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: S1542-3565(17)30691-2
DOI: 10.1016/j.cgh.2017.05.050
Reference: 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.

Cooper, MD

PT
First Author:

RI
Emad Mansoor, MD

Department of Internal Medicine

SC
University Hospitals Cleveland Medical Center

Case Western Reserve University

11100 Euclid Avenue

U
AN
Cleveland, Ohio 44106
M

[email protected]

Second Author:
D

Mohannad Abou Saleh, MBBS

TE

Department of Internal Medicine

University Hospitals Cleveland Medical Center

EP

Case Western Reserve University

C

11100 Euclid Avenue

AC

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

1
 ACCEPTED MANUSCRIPT
11100 Euclid Avenue

Cleveland, Ohio 44106, Wearn 244

[email protected]

+1 216-844-5385

Grant Support: Supported in part by the Cleveland Digestive Diseases Research

PT
Core Center (1P30DK097948).

RI
Abbreviations:

EGIDs- Eosinophilic Gastrointestinal Diseases

SC
GI- Gastrointestinal
EoE- Eosinophilic esophagitis
EoG- Eosinophilic gastritis
EoGE- Eosinophilic gastroenteritis

U
EoC- Eosinophilic colitis
US- United States
AN
EHR- Electronic Health Record
HDG- Health Data Gateway
SNOMED-CT- Systematized Nomenclature Of Medicine – Clinical Terms
M

HIPAA- Health Insurance Portability and Accountability Act

IRB- Institutional Review Board
GERD- Gastroesophageal reflux disease
D

OR- Odds ratio

CI- Confidence Interval
TE

ICD-9- International Classification of Diseases, Ninth Revision

Conflicts of interest: There are no potential conflicts (financial, professional, or

EP

personal) to disclose by all the authors (Emad Mansoor, Mohannad Abou Saleh and
C

Gregory S. Cooper).
AC

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

2
 ACCEPTED MANUSCRIPT
Critical revision: Cooper

Statistical Analysis: Abou Saleh and Mansoor

Obtained funding: Cooper

Study Supervision: Cooper

PT
Word count: 2,981

RI
Abstract:

SC
Background & Aims: Although eosinophilic esophagitis (EoE) has been extensively

studied, there have been few epidemiology studies of other eosinophilic

U
gastrointestinal disorders (EGIDs). Using a large, population-based database, we
AN
investigated epidemiologic features of eosinophilic gastroenteritis (EoGE), and colitis
M

(EoC) in the United States (US).

D

Methods: We collected data from a commercial database (Explorys Inc, Cleveland,

TE

OH) that provided electronic health records from 26 major integrated US healthcare

systems from 1999 to March 2017. We identified a cohort of adult and pediatric
EP

patients with EoGE and EoC from March 2012 through March 2017, based on the
C

Systematized Nomenclature of Medicine – Clinical Terms. We calculated the overall

AC

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).

3
 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 non-

EoE EGIDs were more prevalent in Caucasians than African-Americans and Asians,

and in female patients than male patients. Although EoGE was more prevalent in

PT
children (under 18 years) than adults, EoC was more prevalent in adults (older than 18

RI
years). Compared with controls, individuals with non-EoE EGIDs were more likely to

have been diagnosed with other gastrointestinal or allergic disorders.

SC
Conclusions: In a population-based study in the US, using the Explorys database, we

U
found the overall prevalence rate of EoGE to be 5.1/100,000 persons and the
AN
prevalence rate of EoC to be 2.1/100,000; these values are at the lower end of
M

prevalence rates previously reported in the US.

D

Key words: eosinophilic gastrointestinal diseases; epidemiology; prevalence,

TE

SNOMED-CT
EP

Background and Aims:

C
AC

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

4
 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

United States (US) [6]. EoGE was first described in 1937 [7] and while it can affect

PT
any segment of the GI tract, the stomach and the duodenum are the most frequently

RI
affected organs [8,9]. However, there is a lack of large population-based

epidemiologic studies on EoG, EoGE and EoC. Most of the studies on these disorders

SC
have been niche studies, specific to some locations, and have many limitations,

including small sample sizes and referral bias [10-14].

U
AN
To our knowledge, there has been only one large database study on the prevalence of
M

EoGE and EoC in the US [15], which included cases between 2009 and 2011. Given

the well documented increase over time in the prevalence of EoE, we sought to
D

describe the epidemiology of EoGE and EoC in the US over a 5-year period between
TE

2012 and 2017 by using a population-based database. The aims of the study were to

identify cases of EoGE and EoC, identify other disorders associated with these
EP

EGIDs, and estimate overall prevalence of these EGIDs in US among different age-
C

based, race-based and gender-based subgroups. These data will help better define the
AC

epidemiology of EoGE and EoC.

