Eosinophilic esophagitis (EE) is defined as a chronic immune-mediated disorder with symptoms of esophageal dysfunction and an esophageal mucosal eosinophilic infiltrate [
The aim of this study was to describe the relative frequency and clinical manifestations of EE in a group of children from the western region of Saudi Arabia in order to increase the awareness of the pediatricians and the family physicians to the existence of such disease entity.
This retrospective and observational study included all children and adolescents less than 18 years of age seen at the pediatric gastroenterology service at King Abdulaziz University and International Medical Center in the period between October 2002 and December 2011 with clinical diagnosis of EE. Patients were identified through searching the medical records of each hospital and the endoscopy database. Data were retrieved from the patient’s medical files including demographic data, clinical presentations, anthropometric measurements, laboratory investigations, endoscopic findings, and treatment prescribed. The
This study was approved by the Bioethical and Research Committee of Faculty of Medicine at King Abdulaziz University and the International Medical Center Institutional Review Board. The study was conducted according to the principles of Helsinki Declaration.
Esophageal biopsies were initially fixed in 10% NBF from 18 to 24 hours and embedded in paraffin. Sections of 3–5 micron thick were made and stained with Hematoxylin and Eosin (H&E). The sections were reviewed by a certified single pathologist (RA). The eosinophilic count was assessed by counting eosinophils in up to 5 hps with the highest intraepithelial eosinophils count. Only eosinophils which display both a dark cluster of eosinophilic granules and nucleus with one or two lobes were counted. The other histopathological features that were assessed are eosinophilic microabscesses (defined by aggregates of
The final diagnosis of EE in a child with upper gastrointestinal symptoms was made according to the following criteria [
Extended esophageal pH study was performed by one of the authors (OIS) using a 2.1 mm pH catheter with two antimony electrodes (Medtronic Synectics, Shoreline, MN). The pH electrodes were calibrated in pH 7.0 and 1.0 buffer solutions (Medtronic Synectics) at 37°C, before and after completion of each study. Following calibration, the catheter was placed through the nostril into the esophagus. The exact position was determined by retraction of the probe after an acidic reading from the stomach had been obtained. Data were analyzed using Esophagram software (Medtronic Synectics). The percentage of time pH
Assay of serum samples for total immunoglobulin E (IgE) and fluorescent enzyme immunoassays (RAST-FX5) (Cap System, Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden) was performed for some children. RAST-FX5 is a mix test that can detect specific IgE to 6 major food allergens including cow’s milk proteins, egg white, peanut, soy, wheat, and fish. Skin prick test was performed by one of the authors (AA) as follows: standard allergen extracts and Alyostal ST-IR (Stallergenes S.A. France) were used for the skin prick test. Antihistamines, H1, and H2 had to be withdrawn 14 days in advance. Allergen extracts were applied onto the skin of the ventral surface of the forearm after being wiped with alcohol. Histamine-HCl and NaCl were used as positive and negative controls, respectively. The results was evaluated 10–15 min later. An induration of
Statistical analysis was performed using Statistical Package for Social Sciences version 19 (SPSS, Inc, Chicago, IL, USA). Data were expressed as a percentage of the total for categorical variables, as a mean with standard deviation (SD) for normally distributed continuous variables, or as median with interquartile range for skewed distributed variables. Paired
Out of the total of 2127 children who underwent upper endoscopy for upper gastrointestinal symptoms between 2002 and 2011, 312 (14.7%) children were diagnosed with esophagitis of various etiologies. Only 18 were diagnosed with EE constituting 5.8% of the cases of esophagitis and 0.85% of total number of patients who underwent upper endoscopy in the study period. The clinical and laboratory characteristics at presentation were shown in Table
Clinical and laboratory characteristics of children with eosinophilic esophagitis (
Median age, years (range) | 8.5 (1.5–18) |
Males, |
13 (72.2) |
Symptoms, |
|
Dysphagia | 11 (61.1) |
Vomiting | 10 (55.6) |
Food impaction | 4 (22.2) |
Feeding aversion | 3 (16.7) |
Poor weight gain | 2 (11.1) |
History of atopy, |
10 (55.6) |
First degree relatives with atopy, |
9 (50) |
Growth parameters | |
Weight for age |
0.59 ± 1.5 (−2.3–2.9) |
Height for age |
0.13 ± 1.3 (−2.1–2.1) |
Allergic testing and evaluation | |
Absolute eosinophil counts, mean ± SD |
0.48 ± 0.44 (0.05–1.8) |
Eosinophil percentage, mean ± SD (range) | 5.5 ± 3.8 (1–12.2) |
IgE level (IU/mL), mean ± SD (range) | 259.9 ± 530.4 (26–1848) |
Positive RAST-FX5, |
10 (55.6) |
Positive skin prick test for food allergens, |
11 (61.1) |
Positive skin prick test for aeroallergens, |
3 (16.7) |
Extended esophageal pH study performed on 4 patients showed reflux index of 2.1%, 3.5%, 2.9%, and 2.4%, respectively, indicating normal results.
Allergy testing and evaluation revealed that 7/18 (38.9%) had increased peripheral absolute eosinophil count (normal, 0.04–0.45 × 109/L) and percentage (normal, 1–6%). High total IgE levels (normal,
The classical endoscopic abnormalities were demonstrated in Table
Endoscopic and histopathological characteristics of children with EE.
