Project description:BackgroundFirst-line treatment of eosinophilic esophagitis (EoE) includes monotherapy with proton-pump inhibitors (PPIs), food elimination diet (FED), or topical corticosteroids. Current guidelines suggest patients with EoE should continue any responsive first-line monotherapies. However, the efficacy of FED monotherapy in patients with EoE responsive to PPI monotherapy has not been well studied. Our study aimed to investigate how attempting FED monotherapy after experiencing remission of EoE after PPI monotherapy influenced long-term EoE management.MethodsWe retrospectively identified patients with EoE responsive to PPI monotherapy who trialed FED monotherapy. We then employed a mixed method approach to a prospective cohort. Selected patients were observed long term for quantitative outcomes, while qualitative results were obtained from patient surveys regarding their perspectives on the trial of FED monotherapy.ResultsWe identified 22 patients who trialed FED monotherapy after experiencing remission of EoE following PPI monotherapy. Of these 22 patients, 13 had remission of EoE with FED monotherapy, while 9 had re-activation of EoE. Out of 22 patients, 15 were enrolled in a cohort for observation. No exacerbations of EoE occurred while on maintenance treatment. Most patients stated that they would recommend this process to others with EoE (93.33%) and that trial of FED monotherapy helped them identify a treatment plan that aligned with their lifestyle (80%).ConclusionOur work shows that FED monotherapy can be an effective alternative for patients with EoE responsive to PPI monotherapy that may improve patient quality of life, suggesting alternative treatment options should be considered for monotherapy-responsive EoE.
Project description:BackgroundProton pump inhibitors (PPIs) are a first-line treatment for EoE, but data are limited concerning response durability. We aimed to determine long-term outcomes in EoE patients responsive to PPI-therapy.MethodsWe conducted a retrospective cohort study of newly diagnosed adults with EoE who had initial histologic response (<15 eosinophils per high-power-field) to PPI-only therapy. We extracted data regarding their subsequent clinical course and outcomes. We compared findings between the initial PPI-response endoscopy and the final endoscopy, and assessed factors associated with loss of PPI response.ResultsOf 138 EoE patients with initial histologic response to PPI, 50 had long-term endoscopic follow-up, 40 had clinical follow-up, 10 changed treatments, and 38 had no long-term follow-up. Of those with endoscopic follow-up, mean follow-up-time was 3.6 ± 2.9 years; 30 and 32 patients (60%; 64%) maintained histologic and symptom responses, respectively. However, fibrotic endoscopic findings of EoE were unchanged. Younger age (aOR 1.05, 95% CI: 1.01-1.11) and dilation prior to PPI treatment (aOR 0.21, 95% CI: 0.05-0.83) were the only factors associated with long-term loss of PPI response.ConclusionsLong-term histologic and clinical response rates for PPI therapy were 60% and 64%, respectively. Younger age and dilation at baseline were associated with histologic loss of response. These data can inform long-term EoE treatment selection.
Project description:Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US$ 1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation.
Project description:Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder triggered by specific food antigens, characterized by eosinophil-rich multicellular inflammation and structural changes in the epithelium. Treatment options for EoE include dietary therapy, pharmacological therapy, or a combination of both, chosen based on the patient's preference and clinical progression. Pharmacological options include proton pump inhibitors (PPIs), corticosteroids, and biologic therapy. Although PPI therapy is used for EoE management, its underlying mechanism of action remains unclear. To investigate the effects of omeprazole, an orally bioavailable PPI commonly used for EoE therapy, on the dynamics of esophageal epithelial barrier function and inflammation, we employed air-liquid interface (ALI) culture. We examined how omeprazole affects gene expression changes caused by IL-13 treatment. ALI cultures were treated with 100 ng/ml of IL-13 and/or 50 µM of acid-activated omeprazole for 96 hours, and bulk RNA sequencing was performed to analyze the epithelial-specific transcriptomes of IL-13 and/or omeprazole-treated ALI. Our findings suggest potential gene interactions where omeprazole may mitigate transcriptional changes induced by IL-13, indicating that omeprazole may attenuate IL-13 mediated epithelial dysfunction relevant to EoE pathophysiology by modulating pathways associated with inflammation, tissue repair, and cell-cell communication.
