HSC Section 6 Nov2016 Green Book

Fluticasone vs. Esomeprazole for Esophageal Eosinophilia

response (11). Similar findings have been described by Molina et al. (24) in which clinical remission was achieved in the majority of patients with food impaction or dysphagia despite persistence of eosinophilia. Interestingly, a dissociation was recently reported between clinical response and histological severity in EoE chil- dren with the majority of patients reporting continued symptoms despite histological remission (25). These data combined with ours suggest one cannot use clinical response as a surrogate for histo- logical change. However, whether achieving histological response in EoE is an important outcome is yet to be determined. In the- ory, normalization of the eosinophila may prevent further tissue remodeling, fibrosis, and possibly stricture formation. Esophageal dilation is one of the most effective treatments for alleviating the symptoms of EoE even though it does not address the underlying disease pathophysiology (26). In our cohort, all of the 15 patients (8 in FP arm and 7 in ESO arm) with dysphagia and esophageal eosinophilia who underwent dilation at index endo- scopy had significant improvement in symptoms. Similar clinical improvements have been noted in other studies in EoE (26,27). In contrast, among the 27 patients who did not undergo dilation, only those randomized to ESO had significant improvement in symptoms. As a similar number of patients underwent dilation in each treatment arm and dilation was not performed during the 8-week treatment course or at follow-up endoscopy, it is unlikely that dilation had an effect on the change inMDQ scores before and after therapy. There are some limitations of our study. A placebo arm would have helped better define the natural history of esophageal eosi- nophilia. As we were comparing one medication administered as a pill to another given as an inhaler, we found adding a placebo arm to be challenging. Additionally the delivery system of aerosolized fluticasone may have hampered the true assessment of steroid response rates, and using another agent such as oral viscous budes- onide may give us a different understanding of the true steroid response. Another limitation of our study was the relatively small sample size, which limited the subgroup analyses. Additionally, we used the 2-week dysphagia score, which may not have accurately reflected the symptoms in some EoE patients, particularly in those with intermittent dysphagia. However, the 2-week MDQ was the only validated questionnaire available at the time of this study. To date, no dysphagia questionnaire developed exclusively for EoE has been published. In conclusion, histological response between ESO and FP were similar in the treatment of esophageal eosinophilia, with neither drug having overwhelming treatment success. On the other hand, significant improvement in clinical symptoms was demonstrated with PPI therapy. Further larger studies are needed to better define the optimal treatment for patients with esophageal eosinophilia and to better describe the subgroup and natural history of such patients who respond to PPI therapy.

significant difference in eosinophilia between these two locations. It is noteworthy that studies using oral viscous budesonide, which can be administered as a slurry mixed with a sugar substitute or as a swallowed nebulizer, demonstrated higher response rates (72–80%) (17,18). This suggests that the delivery system, and not the steroid type, may be the reason for low response rates. To fur- ther study and explore this point, a recent study demonstrated that oral viscous budesonide was more effective in reducing eosinophil counts when compared with nebulized budesonide (19). Interestingly, there was a greater number of acid and imped- ance reflux episodes in the FP arm compared to the ESO arm. However, the percentage of patients with abnormal acid (>50) and impedance episodes (>73) was similar between both treatment arms. Therefore, it is unclear whether an increased number of reflux episodes had any role in the response to topical steroids. The rationale for using PPIs for the treatment of esophageal eosi- nophilia is that it may help treat underlying GERD, whichmay con- tribute to EoE (20). It may be difficult to completely separate these two entities and it appears that many adult EoE patients respond at least clinically to PPI therapy. In one study, 8 of 17 (47%) adult patients presenting with food impaction and dense esophageal eosinophilia (>20 eos/hpf) responded clinically to PPI therapy (5). The mechanism for this is not clear, although PPIs may help heal a disrupted epithelial barrier and therefore reduce further immune activation (2). In our study, the four patients with esophageal eosi- nophilia and GERD had a complete response to PPI therapy. The histological response achieved in three patients with PPI therapy despite having a negative 24-h pH study suggests these patients may have PPI-responsive EoE, which stimulates an inter- esting discussion regarding the pathophysiology of this entity. This described response to esomeprazole in GERD-negative esophageal eosinophilia patients can be attributed to anti-inflammatory prop- erties of PPI independent of acid inhibition. Interestingly, PPIs have been shown to exhibit anti-inflammatory properties by act- ing directly on principal cytokines (IL-4 and IL-13) involved in the recruitment of eosinophils in the esophagus (21). Additionally, PPI therapy was shown to block the release of eotaxin-3, which has an integral role in the pathogenesis of EoE (22). Other studies have also reported a histological response to PPI therapy in EoE patients even following a negative 24-h pH study. Peterson et al. (13) dem- onstrated a 33% (4/12) histological response to PPI therapy. Simi- lar results have been reported in children as well. In 43 pediatric EoE patients, a subset of patients responded histologically to PPI therapy following a normal pH study (23). These studies coupled with our data suggest that a subset of patients whose clinical pres- entation suggests EoE and have dense eosinophilia on esophageal biopsies indeed appear to be PPI responsive. Significant clinical improvement was seen in the majority of patients with esophageal eosinophilia taking PPI even though only a few had histological resolution. Other studies have also reported a poor correlation between clinical remission and histological response. In a randomized placebo controlled study, vomiting was the only symptom that significantly improved in EoE children treated with topical steroids and did not correlate with histological

CONFLICT OF INTEREST Guarantor of the article: Fouad J. Moawad, MD.

Specific author contributions: Study concept and design, subject enrollment, acquisition of data, analysis and interpretation of data,

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© 2013 by the American College of Gastroenterology

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