Celiac Disease In Individuals Research Articles

Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk.

Celiac Disease (CeD) is an autoimmune disorder triggered by gluten intake in genetically susceptible individuals. Highest risk individuals are homozygous for the Human Leucocyte Antigen (HLA) DQ2.5 haplotype or DQ2.5/DQ2.2 heterozygous. Both the HLA-DQ2-positive high genetic risk individuals and those that have developed the disease have altered intestinal microbiota, but it remains unclear whether these alterations are a cause or a consequence of CeD. To investigate a potential bidirectional causality between gut microbiota (GM) and CeD in HLA-DQ2 high genetic risk individuals. We performed a bidirectional Two-Sample Mendelian Randomization (2SMR) test using summary statistics from the largest publicly available Genome-Wide Association Study (GWAS) of GM and the summary statistics of the Immunochip CeD study of those individuals with the HLA-DQ2 high-risk haplotype. To test whether changes in GM composition were causally linked to CeD, GM data were used as exposure and CeD data as outcome; to test for reverse causation, the exposure and outcome datasets were inverted. We identified several bacteria from Ruminococcaceae and Lachnospiraceae families of the Firmicutes phylum as potentially causal in both directions. In addition, our results suggest that changes in the abundance of Veillonellaceae family might be causal in the development of CeD, while alterations in Pasteurellaceae family might be a consequence of the disease itself. Our results suggest that the relationship between GM and HLA-DQ2 high risk individuals is highly complex and bidirectional.

Celiac Disease: Updates on Pathology and Differential Diagnosis.

Celiac disease is a gluten-triggered immune-mediated disorder, characterized by inflammation of the enteric mucosa following lymphocytic infiltration and eventually resulting in villous blunting. There have been many developments in refining diagnostic laboratory tests for celiac disease in the last decade. Biopsy-sparing diagnostic guidelines have been proposed and validated in a few recent prospective studies. However, despite these developments, histologic evaluation of duodenal mucosa remains one of the most essential diagnostic tools as it helps in the diagnosis of celiac disease in individuals who do not fulfill the biopsy-sparing diagnostic criteria and in those not responding to a gluten-free diet. Histologic evaluation also allows for the assessment of mucosal recovery after treatment and in the identification of concurrent intestinal diseases. Therefore, pathologists should be familiar with the histologic spectrum of celiac disease and need to be aware of other disorders with similar symptoms and histopathology that may mimic celiac disease. This review aims to provide pathologists with updates on celiac laboratory testing, biopsy-sparing diagnostic criteria, histopathology, complications, and differential diagnoses of celiac disease.

Extraintestinal Manifestations of Celiac Disease: Early Detection for Better Long-Term Outcomes.

Population-based screening studies have shown celiac disease to be one of the most common chronic gastrointestinal diseases. Nevertheless, because of the diverse clinical presentation, the great majority of patients remain unrecognized. Particularly difficult to identify are the multifaceted extraintestinal symptoms that may appear at variable ages. Although the pathogenesis and long-term outcome of these manifestations are still poorly established, there is some evidence that unrecognized celiac disease predisposes to severe complications if not diagnosed and prevented with an early-initiated gluten-free diet. Therefore, it is of utmost importance that physicians of different disciplines learn to recognize celiac disease in individuals with non-gastrointestinal symptoms. In the future, more studies are needed to clarify the factors affecting development and prognosis of the extraintestinal manifestations.

Incidence and Risk of Celiac Disease in Individuals with Type 1 Diabetes over the Lifespan—A Population-Based Cohort Study Using the Health Improvement Network Database

