- Email: [email protected]
Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease
Journal Pre-proof Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease Amnon Sonnenberg, MD, MSc, Kevin O. Turner, DO, Robert M. Genta, MD
PII: DOI: Reference:
S1542-3565(20)30183-X https://doi.org/10.1016/j.cgh.2020.02.015 YJCGH 57005
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 1 February 2020 Please cite this article as: Sonnenberg A, Turner KO, Genta RM, Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease, Clinical Gastroenterology and Hepatology (2020), doi: https://doi.org/10.1016/j.cgh.2020.02.015. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 by the AGA Institute
Sonnenberg 1
CGH-D-20-00009.R1
Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease Amnon Sonnenberg, MD, MSc1, Kevin O. Turner, DO2, Robert M. Genta, MD2,3
NUMBER OF WORDS: text 749 NUMBER OF FIGURES: 0 NUMBER OF TABLES: 1 (and 1 additional table as appendix) RUNNING HEAD: EoE and IBD Comorbidity DECLARATION OF CONFLICT OF INTEREST: A Sonnenberg has no conflict of interest to declare. KO Turner and RM Genta are employed by Inform Diagnostics, Irving, TX. No funding was obtained for this study. AUTHOR CONTRIBUTIONS: Study conception and design: A Sonnenberg, RM Genta; data analysis: A Sonnenberg, RM Genta; writing of manuscript: A Sonnenberg, KO Turner, RM Genta. INSTITUTIONAL AFFILIATIONS: 1Division of Gastroenterology, Portland VA Medical Center and Oregon Health & Science University; 2Inform Diagnostics, Irving, Texas; 3Baylor College of Medicine, Houston, Texas. ADDRESS
FOR
CORRESPONDENCE: Amnon Sonnenberg, Portland VA Medical Center, P3-GI,
Portland OR 97239. Phone: 503-220-8262, Email: [email protected]
Sonnenberg 2
Introduction In a previous study, we found a variety of inverse associations between the occurrence of gastroesophageal reflux disease (GERD) and the occurrence of various forms of inflammatory bowel disease (IBD), as well as microscopic colitis (MC) and its two subtypes of lymphocytic and collagenous colitis (LC and CC) [1]. Two recent studies suggested a 5-fold increase in the occurrence of eosinophilic esophagitis (EoE) among IBD patients [2-3]. The aim of the present study was to confirm these positive associations between EoE and IBD.
Methods The Inform Diagnostics database is a national electronic repository of histopathologic records from patients distributed throughout the entire United States. Because patient records were deidentified before being included in the present analysis, the study protocol was granted exemption by the Institutional Review Board. This database has been used in the past for studies dealing with the epidemiology of various gastrointestinal disorders [4-8]. Patients were diagnosed with IBD, MC, and EoE based on their clinical history and the presence of corresponding histopathologic findings, using the microscopic criteria described in these previous publications. In a case-control study among 302,061 patients undergoing bidirectional endoscopy on the same day, we evaluated whether the occurrence of IBD and MC was influenced by the presence of EoE. The influence of EoE on the occurrence of ileo-colonic inflammatory diseases was expressed as odds ratios (OR) with their 95% confidence intervals (CI), using multivariate logistic regression to adjust for the confounding influence of age, gender, and the histologic presence of gastric H. pylori infection.
Sonnenberg 3
Results The database contained 3,860 UC patients, 3,330 CD patients, 1,476 patients with indeterminate colitis with respect to UC or CD, and 5,296 MC patients. A group of 127,489 patients without any type of IBD, MC or GERD served as control population. Within the case-control population, 1,628 patients were diagnosed with EoE and 12,949 patients harbored H. pylori (Table 1). Cases with IBD or MC were significantly younger than control subjects (p<0.001 for all comparisons). Compared to the control population, IBD was slightly more common in males than females (1.42, 1.36-1.49), whereas MC was strikingly more common in females than males (2.23, 2.09-2.39). Gastric H. pylori infection was significantly less common among all IBD or MC cases than control subjects. EoE was less common in the overall IBD, CD, and MC case populations than the control population. The bottom lines of Table 1 contain the crude and adjusted ORs for the associations between EoE and the various case populations. The adjusted odds revealed a set of inverse relationships between EoE and IBD or MC.
