Table 1. Discriminators of eosinophilic oesophagitis and reflux oesophagitis10
Gastro-oesophageal reflux disease
- Food impaction in older children and adults
- Male to female ratio = 3:1
- Usually atopic comorbidities
- Food impaction rare
- Male to female ratio = 1:1
- Occasionally atopic comorbidities
Oesophageal impedance and pH studies
- Proximal and distal inflammation
- Epithelial hyperplasia
- ≥15 eosinophils/hpf
- Scanty eosinophils (sometimes widespread)
Consideration must also be allowed for ‘PPI-responsive oesophageal eosinophilia’. This is a recently devised term that describes patients with oesophageal eosinophilia in whom PPI therapy is effective despite having no evidence of acid reflux.21 PPI-responsive EoE remains a poorly understood entity. Some suggest that PPIs have a direct anti-inflammatory effect, which causes eosinophil regression, whereas others regard these cases as a subtype of GORD where improvement is due to the anti-secretory effect of PPIs.21 The practical relevance of this condition is yet to be determined.
Treatment of EoE consists of dietary, pharmacological and endoscopic interventions. There are no Australian clinical guidelines for the management of EoE. In many cases, treatment decisions are empirical and the use of pharmacological therapies are off-label.
Dietary modification is an effective first-line treatment for EoE in children and adults. There are three dietary methods that have gained widespread acceptance.
Targeted elimination diet
This approach involves removal from the diet of foods identified on allergy testing or patient history. Allergy testing typically involves skin prick or patch tests of a wide variety of foods.22 Although this approach is often preferred by patients, the success rate is <50%.23
Six food elimination diet
This involves avoidance of the six food types that are most commonly associated with allergy. Milk and wheat are the most frequently implicated foods.1,22 Other foods include eggs, soy, nuts and seafood. A comprehensive meta-analysis of dietary interventions showed this method achieved histological remission in approximately 72% of patients.23 The six food elimination diet is probably the preferred dietary therapy, given its relatively high success rate and acceptability by patients.23
The elemental diet
This regimen substitutes all food intake with a liquid formula composed of amino acids, carbohydrates, fats and minerals. The success rate of elemental diets is in the order of 90% but, in practice, they are rarely tolerated by patients.23 Barriers include high cost, unpleasant taste and the need to forgo all food, with the social limitations that entails.
Medical management is necessary in patients who do not respond to dietary measures alone. Topical glucocorticoids, namely fluticasone and budesonide, are currently regarded as the initial therapy of choice. Although there are no direct comparative data available, both agents are regarded as efficacious.5
These agents are administered by having the patient swallow glucocorticoid solutions, which would normally be inhaled, thereby coating the oesophagus. This is an off-label use of these preparations in Australia. Fluticasone is delivered via a metered dose inhaler (MDI) without a spacer. The drug should be sprayed into the mouth and the patient should be instructed to swallow the contents with 5 mls of water instead of inhaling it. Budesonide is available as a liquid suspension, usually for nebulisation, but for EoE this viscous slurry should be delivered by swallowing. Patients should not eat or drink for 30 minutes following administration, to allow sufficient bind time in the oesophagus.
Studies have consistently shown that both topical agents provide resolution of symptoms and eosinophilic inflammation in the majority of patients.24–26
Optimal dosing is yet to be established and there are no current Australian guidelines. However, recent recommendations have been issued by the ACG. The ACG suggests that patients placed on a budesonide suspension should be prescribed 1 mg daily if younger than 10 years of age, or 2 mg daily for older children or adults.27 With regard to fluticasone, dosages recommended by the ACG are unavailable in Australia.