Number/total | (%) | |
---|---|---|
Endoscopic findings | ||
Longitudinal furrows | 17/18 | (94.4) |
Loss of vascular pattern | 17/18 | (94.4) |
Patchy whitish exudates | 7/18 | (38.9) |
Stricture | 5/18 | (27.8) |
Concentric mucosal rings | 2/18 | (11) |
Crepe paper | 2/18 | (11) |
Normal mucosa | 1/18 | (5.6) |
Histopathological features | ||
Eosinophilic microabscesses | 14/18 | (77.8) |
Intercellular edema | 17/18 | (94.4) |
Basal cell hyperplasia | 18/18 | (100) |
Lamina propria papillae elongation | 14/18 | (77.8) |
Lamina propria fibrosis | 11/12 | (91.7) |
Lamina propria eosinophils | 11/12 | (91.7) |
Eosinophilic degranulation | 17/18 | (94.4) |
Neutrophil infiltration | 2/18 | (11.1) |
Ulceration | 1/18 | (5.6) |
Endoscopic abnormalities seen in our patients. (a) Longitudinal furrows and edema giving the wrinkled appearance (patient 12). (b) Patchy specks or exudates mimicking esophageal candidiasis (patient 13). (c) Ring stricture at the lower esophagus (patient 14). (d) Crepe-paper mucosa in a narrow lumen esophagus (arrow) (patient 18).
The histopathological features of esophageal biopsies at initial diagnosis of eosinophilic esophagitis are summarized in Table
Histopathological abnormalities in our patients with EE. (a) Esophageal mucosa in a patient with eosinophilic esophagitis. Note the marked eosinophilic infiltration close to the surface (20X). (b) An aggregate of eosinophils forming eosinophilic microabscess (arrow) (40X). (c) Fibrosis of lamina propria and lamina propria eosinophils (20X). (d) Follow-up biopsy showing marked reduction in intraepithelial eosinophils and absence of eosinophilic microabscess, intercellular edema, and basal cell hyperplasia (20X).
Six patients underwent a second endoscopy and biopsy following treatment. In four patients, the eosinophilic count dropped significantly to counts less than 10/hpf (Figure
Changes in the mucosal mean peak eosinophil count following treatment in EE (
Six (33%) patients required treatment with oral prednisolone for 4 weeks (1–2 mg/kg/d, maximum 40 mg) followed by gradual weaning over 2 to 4 weeks and maintained with swallowed topical corticosteroids in small doses (50–100
The median duration for followup was 2.5 years (range, 0.5 to 10.1 years). All patients were advised to continue on swallowed low dose of topical corticosteroids. The followup was analyzed according to two subgroups: atopic patients with history of atopy and sensitization to foods (
The prevalence of EE is not certain; however, a prevalence of 40–55 cases per 100,000 individuals has been estimated from western countries [
The traditional meals in West Saudi Arabia consisted of rice, whole wheat, lamb, chicken, fish, fresh vegetables and dates, and other local fruits. Bread, eggs, cheese, beans, olive, and milk are usually served for breakfast and dinner. However, with the rapid expansion of US fast food chains over the last two decades, the food habits in the major cities in Saudi Arabia are becoming similar to the western’s habits with increasing consumption of fast foods, frozen, and prepared foods in supermarkets and restaurants. There was also a noticeable increase in the use of peanut butter. Eating at fast food outlets was found to be a significant risk factor for bronchial asthma development in a study of children from the city of Jeddah and Saudi villages where the traditional dietary habits persisted [
In general, although there were no published data about the prevalence of food allergy in Saudi Arabia, the prevalence of other allergic disorders such as bronchial asthma and allergic rhinitis was increasing [
The implication of testing for IgE-mediated food allergy in the management of EE was studied by many authors. Liacouras and colleagues [
In our patients with EE we practiced simple food elimination guided by history and positive skin prick testing, none of our patients had received elemental diet or extensive food elimination, as we found low compliance because of palatability, cost, and availability. In addition, considering the chronicity of the disease and the tendency to recur after discontinuation of treatment, lifelong food elimination may be difficult [
Increased number of intraepithelial eosinophils has been regarded as the key diagnostic criterion for diagnosis of EE. In this study we choose the presence of intraepithelial eosinophils
There is still uncertainty about the optimal treatment given to patients with EE and the impact of treatment on the long-term outcome of the disease. In our series of children with EE, 6 patients were treated with systemic corticosteroids in the form of oral prednisolone. This approach was supported by an earlier study by Liacouras and colleagues [
Swallowed topical steroids either beclomethasone or fluticasone propionate have been reported to be effective in improving symptoms and histology in the majority of treated children with EE [
This study is limited by its retrospective nature, the relatively small number of patients, and the lack of standardization of the treatment protocol. Future studies should evaluate the need for maintenance treatment, the role for dietary elimination and reintroduction in finding the offending food allergens, the natural course of the disease, and the long-term complications.
In conclusion, eosinophilic esophagitis is an emerging disease that needs to be considered in any child presenting with esophageal dysfunction, unexplained stricture, or gastroesophageal reflux symptoms unresponsive to medical treatment of reflux.
The authors declare no conflict of interests, and the study was not supported by any drug company.