REVIEW URRENT C OPINION

Update on eosinophilic esophagitis Cecelia Damask

Purpose of review The prevalence of eosinophilic esophagitis (EoE) is increasing. It is important for practitioners to be aware of the disease and its presenting symptoms. Recent findings It is important to distinguish EoE from proton-pump inhibitor (PPI)-responsive esophageal eosinophilia. Patients with PPI-responsive esophageal eosinophilia exhibit symptoms of esophageal dysfunction (often with endoscopic findings suggestive of EoE) with esophageal eosinophilia that responds to PPI treatment. Summary EoE was identified as a ‘new disease’ over 20 years ago. Two consensus articles have since been published (as well as an evidence-based approach to the diagnosis and management) highlighting diagnostic criteria, treatment options and potential complications of untreated disease. There is still much that needs to be learned and there are still many controversies left unanswered. No cure has been identified for EoE. Current therapy revolves around diet restriction and use of steroids to reduce the number of eosinophils in the esophagus and improve symptom control. Possibly future research will identify new targets for treatment that hopefully will lead to new treatment options for patients suffering with this disease as well as nonendoscopic methods to monitor treatment response. Keywords dysphagia, eosinophilic esophagitis, eosinophils, food impaction

INTRODUCTION

esophagus and failure to respond to adequate proton-pump inhibitor (PPI) therapy [3,4 ,5]. &&

There is an ongoing controversy as to whether eosinophilic esophagitis (EoE) is a new emerging disease or an existing condition that had been previously undiagnosed. Over the last 2 decades, EoE has emerged as one of the leading causes of food impaction and dysphagia in adults and vague reflux-like symptoms in children [1]. Initially, there were case studies with adult patients with reflux-like symptoms and presentations but they had distinct features that differentiated them from gastroesophageal reflux disease (GERD) [2 ]. Following these early descriptions were a multitude of publications that provided a clearer symptom complex in children and adults that ultimately helped to define EoE as a chronic, immune/ antigen-mediated esophageal disease clinically characterized by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation [3]. EoE is now defined as a clinicopathologic diagnosis characterized by a localized eosinophilic inflammation of the esophagus (with no other gastrointestinal involvement), symptoms of esophageal dysfunction, the presence of 15 or more eosinophils in the most severely involved high-powered field (HPF) isolated to the &&

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HISTORY Eosinophils are resident cells in the gastrointestinal mucosa except for the esophagus [2 ]. Initial reports of esophageal eosinophilia noted on biopsy associated the finding with GERD. In 1993, an article by Attwood et al. [6] was the first to describe EoE as a separate phenomenon from GERD. In 1995, Kelly et al. [7] published their landmark article that described a group of pediatric patients who were resistant to treatment with standard highdose PPI therapy. Several of these children had undergone Nissen fundoplications to try to control their disease. When they examined their esophageal biopsies, the patients were noted to have a high number of eosinophils in their esophagus (mean &&

Lake Mary ENT Allergy and Hearing, Lake Mary, Florida, USA Correspondence to Cecelia Damask, DO, FAAOA, 795 Primera Blvd. Ste 1031, Lake Mary, FL 32746, USA. Tel: +1 407 829 8981; fax: +1 407 942 1049; e-mail: [email protected] Curr Opin Otolaryngol Head Neck Surg 2015, 23:240–246 DOI:10.1097/MOO.0000000000000158 Volume 23  Number 3  June 2015

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Update on eosinophilic esophagitis Damask

KEY POINTS  EoE is a clincopathologic disease due to inflammation of the esophagus.  Both clinical symptoms (i.e., dysphagia, food impaction and others) and esophageal eosinophilia (>15 eosinophils per HPF noted on biopsy) must be present for a diagnosis to be made.  A trial of a PPI for 8 weeks should be done prior to a biopsy to exclude GERD and PPI-responsive esophageal infiltration of eosinophils.  Current therapy revolves around diet restriction and use of steroids to reduce the number of eosinophils in the esophagus and improve symptom control.