Objective: Individuals with type 1 diabetes (T1D) are at increased risk for celiac disease (CD), though the incidence for those diagnosed with T1D beyond childhood is unknown. We used survival analysis to investigate the incidence and risk factors for diagnosis of CD over time in a population-based cohort of children and adults with T1D. Methods: Retrospective cohort study using The Health Improvement Network (THIN), a primary care electronic medical records database of >13 million people in the United Kingdom. Subjects were 1-35 years old at T1D diagnosis; subjects with type 2 diabetes or prevalent CD were excluded. We used Cox proportional hazards regression to identify factors associated with diagnosis of CD during follow-up. Risk factors assessed included age at T1D, sex, year of T1D diagnosis, and time-varying covariates of thyroid disease and adrenal insufficiency. Results: Subjects (n=11,537; 43% female) had a median follow-up time of 6.8 years (IQR 2.5-14.1). CD was diagnosed in 234 (2%), with median time to diagnosis of 2.9 years (IQR 1.2-7.8); 37% were diagnosed > 5 years after T1D. Incidence (per 10,000 person-years) was greater in females than males (26.9 [95% CI 22.4-31.9] vs. 16.4 [95% CI 13.4-19.9]) and in subjects <10 years at T1D diagnosis (50.1 [95% CI 41.4-60.2] vs. 13.3 [95% CI 11.0-15.9]). In multivariable Cox regression, the hazard of CD was higher with younger age (HR 0.88 per year of age at T1D diagnosis, 95% CI 0.80-0.96, p=0.006), in females (HR 1.50, 95% CI 1.16-1.94, p=0.002), and with more recent year of diagnosis (HR 1.09, 95% CI 1.07-1.12, p < 0.001). Conclusions: A significant proportion of CD cases were diagnosed more than 5 years after T1D diagnosis, the time frame currently recommended for screening. A more personalized approach to CD screening, accounting for the greater risk for younger-onset and female patients with T1D, may be warranted to minimize over-testing while limiting missed diagnoses. Disclosure M. Vajravelu: None. D. De Leon: Employee; Spouse/Partner; Merck & Co., Inc.. Research Support; Self; Zealand Pharma A/S. Consultant; Self; XOMA Corporation, ProSciento. Research Support; Self; Biomarin Corporation. D.R. Weber: None. R. Keren: None. M.R. Denburg: Research Support; Self; Mallinckrodt Pharmaceuticals. R. Verma: None.

Gluten-Free Rome: Celiac disease in the bioarchaeological record

Celiac disease, an autoimmune disorder triggered by consumption of the gluten protein, is theorized to have originated alongside the domestication of wheat during the European Agricultural Revolution, ca. 8 000 BCE (Freeman 2013). Human conditions that primarily affect soft tissue, like celiac disease, do not leave tangible evidence on the skeleton and therefore it is difficult to prove their presence. However, recent analyses have employed a suite of macroscopic, molecular, and chemical techniques to establish that a Roman Imperial (100–300 CE) individual from Cosa, Italy, likely suffered from celiac disease. This paper analyzes the works of these researchers and argues that this case study exemplifies modern bioarchaeology, which frequently requires an arsenal of methods beyond visual observation. Using similar syntheses of techniques bioarchaeologists can possibly identify celiac disease in individuals predating 100 CE, recreating the origins of celiac disease as well as tackling other previously ‘impossible’ research questions in this field.

Celiac Crisis: A Rare Presentation of Celiac Disease in Adults

Background: Celiac Disease is an immune-mediated enteropathy resulting from an inappropriate and exaggerated response to dietary gluten [1, 2]. Celiac Crisis is an un-common, life-threatening condition resulting from acute severe diarrheal illness, severe metabolic disturbances, and malabsorption that is usually found in children, with only 22 cases reported in adults [3]. Here we report a case of celiac crisis in a middle aged male with characteristic endoscopic and pathological findings. Case Report: A 58-year-old male with previous history of left facial crush injury necessitating several reconstructive surgeries in 2012 presented with profuse, watery, foul-smelling diarrhea of 2 months duration with episodic fatigue, melena, and 20 kg weight loss. Since his accident in 2012 he had intermittent episodes of loose stools that got significantly worse within 2 months. He had also been diagnosed with Clotridium difficle colitis and received 14 days of oral antibiotics one month prior to his presentation. Physical exam revealed pallor and cachexia. Laboratory findings showed hemoglobin of 4.7 g/dL, INR greater than 10 (without anticoagulation), albumin 1.7 g/dL, potassium 2.9 mmol/L, undetectable levels of fat soluble vitamins, and negative stool studies. Esophagogastroduodenoscopy revealed diffuse granular mucosa in the duodenum with fissuring and scalloping appearance [Fig 1]. Pathologic examination showed severe villous atrophy and hypoplasia (March IV) with increased intra-epithelial lymphocytes [Fig 2]. IgA anti-tissue transglutaminase antibodies titers were >200 U/mL (normal, 0-19 U/mL). He was diagnosed with celiac disease presenting with celiac crisis and was started on a gluten-free diet with vitamin supplementations, following which he made a full recovery.Figure 1Figure 2Discussion: Celiac crisis has been described in association with or following surgery, pregnancy, immunosuppressive therapy, and infection. The probable triggering factor in our patient was clostridium difficle infection. However, another association can also be made between the patient's head trauma and triggering of celiac disease. This link was investigated by a Swedish study, which found a very small excess risk for future celiac disease in individuals with an earlier head trauma [4].Figure 3

