Auckland Allergy & Eczema Clinic

Eosinophilic Esophagitis (EE): An Update

Eosinophilic Esophagitis (EE):
An Update


Eosinophilic esophagitis is a chronic allergic inflammatory condition of the esophagus (the muscular tube that propels food from the mouth to the stomach), that is associated with increased numbers of eosinophils (a type of white blood cells that promotes inflammation, and their numbers are usually elevated in blood above the normal range with allergic reactions and parasitic infections as with worms). in the oesophagus. It affects both adults and children, but males more than female.

EE is characterized by symptoms including but not restricted to solid-food dysphagia (difficulty swallowing) and food impaction in adults, and feeding intolerance and GERD symptoms in children. The majority of these patients are atopic (has asthma, eczema or hay fever), with positive skin prick tests to several allergens including foods, which may contribute to their symptoms. In the past, patients with EE were incorrectly diagnosed as GERD, and treated with acid blockers (proton pump inhibitors). It has been found that patients with EE have normal pH in their GI tract, hence the poor response to acid blockers.


EE appears to be a new disease with a rapidly increasing incidence, possibly due to both increased recognition and a genuine increase in the number of cases. The first case series have been reported in the 1970s (1). Since then there have been more than 200 publications. Increasing recognition is unlikely to fully account for the increasing number of recognized cases because gastrointestinal barium studies have been practiced for decades, and therefore the characteristic ridged pattern seen in the esophagus in patients with EE would have been described earlier

EE shows a worldwide distribution. It has been reported in Australia, Belgium, Chile, Denmark, England, France, Germany, Greece, Italy, Japan, Mexico, The Netherlands, New Zealand, Spain, Sweden, Switzerland and the United States. So far there have been no reports from Africa.

It is distinctly more common in males, and affects patients of all ages. It was previously thought to be more common in children, but this is now believed to be due to previous underdiagnosis in adults. It peaks in young adults 20-40 years.

History of EE

The first report dates back to 1997: Dobbins et al (6) described a man with dysphagia who had dense eosinophilia

In 1978: Landres et al described a male patient with achalasia and eosinophilia

During the next 15 years there were several other reports of the association of severe dysphagia, proximal oesophageal strictures, oesophageal eosinophilc infiltrate & food allergies.

In 1993: Attwood et al (2) provide the first description of EE as a distinct clinical entity & made the first comparison between adults with eosinophilic oesophagitis and GERD (peptic oesophagitis). Attwood reported a series of 12 patients with isolated oesophageal eosinophilia and reflux (1) & their. Clinical Features include:

  • The patients presented with dysphagia and had visually normal oesophageal mucosa, >20 eosinophils per HPF on biopsy (mean 56 eosinophils /HPF
  • Normal 24 hour pH probe monitoring (no reflux) in 11 patients
  • Allergic diseases in 7 patients

In 1995 Hugh Sampson et al described a series of 10 children with abdominal pain after eating, early satiety or food refusal, vomiting or retching, failure to thrive, and non-responsiveness to standard medical therapy (3)

All these patients were treated for several years with various antacids and H2-antihistamines (Ranitidine and Cimetidine), prokinetic agents (omeprazole), and oral steroids.

4 out of the 10 even had a surgical procedure (Nissan fundoplication) for their persistent “reflux” and vomiting. On endoscopy these patients had normal looking oesophageal mucosa, but marked eosinophilia on microscopy.

Following 6-8 weeks of an amino acid-based formula (Neocate) plus rice, symptoms completely resolved in 8 patients and markedly improved in the other 2. Improvement (decreased eosinophilia) was also seen on repeat biopsy.

Symptoms could be reproduced with the introduction of certain foods. 
This study clearly implicated food hypersensitivity in patients with allergic eosinophilic espohagitis. Foods responsible for vast majority of symptoms include:

  • Milk
  • Egg
  • Soy
  • Wheat and other cereal grains
  • Beef & Chicken

Over the next 10 years, EE was increasingly recognised by Allergists, Paeditricians, Gastrenterologists, Pathologists and Radiologists.

1997: Gupta et al began a series of endoscopic observations of features of EE, like the vertical lines which are related to severe inflammation.

1998: The novel treatment of Swallowed (topical) steroids with fluticasone was published by Faubton et al

1999 Ruchelli et al & Walsh et al determined specific pathologic features of EE.


The exact aetiology of EE is unknown, but most investigators agree that EE is driven by an abnormal immune-mediated response.

The known association of eosinophils with food allergies would suggest that food may cause EE.

There are case reports of worsening of EE linked to pollen exposure, implicating environmental allergens as a trigger for EE.

Clinical Features

The presenting symptoms in EE vary with age.