Methods:

Database:

5
 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

patient data from participating institutions and uses a health data gateway (HDG)

PT
server behind the firewall of each participating healthcare organization that collects

RI
de-identified data from various health information systems—EHR using billing

inquiries. Data are then standardized and normalized by Explorys. Diagnoses,

SC
findings, and procedures are mapped into the Systematized Nomenclature Of

Medicine – Clinical Terms (SNOMED–CT) hierarchy while prescription drug orders

U
are mapped into SNOMED (to represent the pharmacological class) and RxNorm (to
AN
represent the drug itself). Each participating healthcare institution has access to
M

Explorys online (password protected), which provides for browsing of the data from

all participating healthcare institutions. Explorys data are automatically updated at

D

least once every 24 hours [16]. Explorys is a Health Insurance Portability and
TE

Accountability Act (HIPAA) compliant platform and thus Institutional Review Board

(IRB) is not required.

C EP

Patient selection:
AC

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

6
 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

the same patient twice

PT
Associated medical conditions of interest:

RI
We identified multiple medical conditions associated with EoGE and EoC as

SC
demonstrated by prior studies [1,17,18,19,20]. Data on these conditions, which

included GI and allergic disorders, were extracted by using SNOMED-CT diagnostic

U
terms for these disorders. The associated GI disorders that were studied included
AN
gastroesophageal reflux disease (GERD), heartburn, dysphagia, nausea and vomiting,
M

failure to thrive, GI hemorrhage, abdominal pain, diarrhea, weight loss, ascites,

volvulus, intussusception, GI perforation, GI obstruction, and eosinophilic

D

esophagitis. The associated allergic disorders that were studied included drug allergy,
TE

rhinitis, asthma, sinusitis, dermatitis, food allergy, eczema and urticaria.

EP

Statistical Analysis:
C
AC

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%

7
 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

with EoGE and EoC from March 2012 through March 2017. We then divided this

PT
number by the total number of patients in the database (from March 2012 to March

RI
2017), thus making sure that all patients in the denominator (population at risk) had an

equal opportunity of being diagnosed with EoGE and EoC if they had the disease.

SC
Similarly, age-based, gender-based and race-based prevalence rates were calculated.

U
The Odds Ratio (OR), its standard error and 95% confidence interval were calculated
AN
according to Altman, 1991 using the MedCalc Statistical Software [21] with a case-
M

control design.
D

We performed sensitivity analyses and estimated the prevalence of EoGE and EoC
TE

after excluding patients with SNOMED-CT diagnoses of other possible causes of GI

tract eosinophilia including Crohn’s disease, ulcerative colitis, celiac disease,

EP

malignant lymphoma, leukemia, systemic vasculitis and parasitic infections

C

(Strongyloides, Ascaris, Ancylostoma. Anisakis, Capillaria and Trichinella).

AC

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.

8
 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

SNOMED-CT diagnosis of EoGE and EoC respectively and represented the EoGE

PT
and EoC case groups.

RI
SC
Eosinophilic Gastroenteritis (EoGE):

U
Of the 1,820 patients with EoGE, the majority were female (57.7%), Caucasian
AN
(77.5%), and adults (>18 years of age) (83.5%) (Table 1). The overall prevalence was
M

5.1 per 100,000 persons. The prevalence in female patients was slightly higher than

male patients (5.3 vs 4.8/100,000), (OR=1.11, 95% CI: 1.01-1.21, p=0.0338). The
D

prevalence of EoGE was highest in Caucasians (compared to Asians and African

TE

Americans) at 6.3/100,000 (OR=1.17, 95% CI: 1.02 to 1.34, p=0.0231). The

prevalence was higher in children (<18 years of age) at 5.3/100,000 (OR=1.04, 95%
EP

CI: 0.92-1.18, p=0.5370) compared to adults (>18 years of age) at 5.1/100,000 (Table
C

2). The 5-year interval age-based prevalence rates for EoGE and EoC are shown in
AC

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

9
 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

was slightly higher in adults (>18 years of age) at 2.3/100,000 (OR=1.43, 95% CI:

PT
1.15-1.79, p=0.0013) compared to children (<18 years of age) at 1.6/100,000 (Table

RI
2).

