Eosinophilic Gastrointestinal Disease and Eosinophilic Esophagitis

How is eosinophilic gastrointestinal disease (EGID) defined?

EGID is a global term that describes an increasingly recognized heterogeneous group of gastrointestinal (GI) diseases found in both children and adults. It is characterized by chronic, nonspecific GI symptoms and a dense eosinophilic inflammatory response that is found in various tissues throughout the GI tract. It can manifest as eosinophilic gastroenteritis, colitis, or the well-studied eosinophilic esophagitis (EoE). Other causes of eosinophilia need to be ruled out prior to making the diagnosis of EGID.

What is EoE?

EoE is the most common form of EGID. It is a clinicopathologic disorder now recognized as a major cause of abdominal pain, vomiting, and feeding problems in young children and food impactions and dysphagia in adults. EoE is a chronic, allergen-driven inflammatory disease process that is defined by symptoms of esophageal dysfunction and mucosal eosinophilia.

What is the incidence of EGID and EoE?

EGID is a rare disorder with an estimated incidence that is likely less than 1 in 100,000. Few retrospective epidemiologic studies have been published with numbers of patients ranging from 8 to 59 that were discovered over a span of up to 37 years. The incidence of EoE, on the other hand, continues to increase with estimates of up to 40 in 100,000. The vast majority of patients with EoE are white males, but both of these disease entities have a widespread geographic and ethnic distribution.

What is the role of the eosinophil in the pathogenesis of EGID and EoE?

EGID and EoE are believed to be allergen-mediated, Th-2 cytokine inflammatory responses that develop in genetically susceptible individuals and are associated with GI eosinophilia. With the exception of the esophagus, eosinophils are prominent resident leukocytes within the intestinal mucosa whose precise role in health remains unclear. Although the exact pathogenesis is uncertain and its study is typically limited to superficial mucosal pinch biopsies, EGIDs are thought to be stimulated by exposure to an environmental or food allergen that leads to chemoattraction and recruitment of additional eosinophils to the GI tract. The exact function of eosinophils in the GI tract are unknown, but a number of basic studies support a role in antigen presentation and as effector cells that can release a host of cytotoxic granules, cytokines, chemokines, transforming growth factors, lipid mediators, and neuromediators.

Gene arrays and genome-wide association studies have identified several key molecules strongly associated with EoE, including thymic stromal lymphopoietin, eotaxin-3, interleukin (IL)–13, and IL-5. Familial susceptibility has also been reported in approximately 10% of patients with EGID.

What are some clinical features of EGID and EoE?

Early descriptions of EGIDs involving the GI tract distal to the esophagus classified the disease based on the identified depth of eosinophilia within the intestinal wall. The mucosal subtype can manifest as bleeding, diarrhea, and pain; muscular subtype as partial or complete intestinal obstruction; and serosal sub-type as abdominal distention ( Table 43-1 ). Recent studies suggest a shift toward the mucosal form of disease. Up to 75% of patients will report a personal history of atopy, including eczema, food allergies, seasonal allergies, or asthma. Additionally, peripheral eosinophilia can occur in up to 80% of patients with EGID, but is variable and can also occur secondary to other comorbid allergic diseases, making this an unreliable biomarker of disease activity.

Patients with EoE can present with a variety of signs and symptoms of esophageal dysfunction, depending on the age of the individual (see Table 43-1 ). Young children, because of developmental level, are unable to articulate symptoms of dysphagia and instead present with symptoms of feeding difficulties. Many of these symptoms are similar to that of gastroesophageal reflux disease, but do not respond to standard medical or surgical antireflux therapies. Often, symptoms may require additional questions during history taking.

What is the natural history of EGID and EoE?

Because of their relatively low incidence and confounding GI symptoms, there is often a delay in diagnosis of both EGID and EoE that can sometimes reach 3 to 4 years. Based on current studies and clinical experiences, the natural history of EGID may include one of three patterns, as patients may suffer from a single occurrence, a recurrent course, or a chronic disease path. Additionally, there are several potential phenotypes based on the depth of intestinal involvement.

Three issues regarding the natural history of EoE have become apparent because of broader clinical experiences. First, EoE is a chronic disease in which most patients will respond to standard medical therapies. Second, complications associated with EoE include food impactions, esophageal narrowing and feeding dysfunction. Who, how and in whom, these develop is uncertain. Third, there does not appear to be any premalignant potential to date, but long-term natural history studies are still required to assess for this concern. Finally, there may be other EoE phenotypes based on whether or not patients respond to diet elimination and topical steroids.

How are EGID and EoE diagnosed?

As mentioned previously, EGID is characterized by nonspecific GI symptoms associated with a dense intestinal eosinophilia. What is considered an “abnormal” number of intestinal eosinophils remains unclear and is a matter that should be discussed between clinicians and pathologists at local institutions. Making the diagnosis of EoE is easier as diagnostic guidelines have been established ( Box 43-1 ).

Any patient with a concern for EGID should undergo a thorough evaluation to exclude any other causes of intestinal eosinophilia. No pathognomonic signs, symptoms, or blood tests exist for defining EGID or EoE. Depending on the specific intestinal organ involved and its accompanying symptoms, there are several approaches.