There is often a long delay between onset of symptoms and the diagnosis. In adults the symptoms include:

  • Intermittent dysphagia, (in approximately 70%) often accompanied by food impaction (in about 30%), is the most characteristic symptom. The inflammation in the esophagus limits its ability to stretch, and the major symptom among adults with EE is difficulty swallowing solid food (dysphagia). The dysphagia is associated with chest discomfort, and if the food is passed down into the stomach the discomfort is relieved. Foods like beef, turkey or chicken normally gets stuck in the oesophagus after it is swallowed, and often vomiting has to be induced to regurgitate it. The impacted food can cause chest pain that may even mimic a heart attack. Occasionally the impacted food has to be relieved in hospital by passing a flexible tube (endoscope) down into the oesophagus. The symptom of dysphagia is usually longstanding, but often intermittent & not interfering with daily life.
  • Gastrooesophageal reflux GERD / Heartburn is often present in adolescents & adults. This makes the differentiation from GERD difficult.


  • Failure to thrive & food refusal in the very young
  • Nausea & Vomiting, regurgitation 25%
  • Abdominal pain 25%
  • Dysphagia.

Other Associated Features

  • About 70% of patients will have allergic symptoms Asthma, eczema or hay fever)
  • 70% also have positive skin prick tests
  • Family history of allergy present in about 50%
  • There may be partial improvement of symptoms after acid blockade (proton pump inhibitors), but eosinophilia persists
  • 50% had peripheral eosinophilia.

How is eosinophilic oesophagitis diagnosed?

Diagnostic Criteria for Eosinophilic Esophagitis

A systematic Review (4) in 2007 showed that significant variability in the diagnostic criteria for EE exists.10 different diagnostic histopathologic cut-points (measured in eosinophils/hpf) have been used in the literature, varying 6-fold from 5 to 30 eosinophils/ phf. The most commonly used criteria were 15, 20, and 24 eos / hpf.. Because eosinophil infiltration can be patchy in EE, it is not known if counts in distal and proximal esophageal specimens can be compared, and cases may be missed when only distal biopsies are obtained. It was also a finding that only a minority of studies reported their biopsy protocol. Prospectively conducted diagnostic and epidemiologic studies are needed, as at this point the review could not recommend a specific cut-point in an evidence-based fashion.

The diagnosis is suspected in a male atopic patient who develops dysphagia to solid foods in the second or third decade of life.

Endoscopy usually performed with flexible endoscope (viewing tube) passed through the mouth and into the esophagus. This allows the doctor to view the inner lining of the esophagus, stomach & duodenum (upper part of the small intestines). Endoscopy may show the following pathologic changes in the upper & mid-oesophagus:

  • Mucosal rings - 81%
  • Vertical furrows – 74%
  • Strictures – 31%
  • Exudates – 15%
  • Small caliber – 10%
  • Edema – 8%

Interestingly, 32% of a large cohort of children with EE had a normal appearing oesaphagus (5)

Endoscopy also allows other causes of dysphagia, like strictures and carcinoma to be excluded.

A biopsy of the esophagus (or ideally several biopsies) is performed during the endoscopy. The biopsy is performed by inserting a long thin biopsy forceps through the channel of the endoscope that pinches off a small sample of tissue from the inner lining of the esophagus. The biopsied tissue is examined under a eosinophils (>20/ high power field) are usually found in the upper half of the epithelium.

24 hour pH monitoring is often done as gastro-oesophageal Reflux Disease (GERD) is often initially suspected and needs to be excluded. In EE the result is usually normal, unlike in GERD.

Blood Tests:

  • About 50% of patients will have elevated eosinophils in the peripheral blood, which is picked up in measuring white cell count & specifically the eosinophil level 
  • ImmunoCAP RAST test might show positive results for foods like, milk, eggs, wheat, soy. 

Skin Prick Test might show positive reactions to the common foods linked with EE.

Atopy Patch Test involves applying the common food allergens (known to be associated with EE) in aluminium chambers under tape occlusion to the back for 48 hours. At 48 hours, when the tape is removed and again at 72 hours, the back is observed for signs of inflammation (redness and induration) at the sites where the foods were applied. The foods commonly used in the atopy patch test include: 

  • Milk 
  • Egg 
  • Soy 
  • Wheat and other cereal grains 
  • Beef 
  • Chicken 

Conditions that are confused with EE include:

The hallmark of Eosinophilic esophagitis is that the walls of the esophagus become filled with large numbers of eosinophils. The normal oesophageal mucosa does not contain eosinophils (or other white blood cells). Eosinophilic infiltration of the esophagus is found in:

