- Email: [email protected]
S1089 To Biopsy or Not Biopsy, That is the Question: A Cost-Effectiveness Model of Biopsy for Eosinophilic Esophagitis in Refractory GERD
Q1- first quartile, Q3-third quartile NERD: non erosive reflux disease EEo: eosinophilic esophagitis *comparison between group A and the other groups NS: not significant
mucosa, 3 muscularis, and 4 with serosal disease. Eleven subjects were identified with unexplained GI symptoms and PE. No significant associations were detected between clinical variables and group membership. Table 1 summarizes findings. Conclusion This is one of the largest series of subjects with EG. EG remains a rare disorder even at a tertiary referral center. No clinical feature was identified to distinguish between subjects with EG and those with unexplained GI symptoms and PE. Therefore, eosinophilic gastroenteritis should be on the differential diagnosis of patients presenting with GI symptoms and eosinophilia. Clinical Features by Disease Groups
AGA Abstracts
S1085 Prevalence of Eosinophilic Esophagitis Among Patients Who Had Esophageal or Upper Gastrointestinal Symptoms Jong-Jae Park, Moon Kyung Joo, Beom Jae Lee, Jin Ki Hwang, Seung Goun Hong, Keyhyeon Kim, Ja In Park, Joo Yeon Oh, Ji Hoon Kim, Jong Eun Yeon, Jae Seon Kim, Kwan Soo Byun, Young-Tae Bak Background: Prevalence of eosinophilic esophagitis (EoE) has been reported variably according to the subject and definition . We evaluated prevalence of EoE among patients who had esophageal or upper gastrointestinal (UGI) symptoms. Methods: Patients who had seven esophageal or UGI symptoms (dysphagia, food impaction, acid regurgitation, heartburn, chest pain, epigastric pain and neasea and/or vomiting) for more than once a week were prospectively collected from Jan. to Oct. 2009. All responded to symptomatic questionnaire, underwent gastroduodenoendoscopy and esophageal biopsies (3 pieces from distal esophagus, 2 from middle). Typical endoscopic findings of EoE (ring-like appearance, liner furrow, whitish papule, shearing or friability) were recorded. EoE was diagnosed if esophageal biopsy showed ≥20 eosinophils/high power field. Results: 122 patients (male:female 63:59, mean age 47.2 years) were enrolled and typical endoscopic findings were found in 31 (25.4%) patients (whitish papule: 19 (15.4%), ring-like appearance: 8 (6.5%), linear furrow: 5 (4.1%)). EoE was diagnosed in 8 (6.6%) patients, and typical endoscopic findings and past history of gastroesophageal reflux disorder, allergic rhinitis, atopy were significantly more common in EoE (+) patients than EoE (-). Diagnostic yield of typical endoscopic findings were 40.0% (2/5 patients) in linear furrow, 25.0% (2/8) in ring-like appearance and 15.8% (3/19) in whitish papule. Most bothersome symptoms among EoE patients were acid regurgitation (3/7, 42.9%), food impaction (2/7, 28.6%), dysphagia and epigastric pain (1/7, 14.3% respectively). Conclusion: Prevalence of EoE among patients with esophageal or UGI symptoms were 6.6% in Korea. Linear furrow and ring-like appearance showed relatively higher diagnostic value. S1086
*Mean (SEM) values
The Rising Incidence of Eosinophilic Esophagitis Correlates With Increased Awareness of the Disease Christopher N. Andrews, Atyab Syed, Stefan J. Urbanski, Paul L. Beck, Martin Storr
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Background: Previous population-based studies suggest that the incidence of eosinophilic esophagitis (EoE) is rising quickly. However it is likely that other factors such as detection bias affect this increase. We hypothesized that physician awareness of EoE as well as practice characteristics influenced the increase in incidence. Methods: Population-based retrospective pathology database analysis identified all esophageal biopsies and all EoE cases from 1/ 2001-12/2008 in Calgary, Canada (population ~1M). A separate comprehensive endoscopy database covering 82% of all biopsy results was analysed to determine the total number of esophagogastroduodenoscopy (EGD) and biopsy rate per EGD over 2004-2008. Poisson regression with scaling for over-dispersion was used for time trend analysis (SAS9.2) and multivariate linear regression assessed endoscopist factors predictive of making an EoE diagnosis. Results: Crude population incidence went from 0.34 per 105 in 2004 to 1.20 per 105 in 2008 (annual increase 33% 95%CI 24-42%, p<0.0001). From 2001-2008, 13,488 endoscopic esophageal biopsies were taken, resulting in 503 new diagnoses of EoE. No EoE diagnoses were made in 2001 (0/1314 biopsies), compared to 6.4% in 2008 (154/2412 biopsies (6.4%), increase 33% annually (95% CI 25-73% , p=0.032). EoE was also specifically mentioned as being not present in 0% of pathology reports in 2001, compared to 5.2% in 2008, suggesting rising pathologist awareness of the disorder.The esophageal biopsy rate increased from 2004 (13 of all EGDs) to 2008 (17% of all EGDs, relative increase 8% annually (95%CI 5-11%, p<0.0001), suggesting an increased endoscopist awareness of the disorder. Gastroenterologists with academic appointments and those in practice less than 5 years were more likely to make EoE diagnoses, whereas endoscopist gender and number of EGDs performed per year did not affect diagnostic rate. Conclusion: The incidence of EoE continues to increase as awareness of the disorder continues to spread amongst endoscopists and pathologists, and patients are more likely to have esophageal biopsy at EGD. The continuing linear increase suggests that many EoE patients remain undiagnosed, and that current incidence reports may still be underestimated; true incidence may not be known until rates plateau.
