Eosinophilic Esophagitis
October  2017

A 29-year-old male applies for life insurance. He states that he is in good health except for a diagnosis of eosinophilic esophagitis. His medical records reveal that his esophagus had been dilated three times between the ages of 15 to 17 years of age. He initially presented to the emergency room at the age of 15 years with an episode of food impaction. He has been treated with corticosteroid inhalers for several years. The current APS notes that he is currently on no medications except for the inhaled corticosteroids, and he has had no medical complaints for the past year.

What are the mortality implications of eosinophilic esophagitis?
Eosinophilic esophagitis (EoE) is defined as a chronic immune/antigen esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil predominant inflammation. Normally, eosinophils are present in the mucosa of the entire digestive tract except for the esophagus. Accordingly, the presence of excess eosinophils in the esophagus is associated with disease. Several studies suggest progression of untreated disease.

Presentation
The presentation of EoE differs by age. Infants and toddlers frequently display feeding difficulties, whereas school-aged children often complain of vomiting and pain. Teens and adults characteristically exhibit dysphagia or food impaction. The typical initial presentation is a male (3:1 male: female ratio) who manifests either in childhood or in the third or fourth decade of life, though EoE can occur at any age. 

EoE is a relatively newly recognized condition, with the first case reports published in the 1970s.  Although it occurs in most ethnic groups, presence in non-hispanic whites predominates.  It has been found in most industrialized nations, with few reports of diagnosis in tropical and developing countries.

The average length of time between symptom onset and diagnosis is four years, so diligence to the symptom complex with a high amount of clinical suspicion is necessary. There appears to be increasing incidence over the past one to two decades that cannot be exclusively attributed to heightened recognition.  The prevalence of EoE in adults in population-based studies is about 30/100,000, while in children it varies between 10-43/100,000 children, depending on the study.

Figure 1 - Disease Course

DiseaseCourse.jpg 

A history of food impaction is found in up to 54 percent of patients ultimately diagnosed with EoE. In one community-based study, approximately 50 percent of patients who initially presented with food impaction were diagnosed with EoE within three years.

Diagnostic criteria

  1. Symptoms related to esophageal dysfunction
  2. Eosinophil predominant inflammation on esophageal biopsy with a peak value of =15 eosinophils per high power field (eos/hpf)
  3. Mucosal eosinophilia isolated to the esophagus and persists after a two-month proton pump inhibitor (PPI) trial
  4. Secondary causes of esophageal eosinophilia must be excluded
  5. A response to treatment (dietary elimination, topical steroids) supports but not required for diagnosis

Endoscopy
A variety of morphologic features are present on endoscopic examination of the esophagus in EoE. None are pathognomonic as they have all been described with other disorders.

  1. Fixed esophageal rings (aka trachealization)
  2. Decreased vascularity or edema
  3. White exudates or plaques (eosinophilic microabscesses)
  4. Longitudinal furrows
  5. Small caliber esophagus
  6. Esophageal strictures
  7. Esophageal lacerations induced by the passage of the endoscope (esophageal fragility)

Esophagus viewed endoscopically
The first picture below is a normal healthy esophagus when viewed endoscopically. The second picture shows a friable, narrow calliber esophagus with white patches of eosinophilic microabscesses. The bottom picture demonstrates fixed esophageal rings (trachealization) with distal narrowing.
Esophagus-1.jpgEsophagus-2.jpgEsophagus-3.jpg

Since esophageal pathology is frequently patchy, it is recommended that biopsies be obtained in both the proximal and distal portions of the esophagus. Two to four biopsies from each location, with special attention to areas of endoscopic pathology, are recommended.

There are no diagnostic blood tests for this disorder. However, 50-60 percent of those with EoE will have elevated serum IgE (>114,000 U/L), and 40 percent to 50 percent will have peripheral eosinophilia.

Differential diagnosis
The differential diagnosis consists of PPI (proton pump inhibitor) responsive esophageal eosinophilia, GERD (gastroesophogeal reflux disease), Celiac disease, Crohn’s disease, infection, vasculitis and other rare diseases and syndromes. The etiology of PPI-responsive esophageal eosinophilia is unclear, yet it appears to be a different entity. EoE does not respond to PPI treatment.

Associations with other disorders
There is a strong association between EoE and other allergic conditions (50-80 percent) including atopic dermatitis, food allergy, environmental allergy and asthma in both children and adults.

Treatment
The ideal endpoint in therapy includes the elimination of clinical symptoms and eosinophilic inflammation. While complete symptom resolution is the goal, improved symptomatology is often the accepted endpoint. The management includes avoidance of food allergen exposures, topical glucocorticosteroids to decrease inflammation of the esophageal mucosa and dilation of esophageal strictures as needed. 

There are three ways to handle the diet-based treatment:

  1. Elemental diet
  2. Empiric food elimination
  3. Allergy testing directed elimination; the elimination of milk, egg, wheat and soy cause improvement in approximately 50% of cases.

Prognosis
This appears to be a chronic disease in both children and adults. Adherence to therapy improves the outcome, with several studies indicating disease progression without treatment. Maintenance therapy should be continued in all patients, as symptoms recur when treatments are discontinued. As this is a new and evolving diagnosis, it is expected that guidelines and recommendations will also be evolving.

Mortality data
History of food impaction and higher levels of esophageal eosinophilia appear to predict higher morbidity of this disease, with increased dysphagia and additional episodes of food impaction. Despite these findings, mortality does not seem to be impacted.  While the long term prognosis of EoE is unclear, it does not appear to significantly shorten life span.

Returning to the case
Although EoE is a chronic disease that waxes and wanes, it does not appear to present a mortality risk. Our Proposed Insured is compliant with his care and therefore was considered a standard mortality risk.

References
Dellon, Evan S., et al. “ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).” The American journal of gastroenterology 108.5 (2013): 679.

DeBrosse, Charles W., et al. “Long-term outcomes in pediatric-onset esophageal eosinophilia.” Journal of Allergy and Clinical Immunology 128.1 (2011): 132-138.

Furuta, Glenn T., et al. “Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment: sponsored by the American Gastroenterological Association (AGA) Institute and North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.” Gastroenterology 133.4 (2007): 1342-1363.

Hopp, Russell J. “Eosinophilic esophagitis in pediatrics: the worst of all possible allergy worlds?.” Journal of allergy 2012 (2011)

Hruz, Petr. “Epidemiology of eosinophilic esophagitis.” Digestive diseases32.1-2 (2014): 40-47.

Liacouras, Chris A., et al. “Eosinophilic esophagitis: updated consensus recommendations for children and adults.” Journal of Allergy and Clinical Immunology 128.1 (2011): 3-20.

Lucendo, Alfredo J., and Susana Jiménez-Contreras. “Endoscopic aspects of eosinophilic esophagitis: from diagnosis to therapy.” Gastrointestinal Endoscopy. InTech, 2011.
Soon, S., et al. “Incidence and prevalence of eosinophilic esophagitis  in children.” Journal pediatric gastroenterology and nutrition 57.1 (2013): 72-80.

Spergel, Jonathan M., et al. “14 years of eosinophilic esophagitis: clinical features and prognosis.” Journal of pediatric gastroenterology and nutrition48.1 (2009): 30-36.

www.uptodate.com last accessed 8/8/2017.