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Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis

2012; Elsevier BV; Volume: 130; Issue: 5 Linguagem: Inglês

10.1016/j.jaci.2012.06.027

1097-6825

Javier Molina‐Infante, Elisa Martín-Noguerol, Manuela Alvarado-Arenas, Sergio L. Porcel-Carreño, Soledad Jimenez-Timon, Francisco Javier Hernandez-Arbeiza,

Eosinophilic Disorders and Syndromes

Eosinophilic esophagitis (EoE) is an increasingly recognized chronic immune/antigen-mediated, food allergy–associated, inflammatory esophageal disorder.1Liacouras C.A. Furuta G.T. Hirano I. Atkins D. Attwood S.E. Bonis P.E. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-10Abstract Full Text Full Text PDF PubMed Scopus (1561) Google Scholar Dietary therapy remains the therapeutic nonpharmacologic cornerstone for EoE. An elemental diet based on an amino acid–based formula is the most effective form of dietary therapy in children, but it is usually kept for treatment failures because of its poor palatability and strictness.1Liacouras C.A. Furuta G.T. Hirano I. Atkins D. Attwood S.E. Bonis P.E. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-10Abstract Full Text Full Text PDF PubMed Scopus (1561) Google Scholar The 6-food elimination diet (SFED) with reintroduction of offending foods and endoscopic re-evaluation has shown a high degree of effectiveness in both children2Kagalwalla A.F. Shah A. Li B.U. Sentongo T.A. Ritz S. Manuel-Rubio M. 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; 53: 145-149Crossref PubMed Scopus (211) Google Scholar and adults3Gonsalves N. Yang G.Y. Doerfler B. Ritz S. Ditto A.M. Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults: food reintroduction identifies causative factors.Gastroenterology. 2012; 142 (e1): 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar with EoE, although this strategy is lengthy and expensive because it requires multiple upper endoscopies. A selective elimination diet based on skin testing has shown promising results in large series in children (75% symptomatic and histologic improvement),4Spergel J.M. Andrews T. Brown-Whitehorn T.F. Beausoleil J.L. Liacouras C.A. Treatment of eosinophilic esophagitis with specific elimination diet directed by a combination of skin prick and patch test.Ann Allergy Asthma Immunol. 2005; 95: 336-343Abstract Full Text PDF PubMed Scopus (405) Google Scholar, 5Spergel J.M. Brown-Whitehorn T. Beausoleil J.L. Shuker M. Liacouras C.A. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis.J Allergy Clin Immunol. 2007; 119: 509-511Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar with high positive (>74%) and negative (88% to 100%) predictive values for almost all foods,5Spergel J.M. Brown-Whitehorn T. Beausoleil J.L. Shuker M. Liacouras C.A. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis.J Allergy Clin Immunol. 2007; 119: 509-511Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar but data in adults thus far are represented by 2 small series of 6 and 2 patients, respectively.6Simon D. Straumann A. Wenk A. Spichtin H. Simon H.-U. Braathen A.R. Eosinophilic esophagitis in adults: no clinical relevance of wheat and rye sensitizations.Allergy. 2006; 61: 1480-1483Crossref PubMed Scopus (81) Google Scholar, 7González-Cervera J. Angueira T. Rodriguez-Domínguez B. Arias A. Yagüe-Compadre J.L. Lucendo A.J. Successful food elimination therapy in adult eosinophilic esophagitis: not all patients are the same.J Clin Gastroenterol. 2012; ([Epub ahead of print])PubMed Google Scholar We prospectively analyzed the efficacy of the elimination diet based on multimodality skin testing in consecutive adults with EoE, which was defined by age greater than 18 years, dysphagia and/or food impaction, and persistent esophageal eosinophilia (>15 eosinophils/high-powered field [hpf]), who are taking high-dose proton-pump inhibitor therapy (omeprazole, 40 mg twice daily). Atopy was defined in both patients and their families by the presence of eczema, allergic rhinoconjunctivitis, reactive airway disease, or food allergies. All patients underwent skin prick tests (SPTs), prick-prick tests (PPTs), and atopy patch tests (APTs) to 26 different foods: milk, egg, grains (wheat, corn, rye, barley, oat, and rice), peanuts, legumes (soy, lentils, peas, and beans), meats (beef, chicken, and pork), vegetables (potato and tomato), seafood (shrimp), fish (hake), and fruits (melon, kiwi, apple, strawberry, banana, and peach). SPTs to commercial food extracts (ALK-Abelló, Madrid, Spain) and PPTs to fresh foods were performed on the forearm with disposable lancets (ALK-Abelló). Reactions were recorded by measuring the largest diameter of the wheal in millimeters at 15 minutes. Histamine (10 mg/mL) was used as a positive control, and saline solution was used as a negative control. The test result was considered positive if the largest wheal diameter was at least 3 mm. APTs were conducted with 2 g of dry foods in 2 mL of isotonic saline solution. The mixtures were placed in aluminum cups (6- or 12-mm Finn chambers on Scanpore; Allerderm Laboratories, Petaluma, Calif) and adhered to the patient's back, as described by Spergel et al.4Spergel J.M. Andrews T. Brown-Whitehorn T.F. Beausoleil J.L. Liacouras C.A. Treatment of eosinophilic esophagitis with specific elimination diet directed by a combination of skin prick and patch test.Ann Allergy Asthma Immunol. 2005; 95: 336-343Abstract Full Text PDF PubMed Scopus (405) Google Scholar, 5Spergel J.M. Brown-Whitehorn T. Beausoleil J.L. Shuker M. Liacouras C.A. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis.J Allergy Clin Immunol. 2007; 119: 509-511Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar The size of the Finn chambers was determined in an age- and size-dependent manner. Undiluted, single-ingredient, commercially prepared baby food, including fruits, vegetables, and meats, was placed in Finn chambers. The patches were removed at 48 hours, and results were read at 72 hours. Reactions considered positive were classified as + for erythema and scattered papules, ++ for erythema and papules, and +++ for erythema and vesicles as per standard patch-testing protocols. A 6-week elimination diet based on SPT, PPT, and APT results was proposed for patients with EoE. An individualized diet was designed by removing every food with at least 1 positive result in any of the 3 skin tests evaluated because it is well known that food allergy cannot be excluded only because SPT responses are negative. Patients were informed extensively by a certified external nutritionist about identifying offending foods, especially cereals; given sample menus; and instructed on methods for reading labels. Afterward, all patients completed a 2-week dietary diary, which was carefully reviewed to document adherence and possible dietary contamination, before initiating the elimination diet. Medications for rhinoconjunctivitis or asthma, including nasal or inhaled glucocorticoids, were permitted during the 6-week period if necessary. Control esophageal biopsy specimens were taken from the upper and lower esophageal thirds, with a minimum of 5 specimens taken at each location. Biopsy specimens were fixed in formalin, embedded in paraffin, and stained with hematoxylin and eosin for histopathologic examination. One hpf had an area of 0.24 mm2. The eosinophil count for each patient was defined by the peak count of intraepithelial eosinophils/hpf (×400 magnification) in the area of highest density of eosinophils along the 3 most densely populated hpfs.1Liacouras C.A. Furuta G.T. Hirano I. Atkins D. Attwood S.E. Bonis P.E. et al.Eosinophilic esophagitis: updated consensus recommendations for children and adults.J Allergy Clin Immunol. 2011; 128: 3-10Abstract Full Text Full Text PDF PubMed Scopus (1561) Google Scholar Disease resolution was defined by both clinical (complete disappearance of symptoms) and histologic (<5 eosinophils/hpf) remission, whereas the outcome was considered a partial response when peak esophageal eosinophilia was between 5 and 15 eosinophils/hpf and symptoms improved but did not resolve. Those patients who were symptomatic with greater than 15 eosinophils/hpf after dietary modification were considered nonresponders. A total of 22 consecutive adults with EoE were evaluated. Demographic, clinical, endoscopic, and histologic baseline characteristics of the cohort were consistent with typical EoE (Table I). The most common food allergies identified by using SPTs, PPTs, and APTs are listed in Table II. Overall, the most common food sensitizations in our population were to legumes, barley, rye, tomato, fruits, nuts, potato, corn, seafood, and egg. Two patients were found not to be sensitized to any food after multiple tests, whereas 5 patients rejected the treatment because of its complexity and preferred to undergo therapy with topical steroids. Finally, 15 patients followed 6-week elimination diet based on multimodality allergy testing. Four (26%) patients achieved complete remission on a selective elimination diet, whereas another patient achieved clinical remission with a partial histologic response (14 eosinophils/hpf). The remaining 10 (66%) patients did not achieve either a clinical or histologic response with the elimination diet (Fig 1). Among the 4 responders to the elimination diet, the foods removed were as follows: patient 1, fish and seafood; patient 2, wheat, egg, milk, barley, rye, legumes, potato, tomato, fish, seafood, and chicken; patient 3, wheat, barley, oat, rice, legumes, nuts, and tomato; and patient 4, milk, rye, corn, rice, nuts, tomato, fish, and seafood. Food reintroduction is being carried currently in patients 2 to 4 to confirm offending allergens, whereas patient 1 simply avoids fish and seafood. Among patients who were reluctant to diet, had negative allergy test results, or were unresponsive to an elimination diet, 14 (82%) of 17 achieved complete remission with topical steroids (swallowed fluticasone propionate nasal drops, 400 μg twice daily for 6 weeks).Table IBaseline characteristics of patients included in the studyTotalNo. of patients22Demographics Male/female17/5 (77%/23%) Age (y)34 (18-62) Familial history of atopy14 (63%) Atopy19 (87%)Rhinoconjunctivitis15 (68%)Reactive airway disease10 (45%)Aeroallergen sensitization16 (72%)Food allergies6 (22%)Main symptom Dysphagia18 (81%) Food impaction12 (54%) Heartburn/regurgitation10 (45%)Endoscopic findings Endoscopic pattern of EoE22 (100%) Linear furrows17 (77%) Whitish exudates12 (54%) Rings10 (45%) Stricture3 (14%)Histopathologic findings Peak eosinophil count/hpf68 (22-133) Eosinophil superficial distribution17 (77%) Degranulating eosinophils15 (68%) Eosinophil microabscesses11 (50%) Basal cell hyperplasia22 (100%) Papillary elongation22 (100%) Intercellular edema22 (100%)Qualitative variables are expressed as absolute values and proportions. Continuous variables are expressed as means (SDs) or medians (ranges) as appropriate. Open table in a new tab Table IIFood sensitization detected by using multimodality allergy testing in 22 adults with EoE in the studySPTPPTAPTNo. of positive results, median (range)2.1 (0-12)6.6 (0-18)0.5 (0-3)Patients with no foods identified10/22 (45%)6/22 (27%)17/22 (77%)Wheat1 (4.5%)4 (18%)0Milk04 (18%)1 (4,5%)Egg2 (9%)5 (22%)0Legumes8 (36%)10 (45%)3 (13%)Fish3 (13%)4 (18%)0Seafood3 (13%)5 (22%)1 (4.5%)Barley2 (9%)8 (36%)0Rye1 (4.5%)8 (36%)0Tomato1 (4.5%)8 (36%)1 (4.5%)Potato1 (4.5%)6 (27%)1 (4.5%)Corn1 (4.5%)6 (27%)0Rice1 (4.5%)2 (9%)0Nuts6 (27%)6 (27%)0Fruits7 (31%)8 (36%)0Chicken1 (4.5%)3 (13%)1 (4.5%)Qualitative variables are expressed as absolute values and proportions. Continuous variables are expressed as means (SDs) or medians (ranges) as appropriate. Open table in a new tab Qualitative variables are expressed as absolute values and proportions. Continuous variables are expressed as means (SDs) or medians (ranges) as appropriate. Qualitative variables are expressed as absolute values and proportions. Continuous variables are expressed as means (SDs) or medians (ranges) as appropriate. To our knowledge, this is the largest series in adult EoE addressing the efficacy of a selective elimination diet based on 3 different skin tests. The first comparative study of dietary therapies for pediatric EoE was published recently.8Henderson C.J. Abonia J.P. King E.C. Putnam P.E. Collins M.H. Franciosi J.P. et al.Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis.J Allergy Clin Immunol. 2012; 129: 1570-1578Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar An elemental diet was the most effective (96%) in achieving remission, and of note, an empiric SFED (81%) was no less successful than the directed diet, as determined by using skin testing (65%). Our results show that a marginal proportion of adult patients might obtain benefit from a selective elimination diet because multimodality skin testing did not detect offending foods for adult EoE in 2 of every 3 patients. Our data are consistent with the reported loss of response to the elimination diet directed by skin testing in children as they become older than 14 years4Spergel J.M. Andrews T. Brown-Whitehorn T.F. Beausoleil J.L. Liacouras C.A. Treatment of eosinophilic esophagitis with specific elimination diet directed by a combination of skin prick and patch test.Ann Allergy Asthma Immunol. 