Eosinophilic esophagitis (EoE) is a disease with increasing incidence in children and adults. Common symptoms of presentation include feeding difficulties, vomiting, failure to thrive, dysphagia, chest pain, food impaction, and abdominal pain. The diagnosis requires at least 15 eosinophils per high-powered field in the esophageal biopsies and symptoms of esophageal dysfunction after other causes have been ruled out.
EoE is a relatively newly described disease defined as a chronic antigen-mediated esophageal disease associated with esophageal dysfunction and resulting from eosinophilic-predominant inflammation. Diagnoses are made when patients meet the following criteria: (1) symptoms of esophageal dysfunction or upper gastrointestinal symptoms; (2) eosinophilic-predominant inflammation in the esophagus, with at least 15 eosinophils per high-powered field in the esophageal mucosal biopsy specimens; and (3) exclusion of other recognized causes of esophageal eosinophilia, including gastroesophageal reflux disease (GERD) and PPI-responsive esophageal eosinophilia.1,2 All clinical and pathologic information should be considered before diagnosing EoE, and should not be interpreted in isolation. It is generally accepted today that EoE is directly related to food antigens.1
EoE is a global disease, with large numbers of cases reported in North and South America, Western and Eastern Europe, and Australia. Fewer cases have been reported in Asia and the Middle East. The prevalence of EoE in the United States was estimated to be 12 per 100,000 people.3 However, the diagnosis of pediatric EoE is increasing at a rapid rate such that recent epidemiologic data indicate that EoE is now a leading cause of dysphagia.4,5 EoE has likely been underdiagnosed in the past and criteria for establishing the diagnosis of EoE have changed over the years. However, the surge cannot be fully explained by increasing awareness of the disease or higher rates of endoscopy with biopsies. In general, the rapid increase is likely due to a true rise of new patients.6 EoE can present at any age, but the majority of affected patients are of the male gender between ages 20 and 30 years.7 Twenty percent of all EoE patients are diagnosed in childhood.8 EoE occurs in most racial and ethnic groups, although many studies have reported predominance in non-Hispanic whites.1,9,10.
Clinical manifestations of EoE in children are nonspecific and vary by age such that diagnosis based on symptoms alone is not feasible. Children typically present with one or more symptoms such as vomiting, regurgitation, nausea, epigastric abdominal pain, chest pain, water brash, globus, decreased appetite, or growth failure.11 Infants and toddlers often present with feeding difficulties with gagging or choking, refusal of food, and vomiting. School-aged children are more likely to present with vomiting or pain and adolescents and adults often present with dysphagia, chest pain, heartburn, food impactions, and epigastric abdominal pain. Food impaction is defined as an event occurring after food ingestion where food matter is retained in the esophagus, usually requiring endoscopic interventions; adult studies showed that the prevalence was 30% to 50% at presentation.9,12 EoE in children is often present in association with other manifestations of atopic disease such as other food allergies, asthma, eczema, chronic rhinitis, and environmental allergies. The presence of other systemic symptoms such as fever should promote evaluation for a disease process other than EoE. Physical examinations are useful in children to identify normal growth and comorbid allergic diseases; however, no features on physical examinations are specific in making the diagnosis of EoE. Any patient with symptoms suggestive of EoE should undergo a careful history evaluation, with particular focus on eating and swallowing habits. Patients with EoE often rapidly adapt eating habits to manage their impaired esophageal function such as a preference for soft or liquid foods, chewing food into a mush, drinking copious amount of water after each bite, swallowing repeatedly to push food down, and avoiding food that tends to get stuck. A number of these compensatory behaviors will escape detection unless the clinician maintains a high clinical suspicion.
Unfortunately, the definitive diagnosis of EoE requires upper endoscopy with biopsies and anesthesia. The presence of esophageal abnormalities identified by endoscopy include mucosal fragility with esophageal lacerations induced by passage of endoscopy, edema, white exudates, longitudinal furrows, transient esophageal rings (feline folds or felinization), and fixed esophageal rings (trachealization).1,13 Strictures often develop in patients with EoE as a result of chronic inflammation and fibrosis. In some cases, the esophageal lumen is diffusely narrowed, which is termed small-caliber esophagus. Endoscopy with esophageal biopsy remains the most reliable test for the diagnosis of EoE. However, the finding of isolated esophageal eosinophilia without determining collaborative symptoms and ruling out other causes of esophageal eosinophilia is inadequate to make the diagnosis of EoE. Esophageal biopsy specimens must be obtained to identify histologic evidence of EoE in patients with unexplained dysphagia other than EoE. Barium contrast radiography can identify a number of anatomic and mucosal abnormalities of EoE, but the sensitivity of radiography as a diagnostic test for this condition is low.
