Endoscopic Findings

Although there are no pathognomonic findings for EoE, esophageal edema, longitudinal furrows, mucosal fragility, whitish exudates, transient esophageal rings (feline folds), fixed esophageal rings (trachealization), diffuse esophageal narrowing, and small-caliber esophagus are its typical macroscopic findings ( Fig. 1 ). Up to one-third of children with EoE may have visually normal esophageal mucosa.

Endoscopic findings of EoE. ( A ) Normal esophageal mucosa. ( B ) Esophageal furrowing. ( C ) Esophageal white mucosal plaques. ( D ) Esophageal mucosal fragility in a patient with EoE after biopsy. ( E ) Esophageal mucosal fragility with so-called crepe paper esophagus. ( F ) Esophageal trachealization.

( Courtesy of [ C , E , F ] The International Gastrointestinal Eosinophilic Researchers (TIGERS) and Children’s Digestive Health and Nutrition Foundation (CDHNF) slide set; and [ E ] Chris A. Liacouras, MD, Philadelphia, PA.)

A novel endoscopic classification and grading system called the EoE Endoscopic Reference Score (EREFS) was recently developed and validated in adults to define common nomenclature, severity description, and disease assessment among providers. The EREFS score is generated based on the presence and/or severity of transient or fixed esophageal rings, exudates, furrowing, mucosal fragility (so-called crepe-paper esophagus), edema (and the associated vascular pattern), as well as stricture. Although this system has good interobserver agreement between practitioners, a validated scoring system in children has yet to be established.

There are many past and present differences in EoE diagnostic practices between pediatric and adult gastroenterologists. For example, adult gastroenterologists have traditionally based the diagnosis of esophageal disorders primarily on symptoms and endoscopic findings, rather than histolopathology. Alternatively, pediatric gastroenterologists have been trained to obtain mucosal biopsies in all diagnostic procedures, even if the mucosa is visually normal. The pediatric approach to diagnosis may be extremely important to identifying the presence of EoE, because it is common for patients of all ages to have a normal-appearing esophagus.

Radiology

Although not recommended routinely for EoE diagnosis, imaging with upper gastrointestinal intestinal series (UGI) or esophagram should be recognized to be a useful test in patients with feeding problems, dysphagia, or food impaction to evaluate for anatomic and mucosal abnormalities such as narrowing, stricture, or formation of rings ( Fig. 2 ). In a cohort of 22 pediatric patients with EoE with strictures who underwent esophagram and endoscopy within 3 months of each other, 12 had esophageal strictures identified by esophagram alone and only 1 had a stricture identified by endoscopy but not esophagram. Furthermore, 3 of 4 patients who received a barium pill had evidence of impaction or delayed pill transit. Although not specific to EoE, these findings may provide valuable adjunctive monitoring and diagnostic information before performing an upper endoscopy. Characterizing a patients’ anatomy may also be useful in preventing unwanted complications, including esophageal perforation. Patients with EoE may be at risk for perforation with instrumentation, and have been described as having crepe-paper esophagus.

Esophagram findings of EoE. ( A ) Diffuse esophageal narrowing. ( B ) Esophageal stricture with 2 pronounced areas of narrowing. ( C ) Esophageal rings indicated by white arrows.

( Courtesy of [ A , C ] TIGERS and CDHNF slide set.)

Histology

EoE is a diagnosis that requires both clinical symptoms (isolated esophageal dysfunction) and abnormal histology, with greater than or equal to 15 esophageal eosinophils per high-power field in the most densely involved esophageal mucosal specimens. Eosinophils are not increased in any other part of the gastrointestinal tract. EoE often presents as a patchy disease, thus multiple biopsies are required. According to several recent guidelines, multiple biopsies should be obtained from both the mid/proximal and distal esophagus of patients who are being concomitantly treated with high-dose PPI therapy for 8 to 12 weeks before endoscopy.

