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Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017
Accepted Manuscript Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017 Emad Mansoor, MD, Mohannad Abou Saleh, MBBS, Gregory S. Cooper, MD
PII: DOI: Reference:
S1542-3565(17)30691-2 10.1016/j.cgh.2017.05.050 YJCGH 55283
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 31 May 2017 Please cite this article as: Mansoor E, Saleh MA, Cooper GS, Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017, Clinical Gastroenterology and Hepatology (2017), doi: 10.1016/j.cgh.2017.05.050. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
ACCEPTED MANUSCRIPT Title: Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017 Short Title: The Prevalence of Eosinophilic Gastroenteritis and Colitis Authors: Emad Mansoor, MD, Mohannad Abou Saleh, MBBS and Gregory S.
First Author: Emad Mansoor, MD Department of Internal Medicine
Case Western Reserve University 11100 Euclid Avenue Cleveland, Ohio 44106 [email protected]
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Second Author:
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University Hospitals Cleveland Medical Center
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Cooper, MD
Mohannad Abou Saleh, MBBS
Department of Internal Medicine
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University Hospitals Cleveland Medical Center
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Case Western Reserve University 11100 Euclid Avenue
Cleveland, Ohio 44106
Corresponding author: Gregory S. Cooper, MD Department of Internal Medicine and Division of Gastroenterology and Liver Disease University Hospitals Cleveland Medical Center Case Western Reserve University
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ACCEPTED MANUSCRIPT 11100 Euclid Avenue Cleveland, Ohio 44106, Wearn 244 [email protected] +1 216-844-5385
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Grant Support: Supported in part by the Cleveland Digestive Diseases Research Core Center (1P30DK097948). Abbreviations:
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EGIDs- Eosinophilic Gastrointestinal Diseases GI- Gastrointestinal EoE- Eosinophilic esophagitis EoG- Eosinophilic gastritis EoGE- Eosinophilic gastroenteritis EoC- Eosinophilic colitis US- United States EHR- Electronic Health Record HDG- Health Data Gateway SNOMED-CT- Systematized Nomenclature Of Medicine – Clinical Terms HIPAA- Health Insurance Portability and Accountability Act IRB- Institutional Review Board GERD- Gastroesophageal reflux disease OR- Odds ratio CI- Confidence Interval ICD-9- International Classification of Diseases, Ninth Revision
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Conflicts of interest: There are no potential conflicts (financial, professional, or
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personal) to disclose by all the authors (Emad Mansoor, Mohannad Abou Saleh and Gregory S. Cooper).
Writing Assistance: There is no writing assistance to disclose. Author Contributions: Study conception and design: Mansoor and Cooper Acquisition of data: Mansoor and Abou Saleh Analysis and interpretation of data: Mansoor and Cooper Drafting of manuscript: Mansoor, Abou Saleh and Cooper
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ACCEPTED MANUSCRIPT Critical revision: Cooper Statistical Analysis: Abou Saleh and Mansoor Obtained funding: Cooper
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Study Supervision: Cooper
Word count: 2,981
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Abstract:
Background & Aims: Although eosinophilic esophagitis (EoE) has been extensively
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studied, there have been few epidemiology studies of other eosinophilic gastrointestinal disorders (EGIDs). Using a large, population-based database, we investigated epidemiologic features of eosinophilic gastroenteritis (EoGE), and colitis
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(EoC) in the United States (US).
Methods: We collected data from a commercial database (Explorys Inc, Cleveland, OH) that provided electronic health records from 26 major integrated US healthcare
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systems from 1999 to March 2017. We identified a cohort of adult and pediatric
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patients with EoGE and EoC from March 2012 through March 2017, based on the Systematized Nomenclature of Medicine – Clinical Terms. We calculated the overall prevalence of EoGE and EoC among different patient groups, and performed age and gender adjusted analyses to assess for differences in the prevalence of associated medical conditions in patients with EoGE and EoC and controls (patients in the database between March 2012 and March 2017 without EGID associated diagnoses).
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ACCEPTED MANUSCRIPT Results: Of the 35,826,830 individuals in the database, we identified 1820 patients with EoGE and 770 with EoC. The overall prevalence rate of EoGE was 5.1/100,000 persons; the overall prevalence rate of EoC was 2.1/100,000 persons. Each of the nonEoE EGIDs were more prevalent in Caucasians than African-Americans and Asians,
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and in female patients than male patients. Although EoGE was more prevalent in children (under 18 years) than adults, EoC was more prevalent in adults (older than 18 years). Compared with controls, individuals with non-EoE EGIDs were more likely to
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have been diagnosed with other gastrointestinal or allergic disorders.
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Conclusions: In a population-based study in the US, using the Explorys database, we found the overall prevalence rate of EoGE to be 5.1/100,000 persons and the prevalence rate of EoC to be 2.1/100,000; these values are at the lower end of
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prevalence rates previously reported in the US.
Key words: eosinophilic gastrointestinal diseases; epidemiology; prevalence,
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SNOMED-CT
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Background and Aims:
Eosinophilic gastrointestinal disorders (EGIDs) are defined by the abnormal eosinophilic infiltration of different segments of the gastrointestinal (GI) tract in the absence of a known secondary cause, presenting with a variety of gastrointestinal manifestations based on the affected GI segment [1]. EGIDs comprise a series of diseases that include eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic gastroenteritis (EoGE) and eosinophilic colitis (EoC) [1]. Among these
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ACCEPTED MANUSCRIPT EGIDs, eosinophilic esophagitis (EoE) has been the most extensively studied, with recent studies showing increasing incidence [2-5] and a recent pooled prevalence estimate of 22.7/100,000 individuals in population-based studies from North America, Europe and Australia [5] and a prevalence estimate of 25.9/100,000 individuals in the
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United States (US) [6]. EoGE was first described in 1937 [7] and while it can affect any segment of the GI tract, the stomach and the duodenum are the most frequently affected organs [8,9]. However, there is a lack of large population-based
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epidemiologic studies on EoG, EoGE and EoC. Most of the studies on these disorders have been niche studies, specific to some locations, and have many limitations,
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including small sample sizes and referral bias [10-14].
To our knowledge, there has been only one large database study on the prevalence of EoGE and EoC in the US [15], which included cases between 2009 and 2011. Given
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the well documented increase over time in the prevalence of EoE, we sought to describe the epidemiology of EoGE and EoC in the US over a 5-year period between 2012 and 2017 by using a population-based database. The aims of the study were to
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identify cases of EoGE and EoC, identify other disorders associated with these
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EGIDs, and estimate overall prevalence of these EGIDs in US among different agebased, race-based and gender-based subgroups. These data will help better define the epidemiology of EoGE and EoC.
Methods:
Database:
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ACCEPTED MANUSCRIPT We performed a retrospective analysis of a large population-based, commercial database (Explorys Inc, Cleveland, OH). This database contains an aggregate of Electronic Health Record (EHR) data from 26 major integrated healthcare systems spread over 50 states in the US from 1999 to 2017. Explorys contains de-identified
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patient data from participating institutions and uses a health data gateway (HDG) server behind the firewall of each participating healthcare organization that collects de-identified data from various health information systems—EHR using billing
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inquiries. Data are then standardized and normalized by Explorys. Diagnoses, findings, and procedures are mapped into the Systematized Nomenclature Of
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Medicine – Clinical Terms (SNOMED–CT) hierarchy while prescription drug orders are mapped into SNOMED (to represent the pharmacological class) and RxNorm (to represent the drug itself). Each participating healthcare institution has access to Explorys online (password protected), which provides for browsing of the data from
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all participating healthcare institutions. Explorys data are automatically updated at least once every 24 hours [16]. Explorys is a Health Insurance Portability and Accountability Act (HIPAA) compliant platform and thus Institutional Review Board
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(IRB) is not required.
Patient selection:
Using the Explorys search tool, we identified an aggregated patient cohort of eligible patients with EoGE and EoC at any point between March 2012 and March 2017. EoGE patients were defined as those having a SNOMED-CT diagnosis of “eosinophilic gastroenteritis” or a SNOMED-CT diagnosis of “eosinophilic gastritis” without a SNOMED-CT diagnosis of “eosinophilic gastroenteritis” in order to prevent
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ACCEPTED MANUSCRIPT including the same patient twice. EoC patients were defined as those having a SNOMED-CT diagnosis of “eosinophilic colitis” without SNOMED-CT diagnoses of “eosinophilic gastroenteritis” or “eosinophilic gastritis” in order to prevent including
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the same patient twice
Associated medical conditions of interest:
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We identified multiple medical conditions associated with EoGE and EoC as demonstrated by prior studies [1,17,18,19,20]. Data on these conditions, which
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included GI and allergic disorders, were extracted by using SNOMED-CT diagnostic terms for these disorders. The associated GI disorders that were studied included gastroesophageal reflux disease (GERD), heartburn, dysphagia, nausea and vomiting, failure to thrive, GI hemorrhage, abdominal pain, diarrhea, weight loss, ascites,
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volvulus, intussusception, GI perforation, GI obstruction, and eosinophilic esophagitis. The associated allergic disorders that were studied included drug allergy,
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rhinitis, asthma, sinusitis, dermatitis, food allergy, eczema and urticaria.
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Statistical Analysis:
For patients with EoGE and EoC, demographics and associated diseases were characterized by descriptive statistics. Univariate analysis was performed to assess the differences in the prevalence of associated medical conditions in patients with EoGE and EoC and controls (patients in the database between March 2012 and March 2017 without EGID associated diagnoses- EoE, EoGE, EoG and EoC) by calculating odds ratios and 95% confidence intervals. Age and gender adjusted odds ratios and 95%
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ACCEPTED MANUSCRIPT confidence intervals were also calculated for associated medical conditions with EoGE and EoC.
For calculation of overall period prevalence, we identified all patients in the database
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with EoGE and EoC from March 2012 through March 2017. We then divided this number by the total number of patients in the database (from March 2012 to March 2017), thus making sure that all patients in the denominator (population at risk) had an
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equal opportunity of being diagnosed with EoGE and EoC if they had the disease.
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Similarly, age-based, gender-based and race-based prevalence rates were calculated.
The Odds Ratio (OR), its standard error and 95% confidence interval were calculated according to Altman, 1991 using the MedCalc Statistical Software [21] with a case-
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control design.
We performed sensitivity analyses and estimated the prevalence of EoGE and EoC after excluding patients with SNOMED-CT diagnoses of other possible causes of GI
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tract eosinophilia including Crohn’s disease, ulcerative colitis, celiac disease,
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malignant lymphoma, leukemia, systemic vasculitis and parasitic infections (Strongyloides, Ascaris, Ancylostoma. Anisakis, Capillaria and Trichinella).
It should be mentioned that as a measure to protect the identities of patients, Explorys rounds cell counts to the nearest 10, and treats all cell counts between zero and 10 as equivalent. For the purposes of our study, we approximated all cell counts between zero and 10 as 5.
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ACCEPTED MANUSCRIPT Results:
A total of 35,826,830 individuals in the database from March 2012 to March 2017 made up the source population. Of these, 1,820 and 770 patients had at least 1
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SNOMED-CT diagnosis of EoGE and EoC respectively and represented the EoGE
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and EoC case groups.
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Eosinophilic Gastroenteritis (EoGE):
Of the 1,820 patients with EoGE, the majority were female (57.7%), Caucasian (77.5%), and adults (>18 years of age) (83.5%) (Table 1). The overall prevalence was 5.1 per 100,000 persons. The prevalence in female patients was slightly higher than
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male patients (5.3 vs 4.8/100,000), (OR=1.11, 95% CI: 1.01-1.21, p=0.0338). The prevalence of EoGE was highest in Caucasians (compared to Asians and African Americans) at 6.3/100,000 (OR=1.17, 95% CI: 1.02 to 1.34, p=0.0231). The
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prevalence was higher in children (<18 years of age) at 5.3/100,000 (OR=1.04, 95%
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CI: 0.92-1.18, p=0.5370) compared to adults (>18 years of age) at 5.1/100,000 (Table 2). The 5-year interval age-based prevalence rates for EoGE and EoC are shown in Figure 1.
