Pediatric patients with eosinophilic esophagitis: An 8-year follow-up

Article Outline

• Abstract
• Methods
  • Patients
  • Demographics and symptoms
  • Pathology
  • Evaluation for atopy
    • Skin prick tests
    • Patch tests
  • Therapeutic interventions
  • Data analysis
• Results
  • Patients
  • Demographics
  • Symptoms
  • Number of endoscopies
  • Distribution of tissue eosinophilia and other abnormal findings on biopsies
  • Other associated conditions
  • Atopy
  • Duration
  • Interventions
• Discussion
• Acknowledgment
• References
• Copyright

Background

Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients.

Objective

We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history.

Methods

We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years.

Results

In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean ± SD, 6.2 ± 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean ± SD, 0.91 ± 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed.

Conclusion

Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus.

Clinical implications

Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.

Key words: Eosinophilic esophagitis, food allergy, atopy patch test, eosinophil, pediatric, eosinophilic gastroenteritis, environmental allergy, atopy, skin test

Abbreviations used: EE, Eosinophilic esophagitis, Hpf, High-power field, SPT, Skin prick test

Eosinophil-associated gastrointestinal disorders in children were first described in 1937.¹ In initial case series of eosinophilic gastroenteritis, the brunt of the disease occurred in the stomach, duodenum, and colon.², ³, ⁴, ⁵, ⁶, ⁷ Gradually, eosinophilic esophagitis (EE) emerged as a clinical entity after several reports separated EE from gastroesophageal reflux on the basis of the number of eosinophils per high-power field (hpf) on histopathology.⁸, ⁹, ¹⁰, ¹¹ Because the normal esophagus is devoid of eosinophils, the presence of a high number of eosinophils in histopathology of the esophagus has become accepted as the histopathologic criterion for the diagnosis of EE.¹², ¹³ However, the histopathology of the remaining segments of the gastrointestinal tract has not been described in patients with EE, other than in the first case series of EE, which described the presence of eosinophils in the antrum and the duodenum.¹⁰, ¹⁴, ¹⁵ The effect of treatment of EE has been assessed on a short-term outcome only, with few data regarding the long-term prognosis of the disorder and its natural history in children.², ⁵, ⁶, ⁸, ⁹, ¹¹, ¹⁴, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹

We conducted a retrospective review of our database of pediatric patients with EE, confirmed by histopathology of esophageal biopsies, and who have had follow-up. We aimed to describe the clinical syndrome, its natural history, and response to therapy; delineate the extent of histopathology in all segments of the gastrointestinal tract; and delineate the rate of relapse of tissue eosinophilia after the esophageal histology had become normal.

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Methods 

Patients 

Pediatric patients evaluated in our center with gastrointestinal symptoms who had esophagogastroduodenoscopy with the diagnosis of EE were included. After obtaining informed consent, patients' data were entered in a database approved by the Institutional Review Board of Cincinnati Children's Hospital Medical Center.

Demographics and symptoms 

Data were extracted from the medical history obtained at the patient's first visit to our center. The age of onset and the age at diagnosis were defined as the age at which the presenting symptom was first noted as recollected by the parents or patients, and the age at the first endoscopy with histopathological diagnosis of EE, respectively.

Pathology 

The diagnosis of EE was made on biopsy specimens that fulfilled the following 3 criteria: infiltration of the mucosa with eosinophils with a peak number of eosinophils per hpf of 24 or more, elongation of the vascular papillae, and thickening of the basal layer. Patients whose biopsy report did not specify the number of eosinophils per hpf were included if the pathologist's final diagnosis was EE. Abnormalities in other segments of the gastrointestinal tract were grouped as mucosal eosinophilia or noneosinophilic inflammation. Resolution was recorded when the pathologist's interpretation of the esophageal biopsy was no diagnostic abnormality. A relapse was recorded when, after a histopathology of no diagnostic abnormalities, a subsequent esophageal biopsy was interpreted as EE according to these criteria.

