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    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

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An Overview of Eosinophilic Esophagitis

Hyojin Park

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Correspondence to: Hyojin Park, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 135-720, Korea, Tel: +82-2-2019-3318, Fax: +82-2-3463-3882, E-mail: hjpark21@yuhs.ac

Received: March 3, 2014; Revised: May 12, 2014; Accepted: July 10, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2014; 8(6): 590-597

Published online November 29, 2014 https://doi.org/10.5009/gnl14081

Copyright © Gut and Liver.

The occurrence of eosinophilic esophagitis (EoE) has increased recently and has become increasingly recognized in the past decade in Western countries. Since the mid-1990s, EoE has been diagnosed by both gastroenterologists and allergy specialists and EoE has rapidly emerged as a distinct disease entity in both pediatric and adult gastroenterology, and the studies of EoE have increased in number.13 However, only limited studies has been published in Asian countries including Korea.4,5

In this paper, we discuss the data published mainly within the last 5 years on the epidemiology, pathogenesis, clinical symptoms, diagnosis, treatment, and prognosis of EoE.

It is debatable whether the reason for the recent high prevalence of EoE is a real increase in the incidence or increased diagnosis due to increased awareness about the disease. However, a recently published 20-year prospective, population-based study from Switzerland in the absence of EoE awareness program suggests actual increase in EoE’s incidence and prevalence (Table 1).6 In a retrospective study in all patients from a Australian provincia city with otherwise unexplained eosinophillic inflammation of the squamous epithelium, no diagnosis of EoE was made between 1981 and 1994 but 12 patients were diagnosed between 1995 and 2000 and 19 patients between 2001 and 2002 indicating a clear increase in incidence of EoE in this area.7 It is estimated that EoE in Westernized countries affects between 40 and 55 individuals per 100,000 population, similar to that of Crohn’s disease.3

Recent meta-analysis studies that surveyed the papers published in English from 1978 to 2005 show the male-to-female ratio of 3:1 with most subjects being in the 30s and 40s.8,9 In a prospective study conducted in the United States, 31 patients with esophageal food impaction were evaluated for 3 years. Seventeen of 31 patients (54.8%) had >20 eosinophils/high-power field [HPF] without gender predilection.7

EoE was diagnosed in 3.4% of children with reflux symptoms1 and 6.8% of children with reflux esophagitis.8 In addition, EoE showed a higher prevalence of 68% to 94% in children with reflux symptoms not responding to proton pump inhibitors (PPIs).1012

EoE is an immune/antigen-mediated disease in which food or environmental antigens stimulate an inflammatory response. EoE is frequently associated with allergy, although the causal relationship is not known. Rates of allergic rhinitis, asthma, and eczema in patients with EoE range from 40% to 75%, 14% to 70%, and 4% to 60%, respectively.3,13,14 The percentage of male in adults and pediatric patients is similar, 75% and 73%, respectively, while the incidence of atopic diseases including asthma, atopic dermatitis, and food allergy are more common (51% to 84%) in children than in adult patients with EoE (29% to 60%) although these diseases are prevalent in both pediatric and adult patients.14

In addition, seasonality associated with EoE suggests that aeroallergen may play a role in the pathogenesis of EoE.3,13 Approximately 53% to 73% of patients with EoE are positive on the skin prick test, which is associated with exogenous allergic reactions related to serum immunoglobulin E (IgE).14 However, the fact that 27% to 47% of patients displayed a negative skin prick test may indicate a role of endogenous nonallergic mechanisms leading to eosinophil infiltration unrelated to IgE.9

Eosinophilic infiltration has been reported to be related to key cytokines, such as interleukin (IL)-4, IL-5, IL-13, and eotaxin,1517 which stimulate the production of eotaxin-3, a potent chemokine in the esophageal mucosa. In turn, eotaxin-3 recruits and activates eosinophils to secrete proinflammatory and profibrotic mediators. IL-5 activates eosinophils, which in turn release transforming growth factor β stimulating fibroblasts and inducing fibrosis. IL-13 upregulates eotaxin-3, which recruits eosinophils in esophageal mucosa. In animal models, intratracheal administration of IL-13 induced infiltration of eosinophils in esophageal mucosa. In other words, these mediators cause eosinophilic infiltration, local tissue damage, perturb inflammatory response, and induce fibrosis, resulting in esophageal remodeling and dysfunction.17,18

The main clinical symptoms are vomiting, dysphagia, and abdominal pain in children, whereas dysphagia with food impaction is common in adults (Table 2).3 Less common symptoms in adults are heartburn, noncardiac chest pain, odynophagia, and vomiting.3,13 Peripheral eosinophilia appears in about 60% of pediatric patients and 5% to 50% of adult patients.19 Increased serum IgE, skin prick test and positive radioallergosorbent test result are observed in 40% to 73% of patients.3,14 Normal 24-hour esophageal pH monitoring pattern is observed in more than 90% of pediatric patients and 85% to 100% of adult patients.14

1. Endoscopic findings

A number of studies have reported several typical endoscopic features of EoE: fixed esophageal rings (corrugated rings or trachealinization), transient esophageal rings (felinization), whitish exudate or papules, longitudinal furrows, small/narrow-caliber esophagus, and mucosal laceration induced by passage of endoscope (fragile crêpe paper-like appearance).8,23 We previously studied the concordance rate and clinical predictors of EoE in endoscopically suspected eosinophilic esophagitis (EsEoE).23 Of 17 patients with EsEoE, five were finally confirmed as EoE by histology (diagnostic concordance rate, 29.4%). In a study by Sgouros et al.,9 normal endoscopic finding was observed in only 8.8% of the patients with EoE.

The most common endoscopic findings of EoE are mucosal or linear sheering after the passage of the endoscope (59.3%), rings or corrugated esophagus (49.2%), strictures (39.7%), whitish exudates or papules (15.7%), and narrow/small-caliber esophagus (5.3%).8 Additionally, longitudinal furrows, diminished/lost vascularity, and fragile crêpe paper-like appearance are observed. Longitudinal furrow, as shown in Fig. 2, was the most common endoscopic finding (6/9, 66.7%), and only one of nine patients with EoE presented normal looking mucosa (11.1%).23 We concluded that patients with dysphagia with two or more of the aforementioned endoscopic findings were more suggestive of EoE. However, we did not find positive correlation between eosinophil density in biopsy specimens, clinical symptoms, and endoscopic features.

Endoscopic ultrasonography (EUS) reveals that longitudinal furrows present as topographical changes caused by thickening of mucosa and submucosa.24 Thickened esophageal wall combined with mucosa, submucosa, and muscularis propria was found in EoE using EUS. Therefore, causes of dysphagia and/or food impaction may be explained by thickened muscle layer consisting of muscular dysfunction.