Discussion Unexpectedly, the present analysis revealed statistically significant inverse relationships between EoE and CD or MC, but not UC. The study by Fan et al. relied on a small group of 12 patients with comorbid occurrence of EoE and IBD, but without a population-based control group. The seeming comorbid clustering of the two diseases may reflect on the accumulation of rare diagnoses in a large tertiary referral center. It is more difficult to reconcile the difference between the results of the present analysis and the publication by Limketkai BN et al. [2]. Both studies relied on the health records from large electronic databases. While the case definition is usually straightforward and mostly unambiguous, the choice of the appropriate control population can sometimes exert a marked influence on the final outcomes of the analysis. For instance, a control group that contains a large group of undiagnosed or hidden cases could shift
Sonnenberg 4
the comparison towards the null hypothesis. For these reasons we decided to exclude patients with any type reflux disease from the control population. Although our patient population comprised mostly adults, EoE is also relatively common in the pediatric population. It is conceivable that a case population comprised of many pediatric patients would reveal associations that are less common among a control population of mostly adults. Because H. pylori infection is inversely associated with all disease states included in the present analysis, we also adjusted our results for its potentially confounding influence. The relatively large difference between the crude and adjusted OR values appears to validate these concerns. The epidemiologic patterns observed by the present analysis fit well with similar patterns previously observed in other types of esophageal disease, such as Barrett’s esophagus and reflux esophagitis, which were also inversely associated with IBD and MC [1]. Antisecretory medication, in the treatment of GERD and EoE, may influence the gastrointestinal microbiome and influence IBD occurrence. This hypothesis lends itself to be tested in additional epidemiologic studies.
References 1. Sonnenberg A, Turner KO, Genta RM. Decreased risk for microscopic colitis and inflammatory bowel disease among patients with reflux disease. Colorectal Dis 2018;20:813820. 2. Fan YC, Steele D, Kochar B, Arsene D, Long MD, Dellon ES. Increased prevalence of esophageal eosinophilia in patients with inflammatory bowel bisease. Inflamm Intest Dis 2018;3:180-186 3. Limketkai BN, Shah SC, Hirano I, Bellaguarda E, Colombel JF. Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis. Gut 2019;68:2152-2160.
Sonnenberg 5
4. Malhotra R, Turner K, Sonnenberg A, Genta RM. High prevalence of inflammatory bowel disease in United States residents of Indian ancestry. Clin Gastroenterol Hepatol 2015;13:683-689. 5. Jensen ET, Shah ND, Hoffman K, Sonnenberg A, Genta RM, Dellon ES. Seasonal variation in detection of esophageal eosinophilia and eosinophilic esophagitis. Aliment Pharmacol Ther 2015:42:461-469. 6. Sonnenberg A, Dellon ES, Turner KO, Genta RM. The influence of Helicobacter pylori on the ethnic distribution of esophageal eosinophilia. Helicobacter 2017;22:e12370. 7. Sonnenberg A, Turner KO, Genta RM. Associations of microscopic colitis with other lymphocytic disorders of the gastrointestinal tract. Clin Gastroenterol Hepatol 2018;16: 1762-1767. 8. Sonnenberg A, Turner KO, Genta RM. Associations of microscopic colitis with other lymphocytic disorders of the gastrointestinal tract. Clin Gastroenterol Hepatol 2018;16:17621767.
