Abstract
Objectives: Otorhinolaryngological conditions seem to be more frequent
in children with Eosinophilic Esophagitis (EoE), including allergic
rhinitis, but, to our best knowledge, there are no studies showing if
the frequency of these conditions is superior in children with EoE. The
aim of this study is to determine whether otorhinolaryngological
manifestations are more prevalent in these children.
Design: Case control study
Setting: Tertiary referral Paediatric Hospital of Lisbon, Portugal.
Participants: Children with EoE (cases) and children diagnosed with
allergic rhinitis but not diagnosed with EoE or other eosinophilic
disorders (controls).
Main outcome measures: Complete otorhinolaryngological evaluation of
children under an observation protocol with questions about ear, nose
and throat symptoms, and previous medical history; physical examination
and the CARAT kids questionnaire to evaluate the level of control of
children’s rhinitis.
Results: This study included 45 children. The study group consisted of
15 children diagnosed with EoE and the control group consisted of 30
cases with allergic rhinitis. Both groups included 6 to 17 years old
children. There were no differences concerning gender, age, total CARAT
kids score or CARAT kids score for questions for upper and lower
respiratory tract (p>0.05). When otorhinolaryngological
symptoms were analysed separately there were no statistically
significant differences between case and control groups
(p>0.05), except for dysphagia (p=0,036) which was more
prevalent in the case group. There were no significant differences
related to the number of symptoms reported, frequency of asthma,
otorhinolaryngological surgeries in the past, drug allergies, and
documented hearing loss (p>0.05). There were no significant
differences in laryngopharyngeal changes seen as markers for
laryngopharyngeal reflux between both groups (p>0.05).
Conclusions: Apparently, otorhinolaryngological conditions are not more
prevalent in children diagnosed with EoE, but future larger studies are
needed to confirm our findings. Yet, Otorhinolaryngologists must be
aware of this condition since early referral of children with symptoms
related to EoE such as dysphagia and atopy to a Gastroenterology
appointment can speed up diagnosis and treatment, potentially reducing
long-term sequelae.
Keywords: Eosinophilic esophagitis, Paediatric Otorhinolaryngology,
allergic rhinitis, children, dysphagia
Key points:
- An association between Eosinophilic Esophagitis and
otorhinolaryngological conditions has been described.
- So far, there are no studies showing if the frequency of
otorhinolaryngological symptoms is higher in children with
Eosinophilic Esophagitis.
- Except for dysphagia, otorhinolaryngological symptoms and conditions
do not seem to be more prevalent in Eosinophilic Esophagitis patients.
- Otorhinolaryngologists must be aware of clinical aspects and natural
history of Eosinophilic Esophagitis when evaluating children with
dysphagia.
- Future larger and prospective studies are needed to clarify the role
of Otorhinolaryngology in the approach of Eosinophilic Esophagitis.
Introduction
Eosinophilic esophagitis (EoE) is a chronic, immune-driven inflammatory
condition of the esophageal mucosa. It is characterized clinically by
symptoms related to esophageal dysfunction, histologically by eosinophil
predominant inflammation (>15 eosinophils per high-power
field) and its diagnosis requires the exclusion of other causes of
esophageal eosinophilia [1]. It is recognized as a distinct
clinicopathological syndrome since 1993 [2]. EoE etiology is not
fully understood. Yet, genetics, environmental factors, allergens and
host factors seem to trigger a T helper cell-2 (Th2) mediated immune
response, as seen in other allergic conditions [3]. Thus, there is a
strong association between EoE and allergic rhinitis, food allergies,
asthma and eczema. A review and meta-analysis demonstrated that up to
93.3% of children with EoE have allergic rhinitis [4].