Duration of Dysphagia is Associated With Increased Frequency of Dysphagia and Food Impaction in Adults With Eosinophilic Esophagitis Erin Toto, Emily Kern, Nelson Moy, Mary Kwasny, Nirmala Gonsalves, Ikuo Hirano Background: Eosinophilic esophagitis (EoE) has become an important cause of dysphagia and food impaction in adults. Limited information is available regarding the natural history of EoE. This study aimed to investigate relationships between disease duration and symptom severity in a large cohort of adult EoE patients. Methods: Retrospective study of adult patients diagnosed with EoE between 2001 and 2008 at an urban university medical center. Results: 387 newly-diagnosed EoE patients were identified with median age at diagnosis of 37 years (range: 14-81 years of age). The majority of patients were male (72.4%) and Caucasian (69.5%). Presenting primary and secondary symptoms included dysphagia (82.2%), heartburn (28.9%), and chest pain (8.3%); 6.7% were asymptomatic at the time of diagnosis (in these cases, endoscopy was done for screening purposes). Over the 7 year study period, there was a decreasing trend in patients presenting with dysphagia and an increase in patients reporting heartburn (p < 0.001 for both). Information regarding symptom duration, frequency, and severity of food impactions (none, self-limited, requiring endoscopic extraction) was available in 125 patients. Of these, the median duration of symptoms was 5 years (range: 0-38 years). The median frequency of dysphagia was once per week (range: none in the past year to daily symptoms); 69.2% of patients reported at least one episode per month. There was a significant difference in the duration of dysphagia among those without food impactions compared to those with impactions (p < 0.001), with the median duration among those with food impactions being two years longer. There was a positive correlation seen between dysphagia duration and frequency of symptoms (r = 0.24, p = 0.005); this correlation was strongest amongst the subset of patients with food impactions that required endoscopic extraction (r = 0.58, p = 0.001). Conclusions: Significant relationships exist between the duration of dysphagia and both the frequency of dysphagia and food impactions in adults with EoE. This suggests that ongoing symptoms predict worsening disease and complication risks. If confirmed by prospective studies, the results would support early therapeutic interventions to prevent disease progression in EoE.
S1087 Eosinophilic Gastroenteritis: Evaluation of the Clinical Spectrum and Diagnostic Characteristics Joseph Y. Chang, Rok Seon Choung, Ru Min Lee, G. Richard Locke, Cathy Schleck, Alan R. Zinsmeister, Nick Talley
S1089 To Biopsy or Not Biopsy, That is the Question: A Cost-Effectiveness Model of Biopsy for Eosinophilic Esophagitis in Refractory GERD Stephen M. Miller, Jay L. Goldstein, Lauren B. Gerson
Background Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal (GI) tract, an adverse immunologic response and GI symptoms. Data are limited to small case series. Aim Evaluate the clinical spectrum of EG in patients diagnosed at our center from 1987. Methods Charts of patients from 1987 to 2007, with a diagnosis of EG, allergic gastroenteropathy, and eosinophilia were reviewed. Cases defined by: 1) presence of GI symptoms; 2) biopsies demonstrating eosinophilic infiltration of the GI tract, eosinophilic ascites, or characteristic radiographic findings with peripheral eosinophilia (PE); and 3) no evidence of parasitic or extra-intestinal disease. Exclusion criteria included eosinophilic esophagitis, Menetrier's disease, IBD, celiac, connective tissue disease, malignancy, amyloid, Churg-Strauss syndrome, and hypereosinophilic syndrome. A group of patients with unexplained GI symptoms and PE was included for comparison. The association of group category with clinical variables was assessed using Fisher's Exact test. A two-tailed alpha level of 0.05 for each variable examined was used to assess statistical significance. Results A total of 59 subjects were identified with EG: 52
AGA Abstracts
Background: The population prevalence of eosinophilic esophagitis (EoE) has been estimated to be approximately 6.5% in adults. [CGH 2009;7:420-6] Current AGA guidelines recommend endoscopic biopsy (Bx) in patients (pts) with dysphagia. [Gastroenterology 2008;135:1392-1413] We conducted a cost-effectiveness model to determine if endoscopic Bx is cost-effective in pts with refractory GERD (failure of symptom control after empiric PPI therapy (Rx)) both with and without (w/o) dysphagia in order to detect EoE. Methods: Applying a standard cost-effectiveness modeling approach, we estimated probabilities from the medical literature and costs using 2009 Medicare rates. We used quality-adjusted life years (QALYs) for GERD pts on and off of PPI Rx. [Am J Gastroenterol 2005] A time horizon of 1 year was used given the lack of data regarding long-term symptom relief for pts with EoE on Rx. We included the following assumptions: (1) 85% of pts with erosive esophagitis (EE) would become asymptomatic on BID PPI. Pts with EE would not have EoE; (2) 70% of pts with non-erosive disease would improve on BID PPI; those not improved would