For example, the ACG recommends that children aged 1–4 years should be started on a 44 µg inhaler, with two sprays twice daily.27 The lowest dose option available in Australia is a 50 µg inhaler, so it is reasonable in the Australian setting to prescribe 50 µg with two sprays twice daily. Patients aged 5–10 years should take a 100 µg inhaler, two sprays twice daily, whereas older children and adults can be prescribed a 250 µg inhaler, two sprays twice daily. Adults may be titrated to a maximum of 1750 µg per day if necessary.27,28 These doses as outlined are available in Australia and deviate only marginally from ACG recommendations.27,29
Most patients are treated with an 8-week course of topical steroids and re-assessed. The vast majority will be symptom-free following this treatment.30,31 Patients who remain symptomatic require a repeat of the 8-week prescription. Studies have shown that topical glucocorticoid therapy usually induces symptomatic remission for approximately 4–6 months, but almost never more than 12 months, after which a second course of steroids is generally necessary.30–32 These data apply to patients not commenced on dietary modification, which should provide a longer period of remission if implemented in addition.32
Consensus on an appropriate maintenance regimen for EoE has not been reached. The disease almost always recurs in patients who discontinue treatment and it is generally agreed that ongoing therapy, whether dietary or pharmacological, is necessary.6 The strategy accepted by most gastroenterologists is to aim for a nutritional regimen that keeps the patient asymptomatic, and to supplement this with topical glucocorticoids only on an as-needed basis.32,33
The correlation between symptoms and the histological severity of EoE is weak, so periodic surveillance endoscopic examination is probably warranted.9 An upper GI endoscopy every three years seems reasonablr for asymptomatic patients or those who require short courses of topical steroids to ensure adequate disease control on histology.6 Therapy can be adjusted accordingly if biopsies reveal ongoing subclinical disease. Endoscopy should be repeated early in patients whose symptoms change or worsen.6
Maintenance therapy with topical agents is generally well tolerated. However, candidal oesophagitis is reported in 15–20% of patients and may be an explanation if symptoms worsen.30,34
Expert consensus recommends systemic steroid treatment for patients with debilitating disease or disease unremittent to topical steroids. Several trials have shown the rapid efficacy of oral corticosteroids for EoE but not confirmed if they are superior to topical agents.27,30,35
Oesophageal dilation is very effective in widening the oesophageal diameter and providing rapid relief of dysphagia.27 It is usually reserved for patients who have failed more conservative measures, or whose oesophageal stenosis is critical.34 This process is onerous for the patient as it involves a series of endoscopic treatments over several weeks.
The results are unlikely to be permanent as endoscopic dilation has no therapeutic effect on the underlying inflammation. Trial data suggest that patients treated with dilation alone (without dietary modification or pharmacotherapy) can expect to remain asymptomatic for approximately 2 years before symptoms return.36,37
The risks include a small but significant chance of laceration, bleeding and perforation during the procedure.36–39 Approximately 2% of patients are also hospitalised with severe post-procedural chest pain, which exposes them to potentially unnecessary work-up or treatment for what is usually a self-resolving discomfort.40
Avoiding allergens can often reverse the disease process of EoE. Successful implementation of a suitable dietary plan can be made easier with assistance from a dietitian. Resources for patients can be found in Box 4.
There is a role for acid suppression in patients with EoE, but it is not a curative measure. The already inflamed oesophagus in EoE is predisposed to injury and hypersensitive to physiologic levels of acid exposure.41 PPI therapy can aid healing and improve symptoms, but it fails to induce total histological remission.5 A suitable PPI regimen for adults with EoE is omeprazole 20 mg taken once daily before meal.25,41 Children can be prescribed esomeprazole at a daily dose of 0.4–0.8 mg/kg.42
EoE is a chronic, relapsing, food-triggered inflammatory disorder with increasing prevalence in Australia. The recognition of EoE as a distinct entity is a major advance for patients presenting with dysphagia and food bolus obstruction.
EoE requires long-term multimodal care. The general practitioner will often be required to coordinate a management plan with specialists and allied health practitioners. Structured evaluation and regular reassessment in primary care are fundamental for the successful management of EoE.
Julian Peter Yaxley MBBS, Resident Medical Officer, Redcliffe Hospital, Redcliffe, QLD. firstname.lastname@example.org
Bhaskar Chakravarty MBBS, FRACP, PhD (Newcastle), PhD (Cambridge), Gastroenterologist, Southcoast Digestive Diseases Centre, Bundall, QLD
Competing interests: None.
