Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis: Comprehensive Appraisal With Off- and On PPI Impedance-pH Monitoring.

OBJECTIVES: Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. METHODS: Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). RESULTS: Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with PPI-responsive EoE and was a predictor of PPI failure. On PPI, a lower PSPW index was the sole reflux parameter distinguishing PPI-refractory from PPI-responsive EoE; all reflux parameters improved in PPI-responsive patients, whereas the PSPW index was not modified in PPI-refractory cases and was independently associated with PPI-responsiveness. MNBI in the distal and mid esophagus improved much more in PPI-responsive than in PPI-refractory EoE. DISCUSSION: Reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases. Low impedance gradient between the mid and distal esophagus may be useful to predict PPI refractoriness. PPIs mainly act by improving chemical clearance, i.e., by an antireflux action supporting long-term prescription in PPI-responsive EoE.

Eosinophilic esophagitis during sublingual and oral allergen immunotherapy.

PURPOSE OF REVIEW: The aim of this review is to discuss the current evidence regarding the development of eosinophilic esophagitis (EoE) in individuals undergoing oral and sublingual immunotherapy (SLIT) for both food and environmental allergens. Cumulative incidence of EoE in patients on allergen immunotherapy for peanut, milk, and egg is estimated. RECENT FINDINGS: De novo development of EoE in patients undergoing oral and SLIT has been demonstrated on the scale of case reports and prospective randomized trials. However, few individuals with EoE-like symptoms during immunotherapy undergo endoscopy, and the long-term outcomes of immunotherapy-associated EoE are unknown. SUMMARY: Evidence exists to suggest that allergen immunotherapy could place individuals at risk for the development of EoE, the true incidence of which may vary depending on antigen exposure and methods used to define the condition.

Complicación tras biopsia en una esofagitis eosinofílica / A complication following a biopsy sample in eosinophilic esophagitis

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Enfermedad celíaca, esofagitis eosinofílica y alergia a cereales: ¿existe alguna conexión? Importancia de los estudios moleculares para su tipificación / Celiac disease, eosinophilic esophagitis and cereal allergies: Is there a connection? Importance of molecular studies for patients classification

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Efficacy of IgE-targeted vs empiric six-food elimination diets for adult eosinophilic oesophagitis.

BACKGROUND: Skin testing-guided elimination diet has proved unsuccessful for adult eosinophilic oesophagitis (EoE), whereas empiric six-food elimination diet (SFED) achieves an efficacy of 70%. OBJECTIVE: To compare the efficacy of food-specific serum IgE-targeted elimination diet (sIgE-ED) and SFED. METHODS: Prospective study in adult patients with EoE. Food-specific serum IgE, skin prick test (SPT) and atopy patch test (APT) to foods included in SFED were performed. Those with ≥1 positive IgE test, defined by ≥0.1 kU/l, followed a 6-week sIgE-ED, whereas non-IgE-sensitized patients underwent a 6-week SFED. Responders to diet (<15 eos/HPF) underwent individual reintroduction of foods followed by histological assessment. RESULTS: Forty-three EoE patients were included (26 sIgE-ED and 17 SFED). Regarding sIgE-ED, the mean number of eliminated foods per patient was significantly lower than in SFED (3.81 vs 6; P < 0.001), being wheat (85%), nuts (73%) and cow's milk (61%) the most commonly foods withdrawn. No difference in histological response was observed between sIgE-ED and SFED (73% vs 53%, P = 0.17). Causative foods identified by food challenge were cow's milk (64%), wheat (28%), egg (21%) and legumes (7%), with a single food trigger in 71% of patients. sIgE exhibited the higher accuracy to predict offending foods in IgE-sensitized patients (sensitivity 87.5%, specificity 68% (κ = 0.43)), with k values of 1 for cow's milk. APT results were all negative. CONCLUSIONS: Histological remission was accomplished in 73% of patients undergoing sIgE-ED, which was nonsignificantly superior to SFED. sIgE effectively identified cow's milk as a food trigger in IgE-sensitized patients.

The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice.