SC
Association of EoGE and EoC with other medical disorders:

U
Among GI symptoms and associated disorders (Table 3), individuals with EoGE and
AN
EoC were more likely than controls to have GERD, heartburn, dysphagia, nausea and
M

vomiting, failure to thrive, GI hemorrhage, abdominal pain, diarrheal disorder,

abnormal weight loss, ascites, volvulus, intussusception, GI perforation and GI

D

obstruction.
TE

Among allergic disorders (Table 4), individuals with EoGE and EoC were more likely
EP

than controls to have drug allergy, rhinitis, asthma, sinusitis, dermatitis, food allergy,
C

eczema and urticaria.

AC

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).

10
 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

(Crohn’s Disease, n=120, ulcerative colitis, n=45, systemic vasculitis=15, celiac

PT
disease=60, malignant lymphoma=25, leukemia=15, Strongyloides=10, Ascaris=0,

RI
Ancylostoma=0, Anisakis=5, Capillaria=0 and Trichinella=0), compared to

5.1/100,000 using the primary definition. However, the prevalence of EoC was

SC
1.5/100,000 after excluding 245 patients (Crohn’s Disease, n=70, ulcerative colitis,

n=110, systemic vasculitis=5, celiac disease=30, malignant lymphoma=10,

U
leukemia=10, Strongyloides=5, Ascaris=0, Ancylostoma=0, Anisakis=5, Capillaria=0
AN
and Trichinella=0), compared to 2.1/100,000 using the primary definition. Of note,
M

IBD made up nearly 23% of all patients with EoC.

D

Discussion:
TE

In this study, we evaluated the prevalence of EoGE and EoC over 5 years in the
EP

Explorys database between 2012 and 2017. Most of the epidemiological studies that
C

have provided prevalence estimates on EoGE and EoC have been small in size. To our
AC

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.

11
 ACCEPTED MANUSCRIPT

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

reported in other studies in the past, thereby lending empiric validity to our study.

PT
Guajardo et al [22] estimated the prevalence of EoGE in the USA to be 2.5/100,000

RI
persons using an electronic survey. Two other studies in the recent past estimated the

overall prevalence of non-EoE EGIDs. Using ICD-9 codes through a large health plan

SC
claims database, Jensen et al [15] estimated the prevalence of EoGE and EoC to be

8.4/100,00 and 3.3/100,000 respectively, higher than our estimates. Additionally,

U
Spergel et al [23] estimated the overall prevalence of the EoGE and/or EoC by
AN
administering an electronic survey to allergists and gastroenterologists about their
M

practice data, and extrapolated the results nationally. They reported a prevalence of

28/100,000 for combined EoGE and/or EoC, higher than our estimate. The difference
D

in the prevalence of non-EoE EGIDs between our study and these studies can be
TE

attributed to the differences in the study design, methods of data collection, data

analyses, time period over which the data was collected as well as the size of source
EP

population. Given that in our study we had large numbers of both non-EoE EGID
C

cases and total number of individuals in the database, our estimates of prevalence
AC

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

12
 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

predominance of EoGE in children in our study. Our result is consistent with the

PT
findings of Jensen [15] who reported that the prevalence of EoGE decreased with age,

RI
with the highest prevalence in individuals under 5 years of age. Moreover, we found

that EoGE and EoC have a slight female predominance that has been reported in prior

SC
studies [15]. Previous studies have reported familial clustering of EoE [4] and non-

EoE EGIDs [25], thereby pointing towards a genetic predisposition [10,14,17,19],

U
however, there are no genetic markers identified that have been shown to be
AN
conserved in Caucasians to justify higher prevalence in this group.
M

While we did not look at region-wise burden of non-EoE EGIDs, it is safe to assume
D

that regional differences in gender, age and race distribution cannot alone account for
TE

our findings of Caucasian and female predominance of all non-EoE EGIDs, and

younger age group predominance of EoGE. Furthermore, health institutions affiliated

EP

with Explorys cover all 50 states and span the East, Midwest, South, Central and West
C

divisions of the US [16], thus providing a broad regional and climatic distribution of
AC

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

13
 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

upon the area of the GI tract affected, the extent of disease and the depth of

PT
eosinophilic inflammation of the bowel wall. As such, patients with the mucosal form

RI
of EoGE may present with vomiting, abdominal pain, diarrhea, failure to thrive;

patients with EoGE of the muscularis layer may present with GI obstruction; and

SC
patients with EoGE of the serosal layer may present with ascites. While, our study did

not look at the depth of eosinophilic inflammation of the bowel wall, we found these

U
and other GI co-morbidities to be significantly associated with non-EoE EGIDs.
AN
M

We also found that each of the non-EoE EGIDs is strongly associated with high rates

of allergic disorders. Multiple studies and case series in the past have described the
D

association between atopic disorders and EoGE [10, 11, 12, 28], while the association
TE

between EoC and atopic disorders has also been described in a few studies [15]. As

opposed to other EGIDs, EoC is considered to be a non-IgE-associated disease [1] and

EP

thus our finding of association between atopy and EoC may be due to the large sample
C

size and thus statistically significant but not clinically meaningful. While consensus
AC

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.