Common microscopic findings of EoE are shown in Fig. 3 . Although the eosinophil is the predominant cell type seen on hematoxylin-eosin staining, additional microscopic findings, such as basal cell hyperplasia with resulting acanthosis, eosinophilic microabscess formation and layering, eosinophilic granules, dilated intercellular spaces, as well as thickened and dense lamina propria fibers, have also been reported. In addition to eosinophils, the feature and predominant inflammatory cells of EoE, many other cell types, including mast cells, basophils, and both B and T lymphocytes, have been discovered in the inflammatory milieu. A unique inflammatory cytokine and genetic profile has also been identified in human esophageal mucosal biopsies from patients with EoE.

Histology of the esophagus. ( A ) Normal esophagus ( B ) EoE esophagus with basal cell hyperplasia and eosinophilic infiltrate. ( C ) EoE esophagus with superficial layering of eosinophils ( black arrow ) and an eosinophilic abscess. Histologic evaluation of the esophagus by hematoxylin and eosin stain.

( Courtesy of [ C ] TIGERS and CDHNF slide set.)

Recent guidelines have stressed the importance of making the distinction between esophageal eosinophilia and EoE. Esophageal eosinophilia is a descriptive term, whereas EoE is a disease and diagnosis. There are many causes of esophageal eosinophilia, including GERD; PPI-REE; bacterial, fungal, or parasitic infections; Crohn disease; primary immune deficiencies; other hypereosinophilic disorders; connective tissue disorders; and side effects of various medications. There may be a some patients with EoE who do not meet the threshold of eosinophils for EoE diagnosis either because of inadequate biopsies and sampling error or partial treatment response, although these patients may have other characteristic histologic features.

Eosinophilic Esophagitis Treatment

After establishing a diagnosis of EoE and initiating therapy, surveillance endoscopy is performed to evaluate for esophageal mucosal healing. At present, there are no other methods that can be used to evaluate the severity of esophageal inflammation. The frequency of endoscopic monitoring varies based on selected therapy. In general, it is recommended that repeat EGD with biopsy be performed to evaluate for response any time a therapy is initiated or altered, because clinical symptoms and histologic inflammation do not correlate.

Eosinophilic Esophagitis Surveillance

How to decide when and how often to perform EGD with biopsy for surveillance of patients with a known diagnosis of EoE is currently not well understood. Because of the invasive nature of endoscopy, patient concerns, possible anesthesia side effects, and increased medical costs, some investigators argue to limit the number of endoscopies. In contrast, limiting these procedures can often delay therapeutic changes such as expanding a patient’s diet or decreasing medication doses.

Moreover, although some physicians use patient symptoms to guide clinical management, the general lack of correlation between clinical symptoms and tissue inflammation in EoE has been well shown, and this approach can often misguide therapeutic decision making. Although in a few cases clinical symptoms and histologic changes have been shown to coincide, this is not typical of most patients. Until less invasive diagnostic tools are available, physicians should recognize the limitations of clinical symptoms for guiding management, and make appropriate decisions regarding the timing of EGD with biopsy.

Emergent Procedures in Eosinophilic Esophagitis

Food impaction accounts for up to 10% of pediatric esophageal foreign bodies and is considered one of the classic disease presentations of EoE in adults. Retrospective pediatric and adult studies suggest that approximately half of all food impactions requiring endoscopy are likely secondary to EoE.

Patients with food impaction typically present with nausea, odynophagia, substernal chest pain, and salivation. Almost all food impactions are secondary to meat. Nevertheless, all patients with suspected food impaction should undergo chest radiograph to rule out other radio-opaque foreign bodies and other complications of ingestion, such as pneumomediastinum and pneumothorax, specifically in the pediatric population, in which patient history may be unreliable. In addition, surgical or otolaryngologic consultation should be considered for patients with proximal foreign bodies, which may be removed more successfully with a rigid endoscope rather than with a flexible instrument.

There has been recent controversy among gastroenterologists regarding whether or not to biopsy at the time of endoscopic food removal. Many patients who present with a food impaction may also have esophageal trachealization, furrows, or white plaques on the esophageal mucosa. In many of these cases, patients who present with impactions are not on a PPI, and physicians may erroneously presume that the endoscopic findings are pathognomonic for EoE. However, this is now appreciated to not be the case. A significant number of these patients respond effectively to treatment with PPI, and in turn have a diagnosis of PPI-REE. Thus, making a formal diagnosis of EoE during the initial EGD for a foreign body impaction in the absence of acid suppression can be challenging unless the EGD is repeated after the patient has been treated with high-dose PPI on a regular basis for 6 to 12 weeks. Regardless, biopsies should be obtained, if possible, during food disimpaction, because important information can be obtained and a biopsy that does not reveal features of EoE in PPI-naive patients may be helpful by suggesting a decreased likelihood of EoE.

