCM were obtained through the National Patient Register and confirmed by patient charts and echocardiography data. During follow-up, 17 patients with CD and 52 reference individuals developed idiopathic DCM. Thus, patients with CD were at an increased risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to 3.00), although the risk estimate failed to attain statistical significance (P=0.052).

    Conclusion: This nationwide study found a moderately but not statistically significantly increased risk of idiopathic DCM in patients with biopsy-verified CD.

  • 9. Ludvigsson, Jonas F.
    et al.
    Elfström, Peter
    Örebro University, School of Health and Medical Sciences.
    Broomé, Ulrika
    Ekbom, Anders
    Karolinska Institutet.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Celiac disease and risk of liver disease: a general population-based study2007In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 5, no 1, p. 63-69Article in journal (Refereed)
    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.

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