Although it is a well-known entity for gastroenterologists, EoE is still
a relatively new diagnosis in the field of Paediatric
Otorhinolaryngology. However, an association between EoE and
otorhinolaryngological symptoms has been described in several studies
[5,9,10]. Chronic rhinosinusitis, airway symptoms such as stridor,
chronic cough and recurrent croup, sleep disorders, subglottic stenosis
and a history of otorhinolaryngological surgeries seem to be more
frequent in these patients [5]. Actually, 10 to 15% of children
with EoE present first to an Otorhinolaryngologist [6]. To our best
knowledge, there are no studies showing if the frequency of
otorhinolaryngological symptoms is higher in children with EoE. The
objective of this study is to understand if children with EoE have more
otorhinolaryngological symptoms than children with allergic rhinitis
only and to highlight the otorhinolaryngological symptoms which are
associated with EoE.
Materials and methods
After approval by the local research ethics committee, a retrospective
case control study was performed in our Otorhinolaryngology Department
which lies within a tertiary referral Paediatric Hospital in Lisbon,
Portugal. The study took place from January 2019 to January 2020.
We selected every child diagnosed with EoE followed in our hospital
until January 2019, with ages between 6 to 17 years. These charts were
collected from the database of Paediatric Gastroenterology consultation.
We excluded children whose parents/caregivers did not understood
Portuguese, children with intellectual disability, without medical
appointments for more than 2 years, with hypereosinophilic syndrome and
other systemic eosinophilic disorders, Crohn’s disease and children with
craniofacial abnormalities.
Children with EoE (cases) were matched to children diagnosed with
allergic rhinitis but not diagnosed with EoE or other eosinophilic
disorders (controls) based on age, gender and level of control of
children’s rhinitis (CARAT kids questionnaire). Children included in the
control group were randomly selected from Immunoallergology consultation
charts.
Children from both groups were evaluated by an Otorhinolaryngologist
according to an observation protocol, after parents/caregivers sign an
informed consent. This protocol had questions about ear, nose and throat
symptoms that happened more than three times a year (Table 1), with
“yes” and “no” answers. It also had questions about previous medical
history concerning otorhinolaryngological infections,
otorhinolaryngological surgeries in the past, asthma, seasonal and drug
allergies and documented hearing loss. Ear, nose and throat physical
examination was also included in the protocol (Table 2). Every child
with at least one ear symptom, frequent ear infections, documented
hearing loss, or at least one alteration in otoscopy, did a Tympanogram.
Every children who had apnoea or snoring had indication for a
nasopharynx radiography. If children had dysphagia, dyspnoea, dysphonia,
choking, pharyngeal globus or itchy throat, frequent nose infections,
alteration in paranasal sinuses palpation and percussion, epistaxis or
polyps, no alterations in nasopharynx radiography and children with an
altered tympanogram, were submitted to a flexible
nasopharyngolaryngoscopy. The CARAT kids questionnaire was used to
evaluate the level of control of children’s rhinitis.
Descriptive statistics are reported as total number and percentage for
categorical variables and for quantitative variables, as mean ± standard
deviation (SD) for parametric variables and as median and interquartile
range for nonparametric variables (variable normality was determined by
Kolmogorov-Smirnov test). To match cases and controls we used
chi-squared test for gender and Mann-Whitney for age and value of CARAT
kids questionnaire. Independent t-test, Mann-Whitney U, Fisher exact,
and chi-squared tests were used to compare both groups concerning ear,
nose and throat symptoms, the number of symptoms according to anatomical
site, previous medical history and findings on physical examination.
Data were analysed with IBM SPSS Statistics 23®. A p value <
0.05 was considered statistically significant.
This study is reported according to the STROBE statement for
observational studies.
Results
We identified 104 children with EoE but 51 were excluded after exclusion
criteria evaluation and 38 did not accept to participate in our study.
Therefore, the analysis included 15 children with EoE (case group) and
30 children with allergic rhinitis (control group) after control
matching by age, gender and level of control of children’s rhinitis.
Patient demographics and characteristics can be found in table 3.
