Eosinophilic Esophagitis

Peter R. McNally, D.O., F.A.C.P., F.A.C.G.

Keywords

Eosinophil, esophagitis, dysphagia, esophageal obstruction, allergic conditions.

Introduction

This manuscript reports on three patients with eosinophilic esophagitis presenting with chronic symptoms of solid food dysphagia. Eosinophilic esophagitis is an uncommon disorder, characterized by chronic dysphagia without associated symptoms of gastroesophageal reflux. It is often accompanied by concomitant allergies, atopy and/or asthma (1-3). To make the diagnosis of eosinophilic esophagitis requires a keen index of suspicion, especially among persons with atopy and dysphagia. Endoscopic findings include multiple mucosal rings in a narrow, non-compliant esophagus with or without vertical groves or lines (2-6). Contrast esophagram is remarkable for "slender" esophagus, or focal segmental stricture (7). Eosinophilia seen in biopsy specimens from the esophagus are required for the diagnosis. Although the number of eosinophils per high power field necessary for the diagnosis varies somewhat from author to author, greater than 24 eosinophils per high power field is generally considered diagnostic for the condition. (1-3). Treatment includes esophageal dilation, systemic and topical corticosteroids, and medical management of coexisting atopic conditions (1,2,5,6).

Methods for Image Capture/Processing

Olympus Evis image management system used for endoscopic images; Sony CD Mavica 3.3 megapixel for radiographic images; and Olympus AO51 (BX51) microscope with U-PMTV collimator and UCMAD3 camera for histologic images.

Case/Body

CASE 1

A 21-year-old active duty soldier was referred to Fitzsimons Army Medical Center, Aurora, Colorado for evaluation of "GERD" and chronic dysphagia. The patient was of good health and upon specific questioning denied symptoms of heartburn. He related a vivid history of solid dysphagia that began at 12 years of age. His first episode of severe dysphagia "food impaction" occurred during a Thanksgiving dinner with turkey. The food impaction was relieved with self-induced vomiting. From that date on, the patient became aware that solids that were poorly chewed or too rapidly swallowed would lead to dysphagia and occasional food impactions. The only occasions that the patient related symptoms of retrostenal discomfort that were consistent with heartburn, occurred after self self-induced vomiting used to relieve food impactions. Interestingly, the patient denied any symptoms of heartburn. Also, the patient had adapted his diet to avoid certain solids and had become a "slow" eater, which diminished symptomatic episodes. The patient presented to his unit medical officer because of the increased frequency of symptoms of hurried meals often required by his rapid deployment unit.

The patient's medical history was remarkable for tonsillectomy and inguinal hernia repair at 5 yrs and 8 yrs, respectively. The patient has known allergies to cats and dogs and was bothered by seasonal rhinitis, treated with antihistamines.

Physical examination revealed a very healthy 24-year-old male standing 74 inches and weighing 170 lbs. Laboratory examination showed a normal complete blood count with peripheral smear and a normal chemistry panel.

Figure 1A	Figure 1B

Barium esophagram revealed a subtle mid-esophageal segment of "coiled stenosis" appearance best seen after passage of the barium column (Figures 1A and 1B). Upper endoscopy confirmed the "coiled spring" appearance of the esophagus ~30 cm from the incisor teeth (Figures 2A and 2B).

Figure 2A	Figure 2B

The luminal stenosis precluded passage of the Olympus GIF-100 series endoscope beyond the stenosis. The "coiled spring" stricture was dilated with through-the-scope (TTS) balloon dilators sizes 8 mm and 10 mm. After the procedure, the patient did complain of moderate chest discomfort and odynophagia that resolved quickly after administration of an intravenous narcotic. The patient was treated with Prilosec 20 mg bid and returned for repeat endoscopy and biopsy at one week and two week intervals. Esophageal biopsies of the "coiled spring" stenosis were remarkable for increased numbers of eosinophils (Figures 3A and 3B). Two Maloney dilators were passed with the second and third endoscopies (sizes 34, 36 French and then sizes 36, 38 French, respectively). With each dilation the patient complained of moderate post procedure chest pain requiring narcotics. The patient was followed at 1 and 6 months and related improved swallowing and his desire to avoid further esophageal dilatation due to the post procedure chest pain experienced with each procedure.