2. Histopathologic features

EoE is characterized by a dense eosinophilic infiltrate into the epithelium of the squamous esophagus, as shown in Fig. 3A. To optimize pathologic diagnosis, endoscopic biopsy should be taken from the proximal and distal esophagus, since eosinophils are not evenly distributed within the esophageal mucosa.21 Eosinophilic infiltration should be absent in gastric and duodenal mucosa. The optimal number of biopsies is essential for accurate diagnosis. The diagnostic sensitivity of 2, 3, and 6 biopsy specimens are 84%, 97%, and 100%, respectively.13

EoE is also characterized by the formation of microabscesses by eosinophil infiltration in the superficial layer of the esophageal epithelium, which is observed in 25% to 45% of the patients with EoE.25,26 The histologic picture of eosinophilic microabscess is shown in Fig. 3B. It is not observed in patients with GERD or peptic esophagitis. Infiltration of the superficial layer by eosinophils lasts after acid blockade therapy for at least 2 months.26 Noncharacteristic findings, such as basal zone hyperplasia and increased papillary size are also observed.14 In our previous study, associated features included degranulation (100%), spongiosis (91.7%), and eosinophilic microabscess (58.3%).27

The 2011 diagnostic guideline describes more than 15 eosinophils/HPF in at least one esophageal biopsy specimen, with few exceptions, and eosinophilia limited to the esophagus. “Few exception” are defined as those patient with <15 eosinophils/HPF with other features of eosinophilic inflammation including microabscess formation, superficial layering or extracellular eosinophil granules.13

3. Esophageal motility studies

The esophageal functions have been studied by barium esophagogram, EUS, manometry, and impedance planimetry. Esophageal manometic studies detect esophageal motility disorders related to EoE. Incordination of esophageal contraction (30%), incomplete relaxation of lower esophageal sphincter, excessive contraction of the esophagus (7%), and ineffective peristalsis (4%) were mainly observed.9 In addition, tertiary esophageal contractions, aperistalsis, multipeaked contractions, diffuse spasm are also frequently observed. About 40% of patients had shown normal manometric findings. Therefore, there are no pathognomic findings of manometry for the diagnosis of EoE. These esophageal motility disorders occur when eosinophilic infiltration affects the muscularis propria, in addition to mucosal infiltration.

The recent introduction of high resolution manometry (HRM) and impedance planimetry allowed the identification of panesophageal pressurization (by manometry) and changes in esophageal compliance with decreased distensibility (by impedance planimetry).28,29 Roman et al.28 found that 37% of EoE patients showed abnormal esophageal motility when HRM was used. The most common findings were weak peristalsis and frequent failed peristalsis, although these findings were also observed in GERD. However, panesophageal pressurization was a specific findings in EoE, which represents a manifestation of reduced esophageal compliance.

4. Laboratory findings

Peripheral eosinophilia is found in 40% to 50% of patients with EoE, and its count decreases after successful treatment with topical corticosteroids.3,13 Peripheral eosinophilia is correlated with the number of esophageal eosinophils. Serum total IgE levels are increased in 50% to 60% of patients with EoE,20,21 although its level does not reflect either histologic inflammation or predictor of therapeutic response. The skin prick test (SPT) is an immediate type allergic test for food allergen and aeroallergen.20,21 SPT is warranted in detecting food allergy associated with EoE, although the usefulness of therapeutic application including specific food avoidance by its positivity is still limited and requires more study to validate its significance.

1. Diet

Food allergy has been commonly observed in 15% to 43% of subjects with EoE.33 Therefore, it has been suggested that identification and elimination of potential food antigens which cause antibody response and eosinophilic infiltration would be an effective preventive ad therapeutic approaches.13,19,20 SPT and patch testing were used to identify the potential food antigens, and the patients were advised to avoid positive foods as identified by these tests. In this study, 18 patients had a concurrent improvement in biopsy and clinical response, and six patients had partial improvement.34 According to the proposal of Markowitz and Liacouras,22 the foods that trigger allergy by testing or past history should be eliminated and if the food allergens are not identified, the foods to which patients are most likely to be allergic (i.e., cow’s milk, soy, eggs, wheat, and peanuts) are empirically eliminated.

A diet eliminating milk, egg, soy, wheat, nuts, and seafood (six food elimination diet, SFED) has been reported to be an effective therapy in EoE. Gonsalves et al.35 demonstrated that SFED significantly improved symptoms, endoscopic features, and histopathology, and reintroduction of food reproduced EoE confirming a role for food allergens.

2. Corticosteroids

The use of steroids is one of the mainstays of pharmacologic treatment. Oral corticosteroid therapy improves the symptoms within 1 week when administered for 1 month,10 but systemic steroids use is associated with side effects. Whereas topical steroids, such as flucatisone and budesonide, known as swallowed inhaled steroid therapy, are effective treatments for improvement of symptoms and resolution of esophageal eosinophilia. In a study in adults that included 21 patients who were administered topical steroids for 6 weeks, all patients had relief of dysphagia that lasted a minimum of months.17 Dry mouth was the only adverse effect noted and esophageal candidiasis was not reported. Three patients relapsed after 4 months.18 Recommended doses of corticosteroid treatment protocol for EoE are shown in Table 4.13 If topical steroids are stopped after initial treatment, most of them recurred. But, there is little data regarding the effectiveness of maintenance treatment. Long-term maintenance treatment with low dose budesonide (0.5 mg/day) for 50 weeks was more effective than placebo in maintaining EoE in clinical and histologic remission,36 although the optimal duration and dose of budesonide are not yet clarified.37

3. Leukotriene antagonist, mast cell stabilizer, and other biologic drugs

Immunotherapy related to allergic medications includes the leukotriene D4 receptor antagonist and anti-IL-5.38 Montelukast, a selective inhibitor of the leukotriene D4 receptor, is also used for the treatment of asthma in adults. In a study reported by Attwood et al.,39 eight adult patients with EoE was started on 10 mg per day dose of montelukast but the dose was increased up to 100 mg daily if required. Once symptom was relieved, the dose was reduced to maintenance levels between 20 and 40 mg per day. Six of eight patients reported complete subjective improvement and five patients remained completely asymptomatic. However, the safety of the high dose used in this study is unclear.26 Montelukast could not completely treat the infiltration of eosinophils in the esophageal tissue.39

Cromolyn sodium, a mast cell stabilizer, is not thought to have apparent therapeutic benefit in patients with EoE.38 A study conducted with mepolizumab, a humanized monoclonal antibody against IL-5, suggested improvement in patient with EoE in clinical symptoms, endoscopic findings, and histologic findings. However, the long-term effect or safety of this drug need to be further investigated.40 Additionally, anti-IL-13 monoclonal antibodies, antieotaxin-3, anti-IgE antibodies and anti-inflammatory drugs have been used either to treat EoE or under development.37,38 However, these biologic agents are not yet in clinical practice in patients and require further scientific evidence.

