Eosinophilic Esophagitis in Children
From The Child's Doctor, Fall 2005
- Amir F. Kagalwalla, MD
- Attending physician, Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago; Associate professor of Pediatrics, Northwestern University Feinberg School of Medicine
- Disclosure: Dr. Kagalwalla has no industry relationships to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.
Other Disclosure Information
At the conclusion of this activity, participants will be
- Recognize the differences between eosinophilic
esophagitis (EE) and gastroesophageal reflux disease
- Identify cases that warrant an evaluation for EE
- Describe the diagnostic features of EE and different treatment
Eosinophilic esophagitis (EE) is a newly recognized clinicopathological disorder. It is the fastest rising diagnosis in pediatric gastroenterology practice at Children’s Memorial Hospital. This disorder is frequently misdiagnosed and treated as severe gastroesophageal reflux disease (GERD). Clinicians should suspect EE when GERD symptoms fail to respond to aggressive acid suppression treatment. Symptoms dramatically improve, however, with elimination diet or with corticosteroid treatment. Prompt referral by primary care physician is essential to establishing the correct diagnosis and instituting appropriate treatment expediently to relieve symptoms and prevent complications.
EE is a chronic inflammatory disorder that is
characterized by dense infiltration of the esophageal epithelium. This condition
is categorized as a food hypersensitivity disorder. Generally, food
hypersensitivity disorders are subdivided into:
• Type 1 immediate or immunoglobulin E (IgE)-mediated
disorders diagnosed with radioallergosorbent (RAST) test or skin prick
• Type 4 delayed or cell-mediated disorders identified
with skin patch test
EE may be classified either as IgE-mediated or
cell-mediated condition, or both, depending on the operative
The dramatic rise in the number of children diagnosed
with this condition, all over the country, is partly explained by increased
awareness and partly by a true increase in prevalence. At Children’s Memorial
the number of children newly diagnosed with EE has progressively risen from only
1 case in 2000 to more than 50 in 2004.
Support for an allergic etiology of EE is provided
• Improvement of clinical symptoms and histology
with elimination of the offending food allergen(s) or with corticosteroid
• Associated atopic manifestations, such as reactive
airway disease, allergic rhinitis and eczema, which are present in 50% of
children with this disorder
• Family history of atopic disease obtained in up to 45%
of children with EE
• Environmental allergies suggested by animal
Genetic predisposition is supported by findings that 10%
of patients have an immediate family member affected with
This disorder is seen in all races, with a male to female
ratio of 4:1. Two peaks at 1 to 4 years of age and 10 to 14 years of age have
been identified. In addition to other atopic conditions, history of food
allergies and peripheral eosinophilia is often
In younger children, symptoms are similar to those seen
with GERD and include vomiting, dysphagia, abdominal pain, chest pain, and
failure to thrive. These symptoms do not completely resolve with acid
suppression treatment and these patients are referred to gastroenterologist for
refractory GERD or to a surgeon for fundoplication. We have also encountered
toddlers with EE presenting with significant food aversion as the primary
manifestation. In adolescents, intermittent episodes of distress causing food
impaction that leads to emergency room visits to have food dislodged is not an
Endoscopy images of the normal esophagus and a case with
GERD (Figures 1, 2) differ significantly from the several distinctive
appearances of the esophagus that suggest EE (Figures
• Multiple white plaques in the
• Furrowing: longitudinal linear creases or folds along
the long axis of the esophagus
• Granular esophagus with multiple tiny
• Trachealization or ringed esophagus, which is when the
esophagus has the appearance of the trachea
• Tubular esophagus with a long mid-esophageal
FIGURE 1: Normal esophagus
FIGURE 2: GERD
FIGURE 3: White plaques
FIGURE 4: Furrowing
FIGURE 5: Granular
FIGURE 6: Ringed
Ringed or tubular esophagus is commonly seen in adolescents and adults with
EE. By contrast in GERD, erythema, erosions or ulcerations are seen.
Endoscopy findings are not diagnostic of EE, however. The
gold standard for the diagnosis of EE is the dense infiltration of eosinophils,
with at least 20 eosinophils per high power field (hpf ) in the esophageal
biopsies. In GERD, eosinophilic inflammation is also present, but the eosinophil
count rarely exceeds 7 to 10 eosinophils per hpf. Other findings, such as basal
cell hyperplasia and increased papillary length are seen in both EE and GERD,
but eosinophilic abscesses (4 or more eosinophils in superficial clusters) are
typically seen only in EE and distinguish EE from GERD. The differences between
EE and GERD are summarized in Table 1.
