Eosinophilic Esophagitis: A Mysterious Allergic Disease
When 14-year old Cole began to regularly complain that he was having difficulty swallowing during meals, his mother sensed something was wrong. Foods he never had trouble with before, like steak, were suddenly getting stuck in his throat causing him to gag.
15-year old Lowell’s symptoms came on rapidly at the age of 10. He started to vomit a lot, until the frequency quickly reached at least once a day. “Looking back, the reflux he was diagnosed with at age 2, was most likely related,” says his mother.
Cole and Lowell are just two of a growing number of patients who have been diagnosed with a mysterious disease known as Eosinophilic Esophagitis, or EoE—an inflammatory condition of the esophagus triggered by a type of white blood cell (eosinophil) that normally resides in miniscule amounts in the blood and intestine to fight parasites. In patients with EoE, these toxin-containing cells are inexplicably found in elevated levels in the esophagus causing inflammation, often in response to one or more of the 8 food allergens responsible for 90% of food allergies in the United States (peanut, tree nut, shellfish, fish, egg, soy, milk, and wheat).
As Dr. Sharon Chinthrajah of the Sean N. Parker Center for Allergy Research at Stanford University explains, “with each exposure to triggering allergens, eosinophils infiltrate the esophagus and release chemical substances into the gastrointestinal tract to fight off the perceived ‘foreign invaders.’ The release of these substances inflames the esophageal lining, causing it to harden, narrow and even change shape overtime. In fact, endoscopic evaluations reveal that many EoE patients have unique esophageal features characterized by concentric rings and linear furrows. What scientists are trying to better understand is how eosinophils are tracking into the esophagus, where they are not meant to be.”
Virtually unknown even 15 years ago, this disease is increasing in prevalence and allergists are seeing more and more of this chronic condition in both adult and pediatric patients. Perhaps surprisingly, it is now even more common than other better-known diseases that affect the gastrointestinal tract, like Crohn’s Disease and Cystic Fibrosis.
Symptoms develop gradually, and can vary with age
The symptoms of EoE can vary with age, making it that much trickier to diagnose.
Infants and toddlers might present with irritability, feeding difficulties such as food regurgitation or refusal, or slow or poor growth. “It’s not unusual,” comments Dr. Chinthrajah, “for children with EoE to be mislabeled as picky eaters.” School-aged children can experience nausea, vomiting and stomach pain, while adolescents and adults most often have difficulty swallowing or food impaction. Unfortunately, because symptoms develop gradually, EoE is often misdiagnosed, or not caught at all until after tissue damage to the esophagus has already taken place.
Is EoE another manifestation of having allergies? “Allergies can contribute to the development of EoE, and 50% to 80% patients with EoE do have allergic disorders like asthma, allergic rhinitis, atopic dermatitis and food allergy,” explains Dr. Chinthrajah. “However, not all patients with EoE have allergies, pointing to other underpinnings of the disease. While its pathogenesis isn’t clear, studies have found several genes that are overexpressed in EoE patients. One of particular interest is the calpain-14 gene (CAPN14) because it is specifically expressed in the surface layer of the esophagus where food first comes in contact with the esophagus. Like other atopic conditions, EoE also appears to be associated with T cell immune responses. Cytokines –chemical messengers released by the T cells—are hypothesized to play an important role in the activation and recruitment of eosinophils in the esophagus.”
If EoE is suspected, the disease is confirmed through an upper endoscopy, during which biopsies are taken from the esophagus lining and evaluated for the presence of eosinophils. A high number of eosinophils in the middle esophagus, along with the patient’s symptoms, and exclusion of gastroesophageal reflux disease, suggest the diagnosis of EoE. Endoscopies are also routinely performed to assess treatment responsiveness. Recently, a new device has come under evaluation that would present a far less invasive alternative, if it becomes available to the public. In this test, the patient swallows an encapsulated sponge or “cytosponge”. Once the capsule dissolves, the sponge is pulled up from an attached string scraping off cells from the esophagus along the way—the presence or lack of eosinophils on the sponge would indicate whether or not treatment is successful.
Pharmacologic treatment works for some, others respond to dietary therapy
Currently, there is no cure for EoE, but corticosteroid medications originally intended for asthma sufferers can alleviate symptoms for some patients. A common therapeutic option involves combining topical steroid budesonide with other components, like Splenda or in Cole’s case, cake mix, to create a viscous slurry. When swallowed, the slurry coats the esophagus, decreasing pathogenic immune cells. While this therapy can be effective for patients like Cole, others do not respond to pharmacologic treatment and require dietary therapy. Still others find that a combination of both works best.
Dietary therapy is typically initiated with an elimination diet to identify and then eliminate the food trigger(s). These diets can range from removing the top 8 food allergens, or 4 food groups initially, and then sequentially reintroducing them. For others the elimination diet requires the complete elimination of all foods for a designated period during which time an amino-acid based formula is consumed. 15-year old Lowell underwent the latter, when he was 11.
For one whole month, he subsisted entirely on the specialized formula, ingesting it through a nasogastric feeding tube when he went to sleep—because, like many patients, he didn’t find the formula palatable. When his foods were reintroduced, starting with the top 8 allergens, his triggers were identified as soy, egg, and milk. These foods were promptly removed from his diet until his symptoms subsided, and the eosinophils went away. But as his mother explains, EoE symptoms tend to wax and wane, and never really go away. New triggers can be identified, often through trial and error in Lowell’s case.
If a month of complete food elimination seems extreme, Dr. Chinthrajah explains that this period can actually be much longer for some patients. What’s more, others afflicted by the disease can’t eat at all and only ever ingest their nutrition through the specialized formula, sometimes by drinking it, other times via feeding tubes.
While the majority of patients respond positively to dietary therapy, it is far from optimal—particularly in growing children. Topical corticosteroids appear to be safe when limited to the duration of treatment (usually 6-8 weeks). But the reported rate of symptom recurrence following treatment cessation is high, and patients are reluctant to use pharmacologic therapy on a long-term basis, which is most likely necessary. That these are two of the few treatment options available to EoE patients, points to the immense need for further research to develop better therapeutic options. Research, including studies conducted at the Sean N. Parker for Allergy Research at Stanford University, seeks to better understand the immunologic mechanisms of the disease in order to develop novel targeted therapies.
Until then, Lowell’s mother advises others who have been diagnosed with EoE or who are caring for a child with this condition, to seek community support as they navigate the disease. In addition to attending EoE conferences where Lowell had a chance to meet other kids also trying to manage the disease, she recommends websites like http://www.apfed.org and http://community.kidswithfoodallergies.org/forum/gastrointestinal-disorders as strong resources for connecting with others.
By Leslie Adato
Leslie Adato is the Director of Digital Communications at the Sean N. Parker Center for Allergy Research at Stanford University. She has a daughter with a peanut allergy and is committed to spreading awareness of Stanford’s cutting edge research, therapies and diagnostics to the community at large.