4. Endoscopic dilation

Endoscopic dilation with balloon is effective for relieving symptoms of dysphagia with the evidence of ring or stricture. Since it does not affect eosinophilic infiltration and inflammation, medical therapy and/or dietary therapy should be undertaken after dilation.21,38 A total of 83% of patients experienced immediate symptomatic improvement after esophageal dilation, but some patients experienced symptomatic recurrences after 3 to 8 months in a long-term follow-up.9

EoE is a chronic disease, in which symptoms and inflammation relapse after cessation of successful treatment, is common.41 EoE does not seem to limit life expectancy, but impairs the quality of life. In an 11.5-year follow-up study, the eosinophilic inflammatory process remained confined to the esophagus without transition to eosinophilic gastroenteritis or other disease.42 It has not been associated with increased risk of malignant conditions. But many uncertainties still exist, particularly natural history and prognosis.37

EoE is a chronic, immune/antigen-mediated esophageal disease characterized by eosinophilic infiltration and typical clinical presentation includes dysphagia and food impaction due to fibrostenosis associated with inflammatory changes and alteration of biomechanical properties. Endoscopic examination reveals mucosal fragility, longitudinal furrows, ring or corrugated mucosa, whitish papules, or small caliber esophagus. After exclusion of other causes of esophageal eosinophilia including PPI-REE or GERD, the tailored treatment of diet therapy, corticosteroids, and/or endoscopic dilation is considered according to its phenotype of whether inflammatory and/or fibrostenotic changes in the esophagus. Further basic and clinical research data are needed to understand its pathophysiology, biomarkers, clinical courses and to update the diagnostic algorithm and develop novel treatments.

Fig. 1.A diagnostic and therapeutic algorithm of eosinophilic esophagitis (EoE). Adapted from Dellon ES. Clin Gastroenterol Hepatol 2012;10:1066–1078, with permission from Elsevier.21

EGD, esophagogastroduodenoscopy; eos, eosinophils; HPF, high-power field; PPI, proton pump inhibitor; GERD, gastroesophageal reflux disease; PPI-REE, PPI-responsive esophageal eosinophilia.

Fig. 2.Endoscopic features. (A) Longitudinal furrows. (B) Furrows and rings (spider web-like appearance).
Fig. 3.Histologic findings. (A) Massive infiltration of eosinophils on the esophageal mucosa, >15 eosinophils/high-power field. (B) Eosinophilic microabscess (H&E stain, ×200).

Eosinophilic Esophagitis Incidence and Cumulative Prevalence (95% CIs) Evaluated in 3-Year Intervals

3-yr intervalIncidence per 100,000 inhabitants (95% CI)Cumulative prevalence per 100,000 inhabitants (95% CI)
1989–19911.2 (0.25–3.52)3.6 (0.75–10.56)
1992–19941.6 (0.42–3.98)7.9 (3.27–16.77)
1995–19971.1 (0.24–3.36)11.5 (5.51–21.14)
1998–20000.7 (0.09–2.74)12.5 (7.05–23.82)
2001–20030.7 (0.09–2.71)13.4 (8.60–26.40)
2004–20064.4 (2.30–7.77)26.6 (18.89–42.38)
2007–20097.4 (4.48–11.34)42.8 (36.96–67.33)

Symptoms Suggestive of Eosinophilic Esophagitis

ChildrenAdult
Feeding aversion/intoleranceDysphagia
Vomiting/regurgitationFood impaction
“GERD refractory to medical management”“GERD refractory to medical management”
“GERD refractory to surgical management”
Food impaction/foreign body impaction
Epigastric abdominal pain
Dysphagia
Failure to thrive

Rationale for the Definition of and Diagnostic Guidelines for Eosinophilic Esophagitis

  • Change in EE abbreviation. EE often has been used as an abbreviation for erosive esophagitis. Use of the abbreviation EoE rather than EE for eosinophilic esophagitis should eliminate the potential for confusion.

  • Inclusion of the word chronic. Clinical experience supports that EoE is a chronic disease that will require long-term follow-up and treatment.

  • Inclusion of the term immune/antigen driven. An increasing body of clinical, translational, and basic evidence supports a role of an aberrant immune response (potentially reversible with treatment) as an underlying pathogenetic feature of EoE.

  • Continued use of the word clinicopathologic. No biomarker or pathognomonic element has been identified that would eliminate the need for both symptoms and an abnormal histology to make the diagnosis.

  • No change in threshold number of 15 eosinophils/HPF. Since the 2007 CR, no studies have identified a clear “lower limit of esophageal eosinophilia” or threshold number that would define EoE or have identified other histologic features or pattern of disease distribution that are pathognomonic of EoE.

  • No change in the use of HPF as the unit of measurement for eosinophilia. No studies have yet determined a standardized size of an HPF, and this might be practically unachievable. This issue is problematic because the size of an HPF can alter the reported number of eosinophils per HPF.

  • Inclusion of topical steroids/diet exclusions as a treatment. Current clinical evidence exists to include this paradigm to differentiate EoE from other diseases. Other potential therapies might exist but have not yet been supported in the literature.

  • Exclusion of GERD reference. A number of other causes of esophageal eosinophilia have been identified, and a broader statement has been included that allows for clinical discretion to be used.

  • Inclusion of patients with less than 15 eosinophils/HPF. A small number of patients with EoE (and who are treated with a PPI) might have less than the threshold number of eosinophils on their mucosal biopsy specimens associated with other features of eosinophilic inflammation, including microabscess formation, superficial layering, or extracellular eosinophil granules. Potential reasons for this finding include but are not limited to inadequate biopsy specimens, sampling error, chronic disease, or partial treatment response.

  • Inclusion of the term PPI-responsive esophageal eosinophilia. Therapeutic/basic studies and clinical experience have identified a potential anti-inflammatory or barrier-healing role for proton pump inhibition in patients with esophageal eosinophilia.