Eosinophilic Colitis (EoC):
Of the 770 patients with EoC, the majority were female (66.2%), Caucasian (81.8%), and adults (>18 years of age) (88.3%) (Table 1). The overall prevalence was 2.1 per
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ACCEPTED MANUSCRIPT 100,000 persons. The prevalence in female patients was slightly higher than male patients (2.6 vs 1.6/100,000), (OR=1.60, 95% CI: 1.37-1.85, p<0.0001). The prevalence of EoC was highest in Caucasians (compared to African Americans and Asians) at 2.8/100,000 (OR=1.19, 95% CI: 0.97 to 1.45, p=0.0975). The prevalence
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was slightly higher in adults (>18 years of age) at 2.3/100,000 (OR=1.43, 95% CI: 1.15-1.79, p=0.0013) compared to children (<18 years of age) at 1.6/100,000 (Table
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2).
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Association of EoGE and EoC with other medical disorders:
Among GI symptoms and associated disorders (Table 3), individuals with EoGE and EoC were more likely than controls to have GERD, heartburn, dysphagia, nausea and vomiting, failure to thrive, GI hemorrhage, abdominal pain, diarrheal disorder,
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abnormal weight loss, ascites, volvulus, intussusception, GI perforation and GI obstruction.
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Among allergic disorders (Table 4), individuals with EoGE and EoC were more likely
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than controls to have drug allergy, rhinitis, asthma, sinusitis, dermatitis, food allergy, eczema and urticaria.
Among age and gender adjusted analyses, all groups were more likely than respective controls to have GI symptoms and associated disorders (Table 5), and associated allergic disorders (Table 6).
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ACCEPTED MANUSCRIPT In sensitivity analyses, in which a more restrictive case definition was used to exclude patients with other possible causes of GI tract eosinophilia, we observed similar prevalence estimates to those obtained using the primary definitions for EoGE but not EoC. The prevalence of EoGE was 4.3/100,000 after excluding 295 patients
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(Crohn’s Disease, n=120, ulcerative colitis, n=45, systemic vasculitis=15, celiac disease=60, malignant lymphoma=25, leukemia=15, Strongyloides=10, Ascaris=0, Ancylostoma=0, Anisakis=5, Capillaria=0 and Trichinella=0), compared to
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5.1/100,000 using the primary definition. However, the prevalence of EoC was 1.5/100,000 after excluding 245 patients (Crohn’s Disease, n=70, ulcerative colitis, systemic
vasculitis=5,
celiac
disease=30,
malignant
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n=110,
lymphoma=10,
leukemia=10, Strongyloides=5, Ascaris=0, Ancylostoma=0, Anisakis=5, Capillaria=0 and Trichinella=0), compared to 2.1/100,000 using the primary definition. Of note,
Discussion:
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IBD made up nearly 23% of all patients with EoC.
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In this study, we evaluated the prevalence of EoGE and EoC over 5 years in the
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Explorys database between 2012 and 2017. Most of the epidemiological studies that have provided prevalence estimates on EoGE and EoC have been small in size. To our knowledge, this is the largest study to date that estimates the prevalence of these two conditions in the US at the national level. This is also the first large study to describe race-based, age-based and sex-based prevalence of non-EoE EGIDs in the United States from national level data. Only one large prior study [15] has described the age and sex based prevalence of non-EoE EGIDs in the past and none has described the race-based epidemiology these diseases at the national level.
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We estimated the overall prevalence rates of EoGE and EoC to be 5.1/100,000 2.1/100,000 respectively. The overall prevalence estimates for each of these conditions in our study does fall in the same order of magnitude of prevalence rates
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reported in other studies in the past, thereby lending empiric validity to our study. Guajardo et al [22] estimated the prevalence of EoGE in the USA to be 2.5/100,000 persons using an electronic survey. Two other studies in the recent past estimated the
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overall prevalence of non-EoE EGIDs. Using ICD-9 codes through a large health plan claims database, Jensen et al [15] estimated the prevalence of EoGE and EoC to be
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8.4/100,00 and 3.3/100,000 respectively, higher than our estimates. Additionally, Spergel et al [23] estimated the overall prevalence of the EoGE and/or EoC by administering an electronic survey to allergists and gastroenterologists about their practice data, and extrapolated the results nationally. They reported a prevalence of
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28/100,000 for combined EoGE and/or EoC, higher than our estimate. The difference in the prevalence of non-EoE EGIDs between our study and these studies can be attributed to the differences in the study design, methods of data collection, data
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analyses, time period over which the data was collected as well as the size of source
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population. Given that in our study we had large numbers of both non-EoE EGID cases and total number of individuals in the database, our estimates of prevalence might be more precise. However, a direct comparison with previous studies for prevalence estimates would not be possible because of the difference in the time period over which prevalence was estimated.
We also found that each of the non-EoE EGIDs is predominantly found in the Caucasian population, similar to EoE [6]. The Caucasian predilection for disease has
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ACCEPTED MANUSCRIPT been reported for EoG [11] and EoGE [13,24]. Additionally, we found that EoGE is more prevalent in children compared to adults. While most previous studies have reported that EoGE typically presents in the third and fourth decades of life [17,24], our study looked at prevalence as opposed to incidence, which could explain the
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predominance of EoGE in children in our study. Our result is consistent with the findings of Jensen [15] who reported that the prevalence of EoGE decreased with age, with the highest prevalence in individuals under 5 years of age. Moreover, we found
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that EoGE and EoC have a slight female predominance that has been reported in prior studies [15]. Previous studies have reported familial clustering of EoE [4] and non-
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EoE EGIDs [25], thereby pointing towards a genetic predisposition [10,14,17,19], however, there are no genetic markers identified that have been shown to be conserved in Caucasians to justify higher prevalence in this group.
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While we did not look at region-wise burden of non-EoE EGIDs, it is safe to assume that regional differences in gender, age and race distribution cannot alone account for our findings of Caucasian and female predominance of all non-EoE EGIDs, and
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younger age group predominance of EoGE. Furthermore, health institutions affiliated
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with Explorys cover all 50 states and span the East, Midwest, South, Central and West divisions of the US [16], thus providing a broad regional and climatic distribution of source population. Further genetic, environmental and behavioral studies are needed to understand the epidemiology of non-EoE EGIDs.
We found that each of the non-EoE EGIDs is strongly associated with high rates of GI disorders. Given the large sample size, all the differences that were statistically significant may not be clinically meaningful. However, these associations have been
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ACCEPTED MANUSCRIPT described in the past by smaller studies [11, 13, 24, 26, 27]. These co-morbid disorders can serve as surrogate markers of presence of non-EoE EGIDs and should trigger evaluation for disease in the appropriate clinical setting. Prior studies [1,15] have suggested that the clinical manifestations of non-EoE EGIDs might be dependent
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upon the area of the GI tract affected, the extent of disease and the depth of eosinophilic inflammation of the bowel wall. As such, patients with the mucosal form of EoGE may present with vomiting, abdominal pain, diarrhea, failure to thrive;
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patients with EoGE of the muscularis layer may present with GI obstruction; and patients with EoGE of the serosal layer may present with ascites. While, our study did
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not look at the depth of eosinophilic inflammation of the bowel wall, we found these and other GI co-morbidities to be significantly associated with non-EoE EGIDs.
We also found that each of the non-EoE EGIDs is strongly associated with high rates
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of allergic disorders. Multiple studies and case series in the past have described the association between atopic disorders and EoGE [10, 11, 12, 28], while the association between EoC and atopic disorders has also been described in a few studies [15]. As
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opposed to other EGIDs, EoC is considered to be a non-IgE-associated disease [1] and
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thus our finding of association between atopy and EoC may be due to the large sample size and thus statistically significant but not clinically meaningful. While consensus guidelines for EoE [29] exist, it is also routine for individuals with non-EoE EGIDs such as EoGE [30] to be referred for evaluation by an allergist and thus there is an inherent bias in patients with EGIDs having high rates of allergic co-morbidities. Furthermore, data is lacking on association of co-morbid GI and allergic disorders with endoscopic or histologic severity of the disease.
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ACCEPTED MANUSCRIPT We further compared the frequencies of allergic and GI disorders in various groups of patients with EoGE and EoC stratified by age and gender. While all the groups were significantly associated with increased frequencies of GI and allergic disorders, the effect sizes of the associations was slightly variable. While there is a lack of large
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studies comparing disease presentation and co-morbid disorders between adults and children with non-EoE EGIDs, our findings are consistent with that of Reed C et al. [31] who evaluated 44 patients with EoGE and did not find any significant differences
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in disease presentation between adults and children.
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This study has a few limitations that should be acknowledged. First, with regards to the estimate on non-EoE EGIDs prevalence rates, we might have underestimated the true prevalence rates since not all individuals with non-EoE EGIDs are brought to medical notice. As patients with a true diagnosis of EGID may not have been captured
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through SNOMED-CT diagnosis codes and others may have been misclassified as having EGID when they had alternative conditions, we could also have under- or overestimated the true prevalence of non-EoE EGIDs. Validation of the SNOMED-
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CT diagnostic code for non-EoE EGIDs was not possible since the patient information
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in the database is de-identified. However, while ICD-9 and SNOMED-CT are both medical terminology systems for recording medical diagnoses and concepts, SNOMED-CT has many more concepts to be coded per clinical document than ICD-9 [32], which makes it more accurate in terms of enlisting pertinent clinical information.
Besides misclassification, another limitation of this study is the inability to capture information that is unavailable in the Explorys database. This includes information
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ACCEPTED MANUSCRIPT about socioeconomic status, geographic data on patient population, endoscopic abnormalities, histology reports, and specific indications for medications prescribed.
Moreover, although Explorys uses a master–patient identifier to match the same
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patient across different healthcare institutions and combine the data [33], a few patients may have received care in multiple institutions within Explorys healthcare partners and thus could have been counted multiple times. However, this is countered
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by the fact that Explorys uses a robust patient matching algorithm [33] and thus the effect of this error might be minimal and might affect the non-EoE EGID and control
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group equally.
Finally, due to the de-identified nature of information, we were unable to look at specific dates due to which our analysis was based on the prevalence of non-EoE
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EGIDs throughout the 5-year study period. Thus, our study did not distinguish between patients with non-EoE EGIDs responsive to treatment and refractory to
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treatment.
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In summary, the analysis of one of the largest samples of EoGE and EoC cases so far, from the large commercial database Explorys, estimates the overall prevalence rates of EoGE and EoC at 5.1/100,000 and 2.1/100,000 persons respectively. These estimates are at the lower end of estimates reported by smaller studies in literature and signify a lower burden of disease compared to EoE [6].
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28. Bischoff SC. Food allergy and eosinophilic gastroenteritis and colitis. Curr Opin
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Allergy Clin Immunol 2010; 10:238-245.
AC C
29. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011;128:3-20.
30. Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE. Eosinophilic gastroenteritis: clinical experience with 15 patients. World J Gastroenterol. 2003;9:2813–2816.
31. Reed C, Woosley JT, Dellon ES. Clinical characteristics, treatment outcomes, and
20
ACCEPTED MANUSCRIPT resource utilization in children and adults with eosinophilic gastroenteritis. Dig Liver Dis 2015; 47:197-201.
SNOMED. J Am Med Inform Assoc 2010;17:602-607.
RI PT
32. Nadkarni PM, Darer JA. Migrating existing clinical content from ICD-9 to
33. Kaelber DC, Foster W, Gilder J, Love TE, Jain AK. Patient characteristics
SC
associated with venous thromboembolic events: a cohort study using pooled
AC C
EP
TE D
M AN U
electronic health record data. J Am Med Inform Assoc 2012;19:965–972.
