A 20-year-old man presented to his gastroenterologist with
progressive dysphagia. At endoscopy, a short distal esophageal stricture was noted, which was dilated.
In addition, the endoscopist noted an "atypical" esophagitis in the proximal esophagus, with an
endoscopic appearance concerning for candidal esophagitis. Biopsies were obtained from both proximal and
Biopsies of the proximal and distal esophageal
mucosa both show squamous hyperplasia with prominent parakeratosis. There is a florid eosinophilic
infiltrate that is particularly prominent in the superficial portion of the mucosa. Numerous eosinophils
are noted within desquamating parakeratotic debris, and several eosinophilic microabscesses are noted
within the squamous mucosa. A PAS stain is negative for Candida.
Case 1 - Figure 1 - Low power view of eosinophilic esophagitis. The squamous mucosa is hyperplastic and there is an adherent inflammatory "pseudomembrane".
Case 1 - Figure 2 - Eosinophilic esophagitis. The squamous mucosa is infiltrated by numerous eosinophils with a predilection for the superficial half of the mucosa. The "pseudomembrane" is composed of numerous eosinophils within parakeratotic debris.
The patient has a history of allergies requiring the
use of an inhaler, and was noted to have mild peripheral blood eosinophilia on a CBC.
Eosinophilic esophagitis (EE) was first described in a case report in 1978 by Landres et
al. .1 Attwood and colleagues subsequently presented the first detailed study of eosinophilic
esophagitis in 1993,2 describing intense eosinophilic infiltration in the esophageal mucosa of 12
patients presenting with severe dysphagia and absence of acid reflux. Although well recognized in
children, eosinophilic esophagitis may be under recognized in the adult population, as only 35% of
reported cases have been in adults.3 Cases reported as allergic esophagitis 4 or corrugated ringed
esophagus 5 likely represent the same condition. Eosinophilic esophagitis is a male-predominant
disease, with approximately 75% of cases occurring in men. When presenting in adulthood, there is an age
peak in the third and fourth decades of life.
Progressive dysphagia is the classical presentation of patients with EE, often to the extent of food
impaction. Vomiting and chest pain are also common symptoms. Children with eosinophilic esophagitis may
also present with refusal to feed and failure to thrive.4,6 Personal and family histories of allergic
diseases such as atopic dermatitis, asthma, and food allergies occur in up to 85% of patients.3 Many
will also have peripheral blood eosinophilia. Importantly, symptoms are not responsive to anti-reflux
Eosinophilic esophagitis presents a variety of endoscopic appearances. Strictures are a common
finding, both focal and long-segment (small caliber esophagus). Corrugation, multiple esophageal rings,
vertical furrows, and mucosal granularity are additional findings that may be seen. Some patients may
have white mucosal patches resembling Candida infection. These patches represent inflammatory
pseudomembranes with numerous eosinophils breaking through the squamous mucosa.3 pH monitoring
studies are normal in patients with EE.
As the name implies, the key histologic feature is intense eosinophilic infiltration in the esophageal
squamous mucosa, with involvement of both the proximal and distal esophagus. In most cases, there is an
eosinophil density of greater than 20 eosinophils/hpf.2,4,7 The eosinophils have a predilection for
the superficial (luminal) portion of the mucosa, and eosinophilic microabscesses are often identified.
An important diagnostic criterion is the persistence or presence of these findings following prolonged
anti-reflux therapy. The eosinophilia is accompanied by squamous hyperplasia, as defined by
subepithelial papillae exceeding 67% of the mucosal thickness and a basal zone that exceeds 15% of the
The pathogenesis of eosinophilic esophagitis is not fully understood, although food and airborne
allergens are suspected etiologic agents. This is supported by positive radioallergosorbent tests
(RASTs) to a variety of foods in many patients with EE.4,6,7 Furthermore, EE responds to dietary
elimination, elemental diets, and corticosteroids, both systemic and topical. To reiterate, it does not
respond to anti-reflux therapy. Given the difficulty in adherence to elimination or elemental diets, the
most promising therapy to date appears to be topical fluticasone propionate.6 The fluticasone
propionate is administered via a metered-dose inhaler, but is ingested, rather than inhaled.
The association of EE with more generalized eosinophilic gastroenteritis is unclear, as esophageal
involvement by eosinophilic gastroenteritis may occur. Thus, whether EE is a distinct entity or part of
the spectrum of eosinophilic gastroenteritis remains to be determined.
The disease process most frequently entering the differential diagnosis of EE is gastroesophageal
reflux disease (GERD). Clinical and histological features may be helpful in making the distinction
between the two conditions. The degree of eosinophilia is greater in EE than in GERD, with the
eosinophil density usually exceeding 20 eosinophils/hpf in EE. In contrast, the eosinophil density in
GERD is much less, with the typical case having less than 5 eosinophils/hpf. Perhaps even more helpful
in making the distinction between EE and GERD are the luminal-predominance of the eosinophilic infiltrate
and the presence of eosinophilic microabscesses in EE, as these features are unusual for GERD.4 The
clinical setting is also helpful in establishing a diagnosis of EE: a history of progressive dysphagia
with food impaction in a young male, the presence of multiple esophageal rings, or a history of
"refractory GERD" should make one consider the possibility of eosinophilic esophagitis.
- Landres RT, Kuster GG, Atrum WB. Eosinophilic esophagitis in a patient with vigorous achalasia.
- Atwood SEA, Smyrk TC, Demeester TR, et al. Esophageal eosinophilia with dysphagia. A distinct
clinicopathologic syndrome. Dig Dis Sci 38:109-116;1993.
- Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointest Endosc 56:260-270;2002.
- Walsh SV, Antonioli DA, Goldman H, et al. Allergic esophagitis in children. A clinicopathologic
entity. Am J Surg Pathol 23:390-396;1999.
- Langdon DE. "Congenital" esophageal stenosis, corrugated ringed esophagus, and eosinophilic
esophagitis. Am J Gastroenterol 95:2123-2124;2000.
- Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: Immunopathological
analysis and response to fluticasone propionate. Gastroenterology
- Orenstein SR, Shalaby TM, DiLorenzo Cet al. The spectrum of pediatric eosinophilic esophagitis
beyond infancy: a clinical series of 30 children. Am J Gastroenterol