Recommended Doses of Corticosteroids for Eosinophilic Esophagitis

Topical swallowed corticosteroids
 Initial doses (see references for preparation and administration information)
  Fluticasone (puffed and swallowed through a metered-dose inhaler)
   Adults: 440–880 μg twice daily
   Children: 88–440 μg twice to 4 times daily (to a maximal adult dose)
  Budesonide (as a viscous suspension)
   Children (<10 yr): 1 mg daily
   Older children and adults: 2 mg daily
Systemic corticosteroids
 For severe cases (e.g., small-caliber esophagus, weight loss, and hospitalization)
 Prednisone: 1–2 mg/kg

  1. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3;1198-1206.
    Pubmed CrossRef
  2. 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.
    Pubmed CrossRef
  3. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133;1342-1363.
    Pubmed CrossRef
  4. 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.
    Pubmed CrossRef
  5. Lee JH, Kim MJ, Kim JH, et al. Clinical analysis of primary eosinophilic esophagitis. J Neurogastroenterol Motil. 2013;19;204-209.
    Pubmed KoreaMed CrossRef
  6. Hruz P, Straumann A, Bussmann 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.e5.
    Pubmed CrossRef
  7. Desai TK, Stecevic V, Chang CH, Goldstein NS, Badizadegan K, Furuta GT. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc. 2005;61;795-801.
    Pubmed CrossRef
  8. Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it’s not just kid’s stuff. Gastrointest Endosc. 2002;56;260-270.
    Pubmed CrossRef
  9. Sgouros SN, Bergele C, Mantides A. Eosinophilic esophagitis in adults: what is the clinical significance?. Endoscopy. 2006;38;515-520.
    Pubmed CrossRef
  10. Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. 1998;26;380-385.
    Pubmed CrossRef
  11. Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology. 2002;122;1216-1225.
    Pubmed CrossRef
  12. Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003;98;777-782.
    Pubmed CrossRef
  13. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128;3-20.e6.
    Pubmed CrossRef
  14. Arora AS, Yamazaki K. Eosinophilic esophagitis: asthma of the esophagus?. Clin Gastroenterol Hepatol. 2004;2;523-530.
    Pubmed CrossRef
  15. Hogan SP, Mishra A, Brandt EB, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001;2;353-360.
    Pubmed CrossRef
  16. Mishra A, Hogan SP, Brandt EB, Rothenberg ME. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168;2464-2469.
    Pubmed CrossRef
  17. Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology. 2003;125;1419-1427.
    Pubmed CrossRef
  18. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009;137;1238-1249.
    Pubmed KoreaMed CrossRef
  19. Aceves SS, Furuta GT, Spechler SJ. Integrated approach to treatment of children and adults with eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008;18;195-217.
    Pubmed CrossRef
  20. Dellon ES. Eosinophilic esophagitis: diagnostic tests and criteria. Curr Opin Gastroenterol. 2012;28;382-388.
    Pubmed CrossRef
  21. Dellon ES. Diagnosis and management of eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2012;10;1066-1078.
    Pubmed KoreaMed CrossRef
  22. Markowitz JE, Liacouras CA. Eosinophilic esophagitis. Gastroenterol Clin North Am. 2003;32;949-966.
    Pubmed CrossRef
  23. Lee KM, Lim HC, Kim JH, Yoon YH, Park HJ, Lee SI. Clinical implications of endoscopically suspected eosinophilic esophagitis. Korean J Gastroenterol. 2010;56;285-292.
    Pubmed CrossRef
  24. Fox VL, Nurko S, Teitelbaum JE, Badizadegan K, Furuta GT. High-resolution EUS in children with eosinophilic “allergic” esophagitis. Gastrointest Endosc. 2003;57;30-36.
    Pubmed CrossRef
  25. Ahmad M, Soetikno RM, Ahmed A. The differential diagnosis of eosinophilic esophagitis. J Clin Gastroenterol. 2000;30;242-244.
    Pubmed CrossRef
  26. Walsh SV, Antonioli DA, Goldman H, et al. Allergic esophagitis in children: a clinicopathological entity. Am J Surg Pathol. 1999;23;390-396.
    Pubmed CrossRef
  27. Kim KH, Chung IH, Kim JH, et al. Analysis of the clinicopathologic features of eosinophilic esophagitis: comparative study with non-obstructive dysphagia. Korean J Gastrointest Endosc. 2011;42;143-151.
  28. Roman S, Hirano I, Kwiatek MA, et al. Manometric features of eosinophilic esophagitis in esophageal pressure topography. Neurogastroenterol Motil. 2011;23;Array-214.
    Pubmed KoreaMed CrossRef
  29. Read AJ, Pandolfino JE. Biomechanics of esophageal function in eosinophilic esophagitis. J Neurogastroenterol Motil. 2012;18;357-364.
    Pubmed KoreaMed CrossRef
  30. Zhang X, Cheng E, Huo X, et al. Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PLoS One. 2012;7;e50037.
    Pubmed KoreaMed CrossRef
  31. Cheng E, Zhang X, Huo X, et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut. 2013;62;824-832.
    Pubmed KoreaMed CrossRef
  32. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointest Endosc. 2006;63;3-12.
    Pubmed CrossRef
  33. Spergel JM, Brown-Whitehorn T, Beausoleil JL, Shuker M, Liacouras CA. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119;509-511.
    Pubmed CrossRef
  34. Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol. 2002;109;363-368.
    Pubmed CrossRef
  35. Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142;1451-1459.e1.
    Pubmed CrossRef
  36. Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology. 2010;139;1526-1537.e1.
    Pubmed CrossRef
  37. Straumann A. Eosinophilic esophagitis: a bulk of mysteries. Dig Dis. 2013;31;6-9.
    Pubmed CrossRef
  38. Segal D, Chande N. The management of eosinophilic esophagitis in adults. J Clin Gastroenterol. 2013;47;570-577.
    Pubmed CrossRef
  39. Attwood SE, Lewis CJ, Bronder CS, Morris CD, Armstrong GR, Whittam J. Eosinophilic oesophagitis: a novel treatment using Montelukast. Gut. 2003;52;181-185.
    Pubmed KoreaMed CrossRef
  40. Garrett JK, Jameson SC, Thomson B, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113;115-119.
    Pubmed CrossRef
  41. Straumann A. The natural history and complications of eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008;18;99-118.
    Pubmed CrossRef
  42. Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003;125;1660-1669.
    Pubmed CrossRef

Article

Review

Gut Liver 2014; 8(6): 590-597

Published online November 29, 2014 https://doi.org/10.5009/gnl14081

Copyright © Gut and Liver.

An Overview of Eosinophilic Esophagitis

Hyojin Park

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Correspondence to: Hyojin Park, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul 135-720, Korea, Tel: +82-2-2019-3318, Fax: +82-2-3463-3882, E-mail: hjpark21@yuhs.ac

Received: March 3, 2014; Revised: May 12, 2014; Accepted: July 10, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

INTRODUCTION

The occurrence of eosinophilic esophagitis (EoE) has increased recently and has become increasingly recognized in the past decade in Western countries. Since the mid-1990s, EoE has been diagnosed by both gastroenterologists and allergy specialists and EoE has rapidly emerged as a distinct disease entity in both pediatric and adult gastroenterology, and the studies of EoE have increased in number.13 However, only limited studies has been published in Asian countries including Korea.4,5

In this paper, we discuss the data published mainly within the last 5 years on the epidemiology, pathogenesis, clinical symptoms, diagnosis, treatment, and prognosis of EoE.