2005; 95: 336-343Abstract Full Text PDF PubMed Scopus (405) Google Scholar and are quite similar to the data reported in the first series addressing the efficacy of SFED in adults,3Gonsalves N. Yang G.Y. Doerfler B. Ritz S. Ditto A.M. Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults: food reintroduction identifies causative factors.Gastroenterology. 2012; 142 (e1): 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar in which 67% of patients who had a food trigger identified by the reintroduction process had a negative SPT response. Elimination of wheat and rye in sensitized patients with EoE did not lead to resolution in a small series of 6 adults with EoE.6Simon D. Straumann A. Wenk A. Spichtin H. Simon H.-U. Braathen A.R. Eosinophilic esophagitis in adults: no clinical relevance of wheat and rye sensitizations.Allergy. 2006; 61: 1480-1483Crossref PubMed Scopus (81) Google Scholar Overall, emerging evidence is highlighting the limited usefulness of skin testing to guide dietary interventions in patients with EoE, especially adults. Among the 10 most common food sensitizations detected by means of skin testing in our series, only seafood and egg from SFEDs were present. Interestingly, a notably higher proportion or responders (complete or partial) in our series were sensitized to legumes (4/5 vs 4/10) and tomato (4/5 vs 3/10) compared with nonresponders. This observation coincides with a recent report from Spain7González-Cervera J. Angueira T. Rodriguez-Domínguez B. Arias A. Yagüe-Compadre J.L. Lucendo A.J. Successful food elimination therapy in adult eosinophilic esophagitis: not all patients are the same.J Clin Gastroenterol. 2012; ([Epub ahead of print])PubMed Google Scholar and might reflect a geographic pattern of sensitization different from that seen in other countries. Unfortunately, the small sample size prevents us from drawing definitive conclusions. APT results were negative in most patients, a result that was similar to that seen in the other 3 adults patients from Spain recently reported as undergoing dietary therapy.7González-Cervera J. Angueira T. Rodriguez-Domínguez B. Arias A. Yagüe-Compadre J.L. Lucendo A.J. Successful food elimination therapy in adult eosinophilic esophagitis: not all patients are the same.J Clin Gastroenterol. 2012; ([Epub ahead of print])PubMed Google Scholar Interestingly, in our series PPTs showed a higher rate of detecting food sensitization compared with SPTs and APTs, and therefore they deserve further consideration in patients with EoE. A relevant matter that might have influenced the response to a selective elimination diet is sensitization to aeroallergens. Adults with EoE are commonly sensitized to inhalant allergens that are believed to play a major causative role in adults with EoE. It is well known that EoE activity has seasonal variations, with documented exacerbations during pollen seasons and resolution during winter months.9Fogg M.I. Ruchelli E. Spergel J.M. Pollen and eosinophilic esophagitis.J Allergy Clin Immunol. 2003; 112: 796-797Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar In our series responders 2, 3, and 4 were sensitized to plant foods holding homologies with pollen sensitivities, but the diet was carried out in autumn and winter in 2 of 5 responders and 5 of 10 nonresponders. Undoubtedly, this is an unresolved issue that should be considered for future research in dietary therapy for adult EoE. In conclusion, a selective elimination diet based on skin testing has suboptimal efficacy for adults with EoE. The usefulness of skin testing for detecting offending foods in adults with EoE is questionable, especially APTs. Our results do not support the development of dietary therapy based exclusively on skin test results for adults with EoE, in whom the SFED seems the better dietary approach until more accurate food testing or genetic profiling predicting the response to diet are available. Variable yield of allergy patch testing in children with eosinophilic esophagitisJournal of Allergy and Clinical ImmunologyVol. 131Issue 2PreviewMolina-Infante et al1 published a prospective study in which they performed selective elimination diets in a cohort of 22 adults with eosinophilic esophagitis (EoE). They reported poor performance of skin prick and allergy patch tests (APTs) at identifying relevant foods. Another striking observation was their low rate of positive patch test results to foods (only 5 patients [23%] having a positive result), which contrasts with the very high rate reported in a previous large pediatric cohort, reaching up to 85%. Full-Text PDF