was 41/HPF). They then put these patients on an elemental diet and the patients had resolution of their symptoms. When repeated biopsies were obtained again after treatment, the patients had a significant decrease in their eosinophils (decreased to a mean of 0.5/HPF). When these patients were challenged with the implicated foods, they had return of their symptoms (nine out of 10 patients) [7]. A multidiscipline group (First International Gastrointestinal Eosinophil Research Symposium Subcommittees) met in 2007 to establish some guidelines for diagnosis and treatment of EoE. These consensus recommendations highlighted that EoE is a clinicopathologic disease. There must be presence of clinical symptoms related to esophageal dysfunction including vomiting, abdominal pain, heartburn, dysphagia, reflux symptoms or feeding difficulties. Also isolated esophageal eosinophilia of greater than 15 eosinophils per HPF needs to be demonstrated. The histology of the remainder of the gastrointestinal tract should be noted to be normal and other gastrointestinal disorders need to be excluded [8]. From 2007 to 2011, the number of scientific publications on EoE doubled. Many of these articles were about esophageal eosinophilia and not truly EoE. Many of these articles made poor use of the 2007 Consensus Recommendations [9]. As there was a lot of mixed information about EoE, a new consensus group convened. This group included multiple different specialties. The Updated Consensus Recommendations for Children and Adults stressed that EoE is a clinicopathologic disease. Both features are needed to make a diagnosis of EoE. Clinically, EoE is characterized by esophageal dysfunction and pathologically one or more biopsies show eosinophil predominant inflammation of

greater than 15 eosinophils per peak HPF. They indicated that the disease is isolated to the esophagus and other gastrointestinal site biopsies are needed to rule out other site involvement. Also other causes need to be excluded such as PPI-responsive esophageal eosinophilia (REE). Also they stressed the need to distinguish between EoE and esophageal eosinophilia [3].

EPIDEMIOLOGY Estimates suggest that in the United States, there are about 40–90 cases of EoE per 100 000 persons [10–12,13 ,14,15]. There is a male predominance and it is more common in whites [3,9,12,13 , 16–19]. EoE can affect patients of any age. There is suggestion of a bimodal peak age of onset [3,20,21]. Cases of EoE have been reported in every continent except Africa and Antarctica. The prevalence is highest in western Europe and the United States [11,12,13 ,23–33]. There is a strong association of EoE with atopic diseases. Patients with EoE have a higher rate of atopy than the general population. Fifty to eighty percent of patients with EoE have other associated atopic conditions such as asthma, atopic dermatitis and allergic rhinitis. Approximately 38–66% of patients with EoE have asthma compared with 9% of the general population. Similarly, 30–93% have allergic rhinitis compared with 25% of the general population [21,34–40]. These reported rates of atopy (asthma, allergic rhinitis and atopic dermatitis) are approximately three times higher than what is seen in the general population [4 ]. There is also a strong association of reported food allergy [either a positive patient history, positive in-vitro test, positive skin prick test (SPT) or clinical reaction] and EoE [10]. Ten to twenty percent of children with EoE have immunoglobulin E-mediated food allergy (urticaria and anaphylaxis) compared with 1–5% of children [20]. There is also a strong family history in patients with EoE [41–43]. Seven percent of patients with EoE have a parent with EoE and 5% have a sibling with EoE [21,34,35]. Similar to asthma and atopic dermatitis, 14% of patients with EoE have a single-nucleotide polymorphism inferring a possible genetic component [44–47]. Data implicate the 5q22 locus in the pathogenesis of EoE and identify TSLP (thymic stromal lymphopoietin) as the most likely candidate gene in the region [48]. The prevalence of EoE is increasing and it is now the most common cause of food impaction in patients presenting to the emergency department [49–52]. EoE is frequently encountered during routine upper endoscopy [9,18,53–56].

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Although the answer is not known as to why it is increasing, there are several hypotheses [57]. One possible explanation is that the incidence is increasing because of increasing recognition. Perhaps, practitioners now have a higher index of suspicion for the disease process and are more likely to take multiple esophageal biopsies during upper endoscopy and therefore more likely to make the diagnosis [1,58,59]. Other possibilities for increased incidence of EoE are the fact that all allergic diseases (asthma, atopic dermatitis, food allergies etc.) in general have been increasing as well in recent history. One broad explanation for the increase in allergic diseases is ‘The Hygiene Hypothesis’, which holds that because the environment in developed countries has become more sterile, our immune systems are exposed to less antigens and tolerance is less likely to develop. Therefore, as EoE is an allergen-mediated disease, it would be expected to increase in parallel with other allergic diseases whose incidences are increasing [60]. Increasing pollen counts may also contribute to the increased incidence of EoE. Several studies have shown a link between the season of the year and new EoE diagnoses, with EoE more commonly being diagnosed in spring or fall when the pollen counts are the highest [12,16,61,62]. The eradication of Helicobacter pylori due to medical treatment may also contribute to increasing incidence of EoE. An inverse relationship between elevated eosinophil counts on esophageal biopsy and the presence of H. pylori was noted in a study that examined over 160 000 biopsies [22,63–65]. One other possible explanation for the increasing incidence of EoE could be related to exposure to antibiotics early in life. Early-life exposure to antibiotics may predispose the development of other allergic diseases (asthma, atopic dermatitis etc.), and a pilot study published last year suggests that the same may be true for EoE [66–71].

