1. 1 Literature Review Peter R. McNally, DO, FACP, FACG University Colorado Denver School of Medicine Center for Human Simulation Aurora, Colorado 80045

2. 2 Kapel RC 1, Miller JK 2, Torres C 3, Aksoy S 3, Lash R 3 and Katzka DA 2. Eosinophilic Esophagitis: A Prevalent Disease in the United States that Affects All Age Groups. Gastroenterology. 2008;134:1316-1321. 2 1 Danbury Hospital, Danbury, Connecticut, 2 University of Pennsylvania, Pennsylvania and 3 Caris Diagnostics, Irving, Texas

3. 3Introduction Eosinophilic Esophagitis (EOE) is a condition of increasing recognition among both adults and children. Eosinophilic Esophagitis (EOE) is a condition of increasing recognition among both adults and children. All physicians should consider EOE in the differential diagnosis among persons with Upper GI symptoms especially dysphagia, abdominal pain and GERD/dyspepsia. All physicians should consider EOE in the differential diagnosis among persons with Upper GI symptoms especially dysphagia, abdominal pain and GERD/dyspepsia. When endoscopy is performed in these patients, proximal esophageal biopsies should be obtained and specifically examined for mucosal eosinophils. When endoscopy is performed in these patients, proximal esophageal biopsies should be obtained and specifically examined for mucosal eosinophils. Blanchard C, et al. Eosinophilic Esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol. 2006;118:1054-1059

4. 4 Aim The value of most current reports on EOE are limited by sample bias (derived from tertiary or academic centers) and small sample size. The value of most current reports on EOE are limited by sample bias (derived from tertiary or academic centers) and small sample size. The aim of this study was determine the clinical features of EOE among a larger and broader population than previously reported from most academic centers. The aim of this study was determine the clinical features of EOE among a larger and broader population than previously reported from most academic centers. This study used a very large computerized pathology database of patients seen at community level practices from across the United States (34 states). This study used a very large computerized pathology database of patients seen at community level practices from across the United States (34 states). Kapel RC, et al. Gastroent. 2008;134:1316-1321.

5. 5 Study Design: Study Population Caris Diagnostic (Irving, Texas) provides GI pathology support for community based free standing endoscopy centers across US. Caris Diagnostic (Irving, Texas) provides GI pathology support for community based free standing endoscopy centers across US. – Case materials derived from 34 states – Majority of patients were adults (98.5% > 18 yr) Database consisted of 414,598 patient cases Database consisted of 414,598 patient cases Study Period: 2002-2006, all evaluable cases included esophageal biopsies Study Period: 2002-2006, all evaluable cases included esophageal biopsies Kapel RC, et al. Gastroent. 2008;134:1316-1321.

6. 6 Study Design: Study Population WinSURGE software used to search the Caris Database for the word “eosinophilic” WinSURGE software used to search the Caris Database for the word “eosinophilic” All identified cases reviewed by 3 pathologists All identified cases reviewed by 3 pathologists Esophageal specimens examined for # eosinophils per 400X high-power field, selected from the 5 most densely populated Esophageal specimens examined for # eosinophils per 400X high-power field, selected from the 5 most densely populated Kapel RC, et al. Gastroent. 2008;134:1316-1321.

7. 7 Study Design: Definition of EOE I: Mean EO >20/HPF in 5 HPF or or II: Mean EO >30/HPF when 30/HPF when < 5 HPF available Kapel RC, et al. Gastroent. 2008;134:1316-1321. Example: >25 eosinophils/HPF

8. 8 Study Results Esophageal Biopsy Specimens from 74,162 EGD’S 98% adult (34 states) 2% < 18 yoa (23 states) 217 Referral Centers Cases of Confirmed EOE Identified (total n=363): 308 Criteria I 55 Criteria II 55 Criteria II Kapel RC, et al. Gastroent. 2008;134:1316-1321.

