Unraveling Rare: Eosinophilic Esophagitis

Eosinophilic Esophagitis (EoE) is a chronic allergic/immunologic disorder leading to inflammation of the esophagus. In this disorder, large numbers of certain white blood cells called eosinophils invade the tissue in the esophagus. In most people, there are no eosinophils in the esophagus. The symptoms vary with age. In infants or young children, a refusal to eat to eat may be seen as well as failure to thrive. In school-aged children, abdominal pain, difficulty swallowing or vomiting may be observed. In teenagers and adults, difficulty swallowing and even food impaction may be seen.

Symptoms:

In adults-

• Difficulty swallowing
• Food impaction
• Chest pain
• Persistent heartburn
• Upper abdominal pain
• Failure to respond to GERD medications
• Regurgitation

In children-

• Feeding problems
• Vomiting
• Abdominal pain
• Difficulty swallowing
• Food impaction
• Failure to respond to GERD medications
• Failure to thrive

Over the last two decades, EoE has been increasingly diagnosed. It seems to be more common in industrialized nations with high socioeconomic development. In some regions, the prevalence rate reaches as high as 50 patients out of every 100,000 inhabitants. It is unknown whether this is a true increase in the number of cases or the increased awareness of this disease. Many studies reveal that it is more common in males with a male to female risk ratio of 3:1. The average age at the time of diagnosis is between 30 and 50 years. While it occurs in all races, it tends to be more common in Caucasians. In most patients, there appears to be a correlation between EoE and allergens, both food and environmental.

EoE appears to be mediated by T 2 helper (TH2) cells, like other allergic disorders. There appears to be some role for adaptive immunity based on experiments with mice. Th2 cytokines and eosinophilic-attraction chemokines such as CCL26 have some influence over the development of EoE, indicating a strong connection with allergies in the respiratory tract and skin. Genome-wide profiling reveal that CCL-26 is overexpressed 50-fold in EoE compared to normal subjects. It has been theorized that this Th2 cell activation leads to the overexpression of CCL-26 and the migration of eosinophils into the esophagus. Subepithelial fibrosis and increased expression of transforming growth factor B (TGF-B) are also observed. Esophageal biopsies also show increased expression of vascular cell adhesion molecule 1 (VCAM-1). Symptoms of dysmotility may be induced by the fibrosis.

A group of scientists at Cincinnati Children’s Hospital discovered a dysregulated microRNA signature for EoE. MicroRNAs control whether genetic messengers can be translated into protein. The investigators found that the dysregulated microRNA was found to be reversible with steroid treatment. In this study, 32 differentially regulated microRNAs were found to be associated. Eosinophil levels were found to be correlated with the expression of the most increased microRNAs (miR-21 and miR-223).

In another study, CHOP experts discovered four new genes associated with EoE. These genes also were also observed to play a role in allergic disorders. These researchers found four distinct genetic loci associated with EoE. STAT-6 and c11orf-30 were previously found to play a role in allergic and autoimmune disorders. ANKRD27 and CAPN14 were specific to EoE. CAPN14 is of particular interest because it is found only in the esophagus.

Diagnosis is based on EGD and esophageal biopsies. Esophageal rings detected on biopsy can be repaired. Linear furrows are another typical finding seen on EGD, but not specific for EoE. White plaques may be observed coating the lining of the esophagus, which may mimic Candida. The mucosa is fragile and can fracture with the passage of the endoscope in EoE. Approximately 10-20% of patients with EoE can have a normal appearing esophagus, thus necessitating biopsies. The current recommendation is to take 2-4 biopsies from the distal esophagus and 2-4 biopsies from the proximal end. The diagnostic histiopathologic finding of EoE is a prominent eosinophilic infiltrate seen diffusely throughout the epithelium. Additionally, surface clustering of eosinophils may be observed. There may also be seen eosinophilic microabscesses.

A main focus in the treatment of EoE is a reduction or resolution of symptoms. In pediatric patients, maintaining proper growth and development is key. Mucosal healing is also a benchmark of treatment. When inflammation is eliminated, certain complications such as esophageal strictures can be eliminated as well. This is supported by studies that show eosinophils contribute to fibrosis and remodeling. Clinical studies, additionally, reveal a positive impact of medical treatment on the markers of fibrosis. Mucosal healing remains an end-point of both research studies and clinical practice.

Since there is some overlay with food allergies, diet must be addressed as well. It is important to attempt to determine specific food allergies and eliminate those from the diet.

There are many research being currently conducted. More information about clinical trials can be found at: https://www.cincinnatichildrens.org/service/c/eosinophilic-disorders/research.

About the Author

Dr. Linda Girgis MD, FAAFP is a family physician in South River, New Jersey. She has been in private practice since 2001. She holds board certification from the American Board of Family Medicine and is affiliated with St. Peter’s University Hospital and Raritan Bay Hospital. She teaches medical students and residents from Drexel University and other institutions.  Dr. Girgis earned her medical degree from St. George’s University School of Medicine. She completed her internship and residency at Sacred Heart Hospital, through Temple University where she was recognized as intern of the year.  She is a blogger for Physician’s Weekly and MedicalPractice Insider as well as a guest columnist for Medcity New, PM360 and HIT Outcomes. She has had articles published in several other media outlets. She has authored the books, “Inside Our Broken Healthcare System”, “The War on Doctors” and “The Healthcare Apocalypse.” She has been interviewed in US News and on NBC Nightly News.