Screening for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Still a Worthwhile Exercise

Screening for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Still a Worthwhile Exercise

Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes

In the past decade, a number of population-based studies have examined the prevalence of coeliac disease in individuals with type 1 diabetes but prevalences have differed considerably. To examine the prevalence of coeliac disease in individuals with type 1 diabetes. A systematic review of English-language articles published in PubMed Medline between 2000 and May 2014. Search terms included 'celiac disease' or 'coeliac disease' and 'diabetes mellitus'. Studies were selected with at least 100 individuals with type 1 diabetes being screened for coeliac disease where the coeliac diagnosis was later confirmed through small intestinal biopsy. Data synthesis used random-effects inverse variance-weighted models, and metaregression was used to examine heterogeneity in subgroups. A pooled analysis, based on 26,605 patients with type 1 diabetes, found a prevalence of biopsy-confirmed coeliac disease of 6.0% (95% CI = 5.0-6.9%). Heterogeneity was large (I(2) = 93.2%). The prevalence was lower in adults with type 1 diabetes (2.7%), and in mixed populations with both children and adults with type 1 diabetes (4.7%) than in children (6.2%) with type 1 diabetes (P < 0.001). Additional subgroup analyses could not explain the large variation in coeliac disease prevalence between studies. More than one in twenty patients with type 1 diabetes have biopsy-verified coeliac disease. This prevalence is high enough to motivate screening for coeliac disease among patients with type 1 diabetes.

Barriers impeding serologic screening for celiac disease in clinically high-prevalence populations

BackgroundCeliac disease is present in ~1% of the general population in the United States and Europe. Despite the availability of inexpensive serologic screening tests, ~85% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis of symptomatic individuals with celiac disease that ranges from ~5.8-11 years. This delay is often attributed to the use of a case-based approach for detection rather than general population screening for celiac disease, and deficiencies at the level of health care professionals. This study aimed to assess if patient-centered barriers have a role in impeding serologic screening for celiac disease in individuals from populations that are clinically at an increased risk for celiac disease.Methods119 adults meeting study inclusion criteria for being at a higher risk for celiac disease were recruited from the general population. Participants completed a survey/questionnaire at the William K. Warren Medical Research Center for Celiac Disease that addressed demographic information, celiac disease related symptoms (gastrointestinal and extraintestinal), family history, co-morbid diseases and conditions associated with celiac disease, and patient-centered barriers to screening for celiac disease. All participants underwent serologic screening for celiac disease using the IgA tissue transglutaminase antibody (IgA tTG) and, if positive, testing for IgA anti-endomysial antibody (IgA EMA) as a confirmatory test.ResultsTwo barriers to serologic testing were significant across the participant pool. These were participants not knowing they were at risk for celiac disease before learning of the study, and participants not knowing where to get tested for celiac disease. Among participants with incomes less than $25,000/year and those less than the median age, not having a doctor to order the test was a significant barrier, and this strongly correlated with not having health insurance. Symptoms and co-morbid conditions were similar among those whose IgA tTG were negative and those who tested positive.ConclusionThere are significant patient-centered barriers that impede serologic screening and contribute to the delayed detection and diagnosis of celiac disease. These barriers may be lessened by greater education of the public and health care professionals about celiac disease symptoms, risk factors, and serologic testing.