Evaluation for atopy 

Skin prick tests (SPTs) performed only at our center were included for consistency of the allergen extract and the interpretation. Patients had SPTs to as many as 62 food and 11 indoor and outdoor environmental allergen extracts. The foods tested were individually selected for each patient on the basis of the clinical history and the food intake. The food allergens including cow's milk, hen's eggs, peanut, soy, wheat, fruits, vegetables, legumes, tree nuts, meats, grains, fish, and crustaceans were tested with commercial extracts (Hollister Steer Laboratories, Spokane, Wash, and Greer Laboratories, Lenoir, NC) at concentrations of 1:10, 1:20, or 1:40. Histamine 1 mg/mL and albumin saline were positive and negative controls, respectively. Tests were read after 15 minutes and interpreted as follows: 0 = negative control; 1+ = very small induration, erythema present; 2+ = 50% of histamine control; 3+ = histamine control; 4+ ≥ histamine control or pseudopodia, with tests graded as 2+ or higher positive, or by measuring the largest wheal diameter, with 3 mm or more than the negative control positive.

In each patient, all available foods were tested by patch test, except for the foods to which the patient had a history of allergic reaction or a positive SPT. Patients discontinued systemic steroids or topical treatment for atopic dermatitis on the test area 2 weeks before testing. Atopy patch tests were placed using commercially available dried powder, flour, or single-ingredient baby food as follows: peanut, tomato, milk, and whole egg dried powder (Walton Feeds, Montpelier, Idaho); egg white powder (Just Whites; Del-El Foods, Elizabeth, NJ); corn, oat, barley, rye, wheat, rice, and soy flour (Bob's Red Mill, Milwaukie, Ore); pears, peach, apple, banana, turkey, green bean, sweet potato, peas, squash, carrot, chicken, and beef (Beech Nut, Canajoharie, NY); and lamb, ham, and veal (Gerber, Parsipanny, NJ). Powders and flours were mixed ½ teaspoon with 3 mL saline to make a paste. A paper disc with saline was the negative control. After loading with the food, 3 patches containing ten 8-mm Finn chambers (T.R.U.E. Test; Allerderm, Phoenix, Ariz) were applied to the skin of the upper back. The patches were removed at 48 hours and scored at 72 hours as follows: 0, no visible findings; 1, erythema but no induration; 2, erythematous, generalized induration and/or a few scattered papules; 3, erythematous, marked induration/papules; 4, erythematous papules and vesicular eruption. A score of 2 or above was considered positive.

Therapeutic interventions 

At each visit, the database recorded the therapeutic interventions prescribed by the treating physicians. Interventions were used for the duration between 2 visits, and the frequency of their use was defined as the number of intervals between visits logged in the database at which the patient was using the therapy. Elimination diet was recorded if specific food items were eliminated from the diet because they had caused an immediate allergic reaction in the past, or were associated with a positive SPT or a RAST level of 2 or more, or a positive atopy patch test. Elemental diet was recorded if the patient's diet consisted only of an amino acid formula. The doses of prescribed medications varied from subject to subject. Topical steroid was recorded when the patient received a steroid inhalation aerosol from a metered dose inhaler, fluticasone propionate (Flovent; Schering Plough, Kenilworth, NJ), puffed in the mouth without a spacer and swallowed. Antacids and proton pump inhibitors were recorded when the class of medication was given in regularly scheduled doses by mouth. Other medications included oral steroids, leukotriene antagonists, and mast cell stabilizers. To examine the effect of treatment on the outcome at the end of follow-up, the patients were placed into 3 age groups and 3 outcome groups: EE resolved, resolved but relapsed, and persistent.

Data analysis 

Data were entered into an Access database (Microsoft Corporation, Redmond, Wash). Analyses were conducted using Statistical Analysis System for Windows, version 9.1 (SAS Institute Inc, Cary, NC). Descriptive statistics (frequency, mean, median, SD, range) were used to describe the population. χ² Analysis was used to test differences for nominal variables and t tests for interval variables with 2 groups. In the analysis of the effect of therapies, a Proc Mixed (ANOVA) was used (SAS Institute Inc), controlling for the amount of time in follow-up.

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Results 

Patients 

Eighty-nine patients who had at least 1 esophagogastroduodenoscopy with 1 histopathologic diagnosis of EE were included in the study. All patients were evaluated in our center between March 31, 1997, and November 30, 2004. The initial histopathologic diagnosis was made in our center for 57 patients. Thirty-two patients whose initial histopathology was interpreted at other institutions and was not available for interpretation at our center were included in our analysis because at least 1 subsequent endoscopy and biopsy at our center was consistent with the diagnosis of EE. However, they were excluded from the analysis of the duration of follow-up because we could not confirm the initial histopathologic diagnosis and date.