21
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Tables: Table 1: Demographic Characteristics of EoGE and EoC Cases
EoC
Total number of cases, n
1820
770
Male, n (%)
770 (42.3)
260 (33.8)
SC
RI PT
EoGE
Children (<18 yrs. of age), n (%)
300 (16.5)
Adults (>18 yrs. of age), n (%)
1520 (83.5)
Race
M AN U
Age group
90 (11.7) 680 (88.3)
1410 (77.5)
630 (81.8)
African American, n (%)
220 (12.1)
100 (13.0)
Asian, n (%)
30 (1.6)
10 (1.3)
AC C
EP
TE D
Caucasian, n (%)
22
ACCEPTED MANUSCRIPT
Source
EoGE cases, Prevalence
EoC cases, n Prevalence (per
Population
n (%)
(per 100,000)
(%)
Overall
35,826,830
1,820 (100)
5.1
770 (100)
2.1
Male
16,044,290
770 (42.3)
4.8
260 (33.8)
1.6
Female
19,782,540
1,050 (57.7)
5.3
SC
Table 2: Prevalence of EoGE and EoC in the Explorys Database from March 2012 to March 2017:
510 (66.2)
2.6
Children (<18yrs.)
5,702,640
300 (16.5)
5.3
90 (11.7)
1.6
Adults (>18 yrs.)
30,042,580
1520 (83.5)
5.1
680 (88.3)
2.3
Caucasian
22,533,420
1410 (77.5)
6.3
630 (81.8)
2.8
African American
3,978,230
220 (12.1)
5.5
100 (13.0)
2.5
Asian
690,920
30 (1.6)
4.3
10 (1.3)
1.4
23
100,000)
RI PT
M AN U
TE D
EP AC C
Group
ACCEPTED MANUSCRIPT
Table 3: Odds Ratios for Associated GI Clinical Features of EoGE and EoC Cases vs Controls (individuals without EGIDs): EoGE
Cases, Odds
n (%)
Ratios EoC Cases, n Odds Ratios [OR, Controls, n (%)
[OR,
95% (%)
95% Confidence
RI PT
GI Diagnoses
Confidence
Interval (CI)]
Interval (CI)]
400 (51.9%)
8.65 [95% CI:
SC
960 (52.7%)
GERD
P<0.0001]
130 (7.1%)
M AN U
7.89 to 9.48,
40 (5.2%)
8.73 [95% CI: 7.31 to 10.44,
Heartburn 390 (21.4%)
TE D
P<0.0001]
10.38 [95% CI:
110 (14.3%)
9.28 to 11.61,
Dysphagia
9.65, P<0.0001]
6.22 [95% CI: 4.53 to
312480 (0.9%)
8.55, P<0.0001]
6.34 [95% CI: 5.18 to
916420 (2.6%)
7.76, P<0.0001]
EP
180 (19.2%)
AC C
8.06 [95% CI: 7.29 to 8.91,
5.83 [95% CI: 4.93 to
1780730 (5.0%)
6.89, P<0.0001]
P<0.0001]
100 (5.5%) FTT (Failure to thrive)
4091580 (11.4%)
P<0.0001]
540 (29.7%)
Nausea and vomiting
8.38 [95% CI: 7.27 to
11.33 [95% CI:
30 (23.4%)
9.26 to 13.86,
7.90 [95% CI: 5.48 to 11.38, P<0.0001]
24
182790 (0.5%)
ACCEPTED MANUSCRIPT
P<0.0001]
350 (19.2%)
170 (22.1%)
7.65 [95% CI: 6.81 to 8.59,
GI hemorrhage
10.79, P<0.0001]
RI PT
480 (62.3%)
9.13 [95% CI: 8.29 to 10.05,
Abdominal pain
270 (14.8%)
SC
20 (2.6%)
8.28 [95% CI:
M AN U
Diarrheal disorder
11.26 [95% CI:
5.92 to 11.58,
7.22 to 17.55,
P<0.0001]
P<0.0001]
130 (16.9%)
8.22 [95% CI:
TE D
7.22 to 9.35,
Weight loss
8.20 [95% CI: 7.09 to
6012700 (16.8%)
9.48, P<0.0001]
P<0.0001]
35(1.9%)
9.58 [95% CI: 7.93 to
84580 (0.2%)
743100 (19.2%)
11.57, P<0.0001]
P<0.0001]
Ascites
7.57 [95% CI: 5.85
EP
60 (3.3%)
20 (2.6%)
to 9.79, P<0.0001]
16.29 [95% CI: 9.79
AC C
15 (0.8%)
21.28 [95% CI:
5.92 [95% CI: 3.80 to
160430 (2.1%)
9.23, P<0.0001]
5 (0.6%)
to 27.08, P<0.0001]
10 (0.5%)
12.81 [95% CI: 5.32
18250 (0.1%)
to 30.87, P<0.0001]
5 (0.6%)
11.43 to 39.63,
Intussusception
1080580 (3.0%)
P<0.0001]
1180 (64.8%)
Volvulus
9.10 [95% CI: 7.68 to
25.17 [95% CI: 10.45 to 60.67, P<0.0001]
P<0.0001]
25
9290 (0.0%)
ACCEPTED MANUSCRIPT
50 (2.7%)
10 (1.3%)
15.15 [95% CI:
7.06 [95% CI: 3.78 to
11.44 to 20.07,
GI perforation
13.17, P<0.0001]
P<0.0001]
90 (11.6%)
11.11 [95% CI:
8.83 [95% CI: 7.08 to
RI PT
260 (14.3%)
9.75 to 12.67,
11.00, P<0.0001]
EP
TE D
M AN U
SC
P<0.0001]
AC C
GI obstruction
66610 (0.2%)
26
528790 (1.5%)
ACCEPTED MANUSCRIPT
Table 4: Odds Ratios for Associated Allergic Clinical Features of EoGE and EoC Cases vs Controls (individuals without EGIDs): EoGE Cases, n Odds (%)
Ratios EoC Cases, n Odds Ratios [OR, Controls, n (%)
[OR,
95% (%)
95% Confidence
Confidence
Interval (CI)]
Interval (CI)] 890 (48.9%)
410 (53.2%)
3.54 [95% CI:
SC
Drug Allergy
Rhinitis
610 (33.5%)
M AN U
3.23 to 3.88, P<0.0001]
210 (27.3%)
5.15 [95% CI: 4.67 to 5.67, P<0.0001]
600 (33.0%)
180 (23.4%)
5.15 [95% CI: 4.67
TE D
Asthma
to 5.67, P<0.0001]
Sinusitis
540 (30.0%)
3.71 [95% CI: 3.36
EP
3.81 [95% CI: 3.45
AC C
550 (30.2%)
220 (28.5%)
450 (24.7%)
12.20 [95% CI:
7619910 (21.3%)
to 4.85, P<0.0001]
3.83 [95% CI: 3.27
3193000 (8.9%)
to 4.49, P<0.0001] 3.19 [95% CI: 2.70
3122770 (8.7%)
3.52 [95% CI: 3.01
3651530 (10.2%)
to 4.12, P<0.0001]
250 (32.5%)
to 4.21, P<0.0001]
Food allergy
4.21 [95% CI: 3.65
to 3.77, P<0.0001]
to 4.11, P<0.0001]
Dermatitis
RI PT
Allergic condition
4.23 [95% CI: 3.64
3641140 (10.2%)
to 4.92, P<0.0001]
140 (18.2%)
10.97 to 13.57,
8.25 [95% CI: 6.87 to 9.91, P<0.0001]
P<0.0001]
27
938450 (2.6%)
ACCEPTED MANUSCRIPT
Eczema
370 (20.3%)
140 (18.2%)
3.78 [95% CI: 3.37
3.29 [95% CI: 2.74
to 4.23, P<0.0001]
130 (7.1%)
to 3.95, P<0.0001]
40 (5.2%)
5.31 [95% CI: 4.44
3.78 [95% CI: 2.75 to 5.20, P<0.0001]
EP
TE D
M AN U
SC
RI PT
to 6.35, P<0.0001]
AC C
Urticaria
2265120 (6.3%)
28
511120 (1.4%)
ACCEPTED MANUSCRIPT
Table 5: Odds Ratios for GI Clinical Features of EoGE and EoC stratified by Age and Gender: EoGE Cases-
EoGE Cases-
EoGE Cases-
EoC Cases-
EoC Cases-
EoC Cases-
EoC Cases-
Cases-
Children, Male
Adults,
Children,
Adults, Male
Children, Male
Adults, Female
Children, Female
Female
Female
Adults, Male
11.79 [95% CI:
8.32 [95% CI:
12.2, [95% CI:
5.54, [95% CI:
17.86 [95%
8.47 [95% CI:
13.81 [95% CI:
CI: 7.19
8.59 to 16.19,
8.59 to 16.19,
7.30 to 9.47,
4.21 to 7.28,
CI: 10.15
7.06 to 10.17,
8.07 to 23.62,
to 9.91,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
to 31.46,
P<0.0001]
P<0.0001]
Nausea and vomiting
P<0.0001]
47.99 [95% CI:
9.18 [95% CI:
104.9, [95% CI:
5.73, [95% CI:
16.63 [95%
5.84 [95% CI:
179.87 [95% CI:
CI: 4.18
19.70
7.39 to 11.41,
54.97 to 200.28
3.04 to 10.82,
CI: 1.03 to
4.04 to 8.46,
70.40 to 459.54,
to 8.71,
to 116.88,
P<0.0001]
, P<0.0001]
P<0.0001]
269.58,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
10.50
28.07 [95% CI:
8.71 [95% CI:
46.47 [CI: 30.04
5.75, [95% CI:
19.34 [95%
5.56 [95% CI:
27.88 CI:
[95% CI:
18.39 to 42.83,
7.45 to 10.18,
to 71.91,
3.91 to 8.46,
CI: 7.67
4.31 to 7.17,
10.92 to 71.18,
8.69
P<0.0001]
P<0.0001]
P<0.0001]
to 48.72,
P<0.0001]
P<0.0001]
P<0.0001]
TE D
6.04 [95%
to 12.68, Dysphagia
M AN U
P<0.0001]
EP
Heartburn
8.44 [95%
AC C
GERD
RI PT
EoGE
SC
GI Diagnoses
P<0.0001]
P<0.0001]
P<0.0001]
7.84 [95%
7.00 [95% CI:
7.97 [CI:
9.93 [95% CI:
4.29, [95% CI:
19.34 [95%
5.54 [95% CI:
3.85 [95% CI: 1.51
CI: 6.49
4.84 to 10.13,
6.97 to 9.12,
6.74 to 14.6243
2.92 to 6.32,
CI: 10.99
4.53 to 6.78,
to 9.82, P<0.0001]
29
ACCEPTED MANUSCRIPT
to 9.47,
P<0.0001]
P<0.0001]
, P<0.0001]
P<0.0001]
P<0.0001]
Abdominal pain
8.76 [95% CI:
19.45 [95% CI:
6.66, [95% CI:
8.70 [95% CI:
5.71 [95% CI:
11.67 [95% CI:
CI: 4.19 to
13.06 to 27.33,
6.09 to 12.61,
12.57 to 30.08,
2.74 to 16.18,
3.45 to 21.91,
3.05 to 10.69,
4.57 to 29.78,
11.69,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
6.96 [95%
43.89 [95% CI:
7.02 [95% CI:
66.70 [95% CI:
5.92 [95% CI:
68.03, [95%
8.93 [95% CI:
40.02 [95% CI:
CI: 5.73 to
28.76 to 66.99,
5.96 to 8.26,
43.10 to 103.22
4.20 to 8.36,
CI: 34.01
7.22 to 11.06,
15.68 to 102.18,
8.46,
P<0.0001]
P<0.0001]
, P<0.0001]
to 136.07,
P<0.0001]
P<0.0001]
P<0.0001]
SC
P<0.0001]
P<0.0001]
9.41 [95%
9.06 [95% CI:
8.68 [95% CI:
13.79 [95% CI:
7.80 [95% CI:
17.00, [95%
7.25 [95% CI:
1.23 [95% CI:
CI: 7.98 to
6.76 to 12.16, P
7.55 to 9.99,
9.69 to 19.64,
5.93 to 10.25,
CI: 9.65
5.99 to 8.77,
0.48 to 3.14,
11.10,
<0.0001]
P< 0.0001]
P<0.0001]
to 29.93,
P<0.0001]
P<0.0001]
P<0.0001] 11.92
Diarrheal
M AN U
P<0.0001]
RI PT
18.89 [95% CI:
15.01 [95% CI:
[95% CI:
6.17 to 36.53, P
7.14 to
<0.0001]
19.92,
disorder
P<0.0001]
Weight loss
8.01 [95%
TE D
GI hemorrhage
7.02 [95%
14.71 [95% CI:
P<0.0001]
EP
thrive)
P<0.0001]
P<0.0001]
6.01 [95% CI: 3.61 to 10.01, P<0.0001]
AC C
FTT (Failure to
to 34.06,
6.74 [95% CI:
23.11 [95% CI: 9.45 to 56.52, P <0.0001]
P<0.0001] 11.35 [95% CI:
58.37, [95%
16.29 [95% CI:
7.13 [95% CI:
4.67 to 27.56,
CI: 23.16
10.41 to 25.49, P
0.44 to 116.02,
P<0.0001]
to 147.10, P
<0.0001]
P<0.0001]
<0.0001]
21.41 [95%
30
7.57 [95% CI:
22.80, [95%
6.74 [95% CI:
12.85 [95% CI:
ACCEPTED MANUSCRIPT
CI: 6.40 to
9.64 to 22.45, P
5.60 to 8.12,
CI:13.84 to 33.1
5.14 to 11.14,
CI: 11.40 to
10.03,
<0.0001]
P<0.0001]
2, P<0.0001]
P<0.0001]
45.60, P<
P<0.0001] 82.02 [95% CI:
5.73 [95% CI:
111.97 [95%
4.11 [95% CI:
CI: 4.91 to
33.65 to 199.95
3.85 to 8.53,
CI:
1.69 to 9.98,
10.93,
, P<0.0001]
P<0.0001]
45.70 to 274.32
P<0.0001]
, P<0.0001]
GI perforation
P<0.0001]
4.51 [95% CI:
399.89 [95% CI:
CI:
2.41 to 8.44,
156.34 to 1022.81,
126.36 to 805.