Prevalence and clinical features of celiac disease in patients with hepatitis B virus infection in Southern Brazil

Celiac disease is an autoimmune disorder that involves gluten intolerance and can be triggered by environmental factors including hepatitis B virus (HBV) infection. This study aimed to describe the prevalence of celiac disease in individuals with HBV infection and to describe the clinical and laboratory characteristics of celiac disease associated with HBV. This cross-sectional study included 50 hepatitis B patients tested for IgA anti-endomysial antibodies (EMAs) and tissue anti-transglutaminase (TTG) between August 2011 and September 2012. Fifty patients were included with a mean age of 46.0 ± 12.6 (46.0) years; 46% were female and 13% were HBeAg+. Six patients had positive serology for celiac disease, four were EMA+, and five were TTG+. When individuals with positive serology for celiac disease were compared to those with negative serology, they demonstrated a higher prevalence of abdominal pain (100% vs. 33.3%, p = 0.008), lower median creatinine (0.7 mg/dL vs. 0.9 mg/dL, p = 0.007) and lower mean albumin (3.6 ± 0.4 g/L vs. 3.9 ± 0.3g/L, p = 0.022). All individuals with positive serology for celiac disease underwent upper digestive endoscopy, and three of the patients exhibited a macroscopic pattern suggestive of celiac disease. Histologically, five patients demonstrated an intra-epithelial lymphocytic infiltrate level > 30%, and four patients showed villous atrophy associated with crypt hyperplasia on duodenal biopsy. An increased prevalence of celiac disease was observed among hepatitis B patients. These patients were symptomatic and had significant laboratory abnormalities. These results indicate that active screening for celiac disease among HBV-infected adults is warranted.

Oxidative modification of a proline-rich gliadin peptide

Prolamins are proline-rich proteins occurring in cereal grains. Prolamins of wheat, barley and rye, or gluten protein, can cause coeliac disease in individuals not tolerating gluten. Degrading harmful prolamins can reduce their toxicity. A model peptide sequenced in α-gliadin, 33-mer (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), was chosen for our study. The metal-catalysed oxidation of 33-mer was studied, instead of enzymatic hydrolysis. Peptide 33-mer was treated in several oxidative systems. Iron-catalysed hydrogen peroxide-induced oxidation showed the greatest modification of 33-mer. Carbonyl groups and dityrosine cross-links were readily formed. At best, the immunological activity of 33-mer was reduced to 18% of its initial level after 24h of oxidation. Oxidative treatment can be further applied for the modification of cereal prolamin proteins, since it appears to be a potential alternative for reduction of coeliac immunological activities in gluten proteins.

Association Between Celiac Disease and Iron Deficiency in Caucasians, but Not Non-Caucasians

Celiac disease is an increasingly recognized disorder in Caucasian populations of European origin. Little is known about its prevalence in non-Caucasians. Although it is thought to be a cause of iron-deficiency anemia, little is known about the extent to which celiac disease contributes to iron deficiency in Caucasians, and especially non-Caucasians. We analyzed samples collected from participants in the Hemochromatosis and Iron Overload Screening study to identify individuals with iron deficiency and to assess the frequency of celiac disease. We analyzed serum samples from white men (≥25 y) and women (≥50 y) who participated in the Hemochromatosis and Iron Overload Screening study; cases were defined as individuals with iron deficiency (serum ferritin level, ≤12 μg/L) and controls were those without (serum ferritin level, >100 μg/L in men and >50 μg/L in women). All samples also were analyzed for human recombinant tissue transglutaminase immunoglobulin A; positive results were confirmed by an assay for endomysial antibodies. Patients with positive results from both celiac disease tests were presumed to have untreated celiac disease, and those with a positive result from only 1 test were excluded from analysis. We analyzed HLA genotypes and frequencies of celiac disease between Caucasians and non-Caucasians with iron deficiency. Celiac disease occurred in 14 of 567 cases (2.5%) and in only 1 of 1136 controls (0.1%; Fisher exact test, P = 1.92 × 10(-6)). Celiac disease was more common in Caucasian cases (14 of 363; 4%) than non-Caucasian cases (0 of 204; P = .003). Only 1 Caucasian control and no non-Caucasian controls had celiac disease. The odds of celiac disease in individuals with iron deficiency was 28-fold (95% confidence interval, 3.7-212.8) that of controls; 13 of 14 cases with celiac disease carried the DQ2.5 variant of the HLA genotype. Celiac disease is associated with iron deficiency in Caucasians. Celiac disease is rare among non-Caucasians-even among individuals with features of celiac disease, such as iron deficiency. Celiac disease also is rare among individuals without iron deficiency. Men and postmenopausal women with iron deficiency should be tested for celiac disease.