9. 9 Study Results Kapel RC, et al. Gastroent. 2008;134:1316-1321. Total EE, N=363

10. 10 Study Results Demographics of EOE Cases (n=363) ♂ to ♀ ratio of 3:1 (270 to 93) ♂ to ♀ ratio of 3:1 (270 to 93) Age range: 1 to 98 yrs, mean 37.6 yrs Age range: 1 to 98 yrs, mean 37.6 yrs Adult n = 321, Children n = 42 Adult n = 321, Children n = 42 #1 Symptom #1 Symptom – Adult Dysphagia 70% – Children GERD 38% Kapel RC, et al. Gastroent. 2008;134:1316-1321.

11. 11 Study Results Kapel RC, et al. Gastroent. 2008;134:1316-1321. Indication for EGD by gender, p = NS

12. 12 Study Results Kapel RC, et al. Gastroent. 2008;134:1316-1321. Indication#Frequency 95% CI Dysphagia22570%64.8-75.1 GERD/ Heartburn 8727%22.3-32.3 Abd Pain/ Dyspepsia4213%9.6-17.3 Odynophagia175%3.1-8.3 Stricture134%2.2-6.8 Indications for EGD in Adult EOE Cases

13. 13 Study Results Kapel RC, et al. Gastroent. 2008;134:1316-1321. Indication#Frequency 95% CI GERD/ Heartburn 163823.6-54.5 Abd Pain/ Dyspepsia133117.7-47.1 Dysphagia112613.9-42.0 Nausea/Vomiting6145.4-28.5 Chest Pain 24.80.6-16.2 Indications for EGD in EOE Cases Younger than 18 yrs

14. 14 Study Results The indications for EGD among adults and those < 18 yr were varied. The indications for EGD among adults and those < 18 yr were varied. – Adults: Dysphagia > GERD > Abd pain – Abd pain > Dysphagia Indications for EGD by gender did not vary. Indications for EGD by gender did not vary. Kapel RC, et al. Gastroent. 2008;134:1316-1321.

15. 15 Study Results Kapel RC, et al. Gastroent. 2008;134:1316-1321.

16. 16 Conclusions: 1. EOE is a disorder of increasing prevalence 2. EOE is found across the nation, and is not confined to tertiary referral or academic institutions 3. EOE is male gender dominant (♂ to ♀ ratio of 3:1) 4. Presenting Symptoms of EOE vary by Age Group Adults: Dysphagia (70%),GERD(27%),Abd pain (13%) <18 yr: GERD (38%), Abd pain(31%),Dysphagia (26%) Kapel RC, et al. Gastroent. 2008;134:1316-1321.

17. 17 Reviewer Comments Kapel, et al, do not answer the following questions? 1. Why is the diagnosis of EOE more common today? a. Physician awareness? b. Changes in allergic disorders or precipitating allergens? 2. Why do the many pts present with EOE during middle age? 3. Why do presenting clinical symptoms vary by age group? 4. Why is EOE dramatically more common among men? Kapel RC, et al. Gastroent. 2008;134:1316-1321.

18. 18 Reviewer Comments 1. Dr. Kapel and colleagues are commended for demonstrating how a large computerized database from a community level health care system of patients with GI disorders can provide enlightening information. 2. Although EOE is a disorder more common among men (3:1), both genders exhibit similar symptoms at presentation with dysphagia #1 among adults and GERD #1 among children. 3. Kapel et al, findings emphasize the need for heightened physician awareness of EOE among community practices across the US and the need to consider EOE in the differential diagnosis of persons with a variety of Upper GI digestive complaints. Kapel RC, et al. Gastroent. 2008;134:1316-1321.

19. 19 Reviewer Comments 1. The clinician is urged to remember that EOE may present with a multitude of Upper GI complaints. Although dysphagia is the most common symptom among adults, EOE should be considered among all patients presenting with symptoms of GERD, abdominal pain, dyspepsia, chest pain, & nausea/vomiting. 2. Most endoscopists are in tuned to the endoscopic findings of multiple esophageal rings and vertical groves, but need to be vigilant and biopsy from involved and uninvolved segments even in the absence of endoscopic findings. Kapel RC, et al. Gastroent. 2008;134:1316-1321.