CLINICAL PRESENTATION The symptoms of EoE often resemble the symptoms of GERD – epigastric pain and vomiting. The predominant presenting symptom of EoE varies by age. Young children are more likely to present with feeding difficulties, failure to thrive and classic GERD symptoms (epigastric pain) whereas older children are more likely to present similar to adults with dysphagia-type complaints and possible food impactions. It may be difficult for a young child to vocalize that they are having difficulty swallowing. They may exhibit refusal behavior and prolonged chewing. Even an older school-aged child or teenager may not complain of outright dysphagia but 242

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may exhibit some compensatory behaviors including taking small bites, drinking after each bite or avoiding problematic foods such as meat and bread [3,34,36,72–75]. Classic symptoms of EoE in adults include dysphagia for solids and food impactions. The dysphagia may be either intermittent or chronic and is present in 25–100% of adult patients with EoE [76]. Although the most common symptom in adults is dysphagia, it is important to note that nonspecific symptoms such as nausea, vomiting and abdominal pain may be the only clinical manifestation of EoE in selected adults [3,5,77 ,78]. Despite increasing awareness of EoE among practicing physicians, there is often a long delay from onset of symptoms to diagnosis. The average diagnostic delay is 7 years with ranges from 2 to 12 years being reported [79,80]. Several different mechanisms have been proposed to be responsible for the dysphagia seen in patients with EoE. Esophageal remodeling is proposed to be the most important. Remodeling may lead to fixed rings, decreased distensibility, strictures and narrowing of the esophagus [81]. It is also thought that alterations in neuromuscular function lead to dysfunction of longitudinal muscle contraction that results in dysmotility [82]. Food impaction can also occur in adults with EoE. It can either precede the diagnosis of EoE or be an ongoing manifestation of the disease. Food impaction warranting endoscopic removal is encountered in 33–54% of adult patients with EoE [3,5]. Classic GERD symptoms of heartburn and acid regurgitation have also been reported in 7–100% of adult patients with EoE [8]. EoE is ultimately diagnosed in approximately 1–9% of patients with GERD symptoms refractory to PPI therapy [32,83,84]. It is important to differentiate the clinical presentation of the two diseases as there is some overlap between the two [16,85]. Also it is important to distinguish EoE from PPI-REE. Patients with PPI-REE exhibit symptoms of esophageal dysfunction (often with endoscopic findings suggestive of EoE) with esophageal eosinophilia that responds to PPI treatment [5]. PPI-REE is considered to be distinct from the esophageal eosinophilia seen in patients with GERD and erosive esophagitis. At this time, the cause of PPI-REE is poorly understood. It may represent an atypical presentation of GERD, a variant of EoE that responds to PPI therapy or a separate entity altogether [86]. &&

ENDOSCOPIC FINDINGS A wide variety of endoscopic findings may be seen in patients with EoE. These findings include concentric Volume 23  Number 3  June 2015

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Update on eosinophilic esophagitis Damask

rings (described as ‘trachealization of the esophagus’), longitudinal furrows, white exudates/plaques (often confused with candidiasis), strictures, narrow-caliber esophagus, furrows and even a normal-appearing esophagus [34,36,74,75,79,87]. Up to one-third of patients with active EoE may have a normal appearing esophagus, especially in children [34]. There is poor correlation between biopsies and symptoms. Patients can have negative biopsies and still have symptoms [73]. Endoscopy with biopsy, however, is currently the only reliable diagnostic test for EoE. Biopsies should ideally be taken from multiple sites in the proximal and distal esophagus as well as intestinal biopsies to rule out other disorders [8]. The histologic abnormalities in patients with EoE are variable and a patchy distribution of esophageal eosinophilia has been reported. This observation stresses the importance of obtaining multiple biopsies in patients suspected of having EoE. A greater number of biopsies maximizes the diagnostic yield [88].

