[Show abstract][Hide abstract] ABSTRACT: Villous atrophy (VA) with intraepithelial lymphocytosis is the histological hallmark of coeliac disease (CD), but reported rates of mucosal recovery are variable.
To determine the impact of age and other demographic variables on the probability of persistent VA on follow-up biopsy.
We identified patients with VA on duodenal histology at all 28 Swedish pathology departments during the years spanning 1969-2008. We examined age, gender, calendar period, duration of disease and educational attainment to determine predictors of persistent VA.
Of 7648 patients with CD who underwent follow-up biopsy, persistent VA was present in 3317 (43%; 95% CI 42-44%). The effect of age on persistent VA varied according to time period; among those biopsied in the years spanning 2000-2008, the prevalence of persistent VA was 31%, and increasing age was associated with increasing rates of persistent VA (17% among those younger than 2 years compared to 56% among those ≥70 years). In contrast, persistent VA did not vary widely by age in earlier years. On multivariate analysis (restricted to the calendar period 2000-2008, 2-5 years after CD diagnosis), persistent VA was more common among males (OR 1.43; 95% CI 1.07-1.90) and less common among patients with higher educational attainment (OR for college degree vs. <2 years of high school 0.52, 95% CI 0.35-0.78).
The prevalence of persistent villous atrophy has changed over time, with greater rates of healing in recent years. Social differences in persistent villous atrophy suggest that access and/or education regarding the gluten-free diet impact mucosal healing.
[Show abstract][Hide abstract] ABSTRACT: Background: Case reports and smaller case-control studies suggest an association between celiac disease (CD) and urticaria but risk estimates have varied considerably across studies and as yet there are no studies on CD and the risk of future urticaria. Objective: To examine the association between CD and urticaria. Methods: We identified 28,900 patients with biopsy-verified CD (equal to Marsh stage 3) and compared them with 143,397 age- and sex-matched controls with regards to the risk of urticaria and chronic urticaria (duration ≥6 weeks). Hazard ratios (HRs) were estimated using a Cox regression model. Results: During follow-up, 453 patients with CD and no previous diagnosis of urticaria developed urticaria (expected n = 300) and 79 of these 453 had chronic urticaria (expected n = 41). The corresponding HRs were 1.51 for any urticaria (95%CI = 1.36-1.68) and 1.92 for chronic urticaria (95%CI = 1.48-2.48). The absolute risk for urticaria in CD was 140/100,000 person-years (excess risk = 47/100,000 person-years). Corresponding figures for chronic urticaria were 24/100,000 person-years and 12/100,000 person-years. Patients with CD were also at increased risk of having both urticaria (odds ratio, OR = 1.31; 95%CI = 1.12-1.52) and chronic urticaria (OR = 1.54; 95%CI = 1.08-2.18) prior to the CD diagnosis. Conclusion: This study suggests that CD is associated with urticaria, especially chronic urticaria.
[Show abstract][Hide abstract] ABSTRACT: This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.Am J Gastroenterol advance online publication, 23 April 2013; doi:10.1038/ajg.2013.79.
The American Journal of Gastroenterology 04/2013; · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:The prevalence of celiac disease (CD) varies greatly, potentially because of incomplete ascertainment of cases and small study samples with limited statistical power. Previous reports indicate that the incidence of CD is increasing. We examined the prevalence of CD in a well-defined US county.METHODS:Population-based study in Olmsted County, Minnesota, USA. Using the infrastructure of the Rochester Epidemiology Project, medical, histopathology, and CD serology records were used to identify all new cases of CD in Olmsted County since 2000. Age- and sex-specific and adjusted (to the US white 2000 population) incidence rates for CD were estimated. Clinical presentation at diagnosis was also assessed.RESULTS:Between 2000 and 2010, 249 individuals (157 female or 63%, median age 37.9 years) were diagnosed with CD in Olmsted County. The overall age- and sex-adjusted incidence of CD in the study period was 17.4 (95% confidence interval (CI)=15.2-19.6) per 100,000 person-years, increasing from 11.1 (95% CI=6.8-15.5) in 2000-2001 to 17.3 (95% CI=13.3-21.3) in 2008-2010. The temporal trend in incidence rates was modeled as a two-slope pattern, with the incidence leveling off after 2004. Based on the two classic CD symptoms of diarrhea and weight loss, the relative frequency of classical CD among incident cases decreased over time between 2000 and 2010 (P=0.044).CONCLUSIONS:The incidence of CD has continued to increase in the past decade in a North-American population.Am J Gastroenterol advance online publication, 19 March 2013; doi:10.1038/ajg.2013.60.