Demographics 

In 89 patients with EE, male sex (78.6%) and white race (94.4%) were common (Table I). There is a peak in diagnosis in children at 1 year of age, then a gradual decline starting from the age of 3 to 17 years, with 2 smaller peaks at 7 and 11 years (Fig 1).

Table I. Sex, race, and age distribution of 89 patients with EE

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• Fig 1. 

  Age distribution, at the time of diagnosis of EE, of 89 patients.

Symptoms 

The constellation of signs and symptoms and the rank order of their occurrence remained unchanged, from the onset of symptoms to the time of the first diagnostic endoscopy (Table II). The most common signs and symptom reported in all children with EE was emesis. In children <5 years of age, emesis, abdominal pain, difficulty swallowing, heartburn, weight loss, poor appetite, and food aversion were reported more frequently than in the older children. Food impaction and nausea were common among the older age group. Lower gastrointestinal symptoms were occasionally the presenting symptoms, such as diarrhea and blood in the stools. There is a nearly 3-year lag between the onset of symptoms and the performance of the first endoscopy (Table I).

Table II. Presenting symptoms of EE in 89 patients

		Age in years at onset∗			Age in years at first endoscopy†
Initial symptom	N	Mean ± SD	Median	Range	Mean ± SD	Median	Range
Upper gastrointestinal
Emesis	53	3.2 ± 3.9	1	0.08-15	6.08 ± 4.5	4.5	0.4-19
Abdominal pain	22	4.9 ± 4.4	5	0.08-16	7.5 ± 4.6	8	0.4-17
Heartburn	19	4.8 ± 5.2	2	0.08-16	7.5 ± 4.9	8	0.4-17
Dysphagia	14	4.3 ± 5.3	1.5	0.08-16	8.6 ± 5.5	9.5	1-17
Nausea	8	7.4 ± 5.1	7.4	1-16	10 ± 5.4	10.25	1-17
Food impaction	6	8.8 ± 6.5	9	2-16	13.5 ± 4.5	14	8-19
Lower gastrointestinal
Diarrhea	14	2.2 ± 2.5	1	0.08-8	5.2 ± 4.2	3.7	0.4-15
Blood in stools	3	1.7 ± 1.3	1	1-3	6.4 ± 5.6	3.4	3-13
Feeding and weight
Weight loss	7	2.46 ± 3.1	1	0.08-8	4.2 ± 3.6	2	0.4-9
Weight gain	7	3.2 ± 4.5	1	0.5-13	5.5 ± 5.5	3	0.6-13.8
Poor appetite	8	4.1 ± 2.7	4.5	0.6-8	6.2 ± 4.1	6.6	0.8-14
Food aversion	3	1.0 ± 0.04	1.0	1-1.08	3.3 ± 2.5	3	1-6
Behavior
Irritability	2	0.12 ± 0.05	0.12	0.08-0.16	1.25 ± 1.06	1.25	0.5-2
Respiratory
Cough	10	3.3 ± 3.22	2.25	0.08-9	4.9 ± 3.1	4.0	0.4-10
Airway symptoms	12	2.43 ± 3.8	0.9	0.08-13	4.1 ± 4.0	2.6	1-13.8
Chest pain	6	7.13 ± 1.33	7	5-9	10.7 ± 3.3	10.5	7.25-15

Number of endoscopies 

The 89 patients had 1 or more upper endoscopies performed (mean, 5.29 ± 3.36; median, 5; range, 1-16) with a total of 471 endoscopies obtained and/or interpreted in our center over the period of follow-up. Only 32 of these patients had biopsies of the ileum, and 38 patients had colonoscopies with biopsies of the colonic mucosa. The 57 patients whose initial diagnostic endoscopy was obtained at our center had a total of 300 endoscopies (mean, 5.26 ± 3.03; median, 4; range, 2-13). The treating physicians, on the basis of clinical findings, made the decision to repeat the endoscopies and hence determined the interval between endoscopies.

