Nonreflux Esophagitis

Clinical Presentation

EoE can present at any age, but the clinical presentation differs between adults and children. In adults, the most common symptom of EoE is dysphagia, particularly to solid foods. In one series, dysphagia was the presenting complaint in 83% of patients. The dysphagia is usually intermittent and rarely accompanied by odynophagia. In severe circumstances, persistent dysphagia and odynophagia can lead to malnutrition. Other symptoms include heartburn (30% to 60% of patients) and noncardiac chest pain. Of particular clinical importance is the frequency with which EoE causes food impaction requiring acute intervention ( Fig. 44.1 ). In one series, food impaction was the presenting complaint in 42% of patients with EoE, and more than half of adult patients with impaction may have esophageal eosinophilia. When interviewing patients complaining of dysphagia, it is important to elicit a history of impaction events leading to retching or regurgitation, and EoE must be considered in all patients presenting with impaction.

In children, the most common presenting complaints are heartburn and abdominal pain, with vomiting or decreased appetite. One large series demonstrated that 38% of children with EoE report heartburn as their primary complaint upon presentation and 31% report abdominal pain or dyspepsia. Other symptoms include growth failure and, rarely, hematemesis. Infants and toddlers present with difficulty feeding, described by caregivers as “gagging” or “choking.” In contrast to adults, dysphagia is uncommon in children until adolescence.

Epidemiology

In children and adults, EoE is a chronic disease that does not resolve spontaneously and often recurs after treatment cessation. With years of persistent inflammation, the disease seems to progress toward a fibrostenotic phenotype; according to one large case series, the risk of fibrostenotic complications doubles with each decade. The disease is more common in Caucasians and has a male predominance, which is consistently reported at 3 to 4 : 1 across all ages. There is also a strong association with atopic diseases, including a correlation with environmental and food allergies.

There is an increasingly large body of evidence showing that EoE is rapidly increasing in incidence and in prevalence, and that this increase cannot be explained simply by increased awareness. Current estimates indicate that the prevalence is likely between 40 and 90 cases per 100,000 persons in the United States. This prevalence is consistent with other Western countries, namely Australia, Switzerland, Spain, and Canada. In patients undergoing endoscopy for dysphagia, the prevalence of EoE is between 12% and 22%.

In terms of incidence, multiple studies suggest that the incidence of EoE has been rapidly increasing since its discovery 20 years ago. In a case series from Hamilton County, Ohio, the incidence increased from 9 per 100,000 to 12.8 per 100,000 people over a 3-year period. This finding is consistent with another report from Olmsted County, Minnesota, showing a dramatic increase in incidence over the 15-year period from 1990 until 2005. A population-based, prospective study from the Swiss EoE study group provides more evidence for a marked increase in incidence. Like the Minnesota group, the Swiss study compares the observed incidence with the rate of upper endoscopy. In both studies, the rise in EoE incidence in excess of increases in the upper endoscopy rate suggests that there is a real increase in disease rather than just an increase in awareness and detection.

The marked increase in incidence of EoE parallels increases in other allergic disease, including asthma, allergic rhinitis, atopic dermatitis, and various food allergies. One potential explanation is the “hygiene hypothesis,” which is a frequently cited and much-discussed theory initially based on epidemiologic studies. It points to the decreased infection burden in industrialized nations with an associated increase in atopic diseases and proposes a causative link. There are animal models that support the “hygiene hypothesis” for certain specific autoimmune diseases, but therapeutic approaches to allergic disease based on the reintroduction of specific infections have shown mixed results. The “hygiene hypothesis” holds a plausible explanation for the rising incidence of EoE, but requires further study. Overall, the rapid rise of EoE is an area of much debate and research. Current thinking is that the increase is likely multifactorial, and hypotheses include a variety of immunologic-, environmental-, and microbiome-related topics.

Diagnostic Work-Up

According to the recently published guideline from the American College of Gastroenterology (ACG), EoE is defined as, “a clinicopathologic disorder diagnosed by clinicians taking into consideration both clinical and pathologic information without either of these parameters interpreted in isolation.” Thus, the diagnostic criteria include a combination of clinical and pathologic findings; no single finding is pathognomonic ( Fig. 44.2 ).

First, the patient must have symptoms of esophageal dysfunction. Second, pathologic examination of esophageal biopsy specimens must demonstrate eosinophil-predominant inflammation with a characteristic peak value of at least 15 eosinophils per high-power field (HPF); previous guidelines have used various thresholds for diagnosis, ranging from 15 to 30 eosinophils/HPF. Third, secondary causes of esophageal eosinophilia should be excluded. Fourth, the mucosal eosinophilia is confined to the esophagus and persists after a proton pump inhibitor (PPI) trial. Patients who meet other criteria for EoE but have histologic and symptomatic resolution with PPI therapy may fall into the diagnostic criteria for a separate entity called PPI-responsive esophageal eosinophilia (REE), which is considered distinct from both EoE and GERD. Finally, a response to EoE-specific treatment, such as dietary elimination or topical corticosteroids, supports the diagnosis of EoE.

To fulfill the ACG histologic criteria for diagnosis, an endoscopic evaluation with biopsy is required. Current recommendations call for two to four biopsy specimens from both the proximal and distal portions of the esophagus. The physician performing the initial endoscopic evaluation should also obtain biopsies of the antrum and/or duodenum in patients with small intestine symptoms or endoscopic abnormalities to rule out other causes of esophageal eosinophilia, such as Crohn disease or rare infectious causes. To evaluate for GERD in patients with esophageal eosinophilia, pH monitoring has historically been a useful diagnostic test. However, a more recent cohort study of patients with esophageal eosinophilia showed a high incidence (71%) of pathologic reflux, and many patients without reflux had improvement in symptoms and pathologic response to PPI therapy. This group found that pH testing was not a useful predictor of patient response to PPI therapy. Therefore, pH testing may be useful in select patients, but it is not required in the work-up of EoE.

The ACG diagnostic criteria are devoid of radiographic or endoscopic findings; however, there are several characteristics of EoE that may be apparent and are increasingly important clinically. Endoscopic findings of EoE include the development of multiple concentric rings (see Fig. 44.1 ), “trachealization” or “feline esophagus,” narrowing, linear furrows, white exudates, and edema. These endoscopic findings may be present in 90% to 95% of cases. Furthermore, the endoscopic appearance of EoE is under examination as a clinically relevant therapeutic outcome measure, and an endoscopic grading system to classify disease severity has been introduced.