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396 Mucosal Healing and Mortality in Celiac Disease
a significant difference in age across BMI categories. There was no difference in BMI between patients on a gluten-free diet compared to a gluten-containing diet (24.8 vs. 23.8; p=0.28). There was no difference in BMI between patients diagnosed < 1 year compared to > 1 year (24.6 vs. 24.5; p=0.94). Conclusion: At our Midwestern United States celiac disease center, there is a high prevalence (40.4%) of celiac patients who are overweight or obese, higher than previously reported. This may reflect the overall obesity epidemic in the United States and/or increased access to palatable gluten-free foods that are calorically dense. The significance of older age at diagnosis of celiac disease in the obese category may reflect delay in diagnosis in this group due to the belief that obesity is inconsistent with a malabsorptive disease. Table 1: Celiac patient characteristics by BMI category (n=136)
394 Celiac Disease Has Higher Treatment Burden Than Common Medical Conditions Sveta Shah, Mona Akbari, Ciaran P. Kelly, Arjun Bhansali, Joshua Hansen, Melinda Dennis, Daniel A. Leffler
n/a, not applicable; BMI, body mass index; SD, standard deviation
Introduction: The only treatment for celiac disease (CD) is the gluten-free diet (GFD), yet estimated adherence to the GFD is low. This suggests high perceived burden of treatment in CD, but data supporting this are scant. In this study, we sought to compare the treatment burden of the GFD in CD with therapies for other chronic medical conditions. Methods: The CD population was drawn from a database of adult patients with biopsy-confirmed CD. The non-celiac population was identified via billing codes in a primary care clinic. Two visual analog scales (VAS) scored 0-100 were included in the survey to measure disease and treatment burden. One VAS assessed the patient's report of their health state related to the disease. Zero indicated “worst imaginable health state” and 100 indicated “best imaginable health state.” A second VAS assessed the patient's report of difficulty of treatment, where zero indicated “very easy” and 100 indicated “very difficult.” Means between different groups were analyzed using one-way ANOVA in Stata. Results: 338 patients with CD and 220 patients without CD responded. Treatment burden could be broadly grouped into high, medium and low perceived burden. Diseases with high treatment burden included endstage renal disease (ESRD), mean 48.8 (SD 32.7), CD, mean 44.9 (SD 30.9) and diabetes mellitus (DM), mean 42.6 (SD 29.8). Diseases with medium treatment burden included irritable bowel syndrome (IBS), mean 39 (SD 22) and inflammatory bowel disease (IBD), mean 36.3 (SD 28.9). Diseases with low treatment burden included hypertension (HTN), mean 24.4 (SD 25.7) and gastroesophageal reflux (GERD), mean 24.1 (SD 27.4). All scores were significantly different (p<0.001). Health state in relation to disease was better in CD (mean 81.6, SD 18) when compared with all other diseases (p<0.001) (HTN: mean 77.4, SD 19.4; IBD: mean 74.2, SD 23.1; GERD: mean 73.7, SD 17; DM: mean 71.5, SD 21.6; ESRD: mean 68.3, SD 22.1; IBS: mean 61.7, SD 21.8). (Figures 1-2). Discussion: Patients with CD reported a remarkably high treatment burden similar to patients with ESRD and DM. Among gastrointestinal conditions, treatment burden exceeded IBD and IBS, and far exceeded GERD. Interestingly, in CD burden of treatment and disease specific health were inversely related; despite high treatment burden, CD patients reported high disease specific health state. The burden of following the GFD may be a reason why adherence is limited and argues for the need for adjunctive therapies. Providers caring for patients with CD should be aware of the treatment burden involved in following a GFD, encouraging multidisciplinary management with dieticians and support groups whenever possible.