HISTOLOGY At least one feature should be present for diagnosis in at least one biopsy: (1) Greater than or equal to 15 intraepithelial eosinophils per HPF in at least one esophageal site [3,5,8]. (2) Altered eosinophil character manifesting as surface layering and abscesses. (3) Epithelial changes such as basal layer hyperplasia and dilated intercellular spaces. (4) Thickened lamina propria fibers.

MANAGEMENT The goals for treatment of EoE are symptom control and improvement of esophageal eosinophilic inflammation with the ideal endpoint being complete resolution of inflammation [5,89 ]. Once a diagnosis of PPI-nonresponsive EoE is confirmed, treatment options include medical management, esophageal dilatation and food elimination diets. In 1998, Faubion et al. [90] were the first authors to report the use of swallowed topical steroids (used for asthma) as a treatment for EoE. They demonstrated an improvement in both symptoms and histology with minimal side-effects. At present, the use of swallowed steroids (‘wrong way’ steroids) is a common therapy [91]. The two most commonly used ‘wrong way’ steroids include swallowed aerosolized fluticasone propionate and oral budesonide mixed with Splenda (McNeil Nutritionals, LLC) to make it viscous [91,92]. There have been variable dosing &&

regimens presented in the literature as well as variable frequency and duration of treatment proposed [91,93,94]. Systemic steroids are also a treatment option if topical steroid therapy fails or rapid control of symptoms is needed. Systemic steroids are an effective treatment option but have increased risks and side-effects compared with topical ‘wrong way’ steroid treatments [89 ,95]. Dietary management offers the possibility of inducing and maintaining prolonged disease remission without the potential complications associated with pharmacologic therapy [96 ]. Several types of dietary therapy have been utilized for patients with EoE. All food can be restricted when using a total elimination diet with an amino acid-based formula. In contrast, selective foods can be eliminated either based on allergy testing or by simply removing the foods most likely known to cause EoE (‘the usual suspects’ – milk, soy, egg, peanut, wheat, fish and meats). Similar results were achieved in both clinical responses and reduction in the number of esophageal eosinophils that remained after therapy in a directed diet restriction and in an empiric diet restriction [97,98]. In contrast, the use of a total elimination diet prompted a greater clinical response and a more significant resolution in esophageal histology [34]. Although the use of an elemental diet is successful in the vast majority of patients with EoE, there are some obstacles to its use. Many patients find that elemental formula is unpalatable; they commonly require the use of a nasogastric or gastrostomy tube for its administration. Their nutritional status must be closely monitored. The formula is expensive. Also there may be qualityof-life and social issues associated with its use [34,97,98]. There are many controversies and unanswered questions/challenges regarding dietary management of EoE. How do we determine which foods to eliminate? How many foods do we eliminate? How do we determine which eliminated foods, if any, are responsible for symptom improvement? The administration of an empiric diet is often easy because allergy testing is not required. However, the empiric diet may not eliminate all foods necessary to induce complete remission. In addition, the diet may eliminate some foods that do not necessarily need to be eliminated and may prolong the process of food elimination and reintroduction. Is allergy testing really necessary for diet restriction? If so, which method is best for allergy testing; in-vitro specific immunoglobulin E testing, skin prick testing or patch testing? The most recent consensus concluded that although SPTs, serum immunoglobulin E tests and food patch tests can be used to help identify foods that are associated with EoE,

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these tests alone are not sufficient to make the diagnosis of food-driven EoE [3]. It further states that clinical history should guide testing and management and test results should always be used in context of clinical history [3,98,99]. Other concerns with restrictive diets include how do we determine effectiveness of dietary treatment? Is repeat endoscopy necessary to monitor response? Is symptomatic remission sufficient? Do we need histologic remission? Recommended therapeutic endpoints in EoE include symptoms (i.e., dysphagia and chest pain), histologic activity and endoscopic activity (especially strictures) [100,101 ]. There is experimental and clinical evidence that eosinophils cause tissue remodeling (i.e., collagen deposition). Esophageal remodeling consists of fibrosis, angiogenesis and smooth muscle hypertrophy and results in clinical consequences of strictures, decreased compliance, dysmotility and food impactions. Therefore, elimination of esophageal eosinophils should prevent complications. However, this requires endoscopy that has associated risks, inconvenience and expense [100]. Histologic remission might require higher doses and additional medications that also have associated risks, inconvenience and expense. There is no proof of efficacy in actually preventing complications [100]. Also we do not know if esophageal remodeling is reversible in all patients. &&