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epigastric pain were more frequent in the youngest patients (24% vs. 18% and 17%; p<0.001), as were nausea/vomiting (6.6% vs. 2.4% and 1.7%; p<0.001). Women had significantly greater frequency of dyspepsia (23.4% vs. 14.4%;p<0.001), nausea/vomiting (5.7% vs. 2.9%; p<0.001), and chest pain (4.2% v 2.8%; p=0.013). Men had more frequent dysphagia (62.9% vs. 52.9%; p<0.001). GERD was equally frequent in men and women. Conclusions: Among adult patients undergoing elective upper endoscopy, dysphagia and GERD were the most common presenting symptoms resulting in the histopathologic diagnosis of EoE. Dysphagia, nausea and dyspepsia decreased with age. The rate of food impaction was low in this patient population (non-emergency room setting) and its frequency was slightly higher in men. Conversely, dyspepsia, nausea and chest pain were more common presentations in women. Over 40% of adult patients presented without dysphagia. These observations may strengthen our recognition of the varied presentations of EoE in adults. S1092 Food Allergen Restricted Diet in the Treatment of Paediatric Eosinophilic Esophagitis Richard Muir, Peter Lewindon, Looi C. Ee, Geoffrey D. Withers Introduction Treatment of Eosinophilic Oesophagitis (EO) in children remains challenging. Elemental diet is the gold standard but use is limited by palatability and long term compliance. Kagawalla's paper reported significant improvement on standard 6 food elimination diet in 74% of patients (<10 eosinophils/HPF). Aims of the study were to assess the efficacy of 6 food elimination diet for 6 weeks in children with EO and the role of allergy testing. Methods Eligibility criteria included children with either a new diagnosis of EO (>15 eos/HPF) or previously diagnosed and on stable treatment for the prior three months. Patients with histological evidence of other gastrointestinal diseases (except GOR) were excluded. Skin Prick Testing (SPT) for food and inhalant allergens using standard extracts was undertaken and Atopy Patch Testing (APT) for egg, dairy, corn, soy, wheat, chicken and beef. Patients commenced a diet excluding cow's milk protein, soy, egg, corn, wheat, seafood, peanuts and tree nuts for 6 weeks. At completion, repeat medical assessment including Endoscopy with biopsy was performed. Results 14 patients were enrolled and 13 patients completed the study protocol at time of presentation. Mean age 9 (1-15 years); 11 males and 2 females. Incidence of other atopic disorders requiring treatment was 10/13 (76%) and coexistent topical steroid therapy for EO was 4/13 (30%). On SPT, 7/13 (53%) had positive results (wheal >3mm) with all 7 demonstrating sensitivity to aeroallergens and 2/7 to food allergens. On APT, 10/13 (77%) had positive results, the most common soy (6), cow's milk, egg and corn (5). At conclusion of diet 3/13 had complete histological remission, 2/13 significant histological improvement (3-10 eos/HPF), 2 partial histological response (>50% reduction eos/HPF), 6 were non-responders. Mean eosinophil count dropped from 47.3 to 30 per HPF. All patients reported subjective improvement in symptoms Conclusion 53% of patients had positive histological response rate (RR) to the exclusion diet, 38% showing either significant histological response or entering remission. This histological RR was disappointing versus Kagawalla's RR 74%. Reasons for a lower RR in our study include possible reduced compliance with prescribed diet and older study population. 53% study population displayed sensitivity to aeroallergens consistent with the observation of increasing aeroallergen sensitivity with age. Conclusions from our allergen tests are difficult with small sample population, but there was no clear correlation between positive SPT, APT and response to diet.
S1090 Celiac Sprue and Eosinophilic Esophagitis: Are Duodenal Biopsies Enough? Jessica B. Johnson, Kathryn R. Byrne, Kathleen K. Boynton, Douglas G. Adler, Kathryn Peterson Background: Recent pediatric studies postulate an association between celiac sprue and eosinophilic esophagitis (EoE), suggesting an increased prevalence of celiac disease in children with EoE. No data have been published regarding the prevalence, detection or impact of celiac disease in adults with EoE. Aims: To estimate the prevalence of gluten sensitivity in adults with EoE. To determine the diagnostic yield of small bowel biopsies in identifying gluten sensitivity in EoE patients. To determine whether the addition of celiac serology testing to small bowel biopsy increases detection of gluten sensitivity in EOE patients. To report on the relationship between treatment of gluten sensitivity with dietary avoidance and resolution of symptoms and pathologic findings of EoE. Methods: A retrospective chart review was done on all patients diagnosed with EoE from Jan to Oct, 2009. Data gathered included sex, age, duodenal biopsy pathology, tissue transglutaminase IgA antibody (TTG) positivity, esophageal eosinophil counts, and EGD findings. Duodenal biopsy findings were correlated with TTG results. Gross and microscopic EGD changes with institution of glutenfree diet were recorded.Results: 29 EoE patients were identified who had both duodenal biopsies (6 total biopsies) and TTG antibodies performed. The average age of patients was 37.4 years (std 10.9), and 13/29 (45%) were female. Gluten sensitivity was identified in 4/ 29 (13.8%) patients either by biopsy or TTG. Interestingly, 3 of the 4 patients had evidence of celiac on TTG testing alone (range of TTG 22-250,ref positive = 19) while demonstrating normal duodenal biopsies, and 1 patient had Marsh 1 changes on a duodenal biopsy with normal TTG antibody. IgE levels were not substantially different between possible celiac patients and nonceliac EoE patients (138+/-198 and 248+/-458). 3 patients followed a glutenfree diet. Upon repeat testing of 2 patients, EoE symptoms and histologic findings had resolved after adopting a gluten-free diet. A gluten-free diet also resulted in improvement in nonspecific abdominal symptoms in 3 patients. Conclusion: Similar to pediatric studies, our data suggest celiac sprue is commonly found in the adult population with EoE. Diagnosis may be challenging, as gluten intolerance may be present on TTG testing despite normal duodenal biopsies in EoE patients. Furthermore, this study suggests that gluten-free diets can offer relief of abdominal and esophageal symptoms in patients with EoE. Consequently, TTG testing may further direct clinical care for patients with EoE and should be considered in the setting of normal duodenal biopsies.
