The ‘skinny’ on eosinophilic esophagitis
ABSTRACTEosinophilic esophagitis—a disease that even most physicians know little about—is becoming increasingly common. Often starting in childhood with eating difficulties and symptoms of gastroesophageal reflux disease, it progresses with increasing inflammation, fibrosis, and strictures until the esophagus is visibly narrowed on radiography. Early recognition and treatment with an allergen-avoidance diet and steroids are critical to avoiding or postponing complications.
KEY POINTS
- Eosinophilic esophagitis is an allergy-mediated, systemic disease.
- It is diagnosed by characteristic symptoms, esophageal biopsy (peak value ≥ 15 eosinophils per high-power field), and response to allergen avoidance or treatment with steroids.
- Therapy with a proton pump inhibitor should be tried even for patients with a classic presentation.
- Strict dietary avoidance of allergens has been shown to resolve the disease but is often impractical.
- Dilation is indicated for a narrowed esophagus but must be done cautiously because of the risk of tearing.
- How best to monitor the disease (eg, by annual endoscopy) is still uncertain.
Distinguishing eosinophilic esophagitis from gastroesophageal reflux disease
Distinguishing eosinophilic esophagitis from gastroesophageal reflux disease can be a challenge, as signs and symptoms overlap.
Veerappan et al23 looked for predictors of eosinophilic esophagitis in 400 adults who underwent routine upper endoscopy, 6.5% of whom had eosinophilic esophagitis. They found significant overlap in medical history for patients with and without the disease; while a higher proportion of patients with eosinophilic esophagitis had a history of asthma, dysphagia, food impactions, dermatitis, and food allergies, these conditions also occurred in other patients.
Similarly, the classic endoscopic findings of eosinophilic esophagitis—rings, furrows, strictures, and plaques—also occur in other conditions.23 Reflux disease can cause scarring from excess acid and may even be associated with eosinophils in the esophagus, indicative of a combination of allergy and reflux. A small-caliber esophagus is also occasionally present in patients with reflux disease.
Ambulatory pH monitoring has been recommended to help determine if gastroesophageal reflux is the cause of esophageal eosinophilia and to guide therapy. However, in a prospective study of 51 patients,24 neither positive nor negative results of initial pH monitoring accurately predicted response to PPIs or steroid therapy. Another study found that half of patients with an eosinophilic esophagitis profile without evidence of acid reflux by pH monitoring responded to treatment with a PPI.25
This raises the question of whether some patients with eosinophilic esophagitis have more acid reflux than is detected by pH monitoring, or alternatively, whether PPIs have other, less-recognized effects besides reducing acidity. Investigators are now ascribing a host of anti-inflammatory actions to PPIs, including effects on antioxidants, inflammatory cells, endothelial cells, and the gut microflora.26 And PPIs may alleviate eosinophilic esophagitis through anti-inflammatory effects rather than by inhibiting secretion of gastric acid.
THREE TYPES OF THERAPY
In general, three types of therapy are available for patients with eosinophilic esophagitis: medications, allergen avoidance, and esophageal dilation (Table 2).
Medications: Try a PPI first, then a corticosteroid
A PPI should be tried even for patients with a classic presentation of eosinophilic esophagitis because some will respond, and long-term PPI therapy is preferable to long-term steroid treatment. Patients should be put on a 2-month course and should then undergo repeat biopsy.
For patients who do not respond to a PPI, a corticosteroid or montelukast can be tried. Topical therapy is showing promise as both a short- and long-term option to bring about remission.27 For administration, a corticosteroid (budesonide or fluticasone) is mixed with a viscous solution, such as water with honey or chocolate syrup, making it thick so it better coats the esophagus. The therapy can be very effective: in up to 8 weeks some patients have a 90% resolution of esophageal eosinophilia. However, about 5% of patients develop a yeast infection, and adrenal suppression is a concern but appears to be uncommon.
Avoidance of allergens
Because eosinophilic esophagitis is an allergic disease, eliminating allergens should be an effective treatment. Unfortunately, from a practical standpoint, elimination is very difficult. The elemental diet formula is expensive and unpalatable, making it impractical for a prolonged period.