396 Mucosal Healing and Mortality in Celiac Disease Benjamin Lebwohl, Fredrik Granath, Anders Ekbom, Scott Montgomery, Joseph A. Murray, Alberto Rubio-Tapia, Peter H. Green, Jonas F. Ludvigsson Background: Celiac disease (CD) is characterized by the presence of villous atrophy (VA) in the small intestine. Mucosal healing was previously thought to be near-universal with the institution of the gluten-free diet, but recent studies have demonstrated that a large proportion of patients exhibit persistent VA on follow-up biopsy. CD is associated with increased mortality, but it is unknown if this excess mortality is influenced by mucosal recovery. Methods: Through biopsy reports from all pathology departments (n=28) in Sweden we identified 7,648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We then used Cox regression to examine overall mortality according mucosal recovery in the follow-up biopsy (persistence of VA vs. recovery). Results: The mean age of CD diagnosis was 28.4 years, 63% were female, and the median follow-up after diagnosis was 11.5 years. Of the 7,648 patients, persistent VA was present in 3,317 (43%). Persistent VA was more common among men than women (45% vs. 42%; p=0.03), was more common among those with lower educational attainment (<2 years of high school: 52%; College: 35%; p<0.0001), and was more common among those with an index biopsy showing subtotal/total VA (42%) than those presenting with partial VA (30%; p<0.0001) In a subset of patients (n=545) baseline and follow-up serology data were available. The proportion of patients with persistent VA was greater in those with persistently positive serologies (139/224, 62%) than in those with conversion to negative serologies (67/321, 21%, p<0.0001). Among the 7,648 patients there were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared to those with mucosal healing (Hazard Ratio 1.01; 95% Confidence Interval 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 0.851.18), including adults older than age 50 years (HR 0.96 95% CI 0.80-1.14). Cause-specific mortality was not associated with persistent VA when considering death from cardiovascular causes (HR 1.03 95% 0.76-1.38), malignancy (HR 1.20 95% CI 0.88-1.66) or respiratory causes (HR 0.78 95% CI 0.41-1.48). Conclusions: Persistent VA is common (43%) and is probably due to poor dietary adherence as indicated by persistence of positive serologic tests. However, it is not associated with increased mortality in this population followed for a median of 11.5 years. The excess mortality reported in CD is not a consequence of persistent VA, and follow-up biopsy for documentation of mucosal healing may not be justified as a way of identifying those at increased risk of death. Routine follow-up biopsies do not contribute to predicting survival in celiac disease.
395 High Prevalence of Overweight and Obese Adult Celiac Patients in the Midwestern United States Sonia Kupfer, Shirley Paski, NurAlima Grandison, Carol E. Semrad Background: Celiac disease is classically considered as a malabsorptive diarrheal disease resulting in malnutrition and low body weight. Increasingly, celiac patients present with atypical signs and symptoms and a normal body mass index (BMI) or even overweight. Two previous studies in the United States reported 22% and 31% of celiac patients as overweight or obese (Cheng J et al 2010, Murray JA et al 2004, respectively). Obesity is epidemic in the United States, particularly in the Midwestern and Southern states. Aim:To determine the prevalence and patient characteristics of BMI categories in adult celiac patients at an academic medical center in the Midwestern United States. Methods: A retrospective chart review of celiac patients evaluated in our gastroenterology clinic between August 2002 and June 2011 was performed. Patients with a secure diagnosis of celiac disease based on positive serologies (tissue transglutaminase and/or endomysial IgA Antibody) and Marsh III lesions on duodenal biopsy were included. Data collection included age at clinic visit (years), time since diagnosis (months), gender, height (meters), weight (kg), and diet (gluten vs. glutenfree). Body mass index was calculated (kg/m2) at the time of the first clinic visit. We compared patient characteristics across four BMI categories: underweight (<18.5); normal (18.5-24.9); overweight (25.0-29.9); obese (>30.0). We also compared BMI according to diet and time from diagnosis. Continuous variables were compared using t-tests or ANOVA. Categorical variables were compared using the χ2 test. Results: In a preliminary assessment, 136 patients (28 male, 108 female) with confirmed celiac disease were identified. 105/136 (77.2%) were on a gluten-free diet. Of the 136 patients with celiac disease, 55 (40.4%) had a BMI in the overweight or obese categories, 70 (51.5%) were normal weight and 11 (8.1%) were underweight. Patient characteristics by BMI category are shown in Table 1. There was