Sonnenberg 6 Table 1. Patient characteristics and associations between EoE and IBD or MC Patient characteristics
Grand Total
IBD N
8,666
(%)
(100.0%)
Ulcerative colitis N
3,860
(%)
(100.0%)
Crohn's disease N
3,330
(%)
(100.0%)
Indeterm. colitis N
1,476
(%)
(100.0%)
Microscopic colitis N
5,296
(%)
(100.0%)
Lymphocytic colitis N
2,964
(%)
(100.0%)
Collagenous colitis N
2,332
(%)
(100.0%)
Control group N
(%)
127,489
(100.0%)
Age Mean age (SD)
47.7
(0.6%)
48.8
(17.2)
45.2
(17.8)
50.7
(17.0)
47.7
(17.5)
48.8
(17.2)
45.2
(17.8)
55.4
(16.9)
<18
325
(3.8%)
111
(2.9%)
174
(5.2%)
40
(2.7%)
21
(0.4%)
15
(0.5%)
6
(0.3%)
2,575
(2.0%)
18-65
6,710
(77.4%)
2,981
(77.2%)
2,631
(79.0%)
1,098
(74.4%)
2,720
(51.4%)
1,664
(56.1%)
1,056
(45.3%)
82,514
(64.7%)
>65
1,631
(18.8%)
768
(19.9%)
525
(15.8%)
338
(22.9%)
2,555
(48.2%)
1,285
(43.4%)
1,270
(54.5%)
42,400
(33.3%)
Sex* Female
4,665
(53.8%)
1,976
(51.2%)
1,893
(56.8%)
796
(53.9%)
4,665
(88.1%)
1,999
(67.4%)
1,893
(81.2%)
79,515
(62.4%)
Male
3,975
(45.9%)
1,880
(48.7%)
1,423
(42.7%)
672
(45.5%)
3,975
(75.1%)
1,895
(63.9%)
1,423
(61.0%)
47,571
(37.3%)
Histopathology Gastric H. pylori EoE
344
(4.0%)
194
(5.0%)
89
(2.7%)
61
(4.1%)
121
(2.3%)
76
(2.6%)
76
(3.3%)
12,484
(9.8%)
98
(1.1%)
65
(1.7%)
26
(0.8%)
7
(0.5%)
27
(0.5%)
20
(0.7%)
7
(0.3%)
1,503
(1.2%)
EoE versus IBD or MC crude OR (95% CI)
0.96
(0.78 - 1.17)
1.44
(1.12 - 1.84)
0.66
(0.44 - 0.95)
0.40
(0.19 - 0.84)
0.43
(0.29 - 0.62)
0.57
(0.35 - 0.86)
0.25
(0.11 - 0.49)
-
adjusted OR (95% CI)**
0.64
(0.51 - 0.78)
0.97
(0.75 - 1.24)
0.41
(0.27 - 0.60)
0.29
(0.12 - 0.56)
0.68
(0.45 - 0.98)
0.80
(0.50 - 1.21)
0.48
(0.20 - 0.93)
-
*Gender non-specified in 444 patients; **significant adjusted OR highlighted using bold font; CI, confidence interval; EoE, eosinophilic esophagitis; IBD, inflammatory bowel disease; MC, microscopic colitis; OR, odds ratio.
Table Appendix. List of the most common symptoms listed as indication for endoscopy Common indication for endoscopy*
IBD N
Grand Total*
8,666
Reflux symptoms
2,890
(%)
Ulcerative colitis N
(100%)
3,860
(33%)
1,442
(%)
(100%)
Crohn's disease N
3,330
(%)
(100%)
Indeterm. colitis N
1,476
(%)
Microscopic colitis N
(100%)
5,296 1,680
(%)
(100%)
Lymphocytic colitis N
2,964
(%)
(100%)
Collagenous colitis N
2,332
Control group**
(%)
(100%)
N
(%)
127,489
(100%)
(37%)
895
(27%)
553
(37%)
(32%)
922
(31%)
758
(33%)
Dysphagia
715
(8%)
363
(9%)
231
(7%)
121
(8%)
429
(8%)
213
(7%)
216
(9%)
12,488
(10%)
Dyspepsia
499
(6%)
241
(6%)
187
(6%)
71
(5%)
365
(7%)
202
(7%)
163
(7%)
17,081
(13%)
(15%)
591
(15%)
430
28,821
(1%)
23
(1%)
Epigastric pain Abdominal pain Diarrhea
1,267 44 2,306
(27%)
1,066
(28%)
9 879
(13%)
246
(17%)
733
(14%)
456
(15%)
277
(12%)
(0%)
12
(1%)
28
(1%)
16
(1%)
12
(1%)
(26%)
361
(24%)
4,485
(85%)
2,522
(85%)
1,963
-
619
(23%) (0%)
(84%)
34,080
(27%)
Anemia
873
(10%)
398
(10%)
339
(10%)
136
(9%)
271
(5%)
112
(4%)
159
(7%)
20,265
(16%)
Weight loss
511
(6%)
226
(6%)
210
(6%)
75
(5%)
765
(14%)
404
(14%)
361
(15%)
10,040
(8%)
*Individual patients may have presented with multiple indications; **patients without any type of IBD, MC, or GERD served as controls.