The American Journal of Gastroenterology 03/2013; · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Celiac disease (CD) is associated with both lymphoproliferative malignancy (LPM) and increased death from LPM. Research suggests that co-existing autoimmune disease may influence survival in LPM. Through Cox regression we examined overall and cause-specific mortality in 316 individuals with CD+LPM versus 689 individuals with LPM only. CD was defined as having villous atrophy according to biopsy reports at any of Sweden's 28 pathology departments, and LPM as having a relevant disease code in the Swedish Cancer Register. During follow-up, there were 551 deaths (CD: n = 200; non-CD: n = 351). Individuals with CD+LPM were at an increased risk of death compared with LPM-only individuals [adjusted hazard ratio (aHR) = 1.23; 95 % confidence interval (CI) = 1.02-1.48]. However, this excess risk was only seen in the first year after LPM diagnosis (aHR = 1.76), with HRs decreasing to 1.09 in years 2-5 after LPM diagnosis and to 0.90 thereafter. Individuals with CD and non-Hodgkin lymphoma (NHL) were at a higher risk of any death as compared with NHL-only individuals (aHR = 1.23; 95 % CI = 0.97-1.56). This excess risk was due to a higher proportion of T cell lymphoma in CD patients. Stratifying for T- and B cell status, the HR for death in individuals with CD+NHL was 0.77 (95 % CI = 0.46-1.31). In conclusion, we found no evidence that co-existing CD influences survival in individuals with LPM. The increased mortality in the first year after LPM diagnosis is related to the predominance of T-NHL in CD individuals. Individuals with CD+LPM should be informed that their prognosis is similar to that of individuals with LPM only. However, this study had low statistical power to rule our excess mortality in patients with CD and certain LPM subtypes.
European Journal of Epidemiology 03/2013; · 5.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Individuals with celiac disease (CD) are at increased risk of lymphoproliferative malignancy (LPM). We examined if a family history of LPM or any cancer influenced the risk of LPM in individuals with CD. METHODS: We identified 28,996 individuals with biopsy-verified CD (equal to villous atrophy, Marsh histopathology stage 3), of whom 616 had family history of LPM. Cox regression then estimated hazard ratios (HRs) for LPM in these 616 compared with two control groups. We also examined the risk of LPM in CD individuals with a family history of any cancer (n = 8,439). RESULTS: During follow-up, 2/616 CD individuals with a family history of LPM, and 235/28,380 CD individuals without a family history of LPM developed LPM themselves. CD individuals with a family history of LPM were not at increased risk of LPM compared to general population controls (HR = 1.18; 95 % CI = 0.27-5.10), or compared to CD individuals without a family history of LPM (adjusted HR = 0.31; 95 % CI = 0.08-1.23). We found no increased risk of LPM in CD individuals with a family history of any cancer. CONCLUSION: This study found no evidence that a family history of LPM or any cancer increases the risk of future LPM in individuals with CD. Despite the large number of study participants, this study is nevertheless limited by few positive events due to a low absolute risk of LPM even in individuals with CD.
Journal of Gastroenterology 02/2013; · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Coeliac disease (CD), characterised by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery. AIMS: To determine whether persistent VA is associated with mortality in CD. METHODS: Through biopsy reports from all pathology departments (n = 28) in Sweden, we identified 7648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We used Cox regression to examine mortality according to follow-up biopsy. RESULTS: The mean age of CD diagnosis was 28.4; 63% were female; and the median follow-up after diagnosis was 11.5 years. The overall mortality rate of patients who underwent follow-up biopsy was lower than that of those who did not undergo follow-up biopsy (Hazard Ratio 0.88, 95% CI: 0.80-0.96). Of the 7648 patients who underwent follow-up biopsy, persistent VA was present in 3317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared with those with mucosal healing (HR: 1.01; 95% CI: 0.86-1.19). Mortality was not increased in children with persistent VA (HR: 1.09 95% CI: 0.37-3.16) or adults (HR 1.00 95% CI: 0.85-1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80-1.14). CONCLUSIONS: Persistent villous atrophy is not associated with increased mortality in coeliac disease. While a follow-up biopsy will allow detection of refractory disease in symptomatic patients, in the select population of patients who undergo repeat biopsy, persistent villous atrophy is not useful in predicting future mortality.
[Show abstract][Hide abstract] ABSTRACT: Small intestinal diseases are a common, though often overlooked cause of diarrhoeal illness. Fully 1% of the Caucasian population are affected by coeliac disease and a substantial portion of children living in poverty in the developing world are affected by environmental enteropathy. These are but two examples of the many diseases that cause mucosal injury to the primary digestive and absorptive organ in our body. While diarrhoea may be a common, though not universally seen symptom of small bowel mucosal disease, the consequent malabsorption can lead to substantial malnutrition and nutrient deficiencies. The small intestine, unlike the colon, has been relatively inaccessible, and systematic evaluation is often necessary to identify and treat small intestinal mucosal diseases that lead to diarrhoea. Immunodeficiency states, including HIV enteropathy, adult autoimmune enteropathy, drug-associated enteropathy, and tropical sprue continue to occur and require specific therapy. All patients with severe diarrhoea or diarrhoea associated with features suggestive of malabsorption may have a disease of the small intestinal mucosa that requires careful evaluation and targeted management.
Best practice & research. Clinical gastroenterology 10/2012; 26(5):581-600. · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article reviews issues related to identifying the appropriate patient to test for celiac disease, the performance characteristics of serologic testing, the role of gene testing for human leukocyte antigen DQ2 and DQ8 haplotypes, and issues related to the performance of small intestinal biopsy. The article concludes with a review of special diagnostic considerations in pediatric patients.
