Article - Eosinophilic Esophagitis

Arnon Lambroza, M.D.

Clinical Associate Professor of Medicine

Weill Medical College of Cornell University

Eosinophilic esophagitis (EoE) is an increasingly recognized disorder that presents with dysphagia and food impaction and is characterized by a dense eosinophilic infiltration of the esophagus. Eosinophils can be found in the esophagus in a number of conditions, including gastroesophageal reflux disease (GERD), collagen vascular disorders, parasitic infection and eosinophilic gastroenteritis. EoE is a primary esophageal disorder in which there are at least 15-20 eosinophils per high power field (hpf) on microscopy, without associated eosinophilic infiltration of the stomach or intestine. Both the proximal and distal esophagus may be involved and the density of eosinophils may be focally variable. By contrast, the eosinophilic changes of GERD are limited only to the distal esophagus, where the density is less than 5-10 eosinophils/hpf. Because of the focal nature of EoE, multiple biopsies should be obtained in order to properly diagnose this condition. One biopsy has a sensitivity of 50%, while five biopsies increase the sensitivity to 100%. My practice is to obtain at least one biopsy at 5, 10, 15 and 20 cm above the GE jct. Other histologic findings seen in EoE include superficial layering of eosinophils in the mucosa as well as the presence of eosinophilic microabscesses which may extend into the esophageal lumen.

There has been a dramatic increase in the diagnosis of EoE over the last few years, both due to an increased awareness of this disorder as well as an actual increase in prevalence.1,2 The first report of EoE was by Landres and colleagues in 1978.3 In 1993, Attwood and DeMeester4 reported on 12 adults (10 males) with dysphagia and no anatomic obstruction who had dense esophageal eosinophilic infiltrates (> 20 eos/hpf). Eleven of these patients had normal ambulatory pH studies. Up to the time of this report, only eight adults with EoE had been described in the literature. By 1998, there were still only 34 reported cases in the English language literature, half of whom were pediatric patients.5

EoE can present in children or adults and there is an approximately 3:1 male to female ratio. The symptoms of EoE in children are mainly abdominal pain (31%), heartburn (27.1%) and dysphagia (26.2%). In adults, the predominant symptoms are dysphagia (70.1%) and heartburn (27.1%).6 Adults with EoE may report a lifelong history of slow eating. In certain locations, EoE may be the most common cause of dysphagia and food impaction in young males with Schatzki rings.7

esophageal radiograph in patients with EEThe esophageal radiograph in patients with EoE may appear unremarkable or may demonstrate a variety of abnormalities such as a narrow caliber esophagus, a proximal stricture or multiple concentric rings. Some of these findings, particularly that of a diffusely narrowed esophagus, may be subtle and overlooked. Administration of a 12.5 mm barium table or a marshmallow bolus may help identify a region of subtle esophageal narrowing.

Vasilopoulos et al.8 have proposed a classification system for EoE that includes three types. Type 1 is called the early small caliber esophagus, type 2 is the advanced small caliber esophagus and type 3 is the ringed esophagus. It is not clear whether these types represent isolated variants of this disorder or whether they are sequential stages in its evolution.

EoE also presents with endoscopic findings which may be obvious or subtle. Obvious changes include a proximal stricture or multiple concentric rings. Many patients with eosinophilic esophagitis are initially thought to have normal endoscopies, when in fact they have subtle but characteristic findings such as linear mucosal furrows, fine whitish exudates and transient rings. Linear furrows are among the most specific endoscopic findings. When noted on exam, endoscopic biopsies almost always reveal the presence of EoE. The whitish exudates seen in EoE can be fine, pinpoint and scattered and are often mistaken for Candida or debris. The exudates actually represent collections of eosinophils, which can also appear as mucosal nodules or plaques.

Perhaps the most characteristic endoscopic finding of EoE, and the one that first introduces many gastroenterologists to this condition, is the appearance of long and deep mucosal tears (with visualization of the submucosa and muscle fibers) following passage of a dilator. These tears or mucosal rents can also occur simply with insertion of the endoscope, particularly when there is an unrecognized diffusely narrowed esophagus. Esophageal perforation during scope passage or dilation has been described in patients with EoE.9 The severe mucosal tears are thought to occur from excess mucosal fragility, decreased esophageal compliance and/or fusion of the various esophageal layers from transmural eosinophilic involvement. Endoscopic ultrasound findings in EoE include thickening of the mucosa, submucosa and muscularis propria.10

Eosinophilic esophagitis is a chronic inflammatory condition whose etiology remains unclear. Many patients with EoE have asthma or other atopic conditions, and some patients also have peripheral eosinophilia. Both IgE dependent (allergic) and non-IgE dependent (non-allergic) mechanisms are thought to be present in these patients.1 The antigens which trigger EoE may include various ingested food allergens as well as inhaled aeroallergens. The resolution of EoE in children placed on a pure elemental diet suggests a major role for food allergens. On the other hand, experimental exposure of the bronchus to the fungal aeroallergen Aspergillus fumigatus has been shown to induce eosinophilic infiltration of the esophagus in animals.11 Cytokines and chemokines such as IL-5 and eotaxin play important roles in the migration and accumulation of eosinophils. T-cells and mast cell may also be involved in the inflammatory response. Eosinophils cause mucosal damage through the release of cytotoxic granule proteins, reactive oxygen intermediates and lipid mediators.1

The treatment options for patients with EoE include food restriction diets, medical therapy and esophageal dilation. Food elimination based upon the results of RAST testing and skin patch testing may sometimes alleviate symptoms, particularly in children. The medical options for treating EoE include topical (swallowed) steroids, oral Prednisone, cromolyn (Gastrochrom) and leukotriene inhibitors (montelukast). The best studied medical treatment is swallowed fluticasone propionate. This is administered as two to four puffs of a fluticasone inhaler (220 µg/puff) taken after breakfast and dinner for six weeks.1 The puffs are sprayed into the back of the throat and swallowed rather than inhaled. The mouth is then rinsed with water (which is spit out) and the patient avoids eating or drinking for three hours.