PII: DOI: Reference:
S1542-3565(20)30183-X https://doi.org/10.1016/j.cgh.2020.02.015 YJCGH 57005
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 1 February 2020 Please cite this article as: Sonnenberg A, Turner KO, Genta RM, Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease, Clinical Gastroenterology and Hepatology (2020), doi: https://doi.org/10.1016/j.cgh.2020.02.015. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 by the AGA Institute
Sonnenberg 1
CGH-D-20-00009.R1
Comorbid Occurrence of Eosinophilic Esophagitis and Inflammatory Bowel Disease Amnon Sonnenberg, MD, MSc1, Kevin O. Turner, DO2, Robert M. Genta, MD2,3
NUMBER OF WORDS: text 749 NUMBER OF FIGURES: 0 NUMBER OF TABLES: 1 (and 1 additional table as appendix) RUNNING HEAD: EoE and IBD Comorbidity DECLARATION OF CONFLICT OF INTEREST: A Sonnenberg has no conflict of interest to declare. KO Turner and RM Genta are employed by Inform Diagnostics, Irving, TX. No funding was obtained for this study. AUTHOR CONTRIBUTIONS: Study conception and design: A Sonnenberg, RM Genta; data analysis: A Sonnenberg, RM Genta; writing of manuscript: A Sonnenberg, KO Turner, RM Genta. INSTITUTIONAL AFFILIATIONS: 1Division of Gastroenterology, Portland VA Medical Center and Oregon Health & Science University; 2Inform Diagnostics, Irving, Texas; 3Baylor College of Medicine, Houston, Texas. ADDRESS
FOR
CORRESPONDENCE: Amnon Sonnenberg, Portland VA Medical Center, P3-GI,
Portland OR 97239. Phone: 503-220-8262, Email: [email protected]
Sonnenberg 2
Introduction In a previous study, we found a variety of inverse associations between the occurrence of gastroesophageal reflux disease (GERD) and the occurrence of various forms of inflammatory bowel disease (IBD), as well as microscopic colitis (MC) and its two subtypes of lymphocytic and collagenous colitis (LC and CC) [1]. Two recent studies suggested a 5-fold increase in the occurrence of eosinophilic esophagitis (EoE) among IBD patients [2-3]. The aim of the present study was to confirm these positive associations between EoE and IBD.
Methods The Inform Diagnostics database is a national electronic repository of histopathologic records from patients distributed throughout the entire United States. Because patient records were deidentified before being included in the present analysis, the study protocol was granted exemption by the Institutional Review Board. This database has been used in the past for studies dealing with the epidemiology of various gastrointestinal disorders [4-8]. Patients were diagnosed with IBD, MC, and EoE based on their clinical history and the presence of corresponding histopathologic findings, using the microscopic criteria described in these previous publications. In a case-control study among 302,061 patients undergoing bidirectional endoscopy on the same day, we evaluated whether the occurrence of IBD and MC was influenced by the presence of EoE. The influence of EoE on the occurrence of ileo-colonic inflammatory diseases was expressed as odds ratios (OR) with their 95% confidence intervals (CI), using multivariate logistic regression to adjust for the confounding influence of age, gender, and the histologic presence of gastric H. pylori infection.
Sonnenberg 3
Results The database contained 3,860 UC patients, 3,330 CD patients, 1,476 patients with indeterminate colitis with respect to UC or CD, and 5,296 MC patients. A group of 127,489 patients without any type of IBD, MC or GERD served as control population. Within the case-control population, 1,628 patients were diagnosed with EoE and 12,949 patients harbored H. pylori (Table 1). Cases with IBD or MC were significantly younger than control subjects (p<0.001 for all comparisons). Compared to the control population, IBD was slightly more common in males than females (1.42, 1.36-1.49), whereas MC was strikingly more common in females than males (2.23, 2.09-2.39). Gastric H. pylori infection was significantly less common among all IBD or MC cases than control subjects. EoE was less common in the overall IBD, CD, and MC case populations than the control population. The bottom lines of Table 1 contain the crude and adjusted ORs for the associations between EoE and the various case populations. The adjusted odds revealed a set of inverse relationships between EoE and IBD or MC.