Distribution of tissue eosinophilia and other abnormal findings on biopsies 

All 89 patients had at least 1 biopsy consistent with EE of the distal esophagus. Throughout the period of follow-up, 85 patients were additionally diagnosed with EE of the proximal esophagus. Histopathology of the stomach and duodenum was described in 42 and 50 patients, respectively. Of the 38 patients who had a colonoscopy, histopathology of the colon was described in 24 (Fig 2). Sixty-nine patients (77%) had histopathology of a gastrointestinal segment other than the esophagus during the period of follow-up.

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• Fig 2. 

  Most commonly encountered combinations of histopathology in segments of the gastrointestinal tract in pediatric subjects with eosinophilic esophagitis. Although all subjects had eosinophilia of the esophagus (black and red bars), a minority had pathology confined just to the esophagus (first group from the bottom). In the rest of the subjects, the distribution of eosinophilic and noneosinophilic inflammation of other gastrointestinal segments varied. The group second from the bottom of the graph had additional pathology in the stomach and duodenum (green and yellow bars). In the next group, the pathology skipped the stomach but involved the duodenum. The fourth group had pathology in all segments of the gastrointestinal. The top 2 groups had, in addition to the esophagus, pathology of the stomach only or the colon only (blue bar).

Of the 471 endoscopies (Table III), the proximal and distal segments of the esophagus had eosinophilic inflammation of the mucosa and, in addition, noneosinophilic inflammation of the esophagus was reported and described as mild, focal, or chronic esophagitis in the proximal esophagus and mild or moderate esophagitis, focal esophagitis, or reflux esophagitis in the distal esophagus. The gastric biopsies had histopathology, which included eosinophilic inflammation described as mild or borderline mucosal eosinophilia, focal or diffuse mucosal eosinophilia, and mild or marked lamina propria eosinophilia. Noneosinophilic inflammation was described as acute and/or chronic gastritis, mild gastritis, and lymphocytic infiltration. Helicobacter pylori was detected in 7 biopsies, 2 biopsies were consistent with chemical gastritis, and 1 biopsy demonstrated polyps. Of the duodenal biopsies with histopathology, other than mucosal eosinophilia, mild, chronic, or focal duodenitis were described, with 2 biopsies showing villous blunting. The ileal biopsies had eosinophilic mucosal inflammation as well as ileitis without eosinophils. The colonic biopsies had eosinophilic mucosal inflammation and noneosinophilic colitis.

Table III. Gastrointestinal histopathologic abnormalities in biopsies of gastrointestinal segments in patients with EE

Other associated conditions 

The associated conditions as extracted from the past medical history of the 89 patients or reported by the parents were atopy: asthma, allergic rhinitis, eczema, anaphylaxis to food, and allergic conjunctivitis in 39%, 30%, 19%, 9%, and 8%, respectively; immunologic: recurrent infections and autoimmune disorders in 13% and 2%, respectively; and developmental and neurologic: developmental delay, seizures, cerebral palsy, autism in 12%, 6%, 4%, and 1%; and chromosomal abnormalities in 1%.

Atopy 

Positive SPTs to food allergens were as common as to environmental allergens and were prevalent in the younger age group (Table IV). The foods giving positive skin tests were egg and peanut (39% each), soy (34%), beans, cow milk, and pea (29% each), mustard (26%), beef and carrot (25% each), and almonds (21%).

Table IV. Environmental and food sensitization in patients with EE

SPTs		Age (y)			Sex (%)
Allergens		<5	>5-10	>10	Male	Female	Total patients (%)
Food
Patients tested (N)		30	17	14	47	14	61
Positive		25	11	10	35 (75%)	11 (78%)	46 (75%)
Environmental
Patients tested (N)		20	12	11	33	10	43
Positive		13	10	11	25 (75%)	9 (90%)	34 (79%)
Food and environmental
Patients tested (N)		17	11	11	30	9	39
Both positive		11	7	8	19	7	26 (67%)
Food negative, environmental positive		2	2	3	5	2	7 (18%)
Food positive, environmental negative		2	2	0	4	0	4 (10%)
Both negative		2	0	0	2	0	2 (5%)