Figure 3A	Figure 3B

CASE 2

An 18-year-old male soldier was seen for evaluation of dysphagia at Eisenhower Army Medical Center, Augusta, Georgia. This patient related symptoms of solid dysphagia since 10 years of age. He had never experienced symptoms of heartburn and episodes of dysphagia were exclusively associated with the ingestion of "poorly" chewed solids. The patient had no significant medical or surgical history. He was allergic to seafood, which caused violent vomiting. Laboratory tests revealed a normal, complete blood count. Esophogram showed the esophagus to be "narrow." Upper endoscopy was performed and remarkable for a narrow non-compliant esophagus with a "coiled spring" and the box appearance for the length of the esophagus, (Figure 4). During endoscopy, the endoscope was snug to the wall of the esophagus, but allowed passage of the instrument into the stomach and duodenum with only mild resistance. Upon withdrawal of the endoscope, a linear mucosal tear is evident along the entire length of the esophagus (Figure 5). After the procedure, the patient voiced no complaints of odynophagia or pain. He returned at two weeks for endoscopy with biopsy and Maloney bougie dilation, sizes 34 and 36 French. Histologic findings of the esophagus were remarkable for increased numbers of eosinophils > 24 per HPF. At four weeks, the patient returned for additional esophageal dilation with 36 and 38 French Maloney bougies; on this occasion, the patient complained of transient post procedure chest discomfort. Symptoms resolved promptly without need for medication. The patient was followed for one year and experienced sustained improved swallowing.

Figure 4	Figure 5

CASE 3

A 20-year-old soldier was referred to Evans Army Hospital, Colorado Springs, Colorado for evaluation solid food dysphagia. He denied any symptoms of heartburn and related the onset of symptoms to occur at about 13 years of age. With slow and careful chewing of his food, the patient rarely experienced dysphagia. During his enlistment in the Army, his meals were frequently hurried requiring avoidance of solids and the need for more liquids with meals. The patient did have a diagnosis of exercise induced bronchospasm and allergies to pollens and mold. He had been treated with an inhaled bronchodilator before physical fitness testing for the last 12 months. Antihistamines were used during the summer and fall months. A barium esophagram performed by his referring primary care giver was reported to be remarkable for "narrow" esophagus. Upper endoscopy revealed diffuse esophageal rings with a parallel band of vertical lines running the entire length of the esophagus, (Figure 6). Biopsies of the esophagus showed increased numbers of eosinophils. The patient underwent two esophageal dilation sessions spaced one month apart with Maloney bougie dilators (34 and 36 French and 36 and 38 French, respectively). Mild chest pain and odynophagia was experienced after the second dilation session. This patient was followed for one year with marked improvement in swallowing.

Figure 6

Summary

This case series reports on three adult males presenting with solid food dyphagia found to have eosinophilic esophagitis. The clinical features of these patients is summarized in Table 1. The mean age at onset of symptoms and age at initial medial presentation were 12 yrs and 20 yrs, respectively. Each related adaptation of his diet to slow and careful mastication of food and avoidance of hasty meals or distractions while eating. Variable degrees of allergic symptoms were evident among all of the patients in this report, to include allergies to pets, pollen, and seafood and exercised induced bronchospasm. Complete blood counts were normal among all patients. None of the patients described symptoms of gastroesophageal reflux and manometry, and ambulatory esophageal pH testing performed on two of the patients was normal. Esophagram was noted to be remarkable for either segmental of diffuse esophageal narrowing in each of the patients. The endoscopic appearance of the esophagus included segmental to continuous esophageal stenosis. The "coiled spring" appearance and "crepe paper" like mucosal non-compliance is unique, and associated with a unique predisposition to tear along the length of the coiled spring. Although esophageal dilation was associated with immediate post procedure pain and discomfort in all of the patients, no serious complication from the cautious dilations occurred, and relief from dysphagia was observed to be durable up to one year of follow follow-up.