S1093 Significant Esophageal Eosinophilia and Typical Endoscopic Features are Highly but Not Exclusively Specific for Eosinofilic Esophagitis Jan Martinek, Alice Strosova, Katerina Kostalova, Tuckova Inna, Petr Hrabal, Filip Zavada, Stepan Suchanek, Magdalena Stefanova, Miroslav Zavoral Background: Eosinophilic esophagitis (EE) is an emerging disease with typical clinical, endoscopic and histo-pathological features. However, some studies suggested that esophageal eosinofilia is not a specific finding for EE. Also endoscopic features of EE (rings, furrows) are considered non-specific. Aim: The aim of our study was to assess the prevalence of esophageal eosiniophilia in a cohort of patients undergoing upper gastrointestinal endoscopy. Methods: A single center prospective study. All patients fulfilling inclusion criteria and agreeing with the participation in the study underwent an upper GI endoscopy including biopsies taken from distal (5 cm above the Z-line) and proximal esophagus. In patients with reflux esophagitis samples were also obtained from the Z-line. The presence and the count of of eosinophils were assessed by two experienced pathologists. Results: 2256 biopsies from 332 patients were analyzed. Eosinophils in the esophageal mucosa were detected in 22 (6.7%) patients. Considering both clinical and histopathological features, EE was diagnosed in 19 patients (5.7%). Among them, in 16 patients the number of eosinophils was higher than 15/HPF and in 14 patients was higher than 20/HPF. In the remaining 3 patients with suspected EE, the number of eosinophils was bellow 15/HPF. In two patients without EE (one with achalasia and one with Barrett esophagus), the number of eosinophils reached high levels (20 and 72/HPF). Dysphagia or food impaction was present in 18 (95%) of the patients with EE, atopy/allergy in 12 (63%) and typical reflux symptoms in 14 (73.7%). Thirteen patients with EE (68%) responded completely or partially to the acid suppressive therapy. The frequency of esophageal eosinophilia in particular endoscopic findings is shown in the Table. Sensitivity, specificity, PPV and NPV of typical endoscopic features (rings, furrows) for diagnosing EE were 72.3%; 96.5%; 98.1% and 59.2%. Conclusions: Significant esophageal eosinophilia is a rare finding among patients with reflux esophagitis, Barrett esophagus or achalasia. On the other hand some patients with clear clinical and endoscopic features of EE do not reach a required number of eosinophils/HPF. Endoscopic findings of rings and/or furrows are moderately sensitive and highly specific for diagnosing of EE. Finally, our results suggest that gastroesophageal reflux plays a role in the development of EE.
S1091 Clinical Presentation of 4905 Adults With Histopathologic Diagnosis of Eosinophilic Esophagitis Robert C. Kapel, Robert M. Genta Background & Aims: Many studies have demonstrated the varied clinical presentations of eosinophilic esophagitis (EoE) in both adults and children. The aim of this study was to examine the presenting symptoms of EoE, by age and gender, in a large group of adult outpatients meeting the histopathologic criteria for this diagnosis. Methods: We utilized the Caris Diagnostics Database of gastrointestinal biopsy specimens from community-based outpatient freestanding endoscopy centers in 42 states, DC, and PR. We analyzed the pathology reports for all esophageal biopsy specimens submitted to Caris Diagnostics from January 2007 through June 2009. We extracted demographic, clinical and endoscopic data from all unique patients, 18 years or older, who had an initial histopathologic diagnosis of EoE “pattern of injury” (>20 eosinophils per high-power field). We excluded patients who presented with a previous diagnosis of EoE, and those who had insufficient clinical data. Results: During the study period 179,685 patients had esophageal biopsies (median age 56 years; 47.6% male); a histopathologic diagnosis of EoE was made in 5,522 patients (3.1%; median age 43; 65.2% male, OR 2.09 95%CI 1.97-2.21). Of the 4,905 patients who met the inclusion criteria, 1,887 were aged 18 to 39 (67.4% male), 2,227 were 40 to 59 (65.3%), and 791 were 60 or older (60.8%). The frequencies of GERD (41%, 40%, 40% in groups of increasing age, respectively); chest pain (4%, 3%, 3%); and food impaction (1.2%, 0.7%, 0.5%) were similar across age groups. Dysphagia was less frequent in the oldest group (55%) than in the younger groups (59% and 61%; p<0.001). Dyspepsia/
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AGA Abstracts
AGA Abstracts
undergo motility and pH testing; (3) Pts found to have EoE would be treated with fluticasone. Allergy testing or immunotherapy treatments were not included; (4) For pts undergoing endoscopy (EGD) w/o Bx, EoE would be missed. Results: Assuming base case probabilities (Table 1), the EGD w/o Bx arm cost $643 and was associated with 0.953 QALYs. The EGD with Bx arm cost $853 and was associated with 0.957 QALYs. The resulting incremental cost-effectiveness ratio (ICER) was $52,500 per QALY for the EGD with Bx arm. Tornedo analysis demonstrated that the results were sensitive to the following variables in descending order of influence: cost of EGD with Bx, cost of EGD w/o Bx, probability of EoE in pts with and w/o dysphagia, and symptom resolution on fluticasone. In one-way sensitivity analysis, the ICER exceeded $100K when the probability of EoE in pts w/o dysphagia was 3% or less, or if symptom resolution on fluticasone was 67% or less. The ICER for the EGD with Bx arm exceeded $100K when the cost > $700. Conclusions: Upper endoscopy with Bx for EoE appears to be a cost-effective approach when the probability of EoE in pts with refractory GERD exceeds 3%. Table 1. Model Probabilities