Patch tests were placed on a subset of 38 patients. Fourteen (37%) had a positive patch test. Of these patients, 5 (36%), 5 (36%), 2 (14%), 1 (7%), and 1 (7%) had 1, 2, 3, 5, and 10 positive foods, respectively. In the 38 patients, the SPT identified 24 (63%) to be atopic (of whom 15 [39.5%] were negative to the patch test), whereas the atopy patch test identified only an additional 5 (13%) patients who were SPT-negative but atopy patch test–positive. Nine (23.7%) patients were negative to both SPTs and patch tests. The foods associated with positive patch tests were beef in 5 (36%) patients; lamb, oat, rye, soy, and wheat in 4 (28% each); corn, egg, ham, pear, and veal in 2 (14% each); and chicken, peach, tomato, turkey, and potato in 1 (7% each).

Duration 

Eighty patients had more than 1 endoscopy with biopsies for follow-up of persistent symptoms and treatment effects. Nine patients had only 1 endoscopy because of recent onset of diagnosis (n = 8) or being lost to follow-up (n = 1). Of the 80 patients who had 2 or more endoscopies, 57 had the initial diagnostic endoscopy performed in our center and were followed for as long as 7.6 years (Fig 3). The analysis of the duration of the disorder and the response to therapeutic intervention is limited to this group of patients. The remaining 23 patients were excluded from the analysis of the duration of follow-up because we could not confirm the initial histopathology diagnosis and date. During the course of follow-up of 57 patients, 8 patients had resolved EE, 30 patients had resolved EE that relapsed, and 19 patients had EE that persisted. For the 38 patients who had a biopsy of both proximal and distal esophagus that normalized, the time from the first diagnostic biopsy to the time of first normal biopsy was 0.91 years (±0.84); median, 0.62; range, 0.175 to 3.56. At the time of normalization, 10 patients still had abnormalities reported in other segments of the gastrointestinal tract, namely, in the stomach, duodenum, ileum, both stomach and duodenum, and both duodenum and colon in 4, 3, 1, 1, and 1 patient, respectively. To obtain a better estimate of the duration of the abnormality of the esophageal pathology, we calculated the time from the first biopsy with an EE diagnosis to the last biopsy with an EE diagnosis that preceded the biopsy with resolved EE. In 21 patients who fulfilled this criterion, the time from the initial diagnosis to the last abnormal before the normal biopsy was a mean of 0.9 years (±.87); median, 0.51; and range, 0.06 to 2.96.

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• Fig 3. 

  Diagram of patients enrolled in the study, number of upper endoscopies, duration of follow-up, and outcome at the end of the follow-up period.

Because the course was marked by normalization and relapse of EE for 30 patients, without an association with any distinct patient characteristics, we questioned whether the duration of follow-up for patients who had a subsequent normal endoscopy was long enough to allow a possible relapse to be detected. We found that the duration of follow-up for the 8 patients with a normal biopsy at the end of follow-up was shorter than the duration of follow-up for the 19 patients whose biopsies of the esophagus remained consistent with EE and the 30 patients who had relapsed.

Interventions 

Patients had multiple therapeutic interventions that temporally overlapped. The duration of use of each intervention, as calculated from the duration of time between visits, was 0.56 years (±0.49; median, 0.38; range, 0.12-3.19). Analysis of the frequency of therapeutic interventions by age groups showed no significant difference (Table V). Analysis of the frequency of therapeutic interventions by the 3 outcome groups showed that the elimination diet was more frequently used in the resolved but relapsed patients and in the patients with persistent EE than in the resolved group (P < .001). Other interventions, including elemental diet, oral steroids, topical steroids, antacids, and proton pump inhibitors, did not result in a significant difference in the overall outcome (Table VI).