EPIDEMIOLOGY

It is debatable whether the reason for the recent high prevalence of EoE is a real increase in the incidence or increased diagnosis due to increased awareness about the disease. However, a recently published 20-year prospective, population-based study from Switzerland in the absence of EoE awareness program suggests actual increase in EoE’s incidence and prevalence (Table 1).6 In a retrospective study in all patients from a Australian provincia city with otherwise unexplained eosinophillic inflammation of the squamous epithelium, no diagnosis of EoE was made between 1981 and 1994 but 12 patients were diagnosed between 1995 and 2000 and 19 patients between 2001 and 2002 indicating a clear increase in incidence of EoE in this area.7 It is estimated that EoE in Westernized countries affects between 40 and 55 individuals per 100,000 population, similar to that of Crohn’s disease.3

Recent meta-analysis studies that surveyed the papers published in English from 1978 to 2005 show the male-to-female ratio of 3:1 with most subjects being in the 30s and 40s.8,9 In a prospective study conducted in the United States, 31 patients with esophageal food impaction were evaluated for 3 years. Seventeen of 31 patients (54.8%) had >20 eosinophils/high-power field [HPF] without gender predilection.7

EoE was diagnosed in 3.4% of children with reflux symptoms1 and 6.8% of children with reflux esophagitis.8 In addition, EoE showed a higher prevalence of 68% to 94% in children with reflux symptoms not responding to proton pump inhibitors (PPIs).1012

PATHOPHYSIOLOGY/PATHOGENESIS

EoE is an immune/antigen-mediated disease in which food or environmental antigens stimulate an inflammatory response. EoE is frequently associated with allergy, although the causal relationship is not known. Rates of allergic rhinitis, asthma, and eczema in patients with EoE range from 40% to 75%, 14% to 70%, and 4% to 60%, respectively.3,13,14 The percentage of male in adults and pediatric patients is similar, 75% and 73%, respectively, while the incidence of atopic diseases including asthma, atopic dermatitis, and food allergy are more common (51% to 84%) in children than in adult patients with EoE (29% to 60%) although these diseases are prevalent in both pediatric and adult patients.14

In addition, seasonality associated with EoE suggests that aeroallergen may play a role in the pathogenesis of EoE.3,13 Approximately 53% to 73% of patients with EoE are positive on the skin prick test, which is associated with exogenous allergic reactions related to serum immunoglobulin E (IgE).14 However, the fact that 27% to 47% of patients displayed a negative skin prick test may indicate a role of endogenous nonallergic mechanisms leading to eosinophil infiltration unrelated to IgE.9

Eosinophilic infiltration has been reported to be related to key cytokines, such as interleukin (IL)-4, IL-5, IL-13, and eotaxin,1517 which stimulate the production of eotaxin-3, a potent chemokine in the esophageal mucosa. In turn, eotaxin-3 recruits and activates eosinophils to secrete proinflammatory and profibrotic mediators. IL-5 activates eosinophils, which in turn release transforming growth factor β stimulating fibroblasts and inducing fibrosis. IL-13 upregulates eotaxin-3, which recruits eosinophils in esophageal mucosa. In animal models, intratracheal administration of IL-13 induced infiltration of eosinophils in esophageal mucosa. In other words, these mediators cause eosinophilic infiltration, local tissue damage, perturb inflammatory response, and induce fibrosis, resulting in esophageal remodeling and dysfunction.17,18

CLINICAL FEATURES

The main clinical symptoms are vomiting, dysphagia, and abdominal pain in children, whereas dysphagia with food impaction is common in adults (Table 2).3 Less common symptoms in adults are heartburn, noncardiac chest pain, odynophagia, and vomiting.3,13 Peripheral eosinophilia appears in about 60% of pediatric patients and 5% to 50% of adult patients.19 Increased serum IgE, skin prick test and positive radioallergosorbent test result are observed in 40% to 73% of patients.3,14 Normal 24-hour esophageal pH monitoring pattern is observed in more than 90% of pediatric patients and 85% to 100% of adult patients.14

DIAGNOSIS

1. Endoscopic findings

A number of studies have reported several typical endoscopic features of EoE: fixed esophageal rings (corrugated rings or trachealinization), transient esophageal rings (felinization), whitish exudate or papules, longitudinal furrows, small/narrow-caliber esophagus, and mucosal laceration induced by passage of endoscope (fragile crêpe paper-like appearance).8,23 We previously studied the concordance rate and clinical predictors of EoE in endoscopically suspected eosinophilic esophagitis (EsEoE).23 Of 17 patients with EsEoE, five were finally confirmed as EoE by histology (diagnostic concordance rate, 29.4%). In a study by Sgouros et al.,9 normal endoscopic finding was observed in only 8.8% of the patients with EoE.

The most common endoscopic findings of EoE are mucosal or linear sheering after the passage of the endoscope (59.3%), rings or corrugated esophagus (49.2%), strictures (39.7%), whitish exudates or papules (15.7%), and narrow/small-caliber esophagus (5.3%).8 Additionally, longitudinal furrows, diminished/lost vascularity, and fragile crêpe paper-like appearance are observed. Longitudinal furrow, as shown in Fig. 2, was the most common endoscopic finding (6/9, 66.7%), and only one of nine patients with EoE presented normal looking mucosa (11.1%).23 We concluded that patients with dysphagia with two or more of the aforementioned endoscopic findings were more suggestive of EoE. However, we did not find positive correlation between eosinophil density in biopsy specimens, clinical symptoms, and endoscopic features.

Endoscopic ultrasonography (EUS) reveals that longitudinal furrows present as topographical changes caused by thickening of mucosa and submucosa.24 Thickened esophageal wall combined with mucosa, submucosa, and muscularis propria was found in EoE using EUS. Therefore, causes of dysphagia and/or food impaction may be explained by thickened muscle layer consisting of muscular dysfunction.