P<0.0001]
P<0.0001]
1493.78,
15.88 [95% CI:
200.72 [95% CI:
384.12 [95%
16.05 [95%
603.93 [95%
[95% CI:
CI:
CI:
CI:
20.54 to
[95% CI:
6.58 to 38.34,
12.29 to 3277.58,
18.55 to
156.37 to 943.5
8.66 to 29.94,
244.27 to 1493.
121.17,
587.40 to 379
P<0.0001]
P<0.0001]
64.80,
8, P<0.0001]
P<0.0001]
16, P<0.0001]
P<0.0001]
8.73,
M AN U
49.88 [95% CI:
19, P<0.0001]
34.67
P<0.0001]
P<0.0001]
83.48
49.98 [95% CI:
200.72 [95%
115.47 [95%
11.70 [95% CI:
194.36, [95%
45.71 [95% CI:
412.39 [95% CI:
[95% CI:
20.52 to 121.73
CI:
CI:
0.73 to 187.68,
CI: 77.06
18.93 to 110.40,
161.22 to 1054.85,
44.63 to
, P<0.0001]
12.29 to 327
47.13 to 282.9
P<0.0001]
to 490.24,
P<0.0001]
P<0.0001]
7.58,
1, P<0.0001]
AC C
156.15, Intussusception
SC
P<0.0001]
318.97, [95%
RI PT
7.33 [95%
TE D
Volvulus
P<0.0001]
5.03 to 32.79,
0.0001]
EP
Ascites
5.60 to 8.12,
P<0.0001]
P<0.0001]
P<0.0001]
17.68
124.25 [95%
14.13 [95%
481.20 [95%
0.97 [95% CI:
43.03, [95%
11.12 [95% CI:
71.21 [95% CI:
[95% CI:
CI:
CI:
CI:
0.06 to15.49,
CI:
5.94 to 20.80,
4.37 to 1159.86,
11.84 to
50.92 to 303.22
9.49 to 21.02
250.89 to 922.9
P<0.0001
2.65 to 698.11
P<0.0001]
P<0.0001]
31
ACCEPTED MANUSCRIPT
26.39,
, P<0.0001]
, P<0.0001]
5, P<0.0001]
, P<0.0001]
9.81 [95%
14.55 [95% CI:
9.72 [95% CI:
8.75 [95% CI:
5.85 [95% CI:
2.45, [95% CI:
8.75 [95% CI:
55.32 [95% CI:
CI: 7.84 to
7.69 to 27.54,
8.07 to 11.69,
6.67 to 11.47,
3.69 to 9.28,
0.15 to 39.70,
6.67 to 11.47,
21.67 to 141.25,
12.28,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
SC
GI obstruction
RI PT
P<0.0001]
EoGE Cases-
Adults, Male Children,
Adults,
Rhinitis
Asthma
EoC Cases- EoC Cases-
Children,
Children,
Adults,
Children,
Female
Male
Female
Female
Adults, Male
3.27 [95% CI:
8.15 [95% CI:
3.49 [95% CI:
7.61 [95% CI:
3.43 [95% CI:
3.61 [95% CI:
4.34 [95% CI:
2.05 [95% CI:
2.78 to 3.84,
6.014 to 11.05,
3.06 to 3.98,
5.30 to 10.92,
2.61 to 4.51, P<
1.80 to 7.21,
3.60 to 5.24,
0.80 to 5.24,
P<0.0001]
P<0.0001]
P<0.0001]
0.0001]
P<0.0001]
P<0.0001
P<0.0001]
0.12 [95% CI:
8.15 [95% CI:
4.68 [95% CI:
5.48 [95% CI:
3.68 [95% CI:
2.30 [95% CI:
3.97 [95% CI:
1.48 [95% CI:
0.10 to 0.14,
6.01 to 11.05,
4.08 to 5.36
3.82 to 7.86,
2.68 to 5.06,
1.15 to 4.60, P<
3.26 to 4.83,
0.58 to 3.77,
P<0.0001]
P<0.0001]
,P<0.0001]
P<0.0001]
P<0.0001]
0.0001]
P<0.0001]
P<0.0001]
4.94 [95% CI:
6.00 [95% CI:
4.96 [95% CI:
8.55 [95% CI:
4.94 [95% CI:
5.60 [95% CI:
3.09 [95% CI:
1.67 [95% CI:
P<0.0001
AC C
Drug Allergy
Female
EoC Cases-
EP
Male
EoGE Cases- EoC Cases-
TE D
Allergic condition
EoGE Cases- EoGE Cases-
M AN U
Table 6: Odds Ratios for Allergic Clinical Features of EoGE and EoC stratified by Age and Gender:
32
ACCEPTED MANUSCRIPT
6.04 to 12.10
4.12 to 5.91
3.18 to 9.86,
2.51 to 3.80,
0.65 to 4.24,
P<0.0001]
P<0.0001]
P<0.0001]
4, P<0.0001]
,P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
3.37 [95% CI:
3.99 [95% CI:
3.68 [95% CI:
4.33 [95% CI:
3.16 [95% CI:
7.98 [95% CI:
3.12 [95% CI:
3.92 [95% CI:
2.80 to 4.05,
2.85 to 5.59,
3.20 to 4.21,
2.94 to 6.4,
2.30to 4.34,
4.53 to 14.06,
2.56 to 3.80,
1.92 to 8.02,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
3.82 [95% CI:
16.13 [95% CI:
3.51 [95% CI:
4.36 [95% CI:
3.28 [95% CI:
19.02 [95% CI:
4.67 [95% CI:
3.97 [95% CI:
3.19 to 4.57,
11.90 to 21.86,
3.04 to 4.05,
3.08 to 6.18,
2.39 to 4.51,
10.80 to 33.50,
3.86 to 5.65,
2.25 to 6.98,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
Food allergy
Eczema
7.43 [95% CI:
SC
37.82 [95%
CI:
32.49 [95% CI:
6.31 to 8.74,
10.58 to 15.7
24.25 to 43.51,
P<0.0001]
8, P<0.0001]
P<0.0001]
3.60 [95% CI:
3.64 [95% CI:
4.27 [95% CI:
5.33 [95% CI:
3.00 [95% CI:
2.90 to 4.46,
3.09 to 4.28,
3.11 to 5.86,
3.71 to 7.65,
P<0.0001]
P<0.0001]
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12.92 [95%
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4.34 to 5.68,
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Dermatitis
4.46 to 8.07,
P<0.0001]
P<0.0001]
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37.82 [95%
5.44 [95% CI:
27.67 to 85.81,
5.42 [95% CI:
CI:
26.82 to 53.3
3.43 to 8.62,
P<0.0001]
4.20 to 6.98,
20.35 to 70.3
4, P<0.0001]
P<0.0001]
P<0.0001
0, P<0.0001]
2.42 [95% CI:
3.59 [95% CI:
1.44 [95% CI:
2.04 to 4.41,
1.21 to 4.85,
2.85 to 4.52,
0.56 to 3.67,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
4.50 [95% CI:
4.35 [ 95%
4.79 [ 95% CI:
Urticaria
48.73 [95% CI:
CI:
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Sinusitis
4.12 to 5.91,
5.06 [95% CI:
6.53 [95% CI:
3.72 to 6.16,
9.67 [95% CI:
2.84 [95% CI:
1.79 to 11.34,
CI: 3.00 to
5.80 [ 95% CI:
3.39 to 7.56,
4.28 to 9.97,
P<0.0001]
6.25 to 15.00,
1.17 to 6.90,
P<0.0001]
6.29,
2.27 to 14.81,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P=0.0002]
33
ACCEPTED MANUSCRIPT
9
7.3 6.9
7
5.1 5
4.3
4.7 4.2
4.1
4
4.9
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4.7
3
2
2.4 1.7
1.9
2.1
1.7
5.4
2.8
5.1
4
3.8
4
EoGE
3.8
EoC 2.7
2.9
0.8
1.7
0.9
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0.8
0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+ (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age)
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0
5.7
2.4
2.3
1.1 1
5.9
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3
5.7
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5.7
6
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7.8
8
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Figure 1: The Age-Based 2012-2017 Prevalence (per 100,000 persons) of Eosinophilic gastroenteritis (EoGE), and
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EP
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Eosinophilic colitis (EoC) in the Explorys Database.
PII: DOI: Reference:
S1542-3565(17)30691-2 10.1016/j.cgh.2017.05.050 YJCGH 55283
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 31 May 2017 Please cite this article as: Mansoor E, Saleh MA, Cooper GS, Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017, Clinical Gastroenterology and Hepatology (2017), doi: 10.1016/j.cgh.2017.05.050. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
ACCEPTED MANUSCRIPT Title: Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017 Short Title: The Prevalence of Eosinophilic Gastroenteritis and Colitis Authors: Emad Mansoor, MD, Mohannad Abou Saleh, MBBS and Gregory S.
First Author: Emad Mansoor, MD Department of Internal Medicine
Case Western Reserve University 11100 Euclid Avenue Cleveland, Ohio 44106 [email protected]
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Second Author:
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University Hospitals Cleveland Medical Center
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Cooper, MD
Mohannad Abou Saleh, MBBS
Department of Internal Medicine
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University Hospitals Cleveland Medical Center
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Case Western Reserve University 11100 Euclid Avenue
Cleveland, Ohio 44106
Corresponding author: Gregory S. Cooper, MD Department of Internal Medicine and Division of Gastroenterology and Liver Disease University Hospitals Cleveland Medical Center Case Western Reserve University
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ACCEPTED MANUSCRIPT 11100 Euclid Avenue Cleveland, Ohio 44106, Wearn 244 [email protected] +1 216-844-5385
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Grant Support: Supported in part by the Cleveland Digestive Diseases Research Core Center (1P30DK097948). Abbreviations:
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EGIDs- Eosinophilic Gastrointestinal Diseases GI- Gastrointestinal EoE- Eosinophilic esophagitis EoG- Eosinophilic gastritis EoGE- Eosinophilic gastroenteritis EoC- Eosinophilic colitis US- United States EHR- Electronic Health Record HDG- Health Data Gateway SNOMED-CT- Systematized Nomenclature Of Medicine – Clinical Terms HIPAA- Health Insurance Portability and Accountability Act IRB- Institutional Review Board GERD- Gastroesophageal reflux disease OR- Odds ratio CI- Confidence Interval ICD-9- International Classification of Diseases, Ninth Revision
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Conflicts of interest: There are no potential conflicts (financial, professional, or
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personal) to disclose by all the authors (Emad Mansoor, Mohannad Abou Saleh and Gregory S. Cooper).