397 Procedure Volume and Practice-Based Characteristics are Associated With Adherence to Celiac Disease Biopsy Guidelines Benjamin Lebwohl, Robert M. Genta, Robert C. Kapel, Peter H. Green, Alfred I. Neugut, Andrew Rundle Background: Celiac disease diagnosis rates are low in the United States. Adherence to the recommendation of submitting ≥4 specimens during duodenal biopsy is low, occurring in only 35% of endoscopies with duodenal biopsies. We sought to determine whether physician characteristics such as procedure volume or practice settings such as proximity to other gastroenterologists are associated with adherence to this recommendation. Methods: Using a large national pathology database, we identified all patients ages ≥18 years who underwent duodenal biopsy submitted during the years 2006-2009. Data from gastroenterologists performing procedures during at least 3 years out of the 4-year period were analyzed, and patients with known CD prior to the endoscopy were excluded. Generalized estimating equations were used to determine whether procedure volume, gastroenterologists per endoscopy suite, and number of gastroenterologists per capita per Km2 area (population density) of the ZIP code of the practice were associated with adherence to submitting ≥4 specimens during duodenal biopsy. Results: We identified 92,580 patients (67% female, mean age 53.5 years) undergoing duodenal biopsy who met the inclusion/exclusion criteria. Specimens
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76%) had undergone 1 previous EGD, but 2 patients had undergone 2, 1 patient had 3, and 1 patient had 4 previous EGD's. The median time from the first EGD until the diagnostic EGD was 39 months (range: 1 month to 13 years). The same endoscopist performed the non-diagnostic and the diagnostic EGD in 10/17 patients (59%). During the prior nondiagnostic EGD, a duodenal biopsy was performed in only 41% of the patients, and ≥4 specimens (the recommended number) were submitted in 29% of the patients. On the diagnostic EGD, ≥4 specimens were submitted in 94%. CD serologies were obtained in 3/ 17 (18%) prior to the non-diagnostic EGD but were obtained in 10/17 (59%) prior to the diagnostic EGD. During the non-diagnostic EGD's, the indications were dyspepsia/abdominal pain (n=5), reflux or Barrett's esophagus (n=4), diarrhea (n=2), dysphagia (n=2), and other (n=4). During the diagnostic EGD, the indications were diarrhea (n=6), positive CD serologies (n=5), abdominal pain/dyspepsia (n=3), dysphagia (n=2), and reflux (n=1). The mean age of diagnosis of those with missed/incident CD was 53.1 years, slightly older than those diagnosed with CD on their first EGD (46.8 years, p=0.11). Both groups were predominantly female (missed/incident CD: 65% vs. 66%, p=0.94). Conclusions: Among patients with CD who had previously undergone a non-diagnostic EGD, most did not have duodenal biopsies taken on a prior EGD. Dyspepsia and reflux were the predominant symptoms among these patients, and most did not initially have CD serologies checked. Routine performance of duodenal biopsy during EGD for the indications of dyspepsia and reflux may improve the under-diagnosis rates, and shorten the time for diagnosis, of patients with CD in the United States.
394 Celiac Disease Has Higher Treatment Burden Than Common Medical Conditions Sveta Shah, Mona Akbari, Ciaran P. Kelly, Arjun Bhansali, Joshua Hansen, Melinda Dennis, Daniel A. Leffler
n/a, not applicable; BMI, body mass index; SD, standard deviation
Introduction: The only treatment for celiac disease (CD) is the gluten-free diet (GFD), yet estimated adherence to the GFD is low. This suggests high perceived burden of treatment in CD, but data supporting this are scant. In this study, we sought to compare the treatment burden of the GFD in CD with therapies for other chronic medical conditions. Methods: The CD population was drawn from a database of adult patients with biopsy-confirmed CD. The non-celiac population was identified via billing codes in a primary care clinic. Two visual analog scales (VAS) scored 0-100 were included in the survey to measure disease and treatment burden. One VAS assessed the patient's report of their health state related to the disease. Zero indicated “worst imaginable health state” and 100 indicated “best imaginable health state.” A second VAS assessed the patient's report of difficulty of treatment, where zero indicated “very easy” and 100 indicated “very difficult.” Means between different groups were analyzed using one-way ANOVA in Stata. Results: 338 patients with CD and 220 patients without CD responded. Treatment burden could be broadly grouped into high, medium and low perceived burden. Diseases with high treatment burden included endstage renal disease (ESRD), mean 48.8 (SD 32.7), CD, mean 44.9 (SD 30.9) and diabetes mellitus (DM), mean 42.6 (SD 29.8). Diseases with medium treatment burden included irritable bowel syndrome (IBS), mean 39 (SD 22) and inflammatory bowel disease (IBD), mean 36.3 (SD 28.9). Diseases with low treatment burden included hypertension (HTN), mean 24.4 (SD 25.7) and gastroesophageal reflux (GERD), mean 24.1 (SD 27.4). All scores were significantly different (p<0.001). Health state in relation to disease was better in CD (mean 81.6, SD 18) when compared with all other diseases (p<0.001) (HTN: mean 77.4, SD 19.4; IBD: mean 74.2, SD 23.1; GERD: mean 73.7, SD 17; DM: mean 71.5, SD 21.6; ESRD: mean 68.3, SD 22.1; IBS: mean 61.7, SD 21.8). (Figures 1-2). Discussion: Patients with CD reported a remarkably high treatment burden similar to patients with ESRD and DM. Among gastrointestinal conditions, treatment burden exceeded IBD and IBS, and far exceeded GERD. Interestingly, in CD burden of treatment and disease specific health were inversely related; despite high treatment burden, CD patients reported high disease specific health state. The burden of following the GFD may be a reason why adherence is limited and argues for the need for adjunctive therapies. Providers caring for patients with CD should be aware of the treatment burden involved in following a GFD, encouraging multidisciplinary management with dieticians and support groups whenever possible.