2. Histopathologic features

EoE is characterized by a dense eosinophilic infiltrate into the epithelium of the squamous esophagus, as shown in Fig. 3A. To optimize pathologic diagnosis, endoscopic biopsy should be taken from the proximal and distal esophagus, since eosinophils are not evenly distributed within the esophageal mucosa.21 Eosinophilic infiltration should be absent in gastric and duodenal mucosa. The optimal number of biopsies is essential for accurate diagnosis. The diagnostic sensitivity of 2, 3, and 6 biopsy specimens are 84%, 97%, and 100%, respectively.13

EoE is also characterized by the formation of microabscesses by eosinophil infiltration in the superficial layer of the esophageal epithelium, which is observed in 25% to 45% of the patients with EoE.25,26 The histologic picture of eosinophilic microabscess is shown in Fig. 3B. It is not observed in patients with GERD or peptic esophagitis. Infiltration of the superficial layer by eosinophils lasts after acid blockade therapy for at least 2 months.26 Noncharacteristic findings, such as basal zone hyperplasia and increased papillary size are also observed.14 In our previous study, associated features included degranulation (100%), spongiosis (91.7%), and eosinophilic microabscess (58.3%).27

The 2011 diagnostic guideline describes more than 15 eosinophils/HPF in at least one esophageal biopsy specimen, with few exceptions, and eosinophilia limited to the esophagus. “Few exception” are defined as those patient with <15 eosinophils/HPF with other features of eosinophilic inflammation including microabscess formation, superficial layering or extracellular eosinophil granules.13

3. Esophageal motility studies

The esophageal functions have been studied by barium esophagogram, EUS, manometry, and impedance planimetry. Esophageal manometic studies detect esophageal motility disorders related to EoE. Incordination of esophageal contraction (30%), incomplete relaxation of lower esophageal sphincter, excessive contraction of the esophagus (7%), and ineffective peristalsis (4%) were mainly observed.9 In addition, tertiary esophageal contractions, aperistalsis, multipeaked contractions, diffuse spasm are also frequently observed. About 40% of patients had shown normal manometric findings. Therefore, there are no pathognomic findings of manometry for the diagnosis of EoE. These esophageal motility disorders occur when eosinophilic infiltration affects the muscularis propria, in addition to mucosal infiltration.

The recent introduction of high resolution manometry (HRM) and impedance planimetry allowed the identification of panesophageal pressurization (by manometry) and changes in esophageal compliance with decreased distensibility (by impedance planimetry).28,29 Roman et al.28 found that 37% of EoE patients showed abnormal esophageal motility when HRM was used. The most common findings were weak peristalsis and frequent failed peristalsis, although these findings were also observed in GERD. However, panesophageal pressurization was a specific findings in EoE, which represents a manifestation of reduced esophageal compliance.

4. Laboratory findings

Peripheral eosinophilia is found in 40% to 50% of patients with EoE, and its count decreases after successful treatment with topical corticosteroids.3,13 Peripheral eosinophilia is correlated with the number of esophageal eosinophils. Serum total IgE levels are increased in 50% to 60% of patients with EoE,20,21 although its level does not reflect either histologic inflammation or predictor of therapeutic response. The skin prick test (SPT) is an immediate type allergic test for food allergen and aeroallergen.20,21 SPT is warranted in detecting food allergy associated with EoE, although the usefulness of therapeutic application including specific food avoidance by its positivity is still limited and requires more study to validate its significance.

TREATMENTS

1. Diet

Food allergy has been commonly observed in 15% to 43% of subjects with EoE.33 Therefore, it has been suggested that identification and elimination of potential food antigens which cause antibody response and eosinophilic infiltration would be an effective preventive ad therapeutic approaches.13,19,20 SPT and patch testing were used to identify the potential food antigens, and the patients were advised to avoid positive foods as identified by these tests. In this study, 18 patients had a concurrent improvement in biopsy and clinical response, and six patients had partial improvement.34 According to the proposal of Markowitz and Liacouras,22 the foods that trigger allergy by testing or past history should be eliminated and if the food allergens are not identified, the foods to which patients are most likely to be allergic (i.e., cow’s milk, soy, eggs, wheat, and peanuts) are empirically eliminated.

A diet eliminating milk, egg, soy, wheat, nuts, and seafood (six food elimination diet, SFED) has been reported to be an effective therapy in EoE. Gonsalves et al.35 demonstrated that SFED significantly improved symptoms, endoscopic features, and histopathology, and reintroduction of food reproduced EoE confirming a role for food allergens.

2. Corticosteroids

The use of steroids is one of the mainstays of pharmacologic treatment. Oral corticosteroid therapy improves the symptoms within 1 week when administered for 1 month,10 but systemic steroids use is associated with side effects. Whereas topical steroids, such as flucatisone and budesonide, known as swallowed inhaled steroid therapy, are effective treatments for improvement of symptoms and resolution of esophageal eosinophilia. In a study in adults that included 21 patients who were administered topical steroids for 6 weeks, all patients had relief of dysphagia that lasted a minimum of months.17 Dry mouth was the only adverse effect noted and esophageal candidiasis was not reported. Three patients relapsed after 4 months.18 Recommended doses of corticosteroid treatment protocol for EoE are shown in Table 4.13 If topical steroids are stopped after initial treatment, most of them recurred. But, there is little data regarding the effectiveness of maintenance treatment. Long-term maintenance treatment with low dose budesonide (0.5 mg/day) for 50 weeks was more effective than placebo in maintaining EoE in clinical and histologic remission,36 although the optimal duration and dose of budesonide are not yet clarified.37

3. Leukotriene antagonist, mast cell stabilizer, and other biologic drugs

Immunotherapy related to allergic medications includes the leukotriene D4 receptor antagonist and anti-IL-5.38 Montelukast, a selective inhibitor of the leukotriene D4 receptor, is also used for the treatment of asthma in adults. In a study reported by Attwood et al.,39 eight adult patients with EoE was started on 10 mg per day dose of montelukast but the dose was increased up to 100 mg daily if required. Once symptom was relieved, the dose was reduced to maintenance levels between 20 and 40 mg per day. Six of eight patients reported complete subjective improvement and five patients remained completely asymptomatic. However, the safety of the high dose used in this study is unclear.26 Montelukast could not completely treat the infiltration of eosinophils in the esophageal tissue.39

Cromolyn sodium, a mast cell stabilizer, is not thought to have apparent therapeutic benefit in patients with EoE.38 A study conducted with mepolizumab, a humanized monoclonal antibody against IL-5, suggested improvement in patient with EoE in clinical symptoms, endoscopic findings, and histologic findings. However, the long-term effect or safety of this drug need to be further investigated.40 Additionally, anti-IL-13 monoclonal antibodies, antieotaxin-3, anti-IgE antibodies and anti-inflammatory drugs have been used either to treat EoE or under development.37,38 However, these biologic agents are not yet in clinical practice in patients and require further scientific evidence.

