AGA InstituteEosinophilic Esophagitis in Children and Adults: A Systematic Review and Consensus Recommendations for Diagnosis and Treatment: Sponsored by the American Gastroenterological Association (AGA) Institute and North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition
Section snippets
Definition
A number of names and acronyms have been applied to this disease, including the following: eosinophilic esophagitis (EE and EoE), primary eosinophilic esophagitis (PEE), allergic eosinophilic esophagitis (AEE), and idiopathic eosinophilic esophagitis (IEE). For the purposes of this review, we will use the acronym EE. Defining EE presents some problems because the presenting symptoms are similar to those of gastroesophageal reflux disease (GERD) and include heartburn, chest pain, feeding
Methodology of Review
A task force of 31 physicians who participated in the First International Gastrointestinal Eosinophil Research Symposium (FIGERS) performed this review. The reviewers were divided into subcommittees along the lines of their recognized expertise in clinical evaluation, endoscopy, histopathology, allergy, and treatment. A systematic review of the English language medical literature through September 2006 was performed using electronic databases (MEDLINE, PubMed, and Ovid), with the key words
Epidemiology
Males are more commonly affected than females. Thirteen studies provided detailed information regarding 323 adult patients (76% males; mean age, 38 years; range, 14–89 years).3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 Sixteen studies identified 754 pediatric patients (66% males; mean age, 8.6 years; range, 0.5–21.1 years).16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31
Geographically, patients with EE have now been identified throughout the United States and Canada, and reports
Children
As with many other diseases, some age-related differences were noted between presenting symptoms in children and adults.3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 30, 36 For instance, feeding refusal or intolerance is a common symptom of EE in children who are perhaps too young to relate the feeling of dysphagia. Children most commonly had GERD-like symptoms (including heartburn and regurgitation), although estimates varied widely across
Natural History
Three studies examined the natural history of EE in 90 adults, with follow-up ranging from 1 to 11.5 years.4, 7, 11 Potter et al followed 29 patients (21 men; mean age, 35 years; range, 16–71 years) who primarily presented with dysphagia and “refractory GERD” symptoms.7 The majority of patients showed evidence of tissue remodeling at endoscopy. Rings, strictures, or small caliber esophagus were found in 86% of patients, whereas radiographic studies showed narrowing in 67%. Importantly, the
Endoscopy
At endoscopy, a number of gross mucosal abnormalities have been identified including longitudinal furrowing, friability, edema, longitudinal shearing, raised white specks, whitish exudates, “crêpe paper mucosa,” narrow caliber esophagus, Schatzki ring, felinization, and transient or fixed rings3, 6, 7, 9, 10, 11, 12, 22, 36, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 (See Table 4 and Figure 1, Figure 2). All listed findings except longitudinal shearing and “crêpe paper” mucosa have been
History of Esophageal Eosinophilia
In 1977, the first report of eosinophilic inflammation of the esophageal epithelium in an adult with dysphagia and no GERD symptoms was published.60 Over the following few years, isolated case reports described additional similar findings in adults and children.61, 62, 63, 64
Throughout the 1980s, a number of reports associated intraepithelial eosinophils in esophageal biopsy specimens with GERD.65, 66, 67, 68, 69 Interestingly, Leape et al67 and Hyams et al68 recognized that a number of
History, Physical Examination, and Testing for Other Atopic Diatheses
Most studies characterizing the allergic phenotype have been performed in children. Allergic responses have been strongly implicated in the etiology of EE based on several lines of evidence. The majority of patients with EE (50%–80%)22 is atopic based on the coexistence of atopic dermatitis, allergic rhinitis, and/or asthma and the presence of allergic antigen sensitization based on skin prick testing or measurement of plasma antigen-specific IgE. Importantly, most patients improve on
Treatment of EE
It is not known whether treatment will impact long-term outcomes of the disease, and the exact end points (reversal of symptoms and/or endoscopically or histologically normal mucosa) are not certain. The lack of evidence makes decisions regarding choice and duration of treatment difficult. Here, we present the evaluation of the data regarding efficacy and safety of known treatments.