CONCLUSION EoE was identified as a ‘new disease’ over 20 years ago. Two consensus articles have since been published (as well as an evidence-based approach to the diagnosis and management) highlighting diagnostic criteria, treatment options and potential complications of untreated disease. There is still much that needs to be learned and there are still many controversies left unanswered. No cure has been identified for EoE. Current therapy revolves around diet restriction and use of steroids to reduce the number of eosinophils in the esophagus and improve symptom control. Possibly future research will identify new targets for treatment that hopefully will lead to new treatment options for patients suffering with this disease as well as nonendoscopic methods to monitor treatment response. Acknowledgements None. Financial support and sponsorship None. 244

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Conflicts of interest The author is on the Speakers’ Bureau for Teva Respiratory.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Dellon ES. Epidemiology of eosinophilic esophagitis. Gastroenterol Clin North Am 2014; 43:201–218. 2. Attwood S, Furuta GT. Historical perspective on an evolving disease. && Gastroenterol Clin North Am 2014; 43:185–199. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource. 3. Liacouras C, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011; 128:3–20. 4. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis. Clinical && presentation in children. Gastroenterol Clin North Am 2014; 43:219–229. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource. 5. Dellon ES, Gonsalves N, Hirano I, et al. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 2013; 108:679–692. 6. Attwood S, Smyrk TC, Demeester TR, et al. Esophageal eosinophilia with dysphagia: a distinct clinicopathologic syndrome. Dig Dis Sci 1993; 38:109– 116. 7. Kelly K, Lazenby AJ, Rowe PC, et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology 1995; 109:1503–1512. 8. Furuta G, Liacouras C, Collins M, et al. Eosinophilic esophagitis in children and adults: a systemic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007; 133:1342–1363. 9. Dellon ES, Aderoju A, Woosley JT, et al. Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review. Am J Gastroenterol 2007; 102:2300–2313. 10. Noel RJ, Putnam PE, Rothenburg ME. Eosinophilic esophagitis. N Engl J Med 2004; 351:940–941. 11. Buckmeier BK, Rothenburg ME, Collins MH. The incidence and prevalence of eosinophilic esophagitis. J Allergy Clin Immunol 2008; 121 (Suppl 2):S71. 12. Prasad GA, Alexander JA, Schleck CD, et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol 2009; 7:1055–1061. 13. Dellon ES, Jensen ET, Martin CF, et al. Prevalence of eosinophilic esophagitis && in the United States. Clin Gastroenterol Hepatol 2014; 12:589–596. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource. 14. Gill R, Durst P, Rewalt M, et al. Eosinophilic esophagitis disease in children from West Virginia: a review of the last decade. Am J Gastroenterol 2007; 102:2281–2285. 15. 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. 16. Dellon ES, Gibbs WB, Fritchie KJ, et al. Clinical, endoscopic, and histologic findings distinguish eosinophilic esophagitis from gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2009; 7:1305–1313. 17. Mackenzie SH, Go M, Chadwick B, et al. Clinical trial: eosinophilic esophagitis in patients presenting with dysphagia: a prospective analysis. Aliment Pharmacol Ther 2008; 28:1140–1146. 18. Veerappan GR, Perry GL, Duncan TJ, et al. Prevalence of eosinophilic esophagitis in an adult population undergoing upper endoscopy: a prospective study. Clin Gastroenterol Hepatol 2009; 7:420–426. 19. Franciosi JP, Tam V, Liacouras CA, et al. A case-control study of sociodemographic and geographic characteristics of 335 children with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2009; 7:415–419. 20. Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr 2009; 48:30–36. 21. Kapel RC, Miller JK, Torres C, et al. Eosinophilic esophagitis: a prevalent disease in the United States that affects all age groups. Gastroenterology 2008; 134:1316–1321. 22. Ronkainen J, Talley NJ, Aro P, et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut 2007; 56:615–620. 23. Hruz P, Straumann A, Bussman C, et al. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol 2011; 128:1349–1350.