4. Endoscopic dilation

Endoscopic dilation with balloon is effective for relieving symptoms of dysphagia with the evidence of ring or stricture. Since it does not affect eosinophilic infiltration and inflammation, medical therapy and/or dietary therapy should be undertaken after dilation.21,38 A total of 83% of patients experienced immediate symptomatic improvement after esophageal dilation, but some patients experienced symptomatic recurrences after 3 to 8 months in a long-term follow-up.9

NATURAL HISTORY AND PROGNOSIS

EoE is a chronic disease, in which symptoms and inflammation relapse after cessation of successful treatment, is common.41 EoE does not seem to limit life expectancy, but impairs the quality of life. In an 11.5-year follow-up study, the eosinophilic inflammatory process remained confined to the esophagus without transition to eosinophilic gastroenteritis or other disease.42 It has not been associated with increased risk of malignant conditions. But many uncertainties still exist, particularly natural history and prognosis.37

CONCLUSIONS

EoE is a chronic, immune/antigen-mediated esophageal disease characterized by eosinophilic infiltration and typical clinical presentation includes dysphagia and food impaction due to fibrostenosis associated with inflammatory changes and alteration of biomechanical properties. Endoscopic examination reveals mucosal fragility, longitudinal furrows, ring or corrugated mucosa, whitish papules, or small caliber esophagus. After exclusion of other causes of esophageal eosinophilia including PPI-REE or GERD, the tailored treatment of diet therapy, corticosteroids, and/or endoscopic dilation is considered according to its phenotype of whether inflammatory and/or fibrostenotic changes in the esophagus. Further basic and clinical research data are needed to understand its pathophysiology, biomarkers, clinical courses and to update the diagnostic algorithm and develop novel treatments.

Fig 1.

Figure 1.A diagnostic and therapeutic algorithm of eosinophilic esophagitis (EoE). Adapted from Dellon ES. Clin Gastroenterol Hepatol 2012;10:1066–1078, with permission from Elsevier.21

EGD, esophagogastroduodenoscopy; eos, eosinophils; HPF, high-power field; PPI, proton pump inhibitor; GERD, gastroesophageal reflux disease; PPI-REE, PPI-responsive esophageal eosinophilia.

Gut and Liver 2014; 8: 590-597https://doi.org/10.5009/gnl14081

Fig 2.

Figure 2.Endoscopic features. (A) Longitudinal furrows. (B) Furrows and rings (spider web-like appearance).
Gut and Liver 2014; 8: 590-597https://doi.org/10.5009/gnl14081

Fig 3.

Figure 3.Histologic findings. (A) Massive infiltration of eosinophils on the esophageal mucosa, >15 eosinophils/high-power field. (B) Eosinophilic microabscess (H&E stain, ×200).
Gut and Liver 2014; 8: 590-597https://doi.org/10.5009/gnl14081

Table 1 Eosinophilic Esophagitis Incidence and Cumulative Prevalence (95% CIs) Evaluated in 3-Year Intervals

3-yr intervalIncidence per 100,000 inhabitants (95% CI)Cumulative prevalence per 100,000 inhabitants (95% CI)
1989–19911.2 (0.25–3.52)3.6 (0.75–10.56)
1992–19941.6 (0.42–3.98)7.9 (3.27–16.77)
1995–19971.1 (0.24–3.36)11.5 (5.51–21.14)
1998–20000.7 (0.09–2.74)12.5 (7.05–23.82)
2001–20030.7 (0.09–2.71)13.4 (8.60–26.40)
2004–20064.4 (2.30–7.77)26.6 (18.89–42.38)
2007–20097.4 (4.48–11.34)42.8 (36.96–67.33)

Incidence is reported per 100,000 inhabitants per year as the mean of a 3-year interval. Cumulative prevalence was calculated per 100,000 inhabitants at the end of the time interval. Adapted from Hruz P, et al. J Allergy Clin Immunol 2011;128:1349–1350.e5, with permission from Elsevier.6

CI, confidence interval.


Table 2 Symptoms Suggestive of Eosinophilic Esophagitis

ChildrenAdult
Feeding aversion/intoleranceDysphagia
Vomiting/regurgitationFood impaction
“GERD refractory to medical management”“GERD refractory to medical management”
“GERD refractory to surgical management”
Food impaction/foreign body impaction
Epigastric abdominal pain
Dysphagia
Failure to thrive

Adapted from Furuta GT, et al. Gastroenterology 2007;133:1342–1363, with permission from Elsevier.3


Table 3 Rationale for the Definition of and Diagnostic Guidelines for Eosinophilic Esophagitis

Change in EE abbreviation. EE often has been used as an abbreviation for erosive esophagitis. Use of the abbreviation EoE rather than EE for eosinophilic esophagitis should eliminate the potential for confusion.

Inclusion of the word chronic. Clinical experience supports that EoE is a chronic disease that will require long-term follow-up and treatment.

Inclusion of the term immune/antigen driven. An increasing body of clinical, translational, and basic evidence supports a role of an aberrant immune response (potentially reversible with treatment) as an underlying pathogenetic feature of EoE.

Continued use of the word clinicopathologic. No biomarker or pathognomonic element has been identified that would eliminate the need for both symptoms and an abnormal histology to make the diagnosis.

No change in threshold number of 15 eosinophils/HPF. Since the 2007 CR, no studies have identified a clear “lower limit of esophageal eosinophilia” or threshold number that would define EoE or have identified other histologic features or pattern of disease distribution that are pathognomonic of EoE.

No change in the use of HPF as the unit of measurement for eosinophilia. No studies have yet determined a standardized size of an HPF, and this might be practically unachievable. This issue is problematic because the size of an HPF can alter the reported number of eosinophils per HPF.

Inclusion of topical steroids/diet exclusions as a treatment. Current clinical evidence exists to include this paradigm to differentiate EoE from other diseases. Other potential therapies might exist but have not yet been supported in the literature.

Exclusion of GERD reference. A number of other causes of esophageal eosinophilia have been identified, and a broader statement has been included that allows for clinical discretion to be used.

Inclusion of patients with less than 15 eosinophils/HPF. A small number of patients with EoE (and who are treated with a PPI) might have less than the threshold number of eosinophils on their mucosal biopsy specimens associated with other features of eosinophilic inflammation, including microabscess formation, superficial layering, or extracellular eosinophil granules. Potential reasons for this finding include but are not limited to inadequate biopsy specimens, sampling error, chronic disease, or partial treatment response.

Inclusion of the term PPI-responsive esophageal eosinophilia. Therapeutic/basic studies and clinical experience have identified a potential anti-inflammatory or barrier-healing role for proton pump inhibition in patients with esophageal eosinophilia.

Adapted from Liacouras CA, et al. J Allergy Clin Immunol 2011;128:3–20.e6, with permission from Elsevier.13

EoE, eosinophilic esophagitis; HPF, high-power field; CR, consensus recommendation; GERD, gastroesophageal reflux disease; PPI, proton pump inhibitor.