Advances in coeliac disease

This article critically summarizes the recent scientific and clinical advances in coeliac disease. Epidemiological studies have shown that coeliac disease is as common in parts of Asia, Africa and Eastern Europe as in the western world. Genome-wide association studies continue to identify genetic susceptibilities that are both unique to coeliac disease and overlap with other autoimmune diseases. Human leukocyte antigen genotyping offers additional sensitivity in detecting coeliac disease in individuals who have self-prescribed gluten-free diets (GFD) or have atypical presentations. Immunological advances have highlighted the potential proinflammatory pitfalls of vitamin A supplementation in active coeliac disease and have enabled identification of oat and barley subsets that may be safely incorporated into coeliac diets. Large population-based studies have expanded our knowledge of the long-term risks of coeliac disease, in addition to excluding infertility as a cause for concern once a GFD has been established. The long-term implications of active coeliac disease emphasize the need for early detection and strict adherence to GFD, which remains the cornerstone of management. Technological advances in food modulation and immuno-therapies offer promise, but remain in the translational phases of clinical trials at present.

Pregnancy Outcome and Risk of Celiac Disease in Offspring: A Nationwide Case-Control Study

Studies on pregnancy characteristics and mode of delivery and risk of later celiac disease in offspring are inconsistent. In recent decades rates of cesarean delivery and preterm birth survival have increased while at the same time the prevalence of celiac disease has doubled. In this population-based case-control study we examined the risk of celiac disease in individuals exposed to cesarean delivery and adverse fetal events (ie, low Apgar score, small for gestational age, low birth weight, preterm birth, and neonatal infections). Prospectively recorded pregnancy data were obtained from the Swedish Medical Birth Register between 1973 and 2008. Study participants consisted of 11,749 offspring with biopsy-verified celiac disease identified through histopathology reports from Sweden's 28 pathology departments, and 53,887 age- and sex-matched controls from the general population. We found a positive association between elective cesarean delivery and later celiac disease (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 1.04-1.26), but no increased risk of celiac disease after emergency (adjusted OR, 1.02; 95% CI, 0.92-1.13) or any cesarean delivery (adjusted OR, 1.06; 95% CI, 0.99-1.13). Infants born small for gestational age were at a 21% increased risk of celiac disease (95% CI, 1.09-1.35), whereas other pregnancy exposures did not increase the risk of future celiac disease. The positive association with elective, but not emergency, cesarean delivery is consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease.