  • GERD
    To date no studies have defined the upper limit of eosinophil numbers in GERD, but typically the number is thought to be <5 per HPF, with the eosinophilia limited to the distal oesophagus. Recent studies have suggested that the numbers might be significantly greater than this and that the eosinophils extend to the proximal oesophagus. Because ethe clinical features of EE & GERD can be indistinguishable, it is imperative that GERD be excluded as a cause of esophageal eosinophilia before making a diagnosis of EE. 
  • Eosinophilic gastroenteritis (EOG) 
    The gastric & duodenal tissues are normal in EE, and this differentiates it from Eosinophilic gastroenteritis. This distinction is important, since it is inlikely that EOG would benefit from swallowed (topical) steroids. 
  • Hypereosinophilic syndrome 
  • Food Allergies 
  • Inflammatory Bowel Disease 
  • Parasitic Infections 

Main differentiation between GERD & EE

gerd vs ee.png

Treatment options for eosinophilic esophagitis

Swallowed (instead of inhaled) Flixotide® (fluticasone propionate) is currently the best treatment for EE. The Flixotide is administered with the same inhaler as for asthma, but without the spacer. The removal of the spacer causes the flixotide to deposit in the mouth rather than inhaled into the lung. Patients are instructed not to eat or drink for 2 hours after each treatment. Improvement in the dysphagia is usually noted within days or weeks, but symptoms will usually recur after stopping treatment. This treatment is more attractive than oral steroids, since only 1% of the drug is absorbed systemically and it undergoes rapid hepatic processing. However, thrush as a side effect may occur when high doses of swallowed flixotide are used.

Oral steroids have shown response in 5 studies.

An exclusion diet should be tried for 6 weeks if food allergens are identified by skin prick test, RAST or Patch Test. Elemental diets (liquid diets that contain only amino acids but no proteins to act as allergens) like Neocate can be tried in children. Whenever diet is implemented for longer than 6 weeks it is mandatory to suggest consultation with a dietitian.

Montelukast is a Leukotriene receptor antagonist, which was originally licensed for the treatment of asthma. Since the dysphagia and food impaction are likely to be related to smooth muscle contraction, leukotriene inhibitors should be an attractive therapeutic option. 6 of the 8 patients in one study experienced a symptomatic improvement with Montelucast, but showed no effect on the epithelial eosinophils. 

Proton pump inhibitors gave symptomatic improvement in 8 out of 30 patients in 3 studies.

Esophageal dilatation can be performed if the esophagus is much narrowed at endoscopy. This involves physically stretching the rings in the esophagus with flexible dilators of different diameters, or with balloons inserted into the esophagus through the lumen of the endoscope. This method of treatment is more useful for the other causes of dysphagia, since EE responds so well to topical steroids (swallowed flixotide). The walls of the esophagus are very friable in EE and stretching can lead to extensive mucosal sheering and perforation. Also, Symptomatic recurrence were recorded in 2 studies after 3 to 8 months.


Eosinophilic Esophagitis s now well recognized, as an increasingly common disease found in all ages, but more common in males. It appears to be increasing in all developed countries.

The clinical hallmark of the disease in adults is intermittent and often painful intermittent difficulty swallowing (dysphagia) and occasional food impaction. In children feeding problems, failure to thrive, regurgitation, vomiting & abdominal pains are more common.

There are no uniform diagnostic criteria for EE, which has hampered better understanding of this disease.

Histologic hallmark is dense infiltration of eosinophils in the oesophagus, with >15-20 eosinophils /HPF.

It is often misdiagnosed as Gastro-eosophageal reflux disease (GERD), but if these patients are investigated properly, they will be found to have normal or only mildly abnormal oesophagus on gross inspection at endoscopy. The pH and manometry studies are inconsistent with the severity of symptoms. No mechanical obstruction is found, and if a biopsy is not taken the diagnosis is often missed.

In a subset of patients with EE, food-induced IgE-mediated reactions have been implicated in the pathogenesis.

Swallowed (topical) fluticasone is the best therapeutic option for symptomatic cases.


  1. Landers R et al.  Eosinophilic esophagitis in patients with vigorous achalasia. Gastroenterology 1978; 74:1298-1301
  2. Attwood SEA, Smyrk TC et al. Esophageal oesinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 1993; 38:109-16
  3. Kelly KJ, Sampson HA et al. Eosinophilic esophagitis attributed to gastrooesophageal reflux: improvement with an amino-acid based formula.Gastroenterol 1995; 109(5):1503-12
  4. Cheung KM, Oliver MR, Cameron DJ, et al Variability in Diagnostic Criteria for Eosinophilic Esophagitis: A Systematic Review  J Pediatr Gastroenterol Nutr 2003;58:516-22
  5. Liacouras CA et al  Eosinophilic esophagitis: a 10 year experience in 381 children. Clin Gastroenterol Hepatol 2205; 3: 1198-1206
  6. Dobbins JW, Sheahan D, Behar J. Eosinophilic gastroenteritis with esophageal involvement. Gastroenterology 1977;72:1312–1316.