mucosa, 3 muscularis, and 4 with serosal disease. Eleven subjects were identified with unexplained GI symptoms and PE. No significant associations were detected between clinical variables and group membership. Table 1 summarizes findings. Conclusion This is one of the largest series of subjects with EG. EG remains a rare disorder even at a tertiary referral center. No clinical feature was identified to distinguish between subjects with EG and those with unexplained GI symptoms and PE. Therefore, eosinophilic gastroenteritis should be on the differential diagnosis of patients presenting with GI symptoms and eosinophilia. Clinical Features by Disease Groups
AGA Abstracts
S1085 Prevalence of Eosinophilic Esophagitis Among Patients Who Had Esophageal or Upper Gastrointestinal Symptoms Jong-Jae Park, Moon Kyung Joo, Beom Jae Lee, Jin Ki Hwang, Seung Goun Hong, Keyhyeon Kim, Ja In Park, Joo Yeon Oh, Ji Hoon Kim, Jong Eun Yeon, Jae Seon Kim, Kwan Soo Byun, Young-Tae Bak Background: Prevalence of eosinophilic esophagitis (EoE) has been reported variably according to the subject and definition . We evaluated prevalence of EoE among patients who had esophageal or upper gastrointestinal (UGI) symptoms. Methods: Patients who had seven esophageal or UGI symptoms (dysphagia, food impaction, acid regurgitation, heartburn, chest pain, epigastric pain and neasea and/or vomiting) for more than once a week were prospectively collected from Jan. to Oct. 2009. All responded to symptomatic questionnaire, underwent gastroduodenoendoscopy and esophageal biopsies (3 pieces from distal esophagus, 2 from middle). Typical endoscopic findings of EoE (ring-like appearance, liner furrow, whitish papule, shearing or friability) were recorded. EoE was diagnosed if esophageal biopsy showed ≥20 eosinophils/high power field. Results: 122 patients (male:female 63:59, mean age 47.2 years) were enrolled and typical endoscopic findings were found in 31 (25.4%) patients (whitish papule: 19 (15.4%), ring-like appearance: 8 (6.5%), linear furrow: 5 (4.1%)). EoE was diagnosed in 8 (6.6%) patients, and typical endoscopic findings and past history of gastroesophageal reflux disorder, allergic rhinitis, atopy were significantly more common in EoE (+) patients than EoE (-). Diagnostic yield of typical endoscopic findings were 40.0% (2/5 patients) in linear furrow, 25.0% (2/8) in ring-like appearance and 15.8% (3/19) in whitish papule. Most bothersome symptoms among EoE patients were acid regurgitation (3/7, 42.9%), food impaction (2/7, 28.6%), dysphagia and epigastric pain (1/7, 14.3% respectively). Conclusion: Prevalence of EoE among patients with esophageal or UGI symptoms were 6.6% in Korea. Linear furrow and ring-like appearance showed relatively higher diagnostic value. S1086
*Mean (SEM) values
The Rising Incidence of Eosinophilic Esophagitis Correlates With Increased Awareness of the Disease Christopher N. Andrews, Atyab Syed, Stefan J. Urbanski, Paul L. Beck, Martin Storr
S1088
Background: Previous population-based studies suggest that the incidence of eosinophilic esophagitis (EoE) is rising quickly. However it is likely that other factors such as detection bias affect this increase. We hypothesized that physician awareness of EoE as well as practice characteristics influenced the increase in incidence. Methods: Population-based retrospective pathology database analysis identified all esophageal biopsies and all EoE cases from 1/ 2001-12/2008 in Calgary, Canada (population ~1M). A separate comprehensive endoscopy database covering 82% of all biopsy results was analysed to determine the total number of esophagogastroduodenoscopy (EGD) and biopsy rate per EGD over 2004-2008. Poisson regression with scaling for over-dispersion was used for time trend analysis (SAS9.2) and multivariate linear regression assessed endoscopist factors predictive of making an EoE diagnosis. Results: Crude population incidence went from 0.34 per 105 in 2004 to 1.20 per 105 in 2008 (annual increase 33% 95%CI 24-42%, p<0.0001). From 2001-2008, 13,488 endoscopic esophageal biopsies were taken, resulting in 503 new diagnoses of EoE. No EoE diagnoses were made in 2001 (0/1314 biopsies), compared to 6.4% in 2008 (154/2412 biopsies (6.4%), increase 33% annually (95% CI 25-73% , p=0.032). EoE was also specifically mentioned as being not present in 0% of pathology reports in 2001, compared to 5.2% in 2008, suggesting rising pathologist awareness of the disorder.The esophageal biopsy rate increased from 2004 (13 of all EGDs) to 2008 (17% of all EGDs, relative increase 8% annually (95%CI 5-11%, p<0.0001), suggesting an increased endoscopist awareness of the disorder. Gastroenterologists with academic appointments and those in practice less than 5 years were more likely to make EoE diagnoses, whereas endoscopist gender and number of EGDs performed per year did not affect diagnostic rate. Conclusion: The incidence of EoE continues to increase as awareness of the disorder continues to spread amongst endoscopists and pathologists, and patients are more likely to have esophageal biopsy at EGD. The continuing linear increase suggests that many EoE patients remain undiagnosed, and that current incidence reports may still be underestimated; true incidence may not be known until rates plateau.