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Update on eosinophilic esophagitis Damask 24. van Rhijn BD, Verheij T, Smout AJ, et al. Rapidly increasing incidence of eosinophilic esophagitis in a large cohort. Neurogastroenterol Motil 2013; 25:47–52. 25. Sealock RJ, Rendon G, El-Serag HB. Systematic review: the epidemiology of eosinophilic oesophagitis in adults. Aliment Pharmacol Ther 2010; 32:712– 719. 26. Fujishiro H, Amano Y, Kushiyama Y, et al. Eosinophilic esophagitis investigated by upper gastrointestinal endoscopy in Japanese patients. J Gastroenterol 2011; 46:1142–1144. 27. Kinoshita Y, Furuta K, Ishimaura M, et al. Clinical characteristics of Japanese patients with eosinophilic esophagitis and eosinophilic gastroenteritis. J Gastroenterol 2013; 48:333–339. 28. Shi YN, Sun SJ, Xiong LS, et al. Prevalence, clinical manifestations and endoscopic features of eosinophilic esophagitis: a pathological review in China. J Dig Dis 2012; 13:304–309. 29. Cherian S, Smith NM, Forbes DA. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Child 2006; 91:1000–1004. 30. Arias A, Lucendo AJ. Prevalence of eosinophilic oesophagitis in adult patients in a central region of Spain. Eur J Gastroenterol Hepatol 2013; 25:208–212. 31. Hasosah MY, Sukkar GA, Alsahafi AF, et al. Eosinophilic esophagitis in Saudi children: symptoms, histology and endoscopy results. Saudi J Gastroenterol 2011; 17:119–123. 32. Foroutan M, Norouzi A, Molaei M, et al. Eosinophilic esophagitis in patients with refractory gastroesophageal reflux disease. Dig Dis Sci 2010; 55:28– 31. 33. Fujiwara Y, Sugawa T, Tanaka F, et al. A multicenter study on the prevalence of eosinophilic esophagitis and PPI-responsive esophageal eosinophilic infiltration. Intern Med 2012; 51:3235–3239. 34. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005; 3:1198–1206. 35. Chehade M, Sampson HA. Epidemiology and etiology of eosinophilic esophagitis. Gastrointest Endosc Clin North Am 2008; 18:33–44. 36. Assa’ad AH, Putnam PE, Collins MH, et al. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol 2007; 119:731–738. 37. Sugnanam KKN, Collins JT, Smith PK, et al. Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis. Allergy 2007; 62:1257– 1260. 38. Guajardo JR, Plotnick LM, Fende JM, et al. Eosinophilic-associated gastrointestinal disorders: a world-wide-web based registry. J Pediatr 2002; 141:576–581. 39. Simon D, Marti H, Heer P, et al. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway disease. J Allergy Clin Immunol 2005; 115:1090–1092. 40. Roy-Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2008; 6:531– 535. 41. Meyer GW. Eosinophilic esophagitis in a father and a daughter. Gastrointest Endosc 2005; 61:932. 42. Patel SM, Falchuk KR. Three brothers with dysphagia caused by eosinophilic esophagitis. Gastrointest Endosc 2005; 61:165–167. 43. Zink DA, Amin M, Gebrara S, et al. Familial dysphagia and eosinophilia. Gastrointest Endosc 2007; 65:330–334. 44. Weidinger S, O’Sullivan M, Illig T, et al. Filaggrin mutations, atopic eczema, hayfever, and asthma in children. J Allergy Clin Immunol 2008; 121:1203– 1209. 45. Weiss ST, Raby BA, Rogers A. Asthma genetics and genomics 2009. Curr Opin Genet Dev 2009; 19:279–282. 46. Flory JH, Sleiman PM, Christie JD, et al. 17q12-21 variants interact with smoke exposure as a risk factor for pediatric asthma but are equally associated withearly-onset versus late-onset asthma in North Americans of European ancestry. J Allergy Clin Immunol 2009; 124:605–607. 47. Steinke JW, Rich SS, Borish L. 5. Genetics of allergic disease. J Allergy Clin Immunol 2008; 121 (Suppl 2):S384–S387. 48. Rothenberg ME, Spergel JM, Sherrill JD, et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet 2010; 42:289– 291. 49. Desai TK, Stecevic V, Chang CH, et al. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc 2005; 61:795–801. 50. Hurtado CW, Furuta GT, Kramer RE. Etiology of esophageal food impactions in children. J Pediatr Gastroenterol Nutr 2011; 52:43–46. 51. Kerlin P, Jones P, Remedios M, et al. Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus. J Clin Gastroenterol 2007; 41:356–361. 52. Sperry SL, Crockett SD, Miller CB, et al. Esophageal foreign-body impactions: epidemiology, time trends, and the impact of the increasing prevalence of eosinophilic esophagitis. Gastrointest Endosc 2011; 74:985–991. 53. Sealock RJ, Kramer JR, Verstovsek G, et al. The prevalence of oesophageal eosinophilia and eosinophilic oesophagitis: a prospective study in unselected patients presenting to endoscopy. Aliment Pharmacol Ther 2013; 37:825–832.