Writing Assistance: There is no writing assistance to disclose. Author Contributions: Study conception and design: Mansoor and Cooper Acquisition of data: Mansoor and Abou Saleh Analysis and interpretation of data: Mansoor and Cooper Drafting of manuscript: Mansoor, Abou Saleh and Cooper
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ACCEPTED MANUSCRIPT Critical revision: Cooper Statistical Analysis: Abou Saleh and Mansoor Obtained funding: Cooper
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Study Supervision: Cooper
Word count: 2,981
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Abstract:
Background & Aims: Although eosinophilic esophagitis (EoE) has been extensively
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studied, there have been few epidemiology studies of other eosinophilic gastrointestinal disorders (EGIDs). Using a large, population-based database, we investigated epidemiologic features of eosinophilic gastroenteritis (EoGE), and colitis
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(EoC) in the United States (US).
Methods: We collected data from a commercial database (Explorys Inc, Cleveland, OH) that provided electronic health records from 26 major integrated US healthcare
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systems from 1999 to March 2017. We identified a cohort of adult and pediatric
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patients with EoGE and EoC from March 2012 through March 2017, based on the Systematized Nomenclature of Medicine – Clinical Terms. We calculated the overall prevalence of EoGE and EoC among different patient groups, and performed age and gender adjusted analyses to assess for differences in the prevalence of associated medical conditions in patients with EoGE and EoC and controls (patients in the database between March 2012 and March 2017 without EGID associated diagnoses).
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ACCEPTED MANUSCRIPT Results: Of the 35,826,830 individuals in the database, we identified 1820 patients with EoGE and 770 with EoC. The overall prevalence rate of EoGE was 5.1/100,000 persons; the overall prevalence rate of EoC was 2.1/100,000 persons. Each of the nonEoE EGIDs were more prevalent in Caucasians than African-Americans and Asians,
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and in female patients than male patients. Although EoGE was more prevalent in children (under 18 years) than adults, EoC was more prevalent in adults (older than 18 years). Compared with controls, individuals with non-EoE EGIDs were more likely to
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have been diagnosed with other gastrointestinal or allergic disorders.
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Conclusions: In a population-based study in the US, using the Explorys database, we found the overall prevalence rate of EoGE to be 5.1/100,000 persons and the prevalence rate of EoC to be 2.1/100,000; these values are at the lower end of
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prevalence rates previously reported in the US.
Key words: eosinophilic gastrointestinal diseases; epidemiology; prevalence,
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SNOMED-CT
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Background and Aims:
Eosinophilic gastrointestinal disorders (EGIDs) are defined by the abnormal eosinophilic infiltration of different segments of the gastrointestinal (GI) tract in the absence of a known secondary cause, presenting with a variety of gastrointestinal manifestations based on the affected GI segment [1]. EGIDs comprise a series of diseases that include eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic gastroenteritis (EoGE) and eosinophilic colitis (EoC) [1]. Among these
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ACCEPTED MANUSCRIPT EGIDs, eosinophilic esophagitis (EoE) has been the most extensively studied, with recent studies showing increasing incidence [2-5] and a recent pooled prevalence estimate of 22.7/100,000 individuals in population-based studies from North America, Europe and Australia [5] and a prevalence estimate of 25.9/100,000 individuals in the
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United States (US) [6]. EoGE was first described in 1937 [7] and while it can affect any segment of the GI tract, the stomach and the duodenum are the most frequently affected organs [8,9]. However, there is a lack of large population-based
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epidemiologic studies on EoG, EoGE and EoC. Most of the studies on these disorders have been niche studies, specific to some locations, and have many limitations,
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including small sample sizes and referral bias [10-14].
To our knowledge, there has been only one large database study on the prevalence of EoGE and EoC in the US [15], which included cases between 2009 and 2011. Given
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the well documented increase over time in the prevalence of EoE, we sought to describe the epidemiology of EoGE and EoC in the US over a 5-year period between 2012 and 2017 by using a population-based database. The aims of the study were to
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identify cases of EoGE and EoC, identify other disorders associated with these
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EGIDs, and estimate overall prevalence of these EGIDs in US among different agebased, race-based and gender-based subgroups. These data will help better define the epidemiology of EoGE and EoC.
Methods:
Database:
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ACCEPTED MANUSCRIPT We performed a retrospective analysis of a large population-based, commercial database (Explorys Inc, Cleveland, OH). This database contains an aggregate of Electronic Health Record (EHR) data from 26 major integrated healthcare systems spread over 50 states in the US from 1999 to 2017. Explorys contains de-identified
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patient data from participating institutions and uses a health data gateway (HDG) server behind the firewall of each participating healthcare organization that collects de-identified data from various health information systems—EHR using billing
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inquiries. Data are then standardized and normalized by Explorys. Diagnoses, findings, and procedures are mapped into the Systematized Nomenclature Of
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Medicine – Clinical Terms (SNOMED–CT) hierarchy while prescription drug orders are mapped into SNOMED (to represent the pharmacological class) and RxNorm (to represent the drug itself). Each participating healthcare institution has access to Explorys online (password protected), which provides for browsing of the data from
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all participating healthcare institutions. Explorys data are automatically updated at least once every 24 hours [16]. Explorys is a Health Insurance Portability and Accountability Act (HIPAA) compliant platform and thus Institutional Review Board
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(IRB) is not required.
Patient selection:
Using the Explorys search tool, we identified an aggregated patient cohort of eligible patients with EoGE and EoC at any point between March 2012 and March 2017. EoGE patients were defined as those having a SNOMED-CT diagnosis of “eosinophilic gastroenteritis” or a SNOMED-CT diagnosis of “eosinophilic gastritis” without a SNOMED-CT diagnosis of “eosinophilic gastroenteritis” in order to prevent
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ACCEPTED MANUSCRIPT including the same patient twice. EoC patients were defined as those having a SNOMED-CT diagnosis of “eosinophilic colitis” without SNOMED-CT diagnoses of “eosinophilic gastroenteritis” or “eosinophilic gastritis” in order to prevent including
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the same patient twice
Associated medical conditions of interest:
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We identified multiple medical conditions associated with EoGE and EoC as demonstrated by prior studies [1,17,18,19,20]. Data on these conditions, which
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included GI and allergic disorders, were extracted by using SNOMED-CT diagnostic terms for these disorders. The associated GI disorders that were studied included gastroesophageal reflux disease (GERD), heartburn, dysphagia, nausea and vomiting, failure to thrive, GI hemorrhage, abdominal pain, diarrhea, weight loss, ascites,
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volvulus, intussusception, GI perforation, GI obstruction, and eosinophilic esophagitis. The associated allergic disorders that were studied included drug allergy,
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rhinitis, asthma, sinusitis, dermatitis, food allergy, eczema and urticaria.
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Statistical Analysis:
For patients with EoGE and EoC, demographics and associated diseases were characterized by descriptive statistics. Univariate analysis was performed to assess the differences in the prevalence of associated medical conditions in patients with EoGE and EoC and controls (patients in the database between March 2012 and March 2017 without EGID associated diagnoses- EoE, EoGE, EoG and EoC) by calculating odds ratios and 95% confidence intervals. Age and gender adjusted odds ratios and 95%
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ACCEPTED MANUSCRIPT confidence intervals were also calculated for associated medical conditions with EoGE and EoC.
For calculation of overall period prevalence, we identified all patients in the database
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with EoGE and EoC from March 2012 through March 2017. We then divided this number by the total number of patients in the database (from March 2012 to March 2017), thus making sure that all patients in the denominator (population at risk) had an
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equal opportunity of being diagnosed with EoGE and EoC if they had the disease.
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Similarly, age-based, gender-based and race-based prevalence rates were calculated.
The Odds Ratio (OR), its standard error and 95% confidence interval were calculated according to Altman, 1991 using the MedCalc Statistical Software [21] with a case-
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control design.
We performed sensitivity analyses and estimated the prevalence of EoGE and EoC after excluding patients with SNOMED-CT diagnoses of other possible causes of GI
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tract eosinophilia including Crohn’s disease, ulcerative colitis, celiac disease,
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malignant lymphoma, leukemia, systemic vasculitis and parasitic infections (Strongyloides, Ascaris, Ancylostoma. Anisakis, Capillaria and Trichinella).
It should be mentioned that as a measure to protect the identities of patients, Explorys rounds cell counts to the nearest 10, and treats all cell counts between zero and 10 as equivalent. For the purposes of our study, we approximated all cell counts between zero and 10 as 5.
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ACCEPTED MANUSCRIPT Results:
A total of 35,826,830 individuals in the database from March 2012 to March 2017 made up the source population. Of these, 1,820 and 770 patients had at least 1
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SNOMED-CT diagnosis of EoGE and EoC respectively and represented the EoGE
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and EoC case groups.
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Eosinophilic Gastroenteritis (EoGE):
Of the 1,820 patients with EoGE, the majority were female (57.7%), Caucasian (77.5%), and adults (>18 years of age) (83.5%) (Table 1). The overall prevalence was 5.1 per 100,000 persons. The prevalence in female patients was slightly higher than
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male patients (5.3 vs 4.8/100,000), (OR=1.11, 95% CI: 1.01-1.21, p=0.0338). The prevalence of EoGE was highest in Caucasians (compared to Asians and African Americans) at 6.3/100,000 (OR=1.17, 95% CI: 1.02 to 1.34, p=0.0231). The
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prevalence was higher in children (<18 years of age) at 5.3/100,000 (OR=1.04, 95%
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CI: 0.92-1.18, p=0.5370) compared to adults (>18 years of age) at 5.1/100,000 (Table 2). The 5-year interval age-based prevalence rates for EoGE and EoC are shown in Figure 1.
Eosinophilic Colitis (EoC):
Of the 770 patients with EoC, the majority were female (66.2%), Caucasian (81.8%), and adults (>18 years of age) (88.3%) (Table 1). The overall prevalence was 2.1 per
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ACCEPTED MANUSCRIPT 100,000 persons. The prevalence in female patients was slightly higher than male patients (2.6 vs 1.6/100,000), (OR=1.60, 95% CI: 1.37-1.85, p<0.0001). The prevalence of EoC was highest in Caucasians (compared to African Americans and Asians) at 2.8/100,000 (OR=1.19, 95% CI: 0.97 to 1.45, p=0.0975). The prevalence
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was slightly higher in adults (>18 years of age) at 2.3/100,000 (OR=1.43, 95% CI: 1.15-1.79, p=0.0013) compared to children (<18 years of age) at 1.6/100,000 (Table
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2).
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Association of EoGE and EoC with other medical disorders:
Among GI symptoms and associated disorders (Table 3), individuals with EoGE and EoC were more likely than controls to have GERD, heartburn, dysphagia, nausea and vomiting, failure to thrive, GI hemorrhage, abdominal pain, diarrheal disorder,
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abnormal weight loss, ascites, volvulus, intussusception, GI perforation and GI obstruction.
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Among allergic disorders (Table 4), individuals with EoGE and EoC were more likely
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than controls to have drug allergy, rhinitis, asthma, sinusitis, dermatitis, food allergy, eczema and urticaria.
Among age and gender adjusted analyses, all groups were more likely than respective controls to have GI symptoms and associated disorders (Table 5), and associated allergic disorders (Table 6).
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ACCEPTED MANUSCRIPT In sensitivity analyses, in which a more restrictive case definition was used to exclude patients with other possible causes of GI tract eosinophilia, we observed similar prevalence estimates to those obtained using the primary definitions for EoGE but not EoC. The prevalence of EoGE was 4.3/100,000 after excluding 295 patients
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(Crohn’s Disease, n=120, ulcerative colitis, n=45, systemic vasculitis=15, celiac disease=60, malignant lymphoma=25, leukemia=15, Strongyloides=10, Ascaris=0, Ancylostoma=0, Anisakis=5, Capillaria=0 and Trichinella=0), compared to
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5.1/100,000 using the primary definition. However, the prevalence of EoC was 1.5/100,000 after excluding 245 patients (Crohn’s Disease, n=70, ulcerative colitis, systemic
vasculitis=5,
celiac
disease=30,
malignant
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n=110,
lymphoma=10,
leukemia=10, Strongyloides=5, Ascaris=0, Ancylostoma=0, Anisakis=5, Capillaria=0 and Trichinella=0), compared to 2.1/100,000 using the primary definition. Of note,
Discussion:
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IBD made up nearly 23% of all patients with EoC.
