Eosinophilic esophagitis: An increasingly recognized cause of dysphagia, food impaction, and refractory heartburn
ABSTRACTEosinophilic esophagitis is an increasingly recognized cause of a variety of esophageal symptoms, including dysphagia, food impaction, atypical chest pain, and heartburn that does not respond to medical therapy. Its cause is unknown, but allergic and immunemediated mechanisms similar to those of asthma and other atopic diseases are implicated.
KEY POINTS
- The diagnosis is made with upper endoscopy and esophageal biopsies that show diffuse infiltration of eosinophils.
- Current treatment in adults is limited and consists of either swallowed fluticasone (Flonase) or a proton pump inhibitor.
- Because many patients with eosinophilic esophagitis have atopic disease, a complete evaluation for dietary allergens and aeroallergens is recommended, as avoidance of these allergens may be helpful in some adults.
- Cautious endoscopic dilation is a treatment option in patients with evidence of esophageal stenosis. Systemic corticosteroids and novel biologic therapy have been used in refractory cases.
NATURAL HISTORY: CHRONIC, RELAPSING, AND MOST LIKELY BENIGN
Our understanding of the natural history of eosinophilic esophagitis is limited, but the available evidence suggests that its prognosis is favorable.
Thirty adults followed for up to 11.5 years remained in good health, maintained their weight, and had no evidence of nutritional deficiencies.26 However, all but 1 patient continued to have dysphagia, with the overall intensity of dysphagia increasing in 7 (23%), remaining stable and persistent in 11 (37%), and decreasing in the remainder. In over half of these patients, the disease impaired quality of life. The only treatment offered was endoscopic dilation, which 11 patients required. Patients with peripheral blood eosinophilia and those with more pronounced findings on endoscopy were more likely to have symptoms at follow-up.
Although dysphagia persisted, the number of eosinophils in esophageal biopsy specimens decreased significantly over time, suggesting that the intense eosinophilic infiltration seen earlier in the disease may evolve into fibrosis and remodeling, similar to that seen in asthma and other chronic atopic diseases. Unlike in Barrett esophagus, a premalignant complication of longstanding GERD, there appeared to be no increased risk of esophageal cancer in these patients with eosinophilic esophagitis during the follow-up period.26
TREATMENT
Dietary therapy
Strict elemental amino-acid diets have resulted in complete symptomatic and histologic resolution of eosinophilic esophagitis in children. However, these elemental diets often have to be given by nasogastric tube because they are unpalatable, and the disease tends to return once the diet is discontinued.27
Elimination diets, based either on avoiding the six foods most commonly associated with allergy (egg, wheat, soy, cow’s milk protein, seafood, peanuts) or on allergy testing such as skin prick testing or atopy patch testing, have shown promise in children.12,28 However, similar large-scale studies of elimination diets in adults have not been conducted.
Allergy evaluation
The recent consensus recommendations devoted considerable attention to the role of allergy evaluation.19 Between 50% and 80% of patients with eosinophilic esophagitis have a coexisting atopic disease such as atopic dermatitis, eczema, allergic rhinitis, or asthma, with a higher prevalence in children than in adults. In these patients, evidence suggests that allergy testing may predict response to therapy. Therefore, the current recommendation is for all patients with eosinophilic esophagitis to undergo a complete evaluation by an experienced allergist.
Checking the peripheral blood eosinophil count before and after treatment is reasonable, as many patients have elevated eosinophil counts that decrease after treatment.
Similarly, many patients with eosinophilic esophagitis have elevated serum total IgE levels, which suggests a concomitant atopic disease. Therefore, total IgE levels should also be checked before and after treatment. Checking for IgE against specific aeroallergens is recommended, but checking for IgE against specific food antigens has not proven beneficial at this time. Similarly, skin prick testing for aeroallergens may be useful, but not for food allergens.
Data on atopy patch testing in eosinophilic esophagitis are currently limited but promising.19
Medical therapy
Swallowed fluticasone (Flonase, using an inhaler) is the mainstay of therapy for both children and adults.
In one case series, 21 adult patients with eosinophilic esophagitis received a 6-week course of swallowed fluticasone 220 μg/puff, two to four puffs twice daily. Symptoms completely resolved in all patients for at least 4 months, and no patient needed endoscopic dilation.29
In another study, 19 patients treated with fluticasone for 4 weeks showed dramatic improvement both symptomatically and histologically. However, after 3 months, 14 (74%) of the 19 patients had a recurrence of symptoms, pointing to the chronic relapsing nature of this disease.30
The only randomized placebo-controlled trial of fluticasone to date has been in children. Konikoff et al31 found that a 3-month course of fluticasone induced remission, defined as less than one eosinophil per high-power field, in 50% of patients, compared with 9% in the placebo group.
Swallowed fluticasone is generally well tolerated, although cases of esophageal candidiasis have been reported.30
Acid suppression still has an unclear role in the treatment of eosinophilic esophagitis. As mentioned above, the disease is defined as the presence or persistence of esophageal eosinophilia after acid reflux has been maximally treated or ruled out. Most patients referred for further evaluation of eosinophilic esophagitis have tried twice-daily proton pump inhibitor therapy without success. The impact of concomitant therapy with a proton pump inhibitor has not yet been determined, but the recent guidelines suggest that these drugs are reasonable as co-therapy in patients who also have GERD symptoms.19
In patients whose symptoms do not improve with fluticasone, several other medications have been used:
Systemic corticosteroids have been used with success in both adults and children with hypereosinophilic syndromes, as well as in patients with refractory eosinophilic esophagitis, but adverse effects limit their routine and long-term use.
Cromolyn sodium (NasalCrom, Intal), a mast cell stabilizer, and montelukast (Singulair), a leukotriene inhibitor, have been used with limited success.32
Mepolizumab (Bosatria), a humanized monoclonal antibody to human interleukin 5, decreased the number of eosinophils in the esophagus and peripheral blood and improved clinical symptoms in patients with refractory eosinophilic esophagitis in a recent open-label trial.33 Further studies with mepolizumab and other biologic agents are expected.
Endoscopic dilation
Endoscopic dilation with either a guidewire or a balloon technique is often used to treat strictures and a diffusely narrowed esophagus in patients with eosinophilic esophagitis.
As mentioned above, a common endoscopic feature is mucosal fragility, which has been described as resembling crepe paper. Shearing and longitudinal splitting of this fragile mucosa may occur after dilation therapy.
Although esophageal dilation may be done safely in patients with eosinophilic esophagitis, the risk of perforation appears to be greater than in those with other indications for dilation.
Nevertheless, immediate symptomatic improvement has been reported in 83% of patients after dilation, with symptoms recurring in 20% within 3 to 8 months.34 Current recommendations suggest that dilation should be done cautiously in patients who have documented esophageal narrowing for which drug therapy has failed.