Duration of Dysphagia is Associated With Increased Frequency of Dysphagia and Food Impaction in Adults With Eosinophilic Esophagitis Erin Toto, Emily Kern, Nelson Moy, Mary Kwasny, Nirmala Gonsalves, Ikuo Hirano Background: Eosinophilic esophagitis (EoE) has become an important cause of dysphagia and food impaction in adults. Limited information is available regarding the natural history of EoE. This study aimed to investigate relationships between disease duration and symptom severity in a large cohort of adult EoE patients. Methods: Retrospective study of adult patients diagnosed with EoE between 2001 and 2008 at an urban university medical center. Results: 387 newly-diagnosed EoE patients were identified with median age at diagnosis of 37 years (range: 14-81 years of age). The majority of patients were male (72.4%) and Caucasian (69.5%). Presenting primary and secondary symptoms included dysphagia (82.2%), heartburn (28.9%), and chest pain (8.3%); 6.7% were asymptomatic at the time of diagnosis (in these cases, endoscopy was done for screening purposes). Over the 7 year study period, there was a decreasing trend in patients presenting with dysphagia and an increase in patients reporting heartburn (p < 0.001 for both). Information regarding symptom duration, frequency, and severity of food impactions (none, self-limited, requiring endoscopic extraction) was available in 125 patients. Of these, the median duration of symptoms was 5 years (range: 0-38 years). The median frequency of dysphagia was once per week (range: none in the past year to daily symptoms); 69.2% of patients reported at least one episode per month. There was a significant difference in the duration of dysphagia among those without food impactions compared to those with impactions (p < 0.001), with the median duration among those with food impactions being two years longer. There was a positive correlation seen between dysphagia duration and frequency of symptoms (r = 0.24, p = 0.005); this correlation was strongest amongst the subset of patients with food impactions that required endoscopic extraction (r = 0.58, p = 0.001). Conclusions: Significant relationships exist between the duration of dysphagia and both the frequency of dysphagia and food impactions in adults with EoE. This suggests that ongoing symptoms predict worsening disease and complication risks. If confirmed by prospective studies, the results would support early therapeutic interventions to prevent disease progression in EoE.
S1087 Eosinophilic Gastroenteritis: Evaluation of the Clinical Spectrum and Diagnostic Characteristics Joseph Y. Chang, Rok Seon Choung, Ru Min Lee, G. Richard Locke, Cathy Schleck, Alan R. Zinsmeister, Nick Talley
S1089 To Biopsy or Not Biopsy, That is the Question: A Cost-Effectiveness Model of Biopsy for Eosinophilic Esophagitis in Refractory GERD Stephen M. Miller, Jay L. Goldstein, Lauren B. Gerson
Background Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal (GI) tract, an adverse immunologic response and GI symptoms. Data are limited to small case series. Aim Evaluate the clinical spectrum of EG in patients diagnosed at our center from 1987. Methods Charts of patients from 1987 to 2007, with a diagnosis of EG, allergic gastroenteropathy, and eosinophilia were reviewed. Cases defined by: 1) presence of GI symptoms; 2) biopsies demonstrating eosinophilic infiltration of the GI tract, eosinophilic ascites, or characteristic radiographic findings with peripheral eosinophilia (PE); and 3) no evidence of parasitic or extra-intestinal disease. Exclusion criteria included eosinophilic esophagitis, Menetrier's disease, IBD, celiac, connective tissue disease, malignancy, amyloid, Churg-Strauss syndrome, and hypereosinophilic syndrome. A group of patients with unexplained GI symptoms and PE was included for comparison. The association of group category with clinical variables was assessed using Fisher's Exact test. A two-tailed alpha level of 0.05 for each variable examined was used to assess statistical significance. Results A total of 59 subjects were identified with EG: 52
AGA Abstracts
Background: The population prevalence of eosinophilic esophagitis (EoE) has been estimated to be approximately 6.5% in adults. [CGH 2009;7:420-6] Current AGA guidelines recommend endoscopic biopsy (Bx) in patients (pts) with dysphagia. [Gastroenterology 2008;135:1392-1413] We conducted a cost-effectiveness model to determine if endoscopic Bx is cost-effective in pts with refractory GERD (failure of symptom control after empiric PPI therapy (Rx)) both with and without (w/o) dysphagia in order to detect EoE. Methods: Applying a standard cost-effectiveness modeling approach, we estimated probabilities from the medical literature and costs using 2009 Medicare rates. We used quality-adjusted life years (QALYs) for GERD pts on and off of PPI Rx. [Am J Gastroenterol 2005] A time horizon of 1 year was used given the lack of data regarding long-term symptom relief for pts with EoE on Rx. We included the following assumptions: (1) 85% of pts with erosive esophagitis (EE) would become asymptomatic on BID PPI. Pts with EE would not have EoE; (2) 70% of pts with non-erosive disease would improve on BID PPI; those not improved would