Discussion Unexpectedly, the present analysis revealed statistically significant inverse relationships between EoE and CD or MC, but not UC. The study by Fan et al. relied on a small group of 12 patients with comorbid occurrence of EoE and IBD, but without a population-based control group. The seeming comorbid clustering of the two diseases may reflect on the accumulation of rare diagnoses in a large tertiary referral center. It is more difficult to reconcile the difference between the results of the present analysis and the publication by Limketkai BN et al. [2]. Both studies relied on the health records from large electronic databases. While the case definition is usually straightforward and mostly unambiguous, the choice of the appropriate control population can sometimes exert a marked influence on the final outcomes of the analysis. For instance, a control group that contains a large group of undiagnosed or hidden cases could shift
Sonnenberg 4
the comparison towards the null hypothesis. For these reasons we decided to exclude patients with any type reflux disease from the control population. Although our patient population comprised mostly adults, EoE is also relatively common in the pediatric population. It is conceivable that a case population comprised of many pediatric patients would reveal associations that are less common among a control population of mostly adults. Because H. pylori infection is inversely associated with all disease states included in the present analysis, we also adjusted our results for its potentially confounding influence. The relatively large difference between the crude and adjusted OR values appears to validate these concerns. The epidemiologic patterns observed by the present analysis fit well with similar patterns previously observed in other types of esophageal disease, such as Barrett’s esophagus and reflux esophagitis, which were also inversely associated with IBD and MC [1]. Antisecretory medication, in the treatment of GERD and EoE, may influence the gastrointestinal microbiome and influence IBD occurrence. This hypothesis lends itself to be tested in additional epidemiologic studies.
References 1. Sonnenberg A, Turner KO, Genta RM. Decreased risk for microscopic colitis and inflammatory bowel disease among patients with reflux disease. Colorectal Dis 2018;20:813820. 2. Fan YC, Steele D, Kochar B, Arsene D, Long MD, Dellon ES. Increased prevalence of esophageal eosinophilia in patients with inflammatory bowel bisease. Inflamm Intest Dis 2018;3:180-186 3. Limketkai BN, Shah SC, Hirano I, Bellaguarda E, Colombel JF. Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis. Gut 2019;68:2152-2160.
Sonnenberg 5
4. Malhotra R, Turner K, Sonnenberg A, Genta RM. High prevalence of inflammatory bowel disease in United States residents of Indian ancestry. Clin Gastroenterol Hepatol 2015;13:683-689. 5. Jensen ET, Shah ND, Hoffman K, Sonnenberg A, Genta RM, Dellon ES. Seasonal variation in detection of esophageal eosinophilia and eosinophilic esophagitis. Aliment Pharmacol Ther 2015:42:461-469. 6. Sonnenberg A, Dellon ES, Turner KO, Genta RM. The influence of Helicobacter pylori on the ethnic distribution of esophageal eosinophilia. Helicobacter 2017;22:e12370. 7. Sonnenberg A, Turner KO, Genta RM. Associations of microscopic colitis with other lymphocytic disorders of the gastrointestinal tract. Clin Gastroenterol Hepatol 2018;16: 1762-1767. 8. Sonnenberg A, Turner KO, Genta RM. Associations of microscopic colitis with other lymphocytic disorders of the gastrointestinal tract. Clin Gastroenterol Hepatol 2018;16:17621767.