There were no significant differences in ear and nose symptoms reported
between case and control groups. Children with EoE had a significantly
higher occurrence of dysphagia (26,7% versus 3,3%, p=0.036) but no
statistically significant differences were found in other throat
symptoms. These results are shown in table 4.
Only one child (6.7%) in the case group and no children in the control
group had frequent ear infections, four children in the case group
(26.7%) and four children in the control group (13.3%) had frequent
nose infections and three children in the case group (20.0%) and two
children in the control group (6.7%) had frequent pharyngolaryngeal
infections. In the case group, four children (26.7%) had had an
otorhinolaryngological surgery in the past, including bilateral
myringotomy with tubes, tonsillectomy and adenoidectomy, and in the
control group, three children (10.0%) had had similar surgeries.
Seventeen children in the control group (56.7%) and eight children in
the case group (53.3%) reported asthma in their previous medical
history. Regarding drug allergies, they were mentioned only by one child
in the case group (6.7%) and by two children in the control group
(6.7%). There were no children in the case group with previous
documented hearing loss, while in the control group there was one child
(3.3%). There were no significant differences in otorhinolaryngological
infections, otorhinolaryngological surgeries in the past, diagnosis of
asthma, drug allergies and documented hearing loss
(p>0.05). In the case group the majority of children had
atopy (80.0%), ten children had a diagnosis of allergic rhinitis
(66.7%) and two had non-allergic rhinitis (13.3%). Seasonal allergies
were more frequent in controls (100%) than in the case group (60.0%)
– p=0.001.
In the case group, 9 children (60.0%) were taking nasal corticosteroids
and 4 of them (26,7%) were also taking swallowed corticosteroids .
There was only one child in the case group (6.7%) taking exclusively
inhaled corticosteroids. In the control group, 23 children (76.7%) were
being treated with nasal corticosteroids and 7 of them (23.3%) were
also taking inhaled corticosteroids. There were two children in the
control group (6.7%) being treated just with inhaled corticosteroids.
There were no significant differences in the number of corticosteroids
taken by children in both groups (p>0.05).
There were no significant differences in the findings in otoscopy and
anterior rhinoscopy between both groups (p>0.05). There
were also no significant differences in Friedman and Mallampati scores
between both groups (p>0.05).
Six children in the case group (40%) and six children in the control
group (20%) did a tympanogram, with no significant differences between
both groups (p>0.05). All children from the control group
had a curve type A Jerger and in the case group all had curve type A
Jerger except in one child that had a type B (due to a perforation post
myringotomy). The number of children with an indication for flexible
nasopharyngolaryngoscopy was significantly greater in the case group
(73.3% vs. 40.0%, P=0.035). There were no significant differences in
nasal, nasopharyngeal and oropharyngeal changes between both groups
(p>0.05). Laryngopharyngeal changes seen as markers for
laryngopharyngeal reflux, particularly posterior pharyngeal wall
cobblestoning, interarytenoid bar with erythema, posterior commissure
with erythema and edema and arytenoid edema, were found in 5 children
from the case group (33.3%) and 5 children from the control group
(16.7%) but there were no significant differences in these changes
between both groups (p>0.05).
Discussion
We presented a retrospective case control study based on the observation
of a group of children with EoE (cases) and a group of children with
allergic rhinitis (controls). As we matched these groups according to
age, gender and level of control of children’s rhinitis with the CARAT
kids questionnaire, it was possible to compare otorhinolaryngological
symptoms, previous medical history and physical examination without bias
related to these parameters.
Although several studies demonstrated an association between EoE and
otorhinolaryngological conditions as airway symptoms, recurrent otitis
media, chronic sinonasal disease and adenotonsillar disease [5,7],
it is not clear if otorhinolaryngological symptoms are more frequent in
children with EoE than in children in the same age group. EoE shares
some features of its pathophysiology with atopic diseases since Th2 is
the most common type of inflammation described in both. Even the recent
finding of a primary Th2-low endotype in EoE is similar to what is seen
in other atopic diseases [8]. Thus, our study is the first case
control study that compares children with EoE with children with
allergic rhinitis in an attempt to understand if the first have more
otorhinolaryngological conditions regardless of atopy, which was present
in the majority of EoE children in other series [4,6].