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epigastric pain were more frequent in the youngest patients (24% vs. 18% and 17%; p<0.001), as were nausea/vomiting (6.6% vs. 2.4% and 1.7%; p<0.001). Women had significantly greater frequency of dyspepsia (23.4% vs. 14.4%;p<0.001), nausea/vomiting (5.7% vs. 2.9%; p<0.001), and chest pain (4.2% v 2.8%; p=0.013). Men had more frequent dysphagia (62.9% vs. 52.9%; p<0.001). GERD was equally frequent in men and women. Conclusions: Among adult patients undergoing elective upper endoscopy, dysphagia and GERD were the most common presenting symptoms resulting in the histopathologic diagnosis of EoE. Dysphagia, nausea and dyspepsia decreased with age. The rate of food impaction was low in this patient population (non-emergency room setting) and its frequency was slightly higher in men. Conversely, dyspepsia, nausea and chest pain were more common presentations in women. Over 40% of adult patients presented without dysphagia. These observations may strengthen our recognition of the varied presentations of EoE in adults. S1092 Food Allergen Restricted Diet in the Treatment of Paediatric Eosinophilic Esophagitis Richard Muir, Peter Lewindon, Looi C. Ee, Geoffrey D. Withers Introduction Treatment of Eosinophilic Oesophagitis (EO) in children remains challenging. Elemental diet is the gold standard but use is limited by palatability and long term compliance. Kagawalla's paper reported significant improvement on standard 6 food elimination diet in 74% of patients (<10 eosinophils/HPF). Aims of the study were to assess the efficacy of 6 food elimination diet for 6 weeks in children with EO and the role of allergy testing. Methods Eligibility criteria included children with either a new diagnosis of EO (>15 eos/HPF) or previously diagnosed and on stable treatment for the prior three months. Patients with histological evidence of other gastrointestinal diseases (except GOR) were excluded. Skin Prick Testing (SPT) for food and inhalant allergens using standard extracts was undertaken and Atopy Patch Testing (APT) for egg, dairy, corn, soy, wheat, chicken and beef. Patients commenced a diet excluding cow's milk protein, soy, egg, corn, wheat, seafood, peanuts and tree nuts for 6 weeks. At completion, repeat medical assessment including Endoscopy with biopsy was performed. Results 14 patients were enrolled and 13 patients completed the study protocol at time of presentation. Mean age 9 (1-15 years); 11 males and 2 females. Incidence of other atopic disorders requiring treatment was 10/13 (76%) and coexistent topical steroid therapy for EO was 4/13 (30%). On SPT, 7/13 (53%) had positive results (wheal >3mm) with all 7 demonstrating sensitivity to aeroallergens and 2/7 to food allergens. On APT, 10/13 (77%) had positive results, the most common soy (6), cow's milk, egg and corn (5). At conclusion of diet 3/13 had complete histological remission, 2/13 significant histological improvement (3-10 eos/HPF), 2 partial histological response (>50% reduction eos/HPF), 6 were non-responders. Mean eosinophil count dropped from 47.3 to 30 per HPF. All patients reported subjective improvement in symptoms Conclusion 53% of patients had positive histological response rate (RR) to the exclusion diet, 38% showing either significant histological response or entering remission. This histological RR was disappointing versus Kagawalla's RR 74%. Reasons for a lower RR in our study include possible reduced compliance with prescribed diet and older study population. 53% study population displayed sensitivity to aeroallergens consistent with the observation of increasing aeroallergen sensitivity with age. Conclusions from our allergen tests are difficult with small sample population, but there was no clear correlation between positive SPT, APT and response to diet.
S1090 Celiac Sprue and Eosinophilic Esophagitis: Are Duodenal Biopsies Enough? Jessica B. Johnson, Kathryn R. Byrne, Kathleen K. Boynton, Douglas G. Adler, Kathryn Peterson Background: Recent pediatric studies postulate an association between celiac sprue and eosinophilic esophagitis (EoE), suggesting an increased prevalence of celiac disease in children with EoE. No data have been published regarding the prevalence, detection or impact of celiac disease in adults with EoE. Aims: To estimate the prevalence of gluten sensitivity in adults with EoE. To determine the diagnostic yield of small bowel biopsies in identifying gluten sensitivity in EoE patients. To determine whether the addition of celiac serology testing to small bowel biopsy increases detection of gluten sensitivity in EOE patients. To report on the relationship between treatment of gluten sensitivity with dietary avoidance and resolution of symptoms and pathologic findings of EoE. Methods: A retrospective chart review was done on all patients diagnosed with EoE from Jan to Oct, 2009. Data gathered included sex, age, duodenal biopsy pathology, tissue transglutaminase IgA antibody (TTG) positivity, esophageal eosinophil counts, and EGD findings. Duodenal biopsy findings were correlated with TTG results. Gross and microscopic EGD changes with institution of glutenfree diet were recorded.Results: 29 EoE patients were identified who had both duodenal biopsies (6 total biopsies) and TTG antibodies performed. The average age of patients was 37.4 years (std 10.9), and 13/29 (45%) were female. Gluten sensitivity was identified in 4/ 29 (13.8%) patients either by biopsy or TTG. Interestingly, 3 of the 4 patients had evidence of celiac on TTG testing alone (range of TTG 22-250,ref positive = 19) while demonstrating normal duodenal biopsies, and 1 patient had Marsh 1 changes on a duodenal biopsy with normal TTG antibody. IgE levels were not substantially different between possible celiac patients and nonceliac EoE patients (138+/-198 and 248+/-458). 3 patients followed a glutenfree diet. Upon repeat testing of 2 patients, EoE symptoms and histologic findings had resolved after adopting a gluten-free diet. A gluten-free diet also resulted in improvement in nonspecific abdominal symptoms in 3 patients. Conclusion: Similar to pediatric studies, our data suggest celiac sprue is commonly found in the adult population with EoE. Diagnosis may be challenging, as gluten intolerance may be present on TTG testing despite normal duodenal biopsies in EoE patients. Furthermore, this study suggests that gluten-free diets can offer relief of abdominal and esophageal symptoms in patients with EoE. Consequently, TTG testing may further direct clinical care for patients with EoE and should be considered in the setting of normal duodenal biopsies.