BACKGROUND: Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response and increases the number of regulatory T cells (Tregs). Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and the allergen-specific Th2 responses and increases local and peripheral Foxp3(+) Tregs. OBJECTIVE: To investigate the role of Tregs in EPIT and characterize their phenotype and maintenance following EPIT. METHODS: Tregs were investigated using in vivo depletion or adoptive transfer into BALB/c mice. Tregs were depleted using anti-CD25 antibody injection during EPIT, and allergen-specific responses were compared with Sham, EPIT alone and naïve mice. To demonstrate that Tregs can mediate protection by their own, and to study their maintenance following the end of EPIT, CD25(+) CD4(+) Tregs isolated from mice just after or 8 weeks after EPIT were transferred into peanut-sensitized mice. Foxp3-IRES-mRFP mice were transferred with EPIT-induced Tregs to analyse the induction of host Tregs. RESULTS: The anti-CD25 antibody injection to EPIT mice abrogated the induction of Tregs in spleen and the expression of Foxp3 in oesophagus. This resulted in levels of peanut-induced eosinophilic infiltration in oesophagus similar to Sham and significantly higher than EPIT. Whereas the transfer of Tregs from Sham-treated mice demonstrated no effect, the transfer of Tregs isolated just after EPIT prevented peanut-induced eosinophil infiltration and eotaxin expression and induced Foxp3 in oesophagus. The transfer of Tregs isolated 8 weeks after EPIT suppressed allergen-specific responses as efficiently as did Tregs isolated just after EPIT and increased spleen Foxp3(+) CD25(+) CD4(+) cells similarly. The use of reporter mice demonstrated an increase in host Tregs. CONCLUSIONS: These results confirm the Tregs-mediated mechanism of EPIT and demonstrate the persistence of efficient Tregs during a long period of time after treatment cessation. This suggests that EPIT induces long-term tolerance in peanut-sensitized mice.

Tolerance of a cow's milk-based hydrolyzed formula in patients with eosinophilic esophagitis triggered by milk.

BACKGROUND: Cow's milk protein, a major food trigger for EoE in both children and adults, should be continuously avoided once identified as such. This study evaluates tolerance of a cow's milk-based extensively hydrolyzed formula (eHF) with regard to disease remission maintenance in adult patients with milk-triggered EoE. METHODS: Seventeen adult patients in whom cow's milk was consecutively demonstrated to trigger EoE after an empiric six-food elimination diet-based study protocol and who subsequently maintained disease remission were prospectively recruited. They were given 400 ml of a cow's milk-based eHF daily for 8 weeks. Intraepithelial peak eosinophil and blood eosinophil counts, esophageal-related symptoms, serum total and specific IgE to major milk proteins, and eosinophil cationic protein were monitored before and after eHF intake. RESULTS: Thirteen male and four female patients aged 17-56 completed the study protocol. 15 patients (88.24%) achieved and maintained EoE remission, while an infiltration of ≥15 eosinophils/hpf reappeared in the remaining two patients. No differences in age, gender, symptoms, and endoscopic appearance at baseline conditions or personal/family allergic background were observed between those patients who tolerated the eHF and those who did not. Symptom scores did not significantly change after eHF intake and were significantly lower than those documented at baseline conditions or after cow's milk challenge. No differences were documented in blood eosinophil counts or serum markers after eHF intake. CONCLUSION: Most adult patients with EoE triggered by cow's milk tolerate a cow's milk-based eHF, thus providing them with a safe, economical alternative to cow's milk.

An allergic phenotype and the use of steroid inhalers predict eosinophilic oesophagitis in patients with asthma.

BACKGROUND: Patients with eosinophilic oesophagitis (EoE) commonly have asthma and atopy. AIMS: To determine the predictive factors of EoE in patients with asthma. METHODS: A retrospective analysis of a large database identified 156 asthma patients with EoE and 276 patients without EoE between 2000 and 2010. Clinical and laboratory characteristics were first analyzed in half of each group. Significant differences and modelling were then applied to the other half of each group in a split half analysis. RESULTS: Odds ratios and P-values found to predict the presence of EoE in asthma patients were: allergic vs. non-allergic asthma (4.07, <0.01), food allergies (45, <0.01), allergic rhinitis (2.13, =0.01) and peripheral eosinophilia (4.51, <0.01). The use of inhaled corticosteroids was negatively associated with EoE (0.41, <0.01) for asthma patients and (0.37, P < 0.01) for allergic type asthma patients. EoE patients were also younger (27.4 vs. 41.6 years old, P < 0.01). By logistic regression analysis, allergic asthma, presence of peripheral eosinophilia and use of inhaled steroids remained significant. From these parameters, a 3.5-point scoring system model for EoE in asthma was formed with an ROC = 0.787 on split analysis. CONCLUSIONS: In descending order, peripheral eosinophilia, allergic asthma and allergic rhinitis are associated with EoE in patients with asthma. Steroid inhalers appear to have a protective effect against EoE. An accurate and simple scoring system can be used as a screening tool to predict the presence of EoE in patients with asthma and dysphagia. EoE should be viewed as part of a generalised allergic phenotype rather than isolated oesophageal disease.