Future Research
Today, the care of patients with EE stands at a crossroad (see Table 6). Clinical experience and the current literature dictate that EE is a chronic disease with few patients, if any, outgrowing their illness. Whether merely a subset or a majority of these patients is at risk to develop irreversible fibrotic changes is not known. If a stricture develops, the timetable is also unknown. These dilemmas complicate the question: What are appropriate treatment end points: symptom resolution,
Update Since the First International Gastrointestinal Eosinophil Research Symposium
At the time of acceptance of this article (July 2007), there has already been a remarkable 25% growth of PubMed articles concerning EE including high-quality articles about epidemiology, diagnosis, pathogenesis, and treatment (including the first controlled clinical trial and early results with a novel targeted biotherapeutic agent). Notably, these studies were contributed by investigators in 3 continents, including Europe (Sweden, Switzerland, and Spain), America (United States and Canada),
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Supported by a small conference grant R13 DK076672 from the National Institutes of Health to The FIGER Symposium; North American Society of Pediatric Gastroenterology, Hepatology; the American Academy of Allergy, Asthma, and Immunology; The American Partnership for Eosinophilic Diseases; a philanthropic contribution from a grateful family; and educational grants (AstraZeneca, Abbot Laboratories, Nutricia, TAP, Ception, GlaxoSmithKline).
Conflict of interest disclosures: Glenn T. Furuta, consultant, Ception Therapeutics; speaker’s bureau, TAP; Chris A. Liacouras, consultant, SHS, Nutricia, Ception, Ross; grant/research support, Wyeth; speaker’s bureau, TAP, Merck; Margaret H. Collins, consultant, GlaxoSmithKline, Ception Therapeutics; Sandeep K. Gupta, consultant, GlaxoSmithKline, TAP, AstraZeneca, Salix; speaker’s bureau, Ross Products, TAP, AstraZeneca; educational grant, Ross Products; Christopher Justinich, no disclosures; Phil E. Putnam, no disclosures; Peter A Bonis, no disclosures; Eric Hassall, consultant, TAP Pharmaceuticals, Abbott Canada, Altana Pharma; clinical research grant, AstraZeneca; Alex Straumann, no disclosures; Marc E. Rothenberg, consultant, Merck, Ception Therapeutics, GlaxoSmithKline, MedaCorp; speaker’s bureau, Merck; Samuel Nurko, grant/research support, Wyeth pharmaceutica, TAP, Sucampo; Nirmala Gonsalves, consultant, Medacorp, Ception Therapeutics; Jonathan Markowitz, consultant, Ception Therapeutics; Don Antonioli, no disclosures; Eduardo Ruchelli, no disclosures; Hector Melin-Aldana, no disclosures; Margret Magid, no disclosures; Ikuo Hirano, no disclosures; David Katzka, no disclosures; Susan R. Orenstein, consultant, Ception Therapeutics, TAP, Braintree, AstraZeneca, Wyeth, Bristol Myers Squibb, McNeil; grant/research support, Braintree; Jonathan M. Spergel, consultant, Novartis, GlaxoSmithKline; grant/research support, Novartis, Nutricia; speaker’s bureau, AstraZeneca, GlaxoSmithKline; Amal Assa’ad, no disclosures; Seema Aceves, no disclosures; Barry K. Wershil, consultant, AP Pharmaceuticals, AstraZeneca; speaker’s bureau, Shire; educational grant, TAP Pharmaceuticals; Thomas Platts-Mills, no disclosures; Tusar Desai, no disclosures; Seema Khan, no disclosures; B Li, no disclosures; Amir F. Kagalwalla, no disclosures.
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Dr Furuta’s current address is: The Children’s Hospital, 13123 East 16th Avenue, Aurora, Colorado 80045. fax: (720) 777-8025.