—  SPECIALTY CONFERENCE  —

Gastrointestinal Pathology

Case 1 - Eosinophilic Esophagitis

Shari Taylor
GI Pathology Partners, PC
Memphis, Tennessee


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Clinical History:
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 distal esophagus.

Histologic Features:
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.

Diagnosis:
Eosinophilic esophagitis.


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.

Additional History:
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.

Discussion:
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 therapy.

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 mucosal thickness.

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.

References

  1. Landres RT, Kuster GG, Atrum WB. Eosinophilic esophagitis in a patient with vigorous achalasia. Gastroenterology 74:1298-1301;1978.
  2. Atwood SEA, Smyrk TC, Demeester TR, et al. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 38:109-116;1993.
  3. Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointest Endosc 56:260-270;2002.
  4. Walsh SV, Antonioli DA, Goldman H, et al. Allergic esophagitis in children. A clinicopathologic entity. Am J Surg Pathol 23:390-396;1999.
  5. Langdon DE. "Congenital" esophageal stenosis, corrugated ringed esophagus, and eosinophilic esophagitis. Am J Gastroenterol 95:2123-2124;2000.
  6. Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: Immunopathological analysis and response to fluticasone propionate. Gastroenterology 122:1216-1225;2002.
  7. Orenstein SR, Shalaby TM, DiLorenzo Cet al. The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children. Am J Gastroenterol 95:1422-1430;2000.