S1093 Significant Esophageal Eosinophilia and Typical Endoscopic Features are Highly but Not Exclusively Specific for Eosinofilic Esophagitis Jan Martinek, Alice Strosova, Katerina Kostalova, Tuckova Inna, Petr Hrabal, Filip Zavada, Stepan Suchanek, Magdalena Stefanova, Miroslav Zavoral Background: Eosinophilic esophagitis (EE) is an emerging disease with typical clinical, endoscopic and histo-pathological features. However, some studies suggested that esophageal eosinofilia is not a specific finding for EE. Also endoscopic features of EE (rings, furrows) are considered non-specific. Aim: The aim of our study was to assess the prevalence of esophageal eosiniophilia in a cohort of patients undergoing upper gastrointestinal endoscopy. Methods: A single center prospective study. All patients fulfilling inclusion criteria and agreeing with the participation in the study underwent an upper GI endoscopy including biopsies taken from distal (5 cm above the Z-line) and proximal esophagus. In patients with reflux esophagitis samples were also obtained from the Z-line. The presence and the count of of eosinophils were assessed by two experienced pathologists. Results: 2256 biopsies from 332 patients were analyzed. Eosinophils in the esophageal mucosa were detected in 22 (6.7%) patients. Considering both clinical and histopathological features, EE was diagnosed in 19 patients (5.7%). Among them, in 16 patients the number of eosinophils was higher than 15/HPF and in 14 patients was higher than 20/HPF. In the remaining 3 patients with suspected EE, the number of eosinophils was bellow 15/HPF. In two patients without EE (one with achalasia and one with Barrett esophagus), the number of eosinophils reached high levels (20 and 72/HPF). Dysphagia or food impaction was present in 18 (95%) of the patients with EE, atopy/allergy in 12 (63%) and typical reflux symptoms in 14 (73.7%). Thirteen patients with EE (68%) responded completely or partially to the acid suppressive therapy. The frequency of esophageal eosinophilia in particular endoscopic findings is shown in the Table. Sensitivity, specificity, PPV and NPV of typical endoscopic features (rings, furrows) for diagnosing EE were 72.3%; 96.5%; 98.1% and 59.2%. Conclusions: Significant esophageal eosinophilia is a rare finding among patients with reflux esophagitis, Barrett esophagus or achalasia. On the other hand some patients with clear clinical and endoscopic features of EE do not reach a required number of eosinophils/HPF. Endoscopic findings of rings and/or furrows are moderately sensitive and highly specific for diagnosing of EE. Finally, our results suggest that gastroesophageal reflux plays a role in the development of EE.
S1091 Clinical Presentation of 4905 Adults With Histopathologic Diagnosis of Eosinophilic Esophagitis Robert C. Kapel, Robert M. Genta Background & Aims: Many studies have demonstrated the varied clinical presentations of eosinophilic esophagitis (EoE) in both adults and children. The aim of this study was to examine the presenting symptoms of EoE, by age and gender, in a large group of adult outpatients meeting the histopathologic criteria for this diagnosis. Methods: We utilized the Caris Diagnostics Database of gastrointestinal biopsy specimens from community-based outpatient freestanding endoscopy centers in 42 states, DC, and PR. We analyzed the pathology reports for all esophageal biopsy specimens submitted to Caris Diagnostics from January 2007 through June 2009. We extracted demographic, clinical and endoscopic data from all unique patients, 18 years or older, who had an initial histopathologic diagnosis of EoE “pattern of injury” (>20 eosinophils per high-power field). We excluded patients who presented with a previous diagnosis of EoE, and those who had insufficient clinical data. Results: During the study period 179,685 patients had esophageal biopsies (median age 56 years; 47.6% male); a histopathologic diagnosis of EoE was made in 5,522 patients (3.1%; median age 43; 65.2% male, OR 2.09 95%CI 1.97-2.21). Of the 4,905 patients who met the inclusion criteria, 1,887 were aged 18 to 39 (67.4% male), 2,227 were 40 to 59 (65.3%), and 791 were 60 or older (60.8%). The frequencies of GERD (41%, 40%, 40% in groups of increasing age, respectively); chest pain (4%, 3%, 3%); and food impaction (1.2%, 0.7%, 0.5%) were similar across age groups. Dysphagia was less frequent in the oldest group (55%) than in the younger groups (59% and 61%; p<0.001). Dyspepsia/
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AGA Abstracts
AGA Abstracts
undergo motility and pH testing; (3) Pts found to have EoE would be treated with fluticasone. Allergy testing or immunotherapy treatments were not included; (4) For pts undergoing endoscopy (EGD) w/o Bx, EoE would be missed. Results: Assuming base case probabilities (Table 1), the EGD w/o Bx arm cost $643 and was associated with 0.953 QALYs. The EGD with Bx arm cost $853 and was associated with 0.957 QALYs. The resulting incremental cost-effectiveness ratio (ICER) was $52,500 per QALY for the EGD with Bx arm. Tornedo analysis demonstrated that the results were sensitive to the following variables in descending order of influence: cost of EGD with Bx, cost of EGD w/o Bx, probability of EoE in pts with and w/o dysphagia, and symptom resolution on fluticasone. In one-way sensitivity analysis, the ICER exceeded $100K when the probability of EoE in pts w/o dysphagia was 3% or less, or if symptom resolution on fluticasone was 67% or less. The ICER for the EGD with Bx arm exceeded $100K when the cost > $700. Conclusions: Upper endoscopy with Bx for EoE appears to be a cost-effective approach when the probability of EoE in pts with refractory GERD exceeds 3%. Table 1. Model Probabilities