Discussion

Dobbins, et al. described the first case of eosinophilic esophagitis more than 20 years ago (4). Since then, ever increasing numbers of case reports, cases series, and even a long term follow-up of 30 adult patients with primary eosinophilic esophagitis have been published (1,2,8,10,11). The disorder is more commonly reported among males, often with a prolonged duration of symptoms before clinical recognition. Symptoms of dysphagia occur exclusively with solids and coincident atopic conditions are common (1-3).

Eosinophilic esophagitis is characterized by an inflammatory reaction confined to the esophagus. The expression of eosinophils, T cells, and mast cells in the mucosal of eosinophilic esophagitis is characteristic of the disorder and strikingly similar to that seen with in the lung of asthmatics (12). Straumann, et al. have shown that the TH2 cytokine and IL-5 allergic response to inhaled allergens is consistently seen in these patients. This suggests a link between allergic asthma and eosinophilic esophagitis (3,12).

Several large series of children with eosinophilic esophagitis have been reported (6,11,13). Carefully conducted skin testing for food allergies among these children have identified food allergies in 19/26 (73%) by pin prick and 21/26 (81%) by patch testing. With meticulous dietary elimination, these investigators showed marked and durable improvement in dysphagia symptoms in 18 of the 24 children with positive pinprick or patch testing. Repeat esophageal biopsy after elimination of food allergies showed normalization of esophageal mucosa in 12 of 24 and decrease in mucosal eosinophil count from 55 eosinophils per HPF to 8.4 per HPF (11). This further supports the theory that extrinsic allergens may be responsible for some cases of eosinophilic esophagitis.

Long standing eosinophilic esophagitis appears to be associated with a wide gamut of radiographic and endoscopic findings. Barium esophagrams have shown short and high grade stenosis to very subtle narrowing often extending the entire length of the esophagus (7,10). Importantly, the finding of a long "small caliber" esophagus reported by Vasilopous, et al. appears to predict the probable occurrence of long painful mucosal tears with esophageal dilation using large diameter dialators (10). Many endoscopists, now recommend cautions dilation of patients with eosinophilic esopahgitis with smaller dilators than usually used with peptic or acid reflux related esophageal strictures (1). However, as seen in the patients described in this report, transient post esophageal dilation chest pain and odynphagia are common even with gentle and conservative esophageal dilation.

The resemblance of the inflammatory reaction of eosinophilic esopahgitis to allergic asthma has lead many to attempt treatment with systemic or topical corticosteroid and leukotriene antagonists. Langdon and others have reported a decrease in the number of mucosal eosinophils with such therapy, but dysphagia symptoms do not improve without dilation to relived esophageal non-compliance (8,9).

In summary, the diagnosis of eosinophilic esophagitis should be considered among persons with coincident atopic conditions and symptoms of solid dysphagia. Similarly, the absence of reflux symptoms in the person with solid dysphagia should spark the idea of possible eosinophilic esophagitis and careful inquiry about atopic conditions should follow. Esophagram findings of subtle diffuse esophageal narrowing or a non-neoplastic or reflux related esophageal stenosis should suggest the diagnosis. These signs as well as the described endoscopic findings of coiled spring ("feline") esophagus, segmental stricture, and vertical lined esophagus should prompt esophageal biopsy of the mid and proximal esophagus. The pathologist should be alerted to the possible diagnosis of eosinophilic esophagitis, so that the number of eosinophils per high power field is carefully counted, as acid reflux esophagitis has been associated with increased numbers of eosinophils, but usually < 5 per HPF. The role for elimination diets, budesonide, mucosal injection with corticosteroids, and montelukast await further study to define their role in the management of this disorder. Lastly, cautious esophageal dilation with smaller dilator diameters appear to be essential for the successful relief of mucosal "stiffness" causing dysphagia and topical or oral corticosteroids appear to be important in prevention of recurrent eosinophilic inflammation and relapse.

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Editor:
John C. Deutsch, M.D.
Duluth, MN

Editorial Board:
Manoop S. Bhutani, M.D.
Galveston, TX
William R. Brugge, M.D.
Boston, MA
Peter R. McNally, D.O.
Denver, CO
Iqbal S. Sandhu, M.D.
Salt Lake City, UT
Thomas J. Savides, M.D.
San Diego, CA