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In this study, we evaluated the prevalence of EoGE and EoC over 5 years in the
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Explorys database between 2012 and 2017. Most of the epidemiological studies that have provided prevalence estimates on EoGE and EoC have been small in size. To our knowledge, this is the largest study to date that estimates the prevalence of these two conditions in the US at the national level. This is also the first large study to describe race-based, age-based and sex-based prevalence of non-EoE EGIDs in the United States from national level data. Only one large prior study [15] has described the age and sex based prevalence of non-EoE EGIDs in the past and none has described the race-based epidemiology these diseases at the national level.
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We estimated the overall prevalence rates of EoGE and EoC to be 5.1/100,000 2.1/100,000 respectively. The overall prevalence estimates for each of these conditions in our study does fall in the same order of magnitude of prevalence rates
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reported in other studies in the past, thereby lending empiric validity to our study. Guajardo et al [22] estimated the prevalence of EoGE in the USA to be 2.5/100,000 persons using an electronic survey. Two other studies in the recent past estimated the
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overall prevalence of non-EoE EGIDs. Using ICD-9 codes through a large health plan claims database, Jensen et al [15] estimated the prevalence of EoGE and EoC to be
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8.4/100,00 and 3.3/100,000 respectively, higher than our estimates. Additionally, Spergel et al [23] estimated the overall prevalence of the EoGE and/or EoC by administering an electronic survey to allergists and gastroenterologists about their practice data, and extrapolated the results nationally. They reported a prevalence of
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28/100,000 for combined EoGE and/or EoC, higher than our estimate. The difference in the prevalence of non-EoE EGIDs between our study and these studies can be attributed to the differences in the study design, methods of data collection, data
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analyses, time period over which the data was collected as well as the size of source
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population. Given that in our study we had large numbers of both non-EoE EGID cases and total number of individuals in the database, our estimates of prevalence might be more precise. However, a direct comparison with previous studies for prevalence estimates would not be possible because of the difference in the time period over which prevalence was estimated.
We also found that each of the non-EoE EGIDs is predominantly found in the Caucasian population, similar to EoE [6]. The Caucasian predilection for disease has
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ACCEPTED MANUSCRIPT been reported for EoG [11] and EoGE [13,24]. Additionally, we found that EoGE is more prevalent in children compared to adults. While most previous studies have reported that EoGE typically presents in the third and fourth decades of life [17,24], our study looked at prevalence as opposed to incidence, which could explain the
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predominance of EoGE in children in our study. Our result is consistent with the findings of Jensen [15] who reported that the prevalence of EoGE decreased with age, with the highest prevalence in individuals under 5 years of age. Moreover, we found
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that EoGE and EoC have a slight female predominance that has been reported in prior studies [15]. Previous studies have reported familial clustering of EoE [4] and non-
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EoE EGIDs [25], thereby pointing towards a genetic predisposition [10,14,17,19], however, there are no genetic markers identified that have been shown to be conserved in Caucasians to justify higher prevalence in this group.
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While we did not look at region-wise burden of non-EoE EGIDs, it is safe to assume that regional differences in gender, age and race distribution cannot alone account for our findings of Caucasian and female predominance of all non-EoE EGIDs, and
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younger age group predominance of EoGE. Furthermore, health institutions affiliated
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with Explorys cover all 50 states and span the East, Midwest, South, Central and West divisions of the US [16], thus providing a broad regional and climatic distribution of source population. Further genetic, environmental and behavioral studies are needed to understand the epidemiology of non-EoE EGIDs.
We found that each of the non-EoE EGIDs is strongly associated with high rates of GI disorders. Given the large sample size, all the differences that were statistically significant may not be clinically meaningful. However, these associations have been
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ACCEPTED MANUSCRIPT described in the past by smaller studies [11, 13, 24, 26, 27]. These co-morbid disorders can serve as surrogate markers of presence of non-EoE EGIDs and should trigger evaluation for disease in the appropriate clinical setting. Prior studies [1,15] have suggested that the clinical manifestations of non-EoE EGIDs might be dependent
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upon the area of the GI tract affected, the extent of disease and the depth of eosinophilic inflammation of the bowel wall. As such, patients with the mucosal form of EoGE may present with vomiting, abdominal pain, diarrhea, failure to thrive;
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patients with EoGE of the muscularis layer may present with GI obstruction; and patients with EoGE of the serosal layer may present with ascites. While, our study did
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not look at the depth of eosinophilic inflammation of the bowel wall, we found these and other GI co-morbidities to be significantly associated with non-EoE EGIDs.
We also found that each of the non-EoE EGIDs is strongly associated with high rates
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of allergic disorders. Multiple studies and case series in the past have described the association between atopic disorders and EoGE [10, 11, 12, 28], while the association between EoC and atopic disorders has also been described in a few studies [15]. As
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opposed to other EGIDs, EoC is considered to be a non-IgE-associated disease [1] and
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thus our finding of association between atopy and EoC may be due to the large sample size and thus statistically significant but not clinically meaningful. While consensus guidelines for EoE [29] exist, it is also routine for individuals with non-EoE EGIDs such as EoGE [30] to be referred for evaluation by an allergist and thus there is an inherent bias in patients with EGIDs having high rates of allergic co-morbidities. Furthermore, data is lacking on association of co-morbid GI and allergic disorders with endoscopic or histologic severity of the disease.
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ACCEPTED MANUSCRIPT We further compared the frequencies of allergic and GI disorders in various groups of patients with EoGE and EoC stratified by age and gender. While all the groups were significantly associated with increased frequencies of GI and allergic disorders, the effect sizes of the associations was slightly variable. While there is a lack of large
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studies comparing disease presentation and co-morbid disorders between adults and children with non-EoE EGIDs, our findings are consistent with that of Reed C et al. [31] who evaluated 44 patients with EoGE and did not find any significant differences
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in disease presentation between adults and children.
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This study has a few limitations that should be acknowledged. First, with regards to the estimate on non-EoE EGIDs prevalence rates, we might have underestimated the true prevalence rates since not all individuals with non-EoE EGIDs are brought to medical notice. As patients with a true diagnosis of EGID may not have been captured
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through SNOMED-CT diagnosis codes and others may have been misclassified as having EGID when they had alternative conditions, we could also have under- or overestimated the true prevalence of non-EoE EGIDs. Validation of the SNOMED-
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CT diagnostic code for non-EoE EGIDs was not possible since the patient information
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in the database is de-identified. However, while ICD-9 and SNOMED-CT are both medical terminology systems for recording medical diagnoses and concepts, SNOMED-CT has many more concepts to be coded per clinical document than ICD-9 [32], which makes it more accurate in terms of enlisting pertinent clinical information.
Besides misclassification, another limitation of this study is the inability to capture information that is unavailable in the Explorys database. This includes information
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ACCEPTED MANUSCRIPT about socioeconomic status, geographic data on patient population, endoscopic abnormalities, histology reports, and specific indications for medications prescribed.
Moreover, although Explorys uses a master–patient identifier to match the same
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patient across different healthcare institutions and combine the data [33], a few patients may have received care in multiple institutions within Explorys healthcare partners and thus could have been counted multiple times. However, this is countered
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by the fact that Explorys uses a robust patient matching algorithm [33] and thus the effect of this error might be minimal and might affect the non-EoE EGID and control
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group equally.
Finally, due to the de-identified nature of information, we were unable to look at specific dates due to which our analysis was based on the prevalence of non-EoE
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EGIDs throughout the 5-year study period. Thus, our study did not distinguish between patients with non-EoE EGIDs responsive to treatment and refractory to
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treatment.
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In summary, the analysis of one of the largest samples of EoGE and EoC cases so far, from the large commercial database Explorys, estimates the overall prevalence rates of EoGE and EoC at 5.1/100,000 and 2.1/100,000 persons respectively. These estimates are at the lower end of estimates reported by smaller studies in literature and signify a lower burden of disease compared to EoE [6].
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ACCEPTED MANUSCRIPT References: 1. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J. Allergy Clin Immunol 2004; 113:11–28.
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2. Dellon ES. Diagnosis and management of eosinophilic esophagitis. Clin Gastroenterol Hepatol 2012;10:1066-1078.
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Editor]. New Engl J Med 2004;351:940-941.
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3. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis [Letter to the
4. Liacouras CA, Sperjel JM, Ruchelli E, et al. Eosinophilic esophagitis: A 10year experience in 381 children. Clin Gastroenterol Hepatol 2005;3:1198-
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1206.
5. Arias A, Perez-Martinez I, Tenias JM, Lucendo AJ. Systematic review with metaanalysis: the incidence and prevalence of eosinophilic oesophagitis in children and
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adults in population-based studies. Aliment Pharmacol Ther 2016;43:3-15.
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6. Mansoor E, Cooper GS. The 2010-2015 Prevalence of Eosinophilic Esophagitis in the USA: A Population-Based Study. Dig Dis Sci 2016; 61:2928-2934. 7. Kaijser R, Kenntnis, Affektionen, et al. Allergic diseases of the gut from the point of view of the surgeon. Arch Klin Chir 1937;188:36–64. 8. Matsushita M, Hajiro K, Morita Y, et al. Eosinophilic gastroenteritis involving the entire digestive tract. Am J Gastroenterol 1995;90:1868–1870. 9. Liacouras CA, Markowitz JE. Eosinophilic esophagitis: A subset of eosinophilic 17
ACCEPTED MANUSCRIPT gastroenteritis. Curr Gastroenterol Rep 1999;1:253–258. 10. Caldwell JM, Collins MH, Stucke EM, et al. Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity,
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and a unique gastric transcriptome. J Allergy Clin Immunol 2014;134:1114–1124. 11. Ko HM, Morotti RA, Yershov O, et al. Eosinophilic gastritis in children: clinicopathological correlation, disease course, and response to therapy. Am J
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Gastroenterol 2014;109:1277–1285.
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12. Lee CM, Changchien CS, Chen PC, et al. Eosinophilic gastroenteritis: 10 years experience. Am J Gastroenterol 1993;88:70–74.
13. Talley NJ, Shorter RG, Phillips SF, et al. Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and
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subserosal tissues. Gut 1990;31:54–58.
14. Zhang L, Duan L, Ding S, et al. Eosinophilic gastroenteritis: clinical manifestations and morphological characteristics, a retrospective study of 42 patients.
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Scand J Gastroenterol 2011;46:1074–1080.
AC C
15. Jensen ET, Martin CF, Kappelman MD, et al. Prevalence of Eosinophilic Gastritis, Gastroenteritis, and Colitis: Estimates From a National Administrative Database. J Pediatr Gastroenterol Nutr 2016;62:36-42. 16. Explorys team. “We unlock the power of BIG DATA to improve healthcare for everyone”.
Explorys.
2015.
Accessed
18
August
25,
2016.
ACCEPTED MANUSCRIPT 17. Zhang MM, Li YQ. Eosinophilic gastroenteritis: A state-of-the-art review. J Gastroenterol Hepatol 2016; [Epub ahead of print].
gastroenteritis. World J Gastroenterol 2013;19:5061-5066.
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18. Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of
19. Yen EF, Pardi DS. Non-IBD colitides (eosinophilic, microscopic). Best Pract Res
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Clin Gastroenterol 2012; 26:611-622.
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20. Alfadda AA, Shaffer EA, Urbanski SJ, Storr MA. Eosinophilic colitis is a sporadic self-limited disease of middle-aged people: a population-based study. Colorectal Dis 2014;16:123-129.
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21. MedCalc Software Team. “Odds ratio calculator”. MedCalc. 2016. Accessed December 4, 2016.
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22. Guajardo JR, Plotnick LM, Fende JM, et al. Eosinophil-associated gastrointestinal
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disorders: a world-wide-web based registry. J. Pediatr. 2002; 141: 576–81.