14
 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

studies comparing disease presentation and co-morbid disorders between adults and

PT
children with non-EoE EGIDs, our findings are consistent with that of Reed C et al.

RI
[31] who evaluated 44 patients with EoGE and did not find any significant differences

in disease presentation between adults and children.

SC
This study has a few limitations that should be acknowledged. First, with regards to

U
the estimate on non-EoE EGIDs prevalence rates, we might have underestimated the
AN
true prevalence rates since not all individuals with non-EoE EGIDs are brought to
M

medical notice. As patients with a true diagnosis of EGID may not have been captured

through SNOMED-CT diagnosis codes and others may have been misclassified as
D

having EGID when they had alternative conditions, we could also have under- or
TE

overestimated the true prevalence of non-EoE EGIDs. Validation of the SNOMED-

CT diagnostic code for non-EoE EGIDs was not possible since the patient information
EP

in the database is de-identified. However, while ICD-9 and SNOMED-CT are both
C

medical terminology systems for recording medical diagnoses and concepts,

AC

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

15
 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

patient across different healthcare institutions and combine the data [33], a few

PT
patients may have received care in multiple institutions within Explorys healthcare

RI
partners and thus could have been counted multiple times. However, this is countered

by the fact that Explorys uses a robust patient matching algorithm [33] and thus the

SC
effect of this error might be minimal and might affect the non-EoE EGID and control

group equally.

U
AN
Finally, due to the de-identified nature of information, we were unable to look at
M

specific dates due to which our analysis was based on the prevalence of non-EoE

EGIDs throughout the 5-year study period. Thus, our study did not distinguish
D

between patients with non-EoE EGIDs responsive to treatment and refractory to

TE

treatment.
EP

In summary, the analysis of one of the largest samples of EoGE and EoC cases so far,
C

from the large commercial database Explorys, estimates the overall prevalence rates
AC

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].

16
 ACCEPTED MANUSCRIPT
References:

1. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J. Allergy

Clin Immunol 2004; 113:11–28.

2. Dellon ES. Diagnosis and management of eosinophilic esophagitis. Clin

PT
Gastroenterol Hepatol 2012;10:1066-1078.

RI
3. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis [Letter to the

SC
Editor]. New Engl J Med 2004;351:940-941.

U
4. Liacouras CA, Sperjel JM, Ruchelli E, et al. Eosinophilic esophagitis: A 10-
AN
year experience in 381 children. Clin Gastroenterol Hepatol 2005;3:1198-
M

1206.
D

5. Arias A, Perez-Martinez I, Tenias JM, Lucendo AJ. Systematic review with meta-
TE

analysis: the incidence and prevalence of eosinophilic oesophagitis in children and

adults in population-based studies. Aliment Pharmacol Ther 2016;43:3-15.

EP

6. Mansoor E, Cooper GS. The 2010-2015 Prevalence of Eosinophilic Esophagitis in

C

the USA: A Population-Based Study. Dig Dis Sci 2016; 61:2928-2934.

AC

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,

and a unique gastric transcriptome. J Allergy Clin Immunol 2014;134:1114–1124.

PT
11. Ko HM, Morotti RA, Yershov O, et al. Eosinophilic gastritis in children:

clinicopathological correlation, disease course, and response to therapy. Am J

RI
Gastroenterol 2014;109:1277–1285.

SC
12. Lee CM, Changchien CS, Chen PC, et al. Eosinophilic gastroenteritis: 10 years

U
experience. Am J Gastroenterol 1993;88:70–74.
AN
13. Talley NJ, Shorter RG, Phillips SF, et al. Eosinophilic gastroenteritis: a

clinicopathological study of patients with disease of the mucosa, muscle layer, and
M

subserosal tissues. Gut 1990;31:54–58.

D

14. Zhang L, Duan L, Ding S, et al. Eosinophilic gastroenteritis: clinical

TE

manifestations and morphological characteristics, a retrospective study of 42 patients.

Scand J Gastroenterol 2011;46:1074–1080.

EP

15. Jensen ET, Martin CF, Kappelman MD, et al. Prevalence of Eosinophilic
C

Gastritis, Gastroenteritis, and Colitis: Estimates From a National Administrative

AC

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 August 25, 2016.