Gonsalves et al28 put 50 adult patients with eosinophilic esophagitis on a diet eliminating the six most common foods believed to trigger the disease—wheat, milk, nuts, eggs, soy, and seafood—and found a marked reduction in eosinophils in the proximal and distal esophagus after 6 weeks. Additional triggers that have been identified include rice, corn, and legumes.29
Unfortunately, maintaining a diet without the most commonly identified allergens is not easy. Although some very motivated patients can do it, it is especially hard for teens and young adults. Variations of the diet, such as eliminating just two foods, make following a plan easier. Omitting milk alone would benefit an estimated 20% of patients with eosinophilic esophagitis.
Identifying food triggers is a challenge in itself as there is no good noninvasive method of identifying the allergens. The radioallergosorbent test measures immunoglobulin (Ig) E, and the skin-prick test measures acute hypersensitivity, but neither is very sensitive for the Th2-mediated reaction involved in eosinophilic esophagitis. In early trials, endoscopy and biopsy were painstakingly performed with the removal and reintroduction of every suspected food allergen, requiring multiple biopsies weekly, which is impractical for safety and economic reasons.
Attempts are being made to devise less invasive methods of sampling the esophageal mucosa. Transnasal endoscopy—done as an outpatient procedure with topical anesthesia—is a possibility. Another possibility is the esophageal string test,30 which involves swalling a weighted capsule on a string and then, after an hour, pulling it up again and testing the tissue on the string.
The “cytosponge,” a new device currently under investigation, also uses a string delivery system. The patient swallows a sponge contained in a gelatin capsule and attached to a string. When the capsule dissolves in the stomach—a process that takes only a few minutes—the sponge expands. The string is then pulled up, causing the sponge to sample the esophageal mucosa and thus obtaining a histologic specimen. This method shows promise as an inexpensive and noninvasive way to monitor the disease, although larger studies are needed to establish efficacy.31
Dilation—proceed with caution
Dilation can be an important therapy, especially in teenagers and adults with a fibrotic, narrowed esophagus.
Early on, the procedure often resulted in complications such as deep mucosal tears and perforations. Jung et al32 retrospectively analyzed 293 dilations in 161 patients with eosinophilic esophagitis and found a deep mucosal tear in 27 patients (9%), three perforations, and one incidence of major bleeding. All complications resolved without surgery. Factors associated with increased risk of complications were luminal narrowing in the upper and middle third of the esophagus, a luminal stricture that could not be traversed with a standard upper endoscope, and use of a Savary dilator.
It is critical that dilation be done slowly—a few millimeters at a time. Several sessions may be needed.
TREATMENT DURING REMISSION IS CONTROVERSIAL
Unless the patient with eosinophilic esophagitis can consistently control the disease by avoiding allergens, the question arises of whether to continue treating a patient who is in remission.
On the one hand, there is no known risk of Barrett esophagus or malignancy when the condition is not treated, and weight loss is uncommon because patients tend to accommodate to the condition. However, the long-term consequences are uncertain. Allergies are chronic, and disease progression with more fibrosis should be prevented. Also, food impaction commonly occurs and this requires aggressive dilation, which is risky.
On the other hand, chronic steroid therapy involves risk. The optimum steroid dosage during remission and whether alternate-day dosing is adequate have yet to be determined.
Long-term trials are needed to answer these questions. In the meantime, most physicians tend to aggressively treat this disease, if not with specific food avoidance, then with steroid maintenance therapy.
MONITORING THE DISEASE
Monitoring eosinophilic esophagitis by clinical indicators is difficult. Once fibrosis develops, symptoms often do not reflect underlying pathology. It may turn out that, as in Crohn disease, monitoring mucosal healing rather than symptoms may be best.
Until we know more about this condition, careful monitoring of patients is important. However, it is too early to give specific guidance, such as endoscopy every 2 months or annually. Whether the eosinophil count should be the critical consideration is also unknown.