Provenance and peer review: Not commissioned, externally peer reviewed.
- Attwood S, Smyrk T, Demeester T, Jones J. Esophageal eosinophilia with dysphagia: A distinct clinicopathologic syndrome. Dig Dis Sci 1993;38:109–16.
- Kelly M, Frazer J. Symptomatic mid-oesophageal webs. JAMA 1966;197:143.
- Landres R, Kuster G, Strum W. Eosinophilic oesophagitis in a patient with vigorous achalasia. Gastroenterology 1978;74:1298–301.
- Bonis PAL, Furuta GT. Clinical manifestations and diagnosis of eosinophilic esophagitis [Internet]. Boston: UpToDate, 2014 [updated 20 November 2014]. Available at www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-eosinophilic-esophagitis [Accessed 29 September 2014].
- Straumann A, Schoepfer A. Update on basic and clinical aspects of eosinophilic esophagitis. Gut 2014;63:1355–63.
- Furuta GT, Liacouras C, Collins M, et al. Eosinophilic oesophagitis in children and adults: A systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007;133:1342–63.
- Australasian Society of Clinical Immunology and Allergy. Eosinophilic Oesophagitis [Internet]. Sydney: ASCIA, 2014 [updated January 2014]. Available at www.allergy.org.au/patients/food-other-adverse-reactions/eosinophilic-oesophagitis [Accessed 18 January 2015].
- Remedios M, Jones D, Kerlin P. Eosinophilic esophagitis: Epidemiology, pathogenesis and management. Drugs 2011;71:527–40.
- Greenup A, Pokorny C. Eosinophilic oesophagitis: Diagnosis and management. Medicine Today 2014;15:29–33.
- Fell J. Recognition, assessment and management of eosinophilic oesophagitis. Arch Dis Child 2013;98:702–06.
- Straumann A, Spichtin H, Grize L, Bucher K, Beglinger C, Simon H. Natural history of primary eosinophilic esophagitis: A follow-up of 30 adult patients for up to 11.5 years. Gastroenterology 2003;125:1660–69.
- DeBrosse C, Franciosi J, King E, et al. Long-term outcomes in paediatric-onset oesophageal eosinophilia. J Allergy Clin Immunol 2011;128:132.
- Spergel J, Brown-Whitehorn T, Beausoleil J, et al. 14 years of eosinophilic oesophagitis: Clinical features and prognosis. J Pediatr Gastr Nutr 2009;48:30–36.
- Assa’ad A, Putnam P, Collins M, et al. Pediatric patients with eosinophilic oesophagitis: An 8 year follow-up. J Allergy Clin Immunol 2007;119:731–38.
- Hsueh-Chieh L, Ching-Liang L, Full-Young C. Eosinophilic oesophagitis in an asymptomatic Chinese. J Chin Med Assoc 2008;71:362–64.
- DeBosse C, Collins M, Buckmeier B, et al. Identification, epidemiology and chronicity of paediatric oesophageal eosinophilia from 1982-1999. J Allergy Clin Immunol 2010; 126:112–19.
- Straumann A. The natural history and complications of eosinophilic oesophagitis. Thorac Surg Clin 2011;21:575–87.
- Shim L, Grehan M. Oesophageal perforation during endoscopy for food impaction in eosinophilic oesophagitis. J Gastroen Hepatol 2010;25:428.
- Straumann A, Bussmann C, Zuber M, Vannini S, Simon H, Schoepfer A. Eosinophilic oesophagitis: Analysis of food impaction and perforation in 251 adolescent and adult patients. Clin Gastroenterol Hepatol 2008;6:598.
- Dellon E, Gonsalves N, Hirano I, Furuta G, Liacouras C, Katzka D. ACG clinical guideline: Evidence based approach to the diagnosis and management of oesophageal eosinophilia and eosinophilic oesophagitis. Am J Gastroenterol 2013;108:679–92.
- Dellon E, Speck O, Woodward K, et al. Am J Gastroenterol 2013;108:1854–60.