<https://www.explorys.com/about-us.html>.

18
 ACCEPTED MANUSCRIPT
17. Zhang MM, Li YQ. Eosinophilic gastroenteritis: A state-of-the-art review. J

Gastroenterol Hepatol 2016; [Epub ahead of print].

18. Ingle SB, Hinge Ingle CR. Eosinophilic gastroenteritis: an unusual type of

gastroenteritis. World J Gastroenterol 2013;19:5061-5066.

PT
RI
19. Yen EF, Pardi DS. Non-IBD colitides (eosinophilic, microscopic). Best Pract Res

Clin Gastroenterol 2012; 26:611-622.

SC
20. Alfadda AA, Shaffer EA, Urbanski SJ, Storr MA. Eosinophilic colitis is a

U
sporadic self-limited disease of middle-aged people: a population-based study.
AN
Colorectal Dis 2014;16:123-129.
M

21. MedCalc Software Team. “Odds ratio calculator”. MedCalc. 2016. Accessed
D

December 4, 2016. <https://www.medcalc.org/calc/odds_ratio.php>.

TE

22. Guajardo JR, Plotnick LM, Fende JM, et al. Eosinophil-associated gastrointestinal
EP

disorders: a world-wide-web based registry. J. Pediatr. 2002; 141: 576–81.

C
AC

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.

19
 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.

25. Aquino A, Dòmini M, Rossi C, D'Incecco C, Fakhro A, Lelli Chiesa P. Pyloric

PT
stenosis due to eosinophilic gastroenteritis: presentation of two cases in mono-ovular

RI
twins. Eur J Pediatr 1999;158:172–73.

SC
26. Klein NC, Hargrove RL, Sleisenger MH, et al. Eosinophilic gastroenteritis.

Medicine (Baltimore) 1970; 49:299-319.

U
AN
27. Lucendo AJ, Arias A. Eosinophilic gastroenteritis: an update. Expert Rev
M

Gastroenterol Hepatol 2012; 6:591-601.

D

28. Bischoff SC. Food allergy and eosinophilic gastroenteritis and colitis. Curr Opin
TE

Allergy Clin Immunol 2010; 10:238-245.

EP

29. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: Updated
C

consensus recommendations for children and adults. J Allergy Clin Immunol

AC

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.

32. Nadkarni PM, Darer JA. Migrating existing clinical content from ICD-9 to

SNOMED. J Am Med Inform Assoc 2010;17:602-607.

PT
RI
33. Kaelber DC, Foster W, Gilder J, Love TE, Jain AK. Patient characteristics

associated with venous thromboembolic events: a cohort study using pooled

SC
electronic health record data. J Am Med Inform Assoc 2012;19:965–972.

U
AN
M
D
TE
C EP
AC

21
 ACCEPTED MANUSCRIPT

Tables:

Table 1: Demographic Characteristics of EoGE and EoC Cases

EoGE EoC

PT
Total number of cases, n 1820 770

RI
Male, n (%) 770 (42.3) 260 (33.8)

SC
Age group

U
Children (<18 yrs. of age), n (%) 300 (16.5) 90 (11.7)

AN
Adults (>18 yrs. of age), n (%) 1520 (83.5) 680 (88.3)

Race

M
Caucasian, n (%) 1410 (77.5) 630 (81.8)

D
TE
African American, n (%) 220 (12.1) 100 (13.0)

Asian, n (%) 30 (1.6) 10 (1.3)

C EP
AC

22
 ACCEPTED MANUSCRIPT

Table 2: Prevalence of EoGE and EoC in the Explorys Database from March 2012 to March 2017:

Group Source EoGE cases, Prevalence EoC cases, n Prevalence (per

Population n (%) (per 100,000) (%) 100,000)

PT
RI
Overall 35,826,830 1,820 (100) 5.1 770 (100) 2.1

SC
Male 16,044,290 770 (42.3) 4.8 260 (33.8) 1.6

Female 19,782,540 1,050 (57.7) 5.3 510 (66.2) 2.6

U
Children (<18yrs.) 5,702,640 300 (16.5) 5.3 90 (11.7) 1.6

AN
Adults (>18 yrs.) 30,042,580 1520 (83.5) 5.1 680 (88.3) 2.3

M
Caucasian 22,533,420 1410 (77.5) 6.3 630 (81.8) 2.8

D
African American 3,978,230 220 (12.1) 5.5 100 (13.0) 2.5

Asian 690,920 30 (1.6)