The use of acid suppression medication is required to fulfill the diagnostic guidelines for EoE. PPI therapy is useful in treating patients with esophageal eosinophilia secondary to GERD. Patients with a significant improvement in their symptoms and esophageal eosinophilia after treatment with PPI either have GERD or a yet undefined condition known as PPI-responsive eosinophilia.14,15 PPI could also be useful as a co-therapy in patients with the diagnosis of EoE because the medication might alleviate symptoms related to secondary GERD, which is commonly present with EoE. PPI therapy alone is not effective as a primary treatment for patients with EoE. The recommended PPI dose that should be used to eliminate PPI-responsive esophageal eosinophilia is 1 mg/kg per dose twice daily, with a maximum dose of 20 to 40 mg once or twice daily for 8 to 12 weeks.
This disease usually remits with treatments of dietary modifications, topical corticosteroids, or both. Dietary therapy is an effective treatment for children and adolescents with EoE. Review of the literature has demonstrated that the use of dietary therapy leads to a high percentage of resolution of both clinical and histologic abnormalities. Three dietary regimens have been shown to be effective: (1) dietary restriction based on eliminating the most likely food antigens; (2) dietary restriction based on multimodality allergy testing (blood radioallergosorbent, skin prick, or patch testing); and (3) the strict use of an amino acid-based formula. Dietary restriction based on elimination of the mostly likely food antigens, known as the six food elimination diet (SFED), include strict avoidance of milk, eggs, soy, wheat, nuts/tree nuts, and fish/shellfish. Similar results have been documented when using either of the first two methods mentioned above; however, neither is as effective as the administration of a strict amino acid-based formula formula.16 Soy, wheat, chicken, and beef are the foods most frequently identified by the atopy patch test and skin prick test. Interestingly, although dairy often produces negative results, sequential re-introduction of foods after SFED suggests that milk is the most common problem food.17 Dietary therapy should be considered in all children with EoE. When deciding on the use of a specific dietary regimen, the patient's lifestyle, adherence to therapy, and family resources need to be considered. Consultation with a registered dietitian is recommended to ensure that proper calories, vitamins, and micronutrients are maintained. It is recommended that the foods proven to cause EoE continue to be restricted from the diet, whereas those foods not definitely proven to be antigenic can be introduced systematically, with careful observation for recurrence of EoE. Restriction of foods proven to trigger EoE might need to be continued indefinitely. Some families who do not have the resources to maintain a complicated allergen-free diet may choose long-term medications as treatment.
Steroids have been shown to improve the clinicopathologic features of EoE in most patients; however, when discontinued, the disease almost always recurs.18 Topical steroids, such as budesonide mixed with sucralose administered as a viscous slurry or fluticasone propionate from a multidose inhaler directed into the patient's mouth without a spacer and having patients swallow rather than inhaled, are usually the choice of treatment.2,11
These treatments have been shown to be effective in resolution of clinical symptoms and eosinophilic infiltration in the esophagus and have far less side effects compared to systemic steroids. Side effects of these more “topical” steroids include increased risks of esophageal candidiasis but not oral candidiasis.19,20 Systemic corticosteroids can be used for emergency cases such as severe dysphagia, hospitalization, and weight loss. Treatment of EoE with cromolyn sodium, leukotriene receptor antagonists, and immunosuppressive agents are not recommended as these have not been shown to have any clinical and histologic benefits in patients with EoE.
The data on the natural history of EoE are currently limited but it is believed that EoE is a chronic disease in most cases.21–23 Multiple studies have shown that EoE recurs almost universally after treatment is withdrawn, although time may vary for individual patients. It is important to consider both the likelihood of achieving response to treatment and the ability and/or willingness of patients and families to adhere with therapy for an extensive period specifically when treatment may impact both the child and other family members. In addition, symptoms and diagnostic procedures may also have a tremendous impact on the health-related quality of life of many pediatric patients as well as the psychologic well-being of their families. We should be mindful of these aspects while treating children with EoE in addition to treatment of clinical signs and symptoms.
Our understanding of EoE has substantially advanced over the past decades. EoE is now a commonly encountered cause of upper gastrointestinal symptoms in both adults and children. Approved and recommended medications and access to nutritional formulas are key milestones for treatment. The care of patients with EoE is multidisciplinary and involves primary care physicians, gastroenterologists, allergists, pathologists, and dietitians.