In our study there is a male preponderance (73.3% of children in the
case group and 66.7% in control group), which is in agreement to the
literature [9,10]. The median age in both groups was higher than the
mean age of presentation in most studies, which is approximately 10
years of age [10].
Concerning otorhinolaryngological symptoms, our study showed they are
not more common in children with EoE than in children with allergic
rhinitis, except for dysphagia which was more common in children with
EoE. In fact, dysphagia is frequently the most common symptom referred
by older children with EoE, usually older than 10 years old [1], but
is usually not the first symptom referred in Otorhinolaryngology clinic
[9]. Kubik et al [9] concluded that
Otorhinolaryngologists need to have a higher level of suspicion of EoE
when evaluating patients with dysphagia and our study confirms it by
acknowledging the importance of this symptom in children with EoE. Our
findings also suggest that airway symptoms such as cough or throat
clearing, previously reported as the most frequent symptoms presented to
a Otorhinolaryngologist in children with EoE [9,10] may not be due
to EoE but to other conditions related to atopy, though they require
further investigation.
Kelly e a [5] reported that almost one third of children with
EoE will require an Otorhinolaryngological surgery, frequently prior to
diagnosis of EoE. However, according to our study, bilateral myringotomy
with tubes, tonsillectomy and adenoidectomy are not more frequent in
children with EoE.
A recent review showed that physical examination of patients with EoE is
often unrevealing [11]. In fact, in our study there were no
differences in the physical examination’s findings even in terms of
laryngopharyngeal markers for laryngopharyngeal reflux in flexible
nasopharyngolaryngoscopy. Laryngopharyngeal reflux can occur with or
without gastroesophageal reflux. Actually, in EoE can occur a chronic
eosinophilic mucosal inflammation of the larynx, mainly in arytenoid and
retrocricoid mucosa, with symptoms of laryngopharyngeal reflux [12]
However, Vavricka et al [13] demonstrated that these
laryngopharyngeal findings are not specific to gastroesophageal reflux,
except for posterior pharyngeal wall cobblestoning, and can lead to an
over-diagnosis of reflux laryngitis. Thus, according to our study
flexible nasopharyngolaryngoscopy seem not to be central in EoE
diagnosis although it is an excellent tool to diagnose airway conditions
such as laryngomalacia, laryngeal cleft or subglottic stenosis which are
reported in children with EoE in some series [9,10,14].
One limitation of this study is the small sample size that can be
justified by the low prevalence of EoE in children but also by the
limited parents/caregivers’ availability to participate in the study,
mostly because of the low receptivity to spend time in another
appointment besides the amount of Immunoallergology and Gastroenterology
consultations these children have. The retrospective nature of this
study is also a limitation, as the patient data collected from the
parents/caregivers’ questionnaires depended necessarily on their memory
of previous symptoms and medical history and the symptom profile had an
inherently subjective nature.
Conclusions
In general, otorhinolaryngological conditions do not seem to be more
prevalent in EoE patients. However, Otorhinolaryngologists must be aware
of clinical aspects and natural history of EoE especially when
evaluating children with dysphagia. The coexistence of atopy and
dysphagia should lead to a suspicion and may trigger a prompt referral
to a Gastroenterology appointment. This awareness can lead clinicians to
initiate therapy earlier for these children, potentially reducing
sequelae. Future larger and prospective studies are needed to confirm
our findings and to understand better the role of Otorhinolaryngology in
the approach of EoE.
This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.
Declarations of interest: none
Data sharing statement
The data that support the findings of this study are available on
request from the corresponding author. The presented data are anonymised
and risk of identification is low and the potential benefits of sharing
these data outweigh the potential harms because they help to inform and
improve future practice for the benefit of global patient care.
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