Food allergy and eosinophilic esophagitis: Learning what to avoid
ABSTRACTFood allergies have increased in prevalence significantly in the past decade and so, apparently, has eosinophilic esophagitis. Although the cause of eosinophilic esophagitis is unknown, allergic responses including food allergies have been implicated. This article reviews both conditions, focusing on how to detect and manage them.
KEY POINTS
- Food allergies can be classified as mediated by immunoglobulin E (IgE-mediated), non-IgE-mediated, or mixed. Their clinical presentation can vary from life-threatening anaphylaxis in IgE-mediated reactions to chronic, delayed symptoms as seen in eosinophilic esophagitis (a mixed reaction).
- The diagnosis of an IgE-mediated food allergy is made by taking a complete history and performing directed testing—skin-prick testing or measurement of foodspecific IgE levels in the serum, or both.
- Despite promising developments, food allergies continue to be treated primarily by telling patients to avoid allergens and to initiate therapy if ingestion occurs.
- Because most patients with eosinophilic esophagitis have a strong history of atopic disease and respond to allergen-free diets, a complete evaluation by a specialist in allergy and immunology is recommended.
Experimental treatments for food allergies
Humanized monoclonal anti-IgE antibodies such as talizumab (also known as TNX-901) and omalizumab (Xolair) have been developed, but their use in food allergy has been limited. In a study in patients with peanut allergy, injections of talizumab increased the threshold for sensitivity to peanuts in most patients, but 25% of the patients did not have any improvement.32 A study of omalizumab in patients with peanut allergy was stopped after adverse reactions developed during oral peanut challenges.33
Oral immunotherapy. Recent studies suggest it may be possible to induce oral tolerance in patients with IgE-mediated food allergy. Pilot studies have shown that frequent, increasing doses of food allergens (egg, milk, and peanut) may raise the threshold at which symptoms occur.34–36 Though these studies suggest that oral immunotherapy may protect some patients against a reaction if they accidentally ingest a food they are allergic to, some patients could not reach the goal doses because allergic symptoms were provoked.
At this early stage, these strategies must be considered investigational, and more randomized, placebo-controlled studies are needed. Further studies will also be needed to assess whether oral immunotherapy induces only short-term desensitization (in which case the allergen needs to be ingested daily to prevent reactions) or sustained tolerance (in which case the antigenic protein can be ingested without symptoms despite periods of abstinence).
THE ROLE OF FOOD ALLERGY IN EOSINOPHILIC ESOPHAGITIS
Eosinophilic esophagitis has been recognized with increasing frequency in both children and adults over the past several years. Symptoms can include difficulty feeding, failure to thrive, vomiting, epigastric or chest pain, dysphagia, and food impaction.
Diagnostic criteria for eosinophilic esophagitis are37:
- Clinical symptoms of esophageal dysfunction
- At least 15 eosinophils per high-power field in at least one esophageal biopsy specimen
- No response to a proton-pump inhibitor in high doses (up to 2 mg/kg/day) for 1 to 2 months, or normal results on pH probe monitoring of the esophagus (the reason for this criterion is that patients with gastroesophageal reflux disease can also have large numbers of eosinophils in the esophagus—more than 100 per highpower field38)
- Exclusion of other causes.
Though the cause of eosinophilic esophagitis is not completely understood, atopy has been strongly implicated as a factor. More than 50% of patients with eosinophilic esophagitis also have an atopic condition (eg, atopic dermatitis, allergic rhinitis, asthma), as well as positive results on skin-prick testing or measurement of antigen-specific IgE in the serum.39–41 Also, since most patients improve with either dietary restriction or elemental diets, food sensitization appears to play a considerable role.
As with atopic conditions such as asthma, atopic dermatitis, allergic rhinitis, and food allergy, eosinophilic esophagitis has been linked with immune responses involving helper T cell 2 (TH2). Adults and children with eosinophilic esophagitis have been found to have elevated eosinophil counts and total IgE levels in peripheral blood.37 In the esophagus, patients have elevated levels of the TH2 cytokines often seen in atopic patients (eg, interleukins 4, 5, and 13) and mast cells.42,43 In mice, eosinophilic esophagitis can be induced by allergen exposure and overexpression of TH2 cytokines.44,45 Expression of eotaxin-3, a potent eosinophil chemoattractant, was noted to be higher in children with eosinophilic esophagitis than in controls.46
Of interest, some patients with eosinophilic esophagitis say their symptoms vary with the seasons, correlating with seasonal changes in esophageal eosinophil levels.47,48
Studies linking eosinophilic esophagitis and food allergy in children
Kelly et al49 reported that 10 children with chronic symptomatic gastroesophageal reflux and eosinophilic esophagitis all had partial or complete resolution of symptoms on an elemental diet.
Markowitz et al50 found that symptoms of chronic reflux disease and eosinophilic esophagitis improved in 49 of 51 children on an elemental diet, and the number of eosinophils in the distal esophagus decreased significantly.
Liacouras et al39 reported similar findings in a 10-year experience. Of 132 children who had eosinophilic esophagitis, 75 improved with dietary restriction based on results of skin-prick and patch testing. The 57 patients who did not respond and 115 others were started on an elemental diet. Of the 164 patients who complied with the elemental diet, 160 had significant improvement of symptoms and a significant decrease in the number of eosinophils in the esophagus. Individual foods were reintroduced approximately every 5 days, and esophagogastroduodenoscopy with biopsies was performed 4 to 8 weeks after the last was reintroduced into the diet.
In a retrospective study, Kagalwalla et al51 reported that 60 children with eosinophilic esophagitis were treated with either an elemental diet or a six-food elimination diet (no milk, soy, wheat, egg, peanut, or seafood). The two groups showed similar clinical and histologic improvements.
Collectively, these studies in pediatric patients imply that food allergy is a significant factor in the pathogenesis of eosinophilic esophagitis.