TE
4.3 10 (1.3) 1.4
C EP
AC

23
 ACCEPTED MANUSCRIPT

Table 3: Odds Ratios for Associated GI Clinical Features of EoGE and EoC Cases vs Controls (individuals without EGIDs):

GI Diagnoses EoGE Cases, Odds Ratios EoC Cases, n Odds Ratios [OR, Controls, n (%)

n (%) [OR, 95% (%) 95% Confidence

PT
Confidence Interval (CI)]

Interval (CI)]

RI
960 (52.7%) 8.65 [95% CI: 400 (51.9%) 8.38 [95% CI: 7.27 to 4091580 (11.4%)

SC
7.89 to 9.48, 9.65, P<0.0001]

GERD

U
P<0.0001]

AN
130 (7.1%) 8.73 [95% CI: 40 (5.2%) 6.22 [95% CI: 4.53 to 312480 (0.9%)
7.31 to 10.44, 8.55, P<0.0001]

M
Heartburn P<0.0001]

D
390 (21.4%) 10.38 [95% CI: 110 (14.3%) 6.34 [95% CI: 5.18 to 916420 (2.6%)

TE
9.28 to 11.61, 7.76, P<0.0001]

Dysphagia P<0.0001]
EP
540 (29.7%) 8.06 [95% CI: 180 (19.2%) 5.83 [95% CI: 4.93 to 1780730 (5.0%)
C

7.29 to 8.91, 6.89, P<0.0001]

AC

Nausea and vomiting P<0.0001]

100 (5.5%) 11.33 [95% CI: 30 (23.4%) 7.90 [95% CI: 5.48 to 182790 (0.5%)
FTT (Failure to thrive) 9.26 to 13.86, 11.38, P<0.0001]

24
 ACCEPTED MANUSCRIPT
P<0.0001]

350 (19.2%) 7.65 [95% CI: 170 (22.1%) 9.10 [95% CI: 7.68 to 1080580 (3.0%)
6.81 to 8.59, 10.79, P<0.0001]

GI hemorrhage P<0.0001]

PT
1180 (64.8%) 9.13 [95% CI: 480 (62.3%) 8.20 [95% CI: 7.09 to 6012700 (16.8%)
8.29 to 10.05, 9.48, P<0.0001]

RI
Abdominal pain P<0.0001]

SC
35(1.9%) 8.28 [95% CI: 20 (2.6%) 11.26 [95% CI: 84580 (0.2%)

U
5.92 to 11.58, 7.22 to 17.55,

AN
Diarrheal disorder P<0.0001] P<0.0001]

270 (14.8%) 8.22 [95% CI: 130 (16.9%) 9.58 [95% CI: 7.93 to 743100 (19.2%)

M
7.22 to 9.35, 11.57, P<0.0001]

D
Weight loss P<0.0001]

TE
60 (3.3%) 7.57 [95% CI: 5.85 20 (2.6%) 5.92 [95% CI: 3.80 to 160430 (2.1%)
Ascites
EP
to 9.79, P<0.0001] 9.23, P<0.0001]

15 (0.8%) 16.29 [95% CI: 9.79 5 (0.6%) 12.81 [95% CI: 5.32 18250 (0.1%)
C

Volvulus to 27.08, P<0.0001] to 30.87, P<0.0001]

AC

10 (0.5%) 21.28 [95% CI: 5 (0.6%) 25.17 [95% CI: 10.45 9290 (0.0%)
11.43 to 39.63, to 60.67, P<0.0001]

Intussusception P<0.0001]

25
 ACCEPTED MANUSCRIPT

50 (2.7%) 15.15 [95% CI: 10 (1.3%) 7.06 [95% CI: 3.78 to 66610 (0.2%)
11.44 to 20.07, 13.17, P<0.0001]

GI perforation P<0.0001]

260 (14.3%) 11.11 [95% CI: 90 (11.6%) 8.83 [95% CI: 7.08 to 528790 (1.5%)

PT
9.75 to 12.67, 11.00, P<0.0001]

GI obstruction P<0.0001]

RI
U SC
AN
M
D
TE
C EP
AC

26
 ACCEPTED MANUSCRIPT

Table 4: Odds Ratios for Associated Allergic Clinical Features of EoGE and EoC Cases vs Controls (individuals without EGIDs):

Allergic condition EoGE Cases, n Odds Ratios EoC Cases, n Odds Ratios [OR, Controls, n (%)

(%) [OR, 95% (%) 95% Confidence

Confidence Interval (CI)]

PT
Interval (CI)]