23. Spergel JM, Book WM, Mays E, et al. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. J Pediatr Gastroenterol Nutr 2011;52:300–306.
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ACCEPTED MANUSCRIPT 24. Chang JY, Choung RS, Lee RM, et al. A shift in the clinical spectrum of eosinophilic gastroenteritis toward the mucosal disease type. Clin Gastroenterol Hepatol 2010;8:669-675.
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25. Aquino A, Dòmini M, Rossi C, D'Incecco C, Fakhro A, Lelli Chiesa P. Pyloric
stenosis due to eosinophilic gastroenteritis: presentation of two cases in mono-ovular
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twins. Eur J Pediatr 1999;158:172–73.
26. Klein NC, Hargrove RL, Sleisenger MH, et al. Eosinophilic gastroenteritis.
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Medicine (Baltimore) 1970; 49:299-319.
27. Lucendo AJ, Arias A. Eosinophilic gastroenteritis: an update. Expert Rev
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Gastroenterol Hepatol 2012; 6:591-601.
28. Bischoff SC. Food allergy and eosinophilic gastroenteritis and colitis. Curr Opin
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Allergy Clin Immunol 2010; 10:238-245.
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29. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011;128:3-20.
30. Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE. Eosinophilic gastroenteritis: clinical experience with 15 patients. World J Gastroenterol. 2003;9:2813–2816.
31. Reed C, Woosley JT, Dellon ES. Clinical characteristics, treatment outcomes, and
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SNOMED. J Am Med Inform Assoc 2010;17:602-607.
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32. Nadkarni PM, Darer JA. Migrating existing clinical content from ICD-9 to
33. Kaelber DC, Foster W, Gilder J, Love TE, Jain AK. Patient characteristics
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electronic health record data. J Am Med Inform Assoc 2012;19:965–972.
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Tables: Table 1: Demographic Characteristics of EoGE and EoC Cases
EoC
Total number of cases, n
1820
770
Male, n (%)
770 (42.3)
260 (33.8)
SC
RI PT
EoGE
Children (<18 yrs. of age), n (%)
300 (16.5)
Adults (>18 yrs. of age), n (%)
1520 (83.5)
Race
M AN U
Age group
90 (11.7) 680 (88.3)
1410 (77.5)
630 (81.8)
African American, n (%)
220 (12.1)
100 (13.0)
Asian, n (%)
30 (1.6)
10 (1.3)
AC C
EP
TE D
Caucasian, n (%)
22
ACCEPTED MANUSCRIPT
Source
EoGE cases, Prevalence
EoC cases, n Prevalence (per
Population
n (%)
(per 100,000)
(%)
Overall
35,826,830
1,820 (100)
5.1
770 (100)
2.1
Male
16,044,290
770 (42.3)
4.8
260 (33.8)
1.6
Female
19,782,540
1,050 (57.7)
5.3
SC
Table 2: Prevalence of EoGE and EoC in the Explorys Database from March 2012 to March 2017:
510 (66.2)
2.6
Children (<18yrs.)
5,702,640
300 (16.5)
5.3
90 (11.7)
1.6
Adults (>18 yrs.)
30,042,580
1520 (83.5)
5.1
680 (88.3)
2.3
Caucasian
22,533,420
1410 (77.5)
6.3
630 (81.8)
2.8
African American
3,978,230
220 (12.1)
5.5
100 (13.0)
2.5
Asian
690,920
30 (1.6)
4.3
10 (1.3)
1.4
23
100,000)
RI PT
M AN U
TE D
EP AC C
Group
ACCEPTED MANUSCRIPT
Table 3: Odds Ratios for Associated GI Clinical Features of EoGE and EoC Cases vs Controls (individuals without EGIDs): EoGE
Cases, Odds
n (%)
Ratios EoC Cases, n Odds Ratios [OR, Controls, n (%)
[OR,
95% (%)
95% Confidence
RI PT
GI Diagnoses
Confidence
Interval (CI)]
Interval (CI)]
400 (51.9%)
8.65 [95% CI:
SC
960 (52.7%)
GERD
P<0.0001]
130 (7.1%)
M AN U
7.89 to 9.48,
40 (5.2%)
8.73 [95% CI: 7.31 to 10.44,
Heartburn 390 (21.4%)
TE D
P<0.0001]
10.38 [95% CI:
110 (14.3%)
9.28 to 11.61,
Dysphagia
9.65, P<0.0001]
6.22 [95% CI: 4.53 to
312480 (0.9%)
8.55, P<0.0001]
6.34 [95% CI: 5.18 to
916420 (2.6%)
7.76, P<0.0001]
EP
180 (19.2%)
AC C
8.06 [95% CI: 7.29 to 8.91,
5.83 [95% CI: 4.93 to
1780730 (5.0%)
6.89, P<0.0001]
P<0.0001]
100 (5.5%) FTT (Failure to thrive)
4091580 (11.4%)
P<0.0001]
540 (29.7%)
Nausea and vomiting
8.38 [95% CI: 7.27 to
11.33 [95% CI:
30 (23.4%)
9.26 to 13.86,
7.90 [95% CI: 5.48 to 11.38, P<0.0001]
24
182790 (0.5%)
ACCEPTED MANUSCRIPT
P<0.0001]
350 (19.2%)
170 (22.1%)
7.65 [95% CI: 6.81 to 8.59,
GI hemorrhage
10.79, P<0.0001]
RI PT
480 (62.3%)
9.13 [95% CI: 8.29 to 10.05,
Abdominal pain
270 (14.8%)
SC
20 (2.6%)
8.28 [95% CI:
M AN U
Diarrheal disorder
11.26 [95% CI:
5.92 to 11.58,
7.22 to 17.55,
P<0.0001]
P<0.0001]
130 (16.9%)
8.22 [95% CI:
TE D
7.22 to 9.35,
Weight loss
8.20 [95% CI: 7.09 to
6012700 (16.8%)
9.48, P<0.0001]
P<0.0001]
35(1.9%)
9.58 [95% CI: 7.93 to
84580 (0.2%)
743100 (19.2%)
11.57, P<0.0001]
P<0.0001]
Ascites
7.57 [95% CI: 5.85
EP
60 (3.3%)
20 (2.6%)
to 9.79, P<0.0001]
16.29 [95% CI: 9.79
AC C
15 (0.8%)
21.28 [95% CI:
5.92 [95% CI: 3.80 to
160430 (2.1%)
9.23, P<0.0001]
5 (0.6%)
to 27.08, P<0.0001]
10 (0.5%)
12.81 [95% CI: 5.32
18250 (0.1%)
to 30.87, P<0.0001]
5 (0.6%)
11.43 to 39.63,
Intussusception
1080580 (3.0%)
P<0.0001]
1180 (64.8%)
Volvulus
9.10 [95% CI: 7.68 to
25.17 [95% CI: 10.45 to 60.67, P<0.0001]
P<0.0001]
25
9290 (0.0%)
ACCEPTED MANUSCRIPT
50 (2.7%)
10 (1.3%)
15.15 [95% CI:
7.06 [95% CI: 3.78 to
11.44 to 20.07,
GI perforation
13.17, P<0.0001]
P<0.0001]
90 (11.6%)
11.11 [95% CI:
8.83 [95% CI: 7.08 to
RI PT
260 (14.3%)
9.75 to 12.67,
11.00, P<0.0001]
EP
TE D
M AN U
SC
P<0.0001]
AC C
GI obstruction
66610 (0.2%)
26
528790 (1.5%)
ACCEPTED MANUSCRIPT
Table 4: Odds Ratios for Associated Allergic Clinical Features of EoGE and EoC Cases vs Controls (individuals without EGIDs): EoGE Cases, n Odds (%)
Ratios EoC Cases, n Odds Ratios [OR, Controls, n (%)
[OR,
95% (%)
95% Confidence
Confidence
Interval (CI)]
Interval (CI)] 890 (48.9%)
410 (53.2%)
3.54 [95% CI:
SC
Drug Allergy
Rhinitis
610 (33.5%)
M AN U
3.23 to 3.88, P<0.0001]
210 (27.3%)
5.15 [95% CI: 4.67 to 5.67, P<0.0001]
600 (33.0%)
180 (23.4%)
5.15 [95% CI: 4.67
TE D
Asthma
to 5.67, P<0.0001]
Sinusitis
540 (30.0%)
3.71 [95% CI: 3.36
EP
3.81 [95% CI: 3.45
AC C
550 (30.2%)
220 (28.5%)
450 (24.7%)
12.20 [95% CI:
7619910 (21.3%)
to 4.85, P<0.0001]
3.83 [95% CI: 3.27
3193000 (8.9%)
to 4.49, P<0.0001] 3.19 [95% CI: 2.70
3122770 (8.7%)
3.52 [95% CI: 3.01
3651530 (10.2%)
to 4.12, P<0.0001]
250 (32.5%)
to 4.21, P<0.0001]
Food allergy
4.21 [95% CI: 3.65
to 3.77, P<0.0001]
to 4.11, P<0.0001]
Dermatitis
RI PT
Allergic condition
4.23 [95% CI: 3.64
3641140 (10.2%)
to 4.92, P<0.0001]
140 (18.2%)
10.97 to 13.57,
8.25 [95% CI: 6.87 to 9.91, P<0.0001]
P<0.0001]
27
938450 (2.6%)
ACCEPTED MANUSCRIPT
Eczema
370 (20.3%)
140 (18.2%)
3.78 [95% CI: 3.37
3.29 [95% CI: 2.74
to 4.23, P<0.0001]
130 (7.1%)
to 3.95, P<0.0001]
40 (5.2%)
5.31 [95% CI: 4.44
3.78 [95% CI: 2.75 to 5.20, P<0.0001]
EP
TE D
M AN U
SC
RI PT
to 6.35, P<0.0001]
AC C
Urticaria
2265120 (6.3%)
28
511120 (1.4%)
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Table 5: Odds Ratios for GI Clinical Features of EoGE and EoC stratified by Age and Gender: EoGE Cases-
EoGE Cases-
EoGE Cases-
EoC Cases-
EoC Cases-
EoC Cases-
EoC Cases-
Cases-
Children, Male
Adults,
Children,
Adults, Male
Children, Male
Adults, Female
Children, Female
Female
Female
Adults, Male
11.79 [95% CI:
8.32 [95% CI:
12.2, [95% CI:
5.54, [95% CI:
17.86 [95%
8.47 [95% CI:
13.81 [95% CI:
CI: 7.19
8.59 to 16.19,
8.59 to 16.19,
7.30 to 9.47,
4.21 to 7.28,
CI: 10.15
7.06 to 10.17,
8.07 to 23.62,
to 9.91,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
to 31.46,
P<0.0001]
P<0.0001]
Nausea and vomiting
P<0.0001]
47.99 [95% CI:
9.18 [95% CI:
104.9, [95% CI:
5.73, [95% CI:
16.63 [95%
5.84 [95% CI:
179.87 [95% CI:
CI: 4.18
19.70
7.39 to 11.41,
54.97 to 200.28
3.04 to 10.82,
CI: 1.03 to
4.04 to 8.46,
70.40 to 459.54,
to 8.71,
to 116.88,
P<0.0001]
, P<0.0001]
P<0.0001]
269.58,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
10.50
28.07 [95% CI:
8.71 [95% CI:
46.47 [CI: 30.04
5.75, [95% CI:
19.34 [95%
5.56 [95% CI:
27.88 CI:
[95% CI:
18.39 to 42.83,
7.45 to 10.18,
to 71.91,
3.91 to 8.46,
CI: 7.67
4.31 to 7.17,
10.92 to 71.18,
8.69
P<0.0001]
P<0.0001]
P<0.0001]
to 48.72,
P<0.0001]
P<0.0001]
P<0.0001]
TE D
6.04 [95%
to 12.68, Dysphagia
M AN U
P<0.0001]
EP
Heartburn
8.44 [95%
AC C
GERD
RI PT
EoGE
SC
GI Diagnoses
P<0.0001]
P<0.0001]
P<0.0001]
7.84 [95%
7.00 [95% CI:
7.97 [CI:
9.93 [95% CI:
4.29, [95% CI:
19.34 [95%
5.54 [95% CI:
3.85 [95% CI: 1.51
CI: 6.49
4.84 to 10.13,
6.97 to 9.12,
6.74 to 14.6243
2.92 to 6.32,
CI: 10.99
4.53 to 6.78,
to 9.82, P<0.0001]
29
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to 9.47,
P<0.0001]
P<0.0001]
, P<0.0001]
P<0.0001]
P<0.0001]
Abdominal pain
8.76 [95% CI:
19.45 [95% CI:
6.66, [95% CI:
8.70 [95% CI:
5.71 [95% CI:
11.67 [95% CI:
CI: 4.19 to
13.06 to 27.33,
6.09 to 12.61,
12.57 to 30.08,
2.74 to 16.18,
3.45 to 21.91,
3.05 to 10.69,
4.57 to 29.78,
11.69,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
6.96 [95%
43.89 [95% CI:
7.02 [95% CI:
66.70 [95% CI:
5.92 [95% CI:
68.03, [95%
8.93 [95% CI:
40.02 [95% CI:
CI: 5.73 to
28.76 to 66.99,
5.96 to 8.26,
43.10 to 103.22
4.20 to 8.36,
CI: 34.01
7.22 to 11.06,
15.68 to 102.18,
8.46,
P<0.0001]
P<0.0001]
, P<0.0001]
to 136.07,
P<0.0001]
P<0.0001]
P<0.0001]
SC
P<0.0001]
P<0.0001]
9.41 [95%
9.06 [95% CI:
8.68 [95% CI:
13.79 [95% CI:
7.80 [95% CI:
17.00, [95%
7.25 [95% CI:
1.23 [95% CI:
CI: 7.98 to
6.76 to 12.16, P
7.55 to 9.99,
9.69 to 19.64,
5.93 to 10.25,
CI: 9.65
5.99 to 8.77,
0.48 to 3.14,
11.10,
<0.0001]
P< 0.0001]
P<0.0001]
to 29.93,
P<0.0001]
P<0.0001]
P<0.0001] 11.92
Diarrheal
M AN U
P<0.0001]
RI PT
18.89 [95% CI:
15.01 [95% CI:
[95% CI:
6.17 to 36.53, P
7.14 to
<0.0001]
19.92,
disorder
P<0.0001]
Weight loss
8.01 [95%
TE D
GI hemorrhage
7.02 [95%
14.71 [95% CI:
P<0.0001]
EP
thrive)
P<0.0001]
P<0.0001]
6.01 [95% CI: 3.61 to 10.01, P<0.0001]
AC C
FTT (Failure to
to 34.06,
6.74 [95% CI:
23.11 [95% CI: 9.45 to 56.52, P <0.0001]
P<0.0001] 11.35 [95% CI:
58.37, [95%
16.29 [95% CI:
7.13 [95% CI:
4.67 to 27.56,
CI: 23.16
10.41 to 25.49, P
0.44 to 116.02,
P<0.0001]
to 147.10, P
<0.0001]
P<0.0001]
<0.0001]
21.41 [95%
30
7.57 [95% CI:
22.80, [95%
6.74 [95% CI:
12.85 [95% CI:
ACCEPTED MANUSCRIPT
CI: 6.40 to
9.64 to 22.45, P
5.60 to 8.12,
CI:13.84 to 33.1
5.14 to 11.14,
CI: 11.40 to
10.03,
<0.0001]
P<0.0001]
2, P<0.0001]
P<0.0001]
45.60, P<
P<0.0001] 82.02 [95% CI:
5.73 [95% CI:
111.97 [95%
4.11 [95% CI:
CI: 4.91 to
33.65 to 199.95
3.85 to 8.53,
CI:
1.69 to 9.98,
10.93,
, P<0.0001]
P<0.0001]
45.70 to 274.32
P<0.0001]
, P<0.0001]
GI perforation
P<0.0001]
4.51 [95% CI:
399.89 [95% CI:
CI:
2.41 to 8.44,
156.34 to 1022.81,
126.36 to 805.
P<0.0001]
P<0.0001]
1493.78,
15.88 [95% CI:
200.72 [95% CI:
384.12 [95%
16.05 [95%
603.93 [95%
[95% CI:
CI:
CI:
CI:
20.54 to
[95% CI:
6.58 to 38.34,
12.29 to 3277.58,
18.55 to
156.37 to 943.5
8.66 to 29.94,
244.27 to 1493.
121.17,
587.40 to 379
P<0.0001]
P<0.0001]
64.80,
8, P<0.0001]
P<0.0001]
16, P<0.0001]
P<0.0001]
8.73,
M AN U
49.88 [95% CI:
19, P<0.0001]
34.67
P<0.0001]
P<0.0001]
83.48
49.98 [95% CI:
200.72 [95%
115.47 [95%
11.70 [95% CI:
194.36, [95%
45.71 [95% CI:
412.39 [95% CI:
[95% CI:
20.52 to 121.73
CI:
CI:
0.73 to 187.68,
CI: 77.06
18.93 to 110.40,
161.22 to 1054.85,
44.63 to
, P<0.0001]
12.29 to 327
47.13 to 282.9
P<0.0001]
to 490.24,
P<0.0001]
P<0.0001]
7.58,
1, P<0.0001]
AC C
156.15, Intussusception
SC
P<0.0001]
318.97, [95%
RI PT
7.33 [95%
TE D
Volvulus
P<0.0001]
5.03 to 32.79,
0.0001]
EP
Ascites
5.60 to 8.12,
P<0.0001]
P<0.0001]
P<0.0001]
17.68
124.25 [95%
14.13 [95%
481.20 [95%
0.97 [95% CI:
43.03, [95%
11.12 [95% CI:
71.21 [95% CI:
[95% CI:
CI:
CI:
CI:
0.06 to15.49,
CI:
5.94 to 20.80,
4.37 to 1159.86,
11.84 to
50.92 to 303.22
9.49 to 21.02
250.89 to 922.9
P<0.0001
2.65 to 698.11
P<0.0001]
P<0.0001]
31
ACCEPTED MANUSCRIPT
26.39,
, P<0.0001]
, P<0.0001]
5, P<0.0001]
, P<0.0001]
9.81 [95%
14.55 [95% CI:
9.72 [95% CI:
8.75 [95% CI:
5.85 [95% CI:
2.45, [95% CI:
8.75 [95% CI:
55.32 [95% CI:
CI: 7.84 to
7.69 to 27.54,
8.07 to 11.69,
6.67 to 11.47,
3.69 to 9.28,
0.15 to 39.70,
6.67 to 11.47,
21.67 to 141.25,
12.28,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
SC
GI obstruction
RI PT
P<0.0001]
EoGE Cases-
Adults, Male Children,
Adults,
Rhinitis
Asthma
EoC Cases- EoC Cases-
Children,
Children,
Adults,
Children,
Female
Male
Female
Female
Adults, Male
3.27 [95% CI:
8.15 [95% CI:
3.49 [95% CI:
7.61 [95% CI:
3.43 [95% CI:
3.61 [95% CI:
4.34 [95% CI:
2.05 [95% CI:
2.78 to 3.84,
6.014 to 11.05,
3.06 to 3.98,
5.30 to 10.92,
2.61 to 4.51, P<
1.80 to 7.21,
3.60 to 5.24,
0.80 to 5.24,
P<0.0001]
P<0.0001]
P<0.0001]
0.0001]
P<0.0001]
P<0.0001
P<0.0001]
0.12 [95% CI:
8.15 [95% CI:
4.68 [95% CI:
5.48 [95% CI:
3.68 [95% CI:
2.30 [95% CI:
3.97 [95% CI:
1.48 [95% CI:
0.10 to 0.14,
6.01 to 11.05,
4.08 to 5.36
3.82 to 7.86,
2.68 to 5.06,
1.15 to 4.60, P<
3.26 to 4.83,
0.58 to 3.77,
P<0.0001]
P<0.0001]
,P<0.0001]
P<0.0001]
P<0.0001]
0.0001]
P<0.0001]
P<0.0001]
4.94 [95% CI:
6.00 [95% CI:
4.96 [95% CI:
8.55 [95% CI:
4.94 [95% CI:
5.60 [95% CI:
3.09 [95% CI:
1.67 [95% CI:
P<0.0001
AC C
Drug Allergy
Female
EoC Cases-
EP
Male
EoGE Cases- EoC Cases-
TE D
Allergic condition
EoGE Cases- EoGE Cases-
M AN U
Table 6: Odds Ratios for Allergic Clinical Features of EoGE and EoC stratified by Age and Gender:
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6.04 to 12.10
4.12 to 5.91
3.18 to 9.86,
2.51 to 3.80,
0.65 to 4.24,
P<0.0001]
P<0.0001]
P<0.0001]
4, P<0.0001]
,P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
3.37 [95% CI:
3.99 [95% CI:
3.68 [95% CI:
4.33 [95% CI:
3.16 [95% CI:
7.98 [95% CI:
3.12 [95% CI:
3.92 [95% CI:
2.80 to 4.05,
2.85 to 5.59,
3.20 to 4.21,
2.94 to 6.4,
2.30to 4.34,
4.53 to 14.06,
2.56 to 3.80,
1.92 to 8.02,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
3.82 [95% CI:
16.13 [95% CI:
3.51 [95% CI:
4.36 [95% CI:
3.28 [95% CI:
19.02 [95% CI:
4.67 [95% CI:
3.97 [95% CI:
3.19 to 4.57,
11.90 to 21.86,
3.04 to 4.05,
3.08 to 6.18,
2.39 to 4.51,
10.80 to 33.50,
3.86 to 5.65,
2.25 to 6.98,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
Food allergy
Eczema
7.43 [95% CI:
SC
37.82 [95%
CI:
32.49 [95% CI:
6.31 to 8.74,
10.58 to 15.7
24.25 to 43.51,
P<0.0001]
8, P<0.0001]
P<0.0001]
3.60 [95% CI:
3.64 [95% CI:
4.27 [95% CI:
5.33 [95% CI:
3.00 [95% CI:
2.90 to 4.46,
3.09 to 4.28,
3.11 to 5.86,
3.71 to 7.65,
P<0.0001]
P<0.0001]
EP
12.92 [95%
RI PT
4.34 to 5.68,
M AN U
Dermatitis
4.46 to 8.07,
P<0.0001]
P<0.0001]
AC C
37.82 [95%
5.44 [95% CI:
27.67 to 85.81,
5.42 [95% CI:
CI:
26.82 to 53.3
3.43 to 8.62,
P<0.0001]
4.20 to 6.98,
20.35 to 70.3
4, P<0.0001]
P<0.0001]
P<0.0001
0, P<0.0001]
2.42 [95% CI:
3.59 [95% CI:
1.44 [95% CI:
2.04 to 4.41,
1.21 to 4.85,
2.85 to 4.52,
0.56 to 3.67,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
4.50 [95% CI:
4.35 [ 95%
4.79 [ 95% CI:
Urticaria
48.73 [95% CI:
CI:
TE D
Sinusitis
4.12 to 5.91,
5.06 [95% CI:
6.53 [95% CI:
3.72 to 6.16,
9.67 [95% CI:
2.84 [95% CI:
1.79 to 11.34,
CI: 3.00 to
5.80 [ 95% CI:
3.39 to 7.56,
4.28 to 9.97,
P<0.0001]
6.25 to 15.00,
1.17 to 6.90,
P<0.0001]
6.29,
2.27 to 14.81,
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P<0.0001]
P=0.0002]
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9
7.3 6.9
7
5.1 5
4.3
4.7 4.2
4.1
4
4.9
M AN U
4.7
3
2
2.4 1.7
1.9
2.1
1.7
5.4
2.8
5.1
4
3.8
4
EoGE
3.8
EoC 2.7
2.9
0.8
1.7
0.9
EP
0.8
0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+ (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age) (age)
AC C
0
5.7
2.4
2.3
1.1 1
5.9
TE D
3
5.7
SC
5.7
6
RI PT
7.8
8
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Figure 1: The Age-Based 2012-2017 Prevalence (per 100,000 persons) of Eosinophilic gastroenteritis (EoGE), and
AC C
EP
TE D
M AN U
SC
RI PT
Eosinophilic colitis (EoC) in the Explorys Database.