Sonnenberg 6 Table 1. Patient characteristics and associations between EoE and IBD or MC Patient characteristics
Grand Total
IBD N
8,666
(%)
(100.0%)
Ulcerative colitis N
3,860
(%)
(100.0%)
Crohn's disease N
3,330
(%)
(100.0%)
Indeterm. colitis N
1,476
(%)
(100.0%)
Microscopic colitis N
5,296
(%)
(100.0%)
Lymphocytic colitis N
2,964
(%)
(100.0%)
Collagenous colitis N
2,332
(%)
(100.0%)
Control group N
(%)
127,489
(100.0%)
Age Mean age (SD)
47.7
(0.6%)
48.8
(17.2)
45.2
(17.8)
50.7
(17.0)
47.7
(17.5)
48.8
(17.2)
45.2
(17.8)
55.4
(16.9)
<18
325
(3.8%)
111
(2.9%)
174
(5.2%)
40
(2.7%)
21
(0.4%)
15
(0.5%)
6
(0.3%)
2,575
(2.0%)
18-65
6,710
(77.4%)
2,981
(77.2%)
2,631
(79.0%)
1,098
(74.4%)
2,720
(51.4%)
1,664
(56.1%)
1,056
(45.3%)
82,514
(64.7%)
>65
1,631
(18.8%)
768
(19.9%)
525
(15.8%)
338
(22.9%)
2,555
(48.2%)
1,285
(43.4%)
1,270
(54.5%)
42,400
(33.3%)
Sex* Female
4,665
(53.8%)
1,976
(51.2%)
1,893
(56.8%)
796
(53.9%)
4,665
(88.1%)
1,999
(67.4%)
1,893
(81.2%)
79,515
(62.4%)
Male
3,975
(45.9%)
1,880
(48.7%)
1,423
(42.7%)
672
(45.5%)
3,975
(75.1%)
1,895
(63.9%)
1,423
(61.0%)
47,571
(37.3%)
Histopathology Gastric H. pylori EoE
344
(4.0%)
194
(5.0%)
89
(2.7%)
61
(4.1%)
121
(2.3%)
76
(2.6%)
76
(3.3%)
12,484
(9.8%)
98
(1.1%)
65
(1.7%)
26
(0.8%)
7
(0.5%)
27
(0.5%)
20
(0.7%)
7
(0.3%)
1,503
(1.2%)
EoE versus IBD or MC crude OR (95% CI)
0.96
(0.78 - 1.17)
1.44
(1.12 - 1.84)
0.66
(0.44 - 0.95)
0.40
(0.19 - 0.84)
0.43
(0.29 - 0.62)
0.57
(0.35 - 0.86)
0.25
(0.11 - 0.49)
-
adjusted OR (95% CI)**
0.64
(0.51 - 0.78)
0.97
(0.75 - 1.24)
0.41
(0.27 - 0.60)
0.29
(0.12 - 0.56)
0.68
(0.45 - 0.98)
0.80
(0.50 - 1.21)
0.48
(0.20 - 0.93)
-
*Gender non-specified in 444 patients; **significant adjusted OR highlighted using bold font; CI, confidence interval; EoE, eosinophilic esophagitis; IBD, inflammatory bowel disease; MC, microscopic colitis; OR, odds ratio.
Table Appendix. List of the most common symptoms listed as indication for endoscopy Common indication for endoscopy*
IBD N
Grand Total*
8,666
Reflux symptoms
2,890
(%)
Ulcerative colitis N
(100%)
3,860
(33%)
1,442
(%)
(100%)
Crohn's disease N
3,330
(%)
(100%)
Indeterm. colitis N
1,476
(%)
Microscopic colitis N
(100%)
5,296 1,680
(%)
(100%)
Lymphocytic colitis N
2,964
(%)
(100%)
Collagenous colitis N
2,332
Control group**
(%)
(100%)
N
(%)
127,489
(100%)
(37%)
895
(27%)
553
(37%)
(32%)
922
(31%)
758
(33%)
Dysphagia
715
(8%)
363
(9%)
231
(7%)
121
(8%)
429
(8%)
213
(7%)
216
(9%)
12,488
(10%)
Dyspepsia
499
(6%)
241
(6%)
187
(6%)
71
(5%)
365
(7%)
202
(7%)
163
(7%)
17,081
(13%)
(15%)
591
(15%)
430
28,821
(1%)
23
(1%)
Epigastric pain Abdominal pain Diarrhea
1,267 44 2,306
(27%)
1,066
(28%)
9 879
(13%)
246
(17%)
733
(14%)
456
(15%)
277
(12%)
(0%)
12
(1%)
28
(1%)
16
(1%)
12
(1%)
(26%)
361
(24%)
4,485
(85%)
2,522
(85%)
1,963
-
619
(23%) (0%)
(84%)
34,080
(27%)
Anemia
873
(10%)
398
(10%)
339
(10%)
136
(9%)
271
(5%)
112
(4%)
159
(7%)
20,265
(16%)
Weight loss
511
(6%)
226
(6%)
210
(6%)
75
(5%)
765
(14%)
404
(14%)
361
(15%)
10,040
(8%)
*Individual patients may have presented with multiple indications; **patients without any type of IBD, MC, or GERD served as controls.