Gastrointestinal endoscopy clinics of North America 10/2012; 22(4):661-77.
[Show abstract][Hide abstract] ABSTRACT: To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking.
We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden's 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE.
During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48-4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57-4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22-4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97-4.17).
Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low.
The Journal of Rheumatology 08/2012; 39(10):1964-70. · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample.
This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD).
CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%).
The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.
The American Journal of Gastroenterology 07/2012; 107(10):1538-44. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the response to discontinuation of olmesartan, an angiotensin II receptor antagonist commonly prescribed for treatment of hypertension, in patients with unexplained severe spruelike enteropathy.
All 22 patients included in this report were seen at Mayo Clinic in Rochester, Minnesota, between August 1, 2008, and August 1, 2011, for evaluation of unexplained chronic diarrhea and enteropathy while taking olmesartan. Celiac disease was ruled out in all cases. To be included in the study, the patients also had to have clinical improvement after suspension of olmesartan.
The 22 patients (13 women) had a median age of 69.5 years (range, 47-81 years). Most patients were taking 40 mg/d of olmesartan (range, 10-40 mg/d). The clinical presentation was of chronic diarrhea and weight loss (median, 18 kg; range, 2.5-57 kg), which required hospitalization in 14 patients (64%). Intestinal biopsies showed both villous atrophy and variable degrees of mucosal inflammation in 15 patients, and marked subepithelial collagen deposition (collagenous sprue) in 7. Tissue transglutaminase antibodies were not detected. A gluten-free diet was not helpful. Collagenous or lymphocytic gastritis was documented in 7 patients, and microscopic colitis was documented in 5 patients. Clinical response, with a mean weight gain of 12.2 kg, was demonstrated in all cases. Histologic recovery or improvement of the duodenum after discontinuation of olmesartan was confirmed in all 18 patients who underwent follow-up biopsies.
Olmesartan may be associated with a severe form of spruelike enteropathy. Clinical response and histologic recovery are expected after suspension of the drug.
Mayo Clinic Proceedings 06/2012; 87(8):732-8. · 5.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adherence to a gluten-free diet is the only effective treatment for celiac disease. It has been recommended that patients be followed up, make regular visits to the clinic, and undergo serologic analysis for markers of celiac disease, although a follow-up procedure has not been standardized. We determined how many patients with celiac disease are actually followed up.
We collected data on 122 patients with biopsy-proven celiac disease, diagnosed between 1996 and 2006 in Olmsted County, Minnesota (70% women; median age, 42 y), for whom complete medical records and verification of residency were available. We determined the frequency at which patients received follow-up examinations, from 6 months to 5 years after diagnosis. The Kaplan-Meier method was used to estimate event rates at 1 and 5 years. Patients were classified according to categories of follow-up procedures recommended by the American Gastroenterological Association (AGA).
We estimated that by 1 and 5 years after diagnosis with celiac disease, 41.0% and 88.7% of the patients had follow-up visits, 33.6% and 79.8% were assessed for compliance with a gluten-free diet, 3.3% and 15.8% met with a registered dietitian, 2.5% and 18.1% had an additional intestinal biopsy, and 22.1% and 65.6% received serologic testing for markers of celiac disease, respectively. Among 113 patients (93%) who were followed up for more than 4 years, only 35% received follow-up analyses that were consistent with AGA recommendations.
Patients with celiac disease are not followed up consistently. Follow-up examinations often are inadequate and do not follow AGA recommendations. Improving follow-up strategies for patients with celiac disease could improve management of this disease.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2012; 10(8):893-899.e1. · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonresponsive celiac disease (CD) is defined by persistent or recurrent symptoms, common after treatment with a gluten-free diet (GFD).
To evaluate the utility of capsule endoscopy (CE) in nonresponsive CD.
Forty-two consecutive patients with nonresponsive CD and 84 age- and sex-matched CD-free controls who underwent CE were included. In addition, capsules taken after treatment with a GFD were retrospectively evaluated in 30 patients with uncomplicated CD.
Diagnostic accuracy of CE for the detection of mucosal abnormalities in nonresponsive CD.
Macroscopic features of villous atrophy were detected in 13 of 42 patients (31%) with nonresponsive CD compared with none among 84 CD-free controls and 14 of 30 patients (47%) with uncomplicated CD. Among nonresponsive CD cases, the overall sensitivity and specificity of CE for the detection of any degree of villous atrophy as graded by histology were 56% and 85%, respectively. Single or multiple erosions/ulcerations of the gut were observed in 19% of nonresponsive CD patients, 18% of CD-free controls, and 31% of patients with uncomplicated CD (P = .35). The presence of erosions/ulcerations was associated with increased aspirin/nonsteroidal anti-inflammatory drug use in nonresponsive CD (P =.05). Two severe complications (ulcerative jejunitis and adenocarcinoma) were detected by CE in nonresponsive CD.
Single-center, retrospective study.
Mucosal abnormalities were observed by CE in patients with both nonresponsive CD and uncomplicated CD. CE can detect severe complications in patients with nonresponsive CD.