Hot Topic Allergy: Dietary therapy in eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a chronic, immune-mediated inflammatory disorder that responds to dietary therapy; however, data evaluating the effectiveness of dietary therapeutic strategies are limited. EE is a recently described disorder identified in patients with symptoms suggestive of gastroesophageal reflux disease (GERD) but unresponsive to conventional reflux therapies. Therapies have included corticosteroids, elemental diet, and diet restriction.

Eosinophilic esophagitis is a disease entity in which patients have (1) elevated eosinophils on esophageal biopsy and (2) symptoms of gastroesophageal reflux. The symptoms do not improve on aggressive acid blockade but do improve on elimination diet or corticosteroid treatment, which tentatively links food allergies to this disorder.

Eosinophilic esophagitis (EoE) is an immune-mediated chronic inflammatory disorder triggered by food antigen(s). A 6-food elimination diet (SFED) excluding cow’s milk, soy, wheat, egg, peanuts/tree nuts, and seafood has been shown to induce remission in a majority of children with EoE. The goal of the present study was to identify specific food antigens responsible for eosinophilic esophageal inflammation in children with EoE who had achieved histological remission with the SFED.

Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis.

The study compared the effectiveness of 3 frequently prescribed dietary therapies (elemental, 6-food elimination, and skin prick and atopy patch-directed elimination diets) and assessed the remission predictability of skin tests and their utility in directing dietary planning.

A retrospective cohort of proton-pump inhibitor-unresponsive, non-glucocorticoid-treated patients with eosinophilic esophagitis who had 2 consecutive endoscopic biopsy specimens associated with dietary intervention was identified. Biopsy histology and remissions (<15 eosinophils/high-power field) after dietary therapy and food reintroductions were evaluated.

Ninety-eight of 513 patients met the eligibility criteria. Of these 98 patients, 50% (n = 49), 27% (n = 26), and 23% (n = 23) received elemental, 6-food elimination, and directed diets, respectively. Remission occurred in 96%, 81%, and 65% of patients on elemental, 6-food elimination, and directed diets, respectively. The odds of postdiet remission versus nonremission were 5.6-fold higher (P = .05) on elemental versus 6-food elimination diets and 12.5-fold higher (P = .003) on elemental versus directed diets and were not significantly different (P = .22) on 6-food elimination versus directed diets. After 116 single-food reintroductions, the negative predictive value of skin testing for remission was 40% to 67% (milk, 40%; egg, 56%; soy, 64%; and wheat, 67%).

All 3 dietary therapies are effective; however, an elemental diet is superior at inducing histologic remission compared with 6-food elimination and skin test-directed diets. Notably, an empiric 6-food elimination diet is as effective as a skin test-directed diet. The negative predictive values of foods most commonly reintroduced in single-food challenges are not sufficient to support the development of dietary advancement plans solely based on skin test results.

Spergel JM, et al. reported that experience with skin prick and atopy patch testing and food elimination diets in patients diagnosed as having EE. These study identify food antigens that cause EE and the characteristics of patients who respond to food elimination vs those who are unresponsive.

Patients diagnosed as having EE had restricted diets based on skin prick and atopy patch testing results. Additional biopsies were performed after 4 to 8 weeks of restricted diet. Demographics, atopic tendencies, and food antigens were identified retrospectively in our food allergy database.

A total of 146 patients diagnosed as having EE were evaluated with skin prick and atopy patch testing. Thirty-nine patients had unequivocal demonstration of food causing EE, with normalization of biopsy results on elimination and reoccurrence on reintroduction. An additional 73 patients, for a total 112 (77%) of 146 patients, had resolution of their EE as demonstrated by biopsy results. Fifteen (10%) of 146 patients were nonresponders manifested by no significant reduction in esophageal eosinophils despite restricted diet based on skin prick and atopy patch testing. Egg, milk, and soy were identified most frequently with skin prick testing, whereas corn, soy, and wheat were identified most frequently with atopy patch testing.

In more than 75% of patients with EE, both symptoms and esophageal inflammation can be significantly improved with dietary elimination of foods. Skin prick and atopy patch testing can help identify foods in most patients.

Skin prick tests and patch tests to identify causative foods

Spergel JM, et al. Reported that identify potential food antigens in eosinophilic esophagitis. Patients with eosinophilic esophagitis were identified by biopsy. Potential food antigens were identified prospectively by skin prick testing and patch testing, which were performed through use of standard methods. Atopic tendencies, demographics, and potential food allergies were identified. Repeat esophageal biopsies were reviewed when possible.

A total of 26 patients (22 male, 4 female) with a biopsied-confirmed diagnosis of eosinophilic esophagitis underwent both skin prick testing and patch testing to identify potential causative foods. Milk and egg were the most common positive foods with skin prick testing. Wheat was the most common positive food with patch testing. The patients were advised to avoid positive foods as identified by skin prick testing and patch testing. In all, 18 patients had resolution of their symptoms, 6 patients had partial improvement, and 2 were lost to follow-up. Overall, after intervention, esophageal eosinophil counts improved from 55.8 to 8.4 eosinophils per high-power field. The foods most commonly identified by patients as causing symptoms were milk and egg. The combination of skin prick testing and patch testing can identify potential causative foods that might contribute to the pathogenesis of eosinophilic esophagitis.

Kagalwalla AF, et al reported that identify specific food antigens responsible for eosinophilic esophageal inflammation in children with EoE who had achieved histological remission with the SFED. The analyzed children with EoE who completed subsequent single-food reintroductions that led to identification of foods causing disease recurrence. Repeat upper endoscopy with biopsies was performed after single-food introductions. Recurrence of esophageal eosinophilia following a food reintroduction identified that food antigen as a cause of EoE.

A total of 36/46  (25 M/11F) children who were initially successfully treated with SFED completed this trial; the mean age was 7.6  ±  4.3 years. The most common foods identified were 25 to cow’s milk (74%), 8 to wheat (26%), 4 to eggs (17%), 3 to soy (10%), and 1 to peanut (6%). Milk was 8 times more likely to cause EoE compared with wheat, the next most common food (95% confidence interval 2.41-26.62, P = 0.0007). Serial single-food reintroductions following induction of histological remission with the SFED can lead to the identification of specific causal food antigen(s) in EoE. Cow’s milk was the most common food identified in subjects with EoE treated with SFED. A subset of children with EoE may develop tolerance to their food sensitivities while on the SFED.

References:

Henderson CJ, et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012 Apr 25.

Spergel JM, et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol. 2005 Oct;95(4):336-43.

Spergel JM, et al. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol. 2002 Feb;109(2):363-8.

Kagalwalla AF, et al. Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr. 2011 Aug;53(2):145-9.

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