| 1. |
- Elfström, Peter, 1974-, et al.
(author)
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Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3
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Other publication (other academic/artistic)abstract
- 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.
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| 2. |
- Ludvigsson, Jonas F., et al.
(author)
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Effect of HLA DQ2, dietary exposure and coeliac disease on the development of antibody response to gliadin in children
- 2006
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 919-928
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study the effect of HLA DQ2, dietary history and development of coeliac disease (CD) on the induction of antibody response to wheat gliadin and cow's milk, beta-lactoglobulin between 1 and 2.5 years of age in children who developed CD and in healthy children. MATERIAL AND METHODS: Infants participating in a birth cohort study (the ABIS study) in Sweden were studied. Thirty-nine children developed CD (=cases), confirmed through biopsy, during follow-up until 2.5-5 years of age. A total of 181 healthy control children were matched for duration of exclusive breast-feeding, birth-weight, gender, maternal smoking and season of birth. IgG and IgA antigliadin and anti-beta-lactoglobulin antibodies were measured using enzyme immunoassay (EIA). The effects of HLA-risk genotypes, DQ2 and DQ8, on CD were also considered. RESULTS: Children who developed CD had higher IgG and IgA antigliadin and anti-beta-lactoglobulin antibody levels at 1 year of age than controls (all comparisons: p<0.001). Similar differences were seen between cases with as yet undiagnosed CD by 1 year of age and controls, and also when cases were compared with HLA-matched controls. Higher levels of IgG and IgA antibodies to beta-lactoglobulin (p=0.003; p=0.001), but not to gliadin, were found in treated cases versus controls at 2.5 years of age. HLA-DQ2-positive healthy children had lower levels of IgG and IgA antigliadin antibodies than HLA-DQ2 negative controls at 1 year of age (p=0.004; p=0.012). CONCLUSIONS: Enhanced humoral response emerging not only to gliadin, but also to other food antigens seems to be primarily associated with CD. Poor induction of antibody response to wheat gliadin in healthy children with the HLA-DQ2 risk molecule could at least partly explain the genetic predisposition to gluten intolerance and CD.
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| 3. |
- Elfström, Peter, 1974-, et al.
(author)
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Risk of primary adrenal insufficiency in patients with celiac disease
- 2007
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In: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3595-3598
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Elfström, Peter, 1974-, et al.
(author)
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Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease
- 2007
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In: Journal of Internal Medicine. - Oxford : Blackwell Publishing. - 0954-6820 .- 1365-2796. ; 262:5, s. 545-554
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Journal article (peer-reviewed)abstract
- 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
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| 5. |
- Ludvigsson, Jonas F., et al.
(author)
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Celiac disease and risk of liver disease : a general population-based study
- 2007
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In: Clinical Gastroenterology and Hepatology. - Amsterdam : Elsevier. - 1542-3565 .- 1542-7714. ; 5:1, s. 63-69
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Journal article (peer-reviewed)abstract
- 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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| 7. |
- Elfström, Peter, 1974-, et al.
(author)
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Risk of Thyroid Disease in Individuals with Celiac Disease
- 2008
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:10, s. 3915-3921
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Journal article (peer-reviewed)abstract
- 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.
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| 8. |
- Ludvigsson, Jonas F., et al.
(author)
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Coeliac disease in the father and risk of adverse pregnancy outcome : a population-based cohort study
- 2006
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:2, s. 178-185
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Journal article (peer-reviewed)abstract
- OBJECTIVE:The risk of adverse foetal outcomes was investigated in offspring to men with coeliac disease (CD) diagnosed prior to infant birth and in offspring to men who did not receive a diagnosis of CD until after the delivery.MATERIAL AND METHODS:A cohort study was based on national registry data restricted to women aged 15-44 years with singleton live-born infants, with linkage between the Swedish national birth registry (1973-2001) and the national inpatient registry (1964-2001). A total of 1059 offspring to men who had received a diagnosis of CD were included: 554 offspring to men diagnosed prior to birth and 505 offspring to men diagnosed after infant birth.RESULTS:Undiagnosed CD in the father was associated with an increased risk of caesarean section (adjusted odds ratio (AOR)=1.83; 95% confidence interval (CI) for AOR=1.13-2.95; p=0.014) but was otherwise not linked to adverse pregnancy outcome: (intrauterine growth retardation (OR=1.37; 95% CI=0.91-2.07), low birth-weight (OR=1.41; 95% CI=0.93-2.12), very low birth-weight (OR=1.21; 95% CI=0.39-3.77), preterm birth (OR=1.10; 95% CI=0.74-1.62), and very preterm (OR=0.62; 95% CI=0.09-4.40)). A paternal diagnosis of CD made before infant birth was not associated with adverse foetal outcome.CONCLUSIONS:CD in the father is not a risk factor for unfavourable foetal outcome. The increased risk for caesarean section in offspring to men with undiagnosed CD in this study may be due to multiple comparisons.
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| 9. |
- Ludvigsson, Jonas F., et al.
(author)
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Small-intestinal histopathology and mortality risk in celiac disease
- 2009
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:11, s. 1171-1178
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Journal article (peer-reviewed)abstract
- CONTEXT: Studies of mortality in celiac disease have not taken small-intestinal pathology into account. OBJECTIVE: To examine mortality in celiac disease according to small-intestinal histopathology. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage 1-2; n = 13,306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age- and sex-matched controls from the general population. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: There were 3049 deaths among patients with celiac disease, 2967 with inflammation, and 183 with latent celiac disease. We found an increased hazard ratio (HR) for death in celiac disease (HR, 1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years), inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years). The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7-7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk increase was also seen in children. Excluding the first year of follow-up, HRs decreased somewhat. CONCLUSION: Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.
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| 10. |
- Ludvigsson, Jonas F., et al.
(author)
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Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa
- 2009
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In: BMC Gastroenterology. - 1471-230X .- 1471-230X. ; 9, s. 57-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Antibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD. METHODS: The records of ten Swedish pathology departments were used to identify individuals with biopsies indicating normal duodenal/jejunal mucosa. Using the national personal identification number, these data were linked with CD serology data (antigliadin, antiendomysial and tissue transglutaminase antibodies); and we thereby identified 3,736 individuals with normal mucosa but positive CD serology. Two independent reviewers then manually reviewed their biopsy reports to estimate comorbidity. We also randomly selected 112 individuals for validation through patient chart review. RESULTS: The majority of the 3,736 individuals were females (62%). Children (0-15 years) made up 21.4%. The median number of biopsy specimen was 3. Our review of biopsy reports found that other gastrointestinal comorbidity was rare (inflammatory bowel disease: 0.4%; helicobacter pylori infection: 0.2%). Some 22% individuals selected for patient chart review had a relative with CD. The most common symptoms among these individuals were diarrhea (46%) and abdominal pain (45%), while 26% had anemia. Although 27% of the individuals selected for validation had been informed about gluten-free diet, only 13% were adhering to a gluten-free diet at the end of follow-up. CONCLUSION: Individuals with positive CD serology but normal mucosa often have CD-like symptoms and a family history of CD.
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