Swallowed fluticasone can lead to symptom resolution as well as histologic improvement in patients with EoE. Resolution of rings and strictures has also been reported. Remedios et al.12 reported on 26 patients with EoE, 19 of whom were treated with four weeks of swallowed fluticasone. All 19 patients had an improvement in symptoms and eleven patients became asymptomatic. All patients had histologic improvement, with the mean eosinophil count/hpf decreasing from 24.98 to 4.46 in the proximal esophagus and from 39.34 to 3.81 in the distal esophagus. Three patients had resolution of mucosal rings and furrows, while one patient had resolution of a proximal esophageal stricture. Despite these good results, 74% of patients experienced some symptom recurrence after completing therapy.

Arora et al.1 reported on the use of topical fluticasone in 21 pts. with EoE who had at least six years of dysphagia. Treatment for six weeks led to the resolution of dysphagia in all patients for at least four months. The authors reported that 50-60% of their patients developed recurrent symptoms at 12-18 months. In a recent abstract, the same group reported a three-year follow-up of 10 patients treated initially with swallowed fluticasone. All patients required subsequent retreatment, often multiple times, with topical steroids. In addition, 70% of the patients also required repeat endoscopic therapy for food impaction. The authors stated that topical steroids may not modify the occurrence of food impaction or the need for endoscopic therapy over the long term in these patients.

Another option for treating patients with EoE is endoscopic dilation. Despite the known risk for deep mucosal tears, chest pain and occasional perforations, endoscopic dilation may still be performed safely and successfully.13,14 Patients with isolated short strictures or rings treated with dilation may experience long-term improvement or resolution of dysphagia. Regardless of whether balloons dilators or bougies are used, the most important principle of dilation in these patients is to do careful graded dilations with visual inspection between all sizes. An increase in dilator size of just 1 mm may cause a deep mucosal tear and necessitate an end to the dilating session. Balloons may have a theoretical advantage in this condition because they induce less shearing force during dilation.

Tailored therapy may be the best approach to patients with EoE. Patients with short strictures or isolated rings may be managed initially with dilation. Progressive dilation is performed carefully, until mild to moderate mucosal trauma is noted. Swallowed fluticasone can then be used if dysphagia persists after dilation. For patients with no apparent esophageal narrowing, as well as those with multiple rings, long strictures or a diffusely narrowed esophagus, topical fluticasone therapy can be tried first. Careful dilation can then be performed in patients whose symptoms persist. Patients who relapse after topical fluticasone can be retreated at full dose and then perhaps maintained on a lower dose for a longer period of time.

The prognosis for patients with EoE is generally very good. Although some patients may progress to more significant fibrosis or esophageal narrowing, many appear to remain stable over time. Symptoms generally respond to treatment with topical fluticasone or esophageal dilation, although the need for retreatment is common. To date, no evidence for any malignant potential of this condition has been identified.

References

  1. Arora AS, Yamazaki K. Eosinophilic esophagitis: asthma of the esophagus? Clin Gastroenterol Hepatol 2004;2:523-530.
  2. Straumann A, Beglinger C. Eosinophilic esophagitis: the endoscopist's enigma (letter). Gastrointest Endosc 2006;63:13-15.
  3. Landres RT, Kuster GGR, Strum WB. Eosinophilic esophagitis in a patient with vigorous achalasia. Gastroenterology 1978;74:1298-1301.
  4. Attwood SEA, Smyrk TC, DeMeester TR, et al. Esophageal eosinophilia with dysphagia: a distinct clinicopathological syndrome. Dig Dis Sciences 1993;38:109-116.
  5. Faubion WA, Perrault J, Burgart LJ, et al. Treatment of eosinophilic esophagitis with inhaled corticosteroids. J Pediatr Gastroenterol Nutr 1998;27:90-93.
  6. Kapel R, Torres C, Aksoy S, et al. Demographic, clinical and pathologic characteristics of eosinophilic esophagitis utilizing a national pathology database (abstract). Am J Gastroenterol 2006;101:S67.
  7. Desai TK, Stecevic V, Chang CH, et al. Association of eosinophilic inflammation with esophageal food impaction in adults. Gastrointest Endosc 2005; 61: 795-801.
  8. Vasilipoulos S, Shaker R. Defiant dysphagia: small-caliber esophagus and refractory benign esophageal strictures. Current Gastroenterology Reports 2001;3:225-230.
  9. Langdon DE. Response to Straumann et al.: primary eosinophilic esophagitis (letter). Gastroenterology 2004 ;127 :364.
  10. Fox VL, Mirko S, Teitelbaum JE. High resolution EUS in children with eosinophilic allergic esophagitis. Gastrointest Endosc 2003;57:30-36.
  11. Mishra A, Hogan SP, Brandt EB, et al. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest 2001;107:83-90.
  12. Remedios M, Campbell C, Jones D, et al. Eosinophilic esophagitis in adults : clinical, endoscopic, histologic findings and response to treatment with fluticasone propionate. Gastrointest Endosc 2006;63:3-12.