396 Mucosal Healing and Mortality in Celiac Disease Benjamin Lebwohl, Fredrik Granath, Anders Ekbom, Scott Montgomery, Joseph A. Murray, Alberto Rubio-Tapia, Peter H. Green, Jonas F. Ludvigsson Background: Celiac disease (CD) is characterized by the presence of villous atrophy (VA) in the small intestine. Mucosal healing was previously thought to be near-universal with the institution of the gluten-free diet, but recent studies have demonstrated that a large proportion of patients exhibit persistent VA on follow-up biopsy. CD is associated with increased mortality, but it is unknown if this excess mortality is influenced by mucosal recovery. Methods: Through biopsy reports from all pathology departments (n=28) in Sweden we identified 7,648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We then used Cox regression to examine overall mortality according mucosal recovery in the follow-up biopsy (persistence of VA vs. recovery). Results: The mean age of CD diagnosis was 28.4 years, 63% were female, and the median follow-up after diagnosis was 11.5 years. Of the 7,648 patients, persistent VA was present in 3,317 (43%). Persistent VA was more common among men than women (45% vs. 42%; p=0.03), was more common among those with lower educational attainment (<2 years of high school: 52%; College: 35%; p<0.0001), and was more common among those with an index biopsy showing subtotal/total VA (42%) than those presenting with partial VA (30%; p<0.0001) In a subset of patients (n=545) baseline and follow-up serology data were available. The proportion of patients with persistent VA was greater in those with persistently positive serologies (139/224, 62%) than in those with conversion to negative serologies (67/321, 21%, p<0.0001). Among the 7,648 patients there were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared to those with mucosal healing (Hazard Ratio 1.01; 95% Confidence Interval 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 0.851.18), including adults older than age 50 years (HR 0.96 95% CI 0.80-1.14). Cause-specific mortality was not associated with persistent VA when considering death from cardiovascular causes (HR 1.03 95% 0.76-1.38), malignancy (HR 1.20 95% CI 0.88-1.66) or respiratory causes (HR 0.78 95% CI 0.41-1.48). Conclusions: Persistent VA is common (43%) and is probably due to poor dietary adherence as indicated by persistence of positive serologic tests. However, it is not associated with increased mortality in this population followed for a median of 11.5 years. The excess mortality reported in CD is not a consequence of persistent VA, and follow-up biopsy for documentation of mucosal healing may not be justified as a way of identifying those at increased risk of death. Routine follow-up biopsies do not contribute to predicting survival in celiac disease.