54. Joo MK, Park JJ, Kim SH, et al. Prevalence and endoscopic features of eosinophilic esophagitis in patients with esophageal or upper gastrointestinal symptoms. J Dig Dis 2012; 13:296–303. 55. Prasad GA, Talley NJ, Romero Y, et al. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol 2007; 102:2627–2632. 56. Ricker J, McNear S, Cassidy T, et al. Routine screening for eosinophilic esophagitis in patients presenting with dysphagia. Therap Adv Gastroenterol 2011; 4:27–35. 57. Bonis PA. Putting the puzzle together: epidemiological and clinical clues in the etiology of eosinophilic esophagitis. Immunol Allergy Clin North Am 2009; 29:41–52. 58. Syed AA, Andrews CN, Shaffer E, et al. The rising incidence of eosinophilic oesophagitis is associated with increasing biopsy rates: a population-based study. Aliment Pharmacol Ther 2012; 36:950–958. 59. Vanderheyden AD, Petras RE, DeYoung BR, et al. Emerging eosinophilic (allergic) esophagitis: increased incidence or increased recognition? Arch Pathol Lab Med 2007; 131:777–779. 60. Okada H, Kuhn C, Feillet H, et al. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol 2010; 160:1–9. 61. Almansa C, Krishna M, Ghabril MS, et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol 2009; 104:828–833. 62. Wang FY, Gupta SK, Fitzgerald JF. Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children? J Clin Gastroenterol 2007; 41:451–453. 63. Dellon ES, Peery AF, Shaheen NJ, et al. Inverse association of esophageal eosinophilia with Helicobacter pylori based on analysis of a US pathology database. Gastroenterology 2011; 141:1586–1592. 64. Furuta K, Adachi K, Aimi M, et al. Case-control study of association of eosinophilic gastrointestinal disorders with Helicobacter pylori infection in Japan. J Clin Biochem Nutr 2013; 53:60–62. 65. Chen Y, Blaser MJ. Inverse associations of Helicobacter pylori with asthma and allergy. Arch Intern Med 2007; 167:821–827. 66. Hviid A, Svanstrom H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 2011; 60:49–54. 67. Marra F, Lynd L, Coombes M, et al. Does antibiotic exposure during infancy lead to development of asthma? A systematic review and metaanalysis. Chest 2006; 129:610–618. 68. Wang JY, Liu LF, Chen CY, et al. Acetaminophen and/or antibiotic use in early life and the development of childhood allergic diseases. Int J Epidemiol 2013; 42:1087–1099. 69. Jensen ET, Kappelman MD, Kim HP, et al. Early life exposures as risk factors for pediatric eosinophilic esophagitis: a pilot and feasibility study. J Pediatr Gastroenterol Nutr 2013; 57:67–71. 70. Brown EM, Arrieta MC, Finlay BB. A fresh look at the hygiene hypothesis: how intestinal microbial exposure drives immune effector responses in atopic disease. Semin Immunol 2013; 25:378–387. 71. Fillon SA, Harris JK, Wagner BD, et al. Novel device to sample the esophageal microbiome – the esophageal string test. PLoS One 2012; 7:e42938. 72. Branum AM, Lukacs SL. Food allergy among U.S. children: trends in prevalence and hospitalizations. NCHS Data Brief 2008; 10:1–8. 73. Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol 2012; 130:461–467. 74. Orenstein SR, Shalaby TM, DiLorenzo C, et al. The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children. Am J Gastroenterol 2000; 95:1422–1430. 75. Baxi S, Shalaby TM, DiLorenzo C, et al. Clinical presentation of patients with eosinophilic inflammation of the esophagus. Gastrointest Endosc 2006; 64:473–478. 76. Dellon ES. Diagnosis and management of eosinophilic esophagitis. Clin Gastroenterol Hepatol 2012; 10:1066–1078. 77. Falk GW. Clinical presentation of eosinophilic esophagitis in adults. Gastro&& enterol Clin North Am 2014; 43:231–242. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource. 78. Dellon ES, Kim HP, Sperry SL, et al. A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 2014; 79:577–585. 79. Straumann A, Spichtin HP, Grize L, et al. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology 2003; 125:1660–1669. 80. Croese J, Fairley SK, Masson JW, et al. Clinical and endoscopic features of eosinophilic esophagitis in adults. Gastrointest Endosc 2003; 58:516–522. 81. Kwiatek MA, Hirano I, Kahrilas PJ, et al. Mechanical properties of the esophagus in eosinophilic esophagitis. Gastroenterology 2011; 140:82–90. 82. Korsapati H, Babaei A, Bhargava V, et al. Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis. Gut 2009; 58:1056–1062. 83. Poh CH, Gasiorowska A, Navarro-Rodriquez T, et al. Upper GI tract findings in patients with heartburn in whom proton pump inhibitor treatment failed versus those not receiving antireflux treatment. Gastrointest Endosc 2010; 71:28–34.