Table 4 Recommended Doses of Corticosteroids for Eosinophilic Esophagitis

Topical swallowed corticosteroids
 Initial doses (see references for preparation and administration information)
  Fluticasone (puffed and swallowed through a metered-dose inhaler)
   Adults: 440–880 μg twice daily
   Children: 88–440 μg twice to 4 times daily (to a maximal adult dose)
  Budesonide (as a viscous suspension)
   Children (<10 yr): 1 mg daily
   Older children and adults: 2 mg daily
Systemic corticosteroids
 For severe cases (e.g., small-caliber esophagus, weight loss, and hospitalization)
 Prednisone: 1–2 mg/kg

Adapted from Liacouras CA, et al. J Allergy Clin Immunol 2011;128: 3–20.e6, with permission from Elsevier.13


References

  1. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol. 2005;3;1198-1206.
    Pubmed CrossRef
  2. 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.
    Pubmed CrossRef
  3. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133;1342-1363.
    Pubmed CrossRef
  4. 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.
    Pubmed CrossRef
  5. Lee JH, Kim MJ, Kim JH, et al. Clinical analysis of primary eosinophilic esophagitis. J Neurogastroenterol Motil. 2013;19;204-209.
    Pubmed KoreaMed CrossRef
  6. Hruz P, Straumann A, Bussmann 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.e5.
    Pubmed CrossRef
  7. Desai TK, Stecevic V, Chang CH, Goldstein NS, Badizadegan K, Furuta GT. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc. 2005;61;795-801.
    Pubmed CrossRef
  8. Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it’s not just kid’s stuff. Gastrointest Endosc. 2002;56;260-270.
    Pubmed CrossRef
  9. Sgouros SN, Bergele C, Mantides A. Eosinophilic esophagitis in adults: what is the clinical significance?. Endoscopy. 2006;38;515-520.
    Pubmed CrossRef
  10. Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. 1998;26;380-385.
    Pubmed CrossRef
  11. Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology. 2002;122;1216-1225.
    Pubmed CrossRef
  12. Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003;98;777-782.
    Pubmed CrossRef
  13. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128;3-20.e6.
    Pubmed CrossRef
  14. Arora AS, Yamazaki K. Eosinophilic esophagitis: asthma of the esophagus?. Clin Gastroenterol Hepatol. 2004;2;523-530.
    Pubmed CrossRef
  15. Hogan SP, Mishra A, Brandt EB, et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001;2;353-360.
    Pubmed CrossRef
  16. Mishra A, Hogan SP, Brandt EB, Rothenberg ME. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168;2464-2469.
    Pubmed CrossRef
  17. Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology. 2003;125;1419-1427.
    Pubmed CrossRef
  18. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009;137;1238-1249.
    Pubmed KoreaMed CrossRef
  19. Aceves SS, Furuta GT, Spechler SJ. Integrated approach to treatment of children and adults with eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008;18;195-217.
    Pubmed CrossRef
  20. Dellon ES. Eosinophilic esophagitis: diagnostic tests and criteria. Curr Opin Gastroenterol. 2012;28;382-388.
    Pubmed CrossRef
  21. Dellon ES. Diagnosis and management of eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2012;10;1066-1078.
    Pubmed KoreaMed CrossRef
  22. Markowitz JE, Liacouras CA. Eosinophilic esophagitis. Gastroenterol Clin North Am. 2003;32;949-966.
    Pubmed CrossRef
  23. Lee KM, Lim HC, Kim JH, Yoon YH, Park HJ, Lee SI. Clinical implications of endoscopically suspected eosinophilic esophagitis. Korean J Gastroenterol. 2010;56;285-292.
    Pubmed CrossRef
  24. Fox VL, Nurko S, Teitelbaum JE, Badizadegan K, Furuta GT. High-resolution EUS in children with eosinophilic “allergic” esophagitis. Gastrointest Endosc. 2003;57;30-36.
    Pubmed CrossRef
  25. Ahmad M, Soetikno RM, Ahmed A. The differential diagnosis of eosinophilic esophagitis. J Clin Gastroenterol. 2000;30;242-244.
    Pubmed CrossRef
  26. Walsh SV, Antonioli DA, Goldman H, et al. Allergic esophagitis in children: a clinicopathological entity. Am J Surg Pathol. 1999;23;390-396.
    Pubmed CrossRef
  27. Kim KH, Chung IH, Kim JH, et al. Analysis of the clinicopathologic features of eosinophilic esophagitis: comparative study with non-obstructive dysphagia. Korean J Gastrointest Endosc. 2011;42;143-151.
  28. Roman S, Hirano I, Kwiatek MA, et al. Manometric features of eosinophilic esophagitis in esophageal pressure topography. Neurogastroenterol Motil. 2011;23;Array-214.
    Pubmed KoreaMed CrossRef
  29. Read AJ, Pandolfino JE. Biomechanics of esophageal function in eosinophilic esophagitis. J Neurogastroenterol Motil. 2012;18;357-364.
    Pubmed KoreaMed CrossRef
  30. Zhang X, Cheng E, Huo X, et al. Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PLoS One. 2012;7;e50037.
    Pubmed KoreaMed CrossRef
  31. Cheng E, Zhang X, Huo X, et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut. 2013;62;824-832.
    Pubmed KoreaMed CrossRef
  32. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointest Endosc. 2006;63;3-12.
    Pubmed CrossRef
  33. Spergel JM, Brown-Whitehorn T, Beausoleil JL, Shuker M, Liacouras CA. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119;509-511.
    Pubmed CrossRef
  34. Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol. 2002;109;363-368.
    Pubmed CrossRef
  35. Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142;1451-1459.e1.
    Pubmed CrossRef
  36. Straumann A, Conus S, Degen L, et al. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology. 2010;139;1526-1537.e1.
    Pubmed CrossRef
  37. Straumann A. Eosinophilic esophagitis: a bulk of mysteries. Dig Dis. 2013;31;6-9.
    Pubmed CrossRef
  38. Segal D, Chande N. The management of eosinophilic esophagitis in adults. J Clin Gastroenterol. 2013;47;570-577.
    Pubmed CrossRef
  39. Attwood SE, Lewis CJ, Bronder CS, Morris CD, Armstrong GR, Whittam J. Eosinophilic oesophagitis: a novel treatment using Montelukast. Gut. 2003;52;181-185.
    Pubmed KoreaMed CrossRef
  40. Garrett JK, Jameson SC, Thomson B, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113;115-119.
    Pubmed CrossRef
  41. Straumann A. The natural history and complications of eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008;18;99-118.
    Pubmed CrossRef
  42. Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003;125;1660-1669.
    Pubmed CrossRef
Gut and Liver

Vol.15 No.5
September, 2021

pISSN 1976-2283
eISSN 2005-1212

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