Stricture Management and Dilations

Esophageal stricture is the most severe complication of EoE. Symptoms of stricture include dysphagia, delayed transit of food, and recurrent impaction. Recent evidence suggests that long-standing, untreated EoE leads to fibrostenosis. Note that not all patients with severe, prolonged esophageal eosinophilia develop strictures. Alternatively, many patients with EoE who have esophageal strictures have developed coping mechanisms to deal with their symptoms, which can mask or further delay diagnosis. For example, patients may chew their food for a prolonged period of time or cut their food into very small pieces. They may also drink large quantities of water during meals in order to ease the passage of food, or they may take longer than an hour to eat a meal. Hence, diagnosis of stricture in EoE may require obtaining a specialized patient history that targets the identification of such behaviors.

EGD is not considered an adequate means of identifying esophageal strictures in EoE. Not only can an esophageal stricture or luminal narrowing be difficult to appreciate by EGD, but esophageal laceration can occur with passage of the scope, because of a small-caliber and/or crepe-paper appearance of the mucosa. An esophagram is helpful in patients with EoE who present with dysphagia or feeding difficulty and may diagnose strictures or narrowing more reliably.

Esophageal stricture formation is rare in pediatric EoE compared with adults with the diagnosis, with the exact rate of this complication in children unknown. Because esophageal narrowing and tissue inflammation have been shown to be reversible in children undergoing treatment of EoE, dilation is most commonly recommended for symptomatic relief in patients who do not respond to medical therapy or who have irreversible stenotic lesions. In contrast, in adults with EoE, some physicians use dilation as a primary monotherapy. Although this method of therapy may provide symptomatic relief, it is important to recognize that dilation does not treat the underlying esophageal inflammation in EoE and almost always needs to be repeated.

Before 2008, the rate of complications from esophageal dilation in patients with EoE was thought to be higher than in other benign esophageal conditions. For example, perforation rates were reported as high as 5%. However, in recent years larger-scale studies, some of which have included pediatric patients, have shown that the rate of perforation is considerably less than had been previously reported. The most recent EoE consensus guidelines report only 3 perforations out of 839 performed dilations. However, the guideline investigators also speculate that this decrease in perforations may reflect growing gastroenterologist experience with dilation in EoE.

To date, there are no standard dilation techniques for children and many of the practices are extrapolated from the adult literature. Bougie dilation and balloon pull-through techniques have both been successful in providing symptomatic relief in adults with esophageal stricture. Although both dilation approaches are reported to be safe in adults, their safety and efficacy have not been formally studied in the pediatric population.

Challenges with Eosinophilic Esophagitis Management

Although established consensus guidelines for EoE diagnosis and management are available, there may be variation in interpretation of clinical history and histologic findings because the disease is patchy and many pathologists do not specify the size of a high-power field. There is also significant variability in the practice among pediatric and adult providers. For example, some providers do not recommend a PPI trial before endoscopy, complicating the diagnostic distinction between GERD and PPI-REE, which may drastically change the management approach.

Another consideration in clinical management is the timing and interpretation of endoscopic evaluation in the context of a patient’s treatment regimen for allergies, asthma, and other disorders. EoE is often comorbid with other allergic disorders, and reports of anecdotal experience have suggested that patients with allergic rhinitis may have a proximal esophageal eosinophilia that resolves with nasal corticosteroids. Nevertheless, at this time, there is no evidence to suggest any endoscopic or histologic benefit in EoE from nasal or inhaled steroids or antihistamines.

In addition, physicians must also always be aware of concomitant medication use. For example, systemic steroid therapy can induce clinical and pathologic remission of EoE. Therefore, unless a patient is being treated primarily for EoE, patients taking systemic corticosteroids should undergo endoscopy at least 4 to 6 weeks after systemic steroid therapy to appropriately assess EoE disease status.