395 High Prevalence of Overweight and Obese Adult Celiac Patients in the Midwestern United States Sonia Kupfer, Shirley Paski, NurAlima Grandison, Carol E. Semrad Background: Celiac disease is classically considered as a malabsorptive diarrheal disease resulting in malnutrition and low body weight. Increasingly, celiac patients present with atypical signs and symptoms and a normal body mass index (BMI) or even overweight. Two previous studies in the United States reported 22% and 31% of celiac patients as overweight or obese (Cheng J et al 2010, Murray JA et al 2004, respectively). Obesity is epidemic in the United States, particularly in the Midwestern and Southern states. Aim:To determine the prevalence and patient characteristics of BMI categories in adult celiac patients at an academic medical center in the Midwestern United States. Methods: A retrospective chart review of celiac patients evaluated in our gastroenterology clinic between August 2002 and June 2011 was performed. Patients with a secure diagnosis of celiac disease based on positive serologies (tissue transglutaminase and/or endomysial IgA Antibody) and Marsh III lesions on duodenal biopsy were included. Data collection included age at clinic visit (years), time since diagnosis (months), gender, height (meters), weight (kg), and diet (gluten vs. glutenfree). Body mass index was calculated (kg/m2) at the time of the first clinic visit. We compared patient characteristics across four BMI categories: underweight (<18.5); normal (18.5-24.9); overweight (25.0-29.9); obese (>30.0). We also compared BMI according to diet and time from diagnosis. Continuous variables were compared using t-tests or ANOVA. Categorical variables were compared using the χ2 test. Results: In a preliminary assessment, 136 patients (28 male, 108 female) with confirmed celiac disease were identified. 105/136 (77.2%) were on a gluten-free diet. Of the 136 patients with celiac disease, 55 (40.4%) had a BMI in the overweight or obese categories, 70 (51.5%) were normal weight and 11 (8.1%) were underweight. Patient characteristics by BMI category are shown in Table 1. There was
397 Procedure Volume and Practice-Based Characteristics are Associated With Adherence to Celiac Disease Biopsy Guidelines Benjamin Lebwohl, Robert M. Genta, Robert C. Kapel, Peter H. Green, Alfred I. Neugut, Andrew Rundle Background: Celiac disease diagnosis rates are low in the United States. Adherence to the recommendation of submitting ≥4 specimens during duodenal biopsy is low, occurring in only 35% of endoscopies with duodenal biopsies. We sought to determine whether physician characteristics such as procedure volume or practice settings such as proximity to other gastroenterologists are associated with adherence to this recommendation. Methods: Using a large national pathology database, we identified all patients ages ≥18 years who underwent duodenal biopsy submitted during the years 2006-2009. Data from gastroenterologists performing procedures during at least 3 years out of the 4-year period were analyzed, and patients with known CD prior to the endoscopy were excluded. Generalized estimating equations were used to determine whether procedure volume, gastroenterologists per endoscopy suite, and number of gastroenterologists per capita per Km2 area (population density) of the ZIP code of the practice were associated with adherence to submitting ≥4 specimens during duodenal biopsy. Results: We identified 92,580 patients (67% female, mean age 53.5 years) undergoing duodenal biopsy who met the inclusion/exclusion criteria. Specimens
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76%) had undergone 1 previous EGD, but 2 patients had undergone 2, 1 patient had 3, and 1 patient had 4 previous EGD's. The median time from the first EGD until the diagnostic EGD was 39 months (range: 1 month to 13 years). The same endoscopist performed the non-diagnostic and the diagnostic EGD in 10/17 patients (59%). During the prior nondiagnostic EGD, a duodenal biopsy was performed in only 41% of the patients, and ≥4 specimens (the recommended number) were submitted in 29% of the patients. On the diagnostic EGD, ≥4 specimens were submitted in 94%. CD serologies were obtained in 3/ 17 (18%) prior to the non-diagnostic EGD but were obtained in 10/17 (59%) prior to the diagnostic EGD. During the non-diagnostic EGD's, the indications were dyspepsia/abdominal pain (n=5), reflux or Barrett's esophagus (n=4), diarrhea (n=2), dysphagia (n=2), and other (n=4). During the diagnostic EGD, the indications were diarrhea (n=6), positive CD serologies (n=5), abdominal pain/dyspepsia (n=3), dysphagia (n=2), and reflux (n=1). The mean age of diagnosis of those with missed/incident CD was 53.1 years, slightly older than those diagnosed with CD on their first EGD (46.8 years, p=0.11). Both groups were predominantly female (missed/incident CD: 65% vs. 66%, p=0.94). Conclusions: Among patients with CD who had previously undergone a non-diagnostic EGD, most did not have duodenal biopsies taken on a prior EGD. Dyspepsia and reflux were the predominant symptoms among these patients, and most did not initially have CD serologies checked. Routine performance of duodenal biopsy during EGD for the indications of dyspepsia and reflux may improve the under-diagnosis rates, and shorten the time for diagnosis, of patients with CD in the United States.