Since it is now only 10 years since the description of
the first pediatric case series of EE, the natural history of this disorder in
children is unknown and remains to be defined. Since 4% to 6% of children with
EE present with stricture of the esophagus, it is felt to be a complication of
persistent esophageal inflammation. Although links between EE and dysplasia have
not been described, concerns about this possibility remain, since long term
follow-up data is currently unavailable.
A 24-hour pH probe study is helpful to exclude GERD,
particularly in the younger children with reflux-type symptoms. A number of
studies have utilized results of positive RAST, skin prick tests, and skin patch
tests to eliminate the specific incriminating food allergen(s) from the diet.
Elimination of food antigen based on the results of RAST and skin prick tests,
however, has failed to improve symptoms, suggesting that the food allergy is not
primarily IgE-mediated. A recent study of food elimination based on positive
response to a combination of skin prick and skin patch tests reported
significant clinical and histological improvement in all EE patients. The
mechanism responsible for causing allergen induced esophageal inflammation
appears to be cell-mediated hypersensitivity from this
Treatment of EE is challenging to the physician and
difficult for the patient and family. The goals of treatment include resolution
of symptoms and of the esophageal inflammation, and prevention of complications,
such as strictures.
The most commonly utilized dietary approach eliminates
all intact protein by administering an amino acid-based formula. This approach
is highly effective, although compliance difficulties related to poor taste are
overcome, in a majority of patients, with either nasogastric or gastrostomy tube
feeding. Furthermore, these elemental formulas are quite expensive, and the
prospect of eliminating all solid foods from the child’s diet is distressing to
At Children’s Memorial, we have developed a new dietary
approach that eliminates the 6 most common foods responsible for food allergies.
These include milk protein, soy, wheat, egg, peanut (and all tree nuts), and all
sea food. We have recently demonstrated that both symptom resolution and mucosal
healing with elimination diet are comparable to that with amino acid-based
elemental diet. The evident advantages include ability to eat solid foods, lack
of tube feeding, and lower cost. The limitation of this approach is that it
requires participation of an experienced dietitian to counsel families on proper
diet implementation and prevention of repeated contamination due to the
ubiquitous use of these food proteins in processed foods. Once the esophageal
inflammation resolves, foods are re-introduced singly every 6 weeks until the
offending food allergens are identified and excluded permanently. (Figures 7, 8
show the change in eosinophilic infiltration before and after the elimination
FIGURE 7: Pre-elimination diet biopsy
FIGURE 8: Post-elimination diet biopsy
Biopsy images courtesy of Hector Melin-Aldano, MD, Pathology
Corticosteroids, swallowed or systemic, are also effective, but both symptoms
and inflammation recur once treatment is discontinued. Since long term steroid
use is associated with potential side effects, including candidiasis and
suppressed linear growth, and because steroids are only palliative, at
Children’s Memorial we prefer the dietary approach, reserving corticosteroids
for cases that are resistant to elimination of food allergens.
Resources for families of children with EE
For EE information and support resources, families can be
referred to the American Partnership for Eosinophilic Disorders (www.apfed.org)
and the Food Allergy Network (www.foodallergy.org).
Also, the Food Allergen and Consumer Protection Act,
which goes into effect January 2006, will require manufacturers of all foods,
flavorings and spices to identify on the label 8 food antigens – milk protein,
egg, soy, peanut, tree nut, wheat, seafood, and shell fish. This law will make
it extremely easy for patients with EE to know whether these allergens are
present in products and avoid the restricted food
A high index of suspicion of EE is necessary to identify
children with refractory GERD symptoms resistant to acid suppression treatment,
male toddlers with food aversion, or adolescents presenting with food impaction.
These children should be referred to pediatric gastroenterologist for endoscopy
and esophageal biopsies. History of food allergies and atopic disease, such as
asthma, allergic rhinitis, and eczema, as well as unexplained peripheral
eosinophilia, are additional risk factors that should heighten suspicion of EE.
GERD is the main differential diagnostic consideration and should be excluded.
Treatment is challenging, and the dietary elimination/ reintroduction approach
FOR FURTHER READING
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