- Wolf W, Jerath M, Sperry S, Shaheen N, Dellon E. Dietary elimination therapy is an effective option for adults with eosinophilic oesophagitis. Clin Gastroenterol Hepatol 2014;12:1272–79.
- Arias A, Gonzalez-Cervera J, Tenias J, Lucendo A. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic oesophagitis: A systematic review and meta-analysis. Gastroenterology 2014;146:1639–48.
- Remedios M, Campbell C, Jones D, Kerlin P. Eosinophilic oesophagitis: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointest Endosc 2006;63:3–12.
- Kornifoff M, Noel R, Blanchard C, et al. A randomised, double-blind, placebo-controlled trial of fluticasone propionate for paediatric eosinophilic oesophagitis. Gastroenterology 2006;131:1381–91.
- Straumann A, Conus S, Degen L, Felder S, Kummer M, Engel H. Budesonide is effective in adolescent and adult patients with active eosinophilic oesophagitis. Gastroenterology 2010;139:1526–37.
- Kim H, Vance R, Shaheen N, Dellon E. The prevalence and diagnostic utility of endoscopic features of eosinophilic oesophagitis:A meta-analysis. Clin Gastroenterol Hepatol 2012;10:988–96.
- Liacouras C, Furtura G, Hirano I, et al. Eosinophilic oesophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011;128:3–20.
- MIMS. 50th edn. Fluticasone. Sydney: MIMS Australia, 2013; p. 441.
- Schaefer E, Fitzgerald J, Molleston J, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic oesophagitis: A randomised trial in children. Clin Gastroenterol Hepatol 2008;6:165–73.
- Arora A, Perrault J, Smyrk T. Topical corticosteroid treatment of dysphagia due to eosinophilic oesophagitis in adults. Mayo Clin Proc 2003;78:830–35.
- Helou E, Simonson J, Arora A. 3 year follow up of topical corticosteroid treatment for eosinophilic oesophagitis in adults. Am J Gastroenterol 2008;103:2194–99.
- Bonis PAL, Furuta GT. Treatment of eosinophilic esophagitis [Internet]. Boston: UpToDate, 2014 [updated 4 December 2014]. Available at www.uptodate.com/contents/treatment-of-eosinophilic-esophagitis [Accessed 7 October 2014].
- Noel R, Putnam P, Collins M, et al. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic oesophagitis. Clin Gastroenterol Hepatol 2004;2:568–75.
- Kaplan M, Mutlu E, Jakate S, et al. Endoscopy in eosinophilic oesophagitis: Feline oesophagus and perforation risk. Clin Gastroenterol Hepatol 2003;1:433–37.
- Cohen M, Kaufman A, Palazzo J, Nevin D, DiMarino A, Cohen S. An audit of endoscopic complications in adult eosinophilic oesophagitis. Clin Gastroenterol Hepatol 2007;5:1149–53.
- Liacouras C, Spergel J, Ruchelli E, et al. Eosinophilic oesophagitis: A 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005;3:1198–1206.
- Jung K, Gunderson N, Kopacova J, et al. Occurrence of and risk factors for complications after endoscopic dilation in eosinophilic oesophagitis. Gastrointest Endosc 2011;73:15–21.
- Schoepfer A, Gonsalves N, Bussmann C, et al. Oesophageal dilation in eosinophilic oesophagitis: Effectiveness, safety, and impact on the underlying inflammation. Am J Gastroenterol 2010;105:1062.
- Dellon E, Liacouras C. Advances in clinical management of eosinophilic oesophagitis. Gastroenterology 2014;147:1238–54.
- Krarup A, Villadsen G, Mejlgaard E, Olesen S, Drewes A, Funch-Jensen P. Acid hypersensitivity in patients with eosinophilic oesophagitis. Scand J Gastroenterol 2010;45:273–81.
- Gastrointestinal Expert Group. Disorders of the oesophagus: Children with gastro-oesophageal reflux. In: eTG complete [internet]. Melbourne: Therapeutic Guidelines Ltd, 2014. Available at www.tg.org.au [Accessed 16 September 2015].