RI
Drug Allergy 890 (48.9%) 3.54 [95% CI: 410 (53.2%) 4.21 [95% CI: 3.65 7619910 (21.3%)

SC
3.23 to 3.88, to 4.85, P<0.0001]

P<0.0001]

U
Rhinitis 610 (33.5%) 5.15 [95% CI: 4.67 210 (27.3%) 3.83 [95% CI: 3.27 3193000 (8.9%)

AN
to 5.67, P<0.0001] to 4.49, P<0.0001]

M
Asthma 600 (33.0%) 5.15 [95% CI: 4.67 180 (23.4%) 3.19 [95% CI: 2.70 3122770 (8.7%)

D
to 5.67, P<0.0001] to 3.77, P<0.0001]

TE
Sinusitis 540 (30.0%) 3.71 [95% CI: 3.36 220 (28.5%) 3.52 [95% CI: 3.01 3651530 (10.2%)
to 4.11, P<0.0001] to 4.12, P<0.0001]
EP
Dermatitis 550 (30.2%) 3.81 [95% CI: 3.45 250 (32.5%) 4.23 [95% CI: 3.64 3641140 (10.2%)
C

to 4.21, P<0.0001] to 4.92, P<0.0001]

AC

Food allergy 450 (24.7%) 12.20 [95% CI: 140 (18.2%) 8.25 [95% CI: 6.87 938450 (2.6%)
10.97 to 13.57, to 9.91, P<0.0001]

P<0.0001]

27
 ACCEPTED MANUSCRIPT

Eczema 370 (20.3%) 3.78 [95% CI: 3.37 140 (18.2%) 3.29 [95% CI: 2.74 2265120 (6.3%)
to 4.23, P<0.0001] to 3.95, P<0.0001]

Urticaria 130 (7.1%) 5.31 [95% CI: 4.44 40 (5.2%) 3.78 [95% CI: 2.75 511120 (1.4%)
to 6.35, P<0.0001] to 5.20, P<0.0001]

PT
RI
U SC
AN
M
D
TE
C EP
AC

28
 ACCEPTED MANUSCRIPT

Table 5: Odds Ratios for GI Clinical Features of EoGE and EoC stratified by Age and Gender:

GI Diagnoses EoGE 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

Adults, Female Female

Male

PT
8.44 [95% 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:

RI
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,

SC
to 9.91, P<0.0001] P<0.0001] P<0.0001] P<0.0001] to 31.46, P<0.0001] P<0.0001]

GERD P<0.0001] P<0.0001]

U
6.04 [95% 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:

AN
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,

M
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] P<0.0001]

D
Heartburn

TE
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,
EP
8.69 P<0.0001] P<0.0001] P<0.0001] P<0.0001] to 48.72, P<0.0001] P<0.0001]
C

to 12.68, P<0.0001]
AC

Dysphagia 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
Nausea and

vomiting 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] to 34.06, P<0.0001]

P<0.0001] P<0.0001]

7.02 [95% 18.89 [95% CI: 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,

PT
11.69, P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001]
FTT (Failure to

P<0.0001]

RI
thrive)

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:

SC
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,

U
8.46, P<0.0001] P<0.0001] , P<0.0001] P<0.0001] to 136.07, P<0.0001] P<0.0001]

AN
GI hemorrhage 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:

M
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,

D
11.10, <0.0001] P< 0.0001] P<0.0001] P<0.0001] to 29.93, P<0.0001] P<0.0001]

TE
Abdominal pain P<0.0001] P<0.0001]
EP
11.92 15.01 [95% CI: 11.35 [95% CI: 58.37, [95% 16.29 [95% CI: 7.13 [95% CI:
6.01 [95% CI: 23.11 [95% CI:
[95% CI: 6.17 to 36.53, P 3.61 to 10.01, 9.45 to 56.52, P 4.67 to 27.56, CI: 23.16 10.41 to 25.49, P 0.44 to 116.02,
C

P<0.0001] <0.0001]
7.14 to <0.0001] P<0.0001] to 147.10, P <0.0001] P<0.0001]
AC

19.92, <0.0001]
Diarrheal

disorder P<0.0001]

Weight loss 8.01 [95% 14.71 [95% CI: 6.74 [95% CI: 21.41 [95% 7.57 [95% CI: 22.80, [95% 6.74 [95% CI: 12.85 [95% CI:

30
 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 5.60 to 8.12, 5.03 to 32.79,

10.03, <0.0001] P<0.0001] 2, P<0.0001] P<0.0001] 45.60, P< P<0.0001] P<0.0001]

P<0.0001] 0.0001]