Table V. Therapeutic interventions by age in 89 patients with EE

	<5 y	5-10 y	>10 y	Total
Therapy	N = 45	N = 20	N = 24	N = 89
Dietary
Elimination	17	10	6	33
Elemental	23	3	6	32
Glucocorticoids
Swallowed aerosols	16	17	4	37
Oral	11	6	12	29
Acid suppression
H2 blockers	9	4	4	17
Proton pump inhibitors	33	17	21	71
Other medications	22	14	13	49

Table VI. Therapeutic interventions distributed by outcome at the end of the follow-up period in 57 patients with EE

	Outcome
	EE resolved		EE resolved then relapsed		EE persisted
	N = 8		N = 30		N = 19
Therapy	No. of patients∗	Frequency of use†	No. of patients	Frequency of use	No. of patients	Frequency of use	P value‡
Dietary
Elimination	2	0.65	12	1.4	15	4	.001
Elemental	2	1.30	10	3.4	4	1	.4
Glucocorticoids
Swallowed aerosols	4	0.8	21	2.9	14	3.1	.2
Oral	1	1.25	8	1.4	4	0.57	.6
Acid suppression
H2 blockers	1	0.12	8	1.0	6	0.68	.7
Proton pump inhibitors	6	1.75	20	4.2	13	4.47	.3
Other medications	3	1.25	22	3.2	11	4.1	.2

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Discussion 

Herein we report several new findings concerning pediatric EE. The first is the prolonged lag of time, as long as 3 years, between onset of symptoms and the first diagnostic endoscopy. The symptoms had remained the same at the time of onset and at the time of the first endoscopy, which suggests that the persistence of symptoms, rather than their severity, was the reason for the endoscopic evaluation. Another intriguing finding is the age distribution of the affected children. The highest incidence in infants 1 year and younger, taken together with the long lag time in diagnosis, leads to speculation that infants with EE are either born with the disorder or acquire it soon after their birth. The high prevalence of food sensitization, as detected by SPTs, suggests that infants have an atopic phenotype with end-organ expression in the esophagus and the remainder of the gastrointestinal tract. This may be accompanied by other end-organ expression of the atopic phenotype as reflected by the high prevalence of eczema and asthma. Another finding in this report is that the initial duration of EE pathology until first resolution is a mean of 0.9 years (±.87); median, 0.51; range, 0.06 to 2.96. This points to the need in future studies to assess the result of any intervention, not only the short-term, but also the long-term outcome that may extend over a period of several years. This is underscored by the finding that the longer the period of follow-up, the more likely a relapse is detected; there was a relapse rate of 53% in patients who were followed for a mean of 3 ± 1.4 years. Another finding in this report is that eosinophilic infiltration of other gastrointestinal segments is frequently associated with EE. At present, the significance of this finding has to be interpreted with caution because there is not uniform agreement about normal levels of eosinophils in various gastrointestinal segments, and in the previously published literature, there is a paucity of reports that include a detailed description of both the esophagus and the rest of the gastrointestinal tract. Nevertheless, this provocative finding suggests that EE can evolve into a more general gastrointestinal disorder than previously appreciated and may account for persistence of symptoms in many patients. Given the chronic nature of the disorder, each patient underwent several therapeutic interventions, quite often concomitantly. Although this precludes a meaningful analysis of the effect of each intervention on the outcome, the outcome of 1 intervention, elimination diet, was significantly associated with persistence or relapse of EE, whereas no other patient characteristics analyzed accounted for the difference in outcome. Finally, the racial distribution of this atopy-associated disorder is different from the known disproportionately increased prevalence of atopy in African Americans.

Straumann et al²² has examined the natural history of this disorder in 30 adult patients who were followed for a mean of 7.2 years. Similar to our findings, they described a chronic disorder with persistence of the pathologic findings as well as the clinical symptoms. Liacouras et al¹⁴ followed the outcome of various therapeutic and dietary interventions in 381 pediatric patients for only 6 months for pharmacologic therapies and 9 months for dietary therapies. Nevertheless, their outcomes are consistent with ours in that, with all pharmacologic therapies, and with elimination diets, relapse was common.

In summary, in a retrospective review of data from 89 patients diagnosed with EE and followed over a period of 8 years, we determined that EE in the pediatric population is a chronic and relapsing condition, highly associated with atopy, in which histopathologic abnormalities extend to other segments of the gastrointestinal tract, and for which a long-term curative therapy has not yet been established.

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We thank Michelle Lierl, MD, and Kimberly Risma, MD, PhD, for critical review of the manuscript and Andrea Lippelman for editorial revision. We are grateful to the Campaign Urging Cure for Eosinophilic Disorders (CURED), the Food Allergy Project, and the Buckeye Foundation.

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