Meta-analysis: coeliac disease and hypertransaminasaemia

There may be a positive association between coeliac disease and serum hypertransaminasaemia but evidence is conflicting. To conduct a systematic review and meta-analysis to determine the prevalence of coeliac disease in adults presenting with cryptogenic serum hypertransaminasaemia and the prevalence of hypertransaminasaemia in patients with newly diagnosed coeliac disease. MEDLINE and EMBASE were searched up to August 2010. Case series and case-control studies recruiting adults with either cryptogenic hypertransaminasaemia that applied serological tests for coeliac disease and/or distal duodenal biopsy to participants or newly diagnosed biopsy-proven coeliac disease that assessed serum transaminases were eligible. The pooled prevalence of coeliac disease in individuals presenting with abnormal serum transaminases and the pooled prevalence of hypertransaminasaemia in newly diagnosed coeliac disease were calculated with 95% confidence intervals (CI). Eleven eligible studies were identified. Pooled prevalences of positive coeliac serology and biopsy-proven coeliac disease in cryptogenic hypertransaminasaemia were 6% (95% CI 3% to 10%) and 4% (95% CI 1% to 7%) respectively. Pooled prevalence of abnormal serum transaminases in newly diagnosed coeliac disease was 27% (95% CI 13% to 44%). Exclusion of gluten led to normalisation of serum transaminase levels in 63% to 90% of patients within 1 year. Undetected coeliac disease is a potential cause for cryptogenic hypertransaminasaemia in 3% to 4% of cases. More than 20% of individuals with newly diagnosed coeliac disease may have abnormal serum transaminases and these normalise on a gluten-free diet in the majority of cases.

The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta‐analysis

The aim of this article was to review and conduct a meta-analysis of the paediatric literature on the neurology of coeliac disease. We conducted a review of paediatric studies published in English assessing neurological illness in coeliac disease identified through a MEDLINE search (1950-2009). Calculation of computed relative risk, odds ratio, and risk difference was performed using the fixed effect method if applicable. Fifteen studies were analysed (11 772 participants). The meta-analysis showed that (1) the relative risk of epilepsy in individuals with coeliac disease, and of coeliac disease in individuals with epilepsy, compared with the general population, was 2.1 and 1.7, respectively, and the risk difference was close to zero, indicating that it was probably a chance association; and (2) the relative risk of headache in individuals with the disease compared with comparison groups was 3.2. In two studies, cerebellar ataxia was documented in 2.7 to 5.4% of participants; in two further studies, the risk of cerebellar dysfunction was zero. Two studies found an association between coeliac disease and peripheral neuropathy. Brain white matter lesions were recorded in two other studies. An association between autism and coeliac disease is disputed. Interpretation Children with coeliac disease are at risk of developing neurological complications, but the risk is lower than in adulthood. The discrepancy might be due to short disease duration, early elimination of gluten from the diet, stricter adherence to diet, or different susceptibility to immune-mediated disorders.

Yield of Diagnostic Tests for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome

Individuals with irritable bowel syndrome (IBS) report abdominal pain, bloating, and diarrhea, symptoms similar to those in celiac disease. Studies suggest that the prevalence of celiac disease is increased in individuals with IBS; however, evidence is conflicting, and current guidelines do not always recommend screening for celiac disease in these individuals. We conducted a systematic review and meta-analysis to estimate prevalence of celiac disease in unselected adults who met diagnostic criteria for IBS. MEDLINE (1950 to May 31, 2008) and EMBASE (1980 to May 31, 2008) were searched. Case series and case-control studies that used serologic tests for celiac disease were eligible for inclusion. Prevalence of positive serologic indications of celiac disease and biopsy-proved celiac disease were extracted and pooled for all studies and were compared between cases and controls using an odds ratio and 95% confidence interval. Fourteen studies were identified comprising 4204 individuals, of whom 2278 (54%) met diagnostic criteria for IBS. Pooled prevalence of positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease were 4.0% (95% confidence interval, 1.7-7.2), 1.63% (0.7-3.0), and 4.1% (1.9-7.0), respectively. Pooled odds ratios (95% confidence intervals) for positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS compared with controls without IBS were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6). Prevalence of biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS was more than 4-fold that in controls without IBS.

Yield of Diagnostic Tests for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Systematic Review and Meta-analysis

Yield of Diagnostic Tests for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Systematic Review and Meta-analysis

Yield of Diagnostic Tests for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Systematic Review and Meta-analysis

Yield of Diagnostic Tests for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Systematic Review and Meta-analysis

Risk of Thyroid Disease in Individuals with Celiac Disease

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. 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 of more than 1 yr and with no thyroid 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. 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). 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.