7.33 [95% 82.02 [95% CI: 5.73 [95% CI: 111.97 [95% 4.11 [95% CI: 318.97, [95% 4.51 [95% CI: 399.89 [95% CI:

PT
CI: 4.91 to 33.65 to 199.95 3.85 to 8.53, CI: 1.69 to 9.98, CI: 2.41 to 8.44, 156.34 to 1022.81,

10.93, , P<0.0001] P<0.0001] 45.70 to 274.32 P<0.0001] 126.36 to 805. P<0.0001] P<0.0001]

RI
Ascites P<0.0001] , P<0.0001] 19, P<0.0001]

SC
34.67 384.12 [95% 16.05 [95% 603.93 [95% 49.88 [95% CI: 1493.78, 15.88 [95% CI: 200.72 [95% CI:

U
[95% CI: CI: CI: CI: 20.54 to [95% CI: 6.58 to 38.34, 12.29 to 3277.58,

AN
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
Volvulus P<0.0001] P<0.0001]

D
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:

TE
[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,
EP
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]

156.15, 7.58, 1, P<0.0001] P<0.0001]

C

Intussusception P<0.0001] P<0.0001]

AC

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,

GI perforation 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]

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,

PT
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]

RI
GI obstruction

SC
Table 6: Odds Ratios for Allergic Clinical Features of EoGE and EoC stratified by Age and Gender:

U
AN
EoGE Cases- EoGE Cases- EoGE Cases- EoGE Cases- EoC Cases- EoC Cases- EoC Cases- EoC Cases-

M
Allergic Adults, Male Children, Adults, Children, Adults, Male Children, Adults, Children,
condition
Male Female Female Male Female Female

D
TE
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,
Drug Allergy
EP
P<0.0001] P<0.0001] P<0.0001 P<0.0001] 0.0001] P<0.0001] P<0.0001 P<0.0001]
C

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:
AC

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,
Rhinitis
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:
Asthma

32
 ACCEPTED MANUSCRIPT
4.12 to 5.91, 4.46 to 8.07, 4.34 to 5.68, 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,
Sinusitis

PT
P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001]

RI
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,
Dermatitis

SC
P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001]

U
12.92 [95% 7.43 [95% CI: 37.82 [95% 48.73 [95% CI: 37.82 [95%

AN
CI: 32.49 [95% CI: 6.31 to 8.74, CI: 5.44 [95% CI: 27.67 to 85.81, 5.42 [95% CI: CI:
Food allergy
10.58 to 15.7 24.25 to 43.51, P<0.0001] 26.82 to 53.3 3.43 to 8.62, P<0.0001] 4.20 to 6.98, 20.35 to 70.3

M
8, P<0.0001] P<0.0001] 4, P<0.0001] P<0.0001] P<0.0001 0, P<0.0001]

D
3.60 [95% CI: 3.64 [95% CI: 4.27 [95% CI: 5.33 [95% CI: 3.00 [95% CI: 2.42 [95% CI: 3.59 [95% CI: 1.44 [95% CI:

TE
2.90 to 4.46, 3.09 to 4.28, 3.11 to 5.86, 3.71 to 7.65, 2.04 to 4.41, 1.21 to 4.85, 2.85 to 4.52, 0.56 to 3.67,
Eczema
EP
P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001] P<0.0001]

4.79 [ 95% CI: 4.50 [95% CI: 4.35 [ 95%

C

3.72 to 6.16, 1.79 to 11.34, CI: 3.00 to

AC

5.06 [95% CI: 6.53 [95% CI: 9.67 [95% CI: 2.84 [95% CI: 5.80 [ 95% CI:
Urticaria P<0.0001] P<0.0001]
3.39 to 7.56, 4.28 to 9.97, 6.25 to 15.00, 1.17 to 6.90, 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

7.8
8

PT
7.3
6.9
7

RI
5.9
6 5.7 5.7 5.7
5.4

SC
5.1 5.1
4.9
5 4.7 4.7
4.3

U
4.1 4.2
4 4 EoGE
3.8 3.8

AN
4
EoC
3 2.9
2.8 2.7
3

M
2.4 2.3 2.4
2.1
1.9
2 1.7 1.7 1.7

D
1.1
0.8 0.8 TE 0.9
1
EP
0
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)
C
AC
 ACCEPTED MANUSCRIPT

Figure 1: The Age-Based 2012-2017 Prevalence (per 100,000 persons) of Eosinophilic gastroenteritis (EoGE), and

Eosinophilic colitis (EoC) in the Explorys Database.

PT
RI
U SC
AN
M
D
TE
C EP
AC