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Allergy 84. Garcia-Compean D, Gonzalez JA, Marrufo Garcia CA, et al. Prevalence of eosinophilic esophagitis in patients with refractory gastroesophageal reflux disease symptoms: a prospective study. Dig Liver Dis 2011; 43:204– 208. 85. Mulder DJ, Hurlbut DJ, Noble AJ, et al. Clinical features distinguish eosinophilic and reflux-induced esophagitis. J Pediatr Gastroenterol Nutr 2013; 56:263–270. 86. Molina-Infante J, Katzka DA, Gisbert JP. Review article: proton pump inhibitor therapy for suspected eosinophilic oesophagitis. Aliment Pharmacol Ther 2013; 37:1157–1164. 87. Siafakas CG, Ryan CK, Brown MR, et al. Multiple esophageal rings: an association with eosinophilic esophagitis: case report and review of the literature. Am J Gastroenterol 2000; 95:1572–1575. 88. Gonsalves N, Policarpio-Nicolas M, Zhang Q, et al. Histopathologic variability and endoscopic correlates in adults with eosinophilic esophagitis. Gastrointest Endosc 2006; 64:313–319. 89. Contreras E, Gupta SK. Steroids in pediatric eosinophilic esophagitis. && Gastroenterol Clin North Am 2014; 43:345–356. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource. 90. Faubion WA Jr, Perrault J, Burgart LJ, et al. Treatment of eosinophilic esophagitis with inhaled corticosteroids. J Pediatr Gastroenterol Nutr 1998; 27:90–93. 91. Arora AS, Yamazaki K. Eosinophilic esophagitis: asthma of the esophagus? Clin Gastroenterol Hepatol 2004; 2:523–530. 92. Aceves SS, Bastian JF, Newbury RO. Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children. Am J Gastroenterol 2007; 102:2271–2279.

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www.co-otolaryngology.com

93. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology 2006; 131:1381–1391. 94. Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology 2002; 122:1216–1225. 95. Schafer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol 2008; 6:165–173. 96. Gonsalves N, Kagalwalla AF. Dietary treatment of eosinophilic esophagitis. && Gastroenterol Clin North Am 2014; 43:375–383. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource. 97. Kagalwalla AF, Sentongo TA, Ritz S, et al. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol 2006; 4:1097–1102. 98. Spergel JM, Sentongo TA, Ritz S, et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol 2005; 95:336–343. 99. Spergel JM, Brown-Whitehorn T, Beausoleil JL, et al. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol 2007; 119:509–511. 100. Mishra A, Wang M, Pemmaraju VR, et al. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology 2008; 134:204–214. 101. Schoepher AM, Hirano I, Katzka DA, et al. Eosinophilic eosphagitis: overview && of clinical management. Gastroenterol Clin North Am 2014; 43:329–344. The Gastroenterology Clinics published a whole series of topics related to EoE last year. This is an outstanding resource.

Volume 23  Number 3  June 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Update on eosinophilic esophagitis.

The prevalence of eosinophilic esophagitis (EoE) is increasing. It is important for practitioners to be aware of the disease and its presenting sympto...
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