Project description:Eosinophilic esophagitis (EoE) is an immune-mediated disease triggered by food antigens for which dietary elimination treatment can induce and sustain histologic remission. Our review aims to describe the state of the art regarding dietary treatment of EoE, highlighting a number of areas of controversy related to dietary therapy in EoE, including novel modalities for determining food triggers, making the empiric dietary elimination process more efficient, issues of cross-contamination and "dosing" of how much food to avoid or add back, costs and effects on quality of life, long-term efficacy, and the risk of developing immediate IgE-type reactions after initial dietary elimination. Elemental formulas, empiric elimination diets, and targeted allergy test-directed elimination diets are well-described treatments for EoE. Although elemental diets are most efficacious, their clinical use is limited by cost and the palatability of an exclusively liquid diet. While empiric elimination is less effective than elemental formula-based diets, they are more easily implemented and often sustainable. Since the comparative effectiveness of elimination diets with proton-pump inhibitors and swallowed topical steroids remains unknown, there are multiple areas to address with future research.
Project description:ObjectivesEosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.MethodsThis prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.ResultsWe found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein (P < 0.05) and a significant increase in filaggrin levels after PPI treatment (P < 0.01).ConclusionsEsophageal miRNA levels found are able to discriminate between both PPI-R and PPI-NR at baseline, and before and after treatment in PPI-R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI-R patients after PPI therapy.
Project description:Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.
Project description:Purpose of reviewManagement for patients with refractory eosinophilic esophagitis (EoE) remains a clinical challenge. This review aims to define refractory EoE, explore rates and reasons for nonresponse, and discuss the evidence that informs the approach to these patients.Recent findingsMany patients will fail first-line therapies for EoE. Longer duration of therapy can increase response rates, and initial nonresponders may respond to alternative first-line therapies. There are ongoing clinical trials evaluating novel therapeutics that hold promise for the future of EoE management. Increasingly, there is recognition of the contribution of oesophageal hypervigilance, symptom-specific anxiety, abnormal motility and oesophageal remodelling to ongoing clinical symptoms in patients with EoE.SummaryFor refractory EoE, clinicians should first assess for adherence to treatment, adequate dosing and correct administration. Extending initial trials of therapy or switching to an alternative first-line therapy can increase rates of remission. Patients who are refractory to first-line therapy can consider elemental diets, combination therapy or clinical trials of new therapeutic agents. Patients with histologic remission but ongoing symptoms should be evaluated for fibrostenotic disease with EGD, barium esophagram or the functional luminal imaging probe (FLIP) and should be assessed for the possibility of oesophageal hypervigilance.
Project description:Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.
Project description:ObjectivesDietary elimination for treatment of eosinophilic esophagitis (EoE) is limited by lack of accuracy in current allergy tests. We aimed to develop an immunologic approach to identify dietary triggers and prospectively test allergen-specific immune signature-guided dietary elimination therapy.MethodsIn the first phase, we developed and assessed 2 methods for determining selected food triggers using samples from 24 adults with EoE: a CD4+ T-cell proliferation assay in peripheral blood and food-specific tissue IgG4 levels in esophageal biopsies. In the second phase, we clinically tested elimination diets created from these methods in a prospective cohort treated for 6 weeks (NCT02722148). Outcomes included peak eosinophil counts (eos/hpf), endoscopic findings (measured by the EoE Endoscopic Reference Score), and symptoms (measured by the EoE Symptom Activity Index).ResultsParameters were optimized with a positive test on either assay, yielding agreements of 60%, 75%, 53%, 58%, and 53% between predicted and known triggers of peanut, egg, soy, wheat, and milk, respectively. In clinical testing, the mean number of foods eliminated based on the assays was 3.4, and 19 of 22 subjects were compliant with treatment. After treatment, median peak eosinophil counts decreased from 75 to 35 (P = 0.007); there were 4 histologic responders (21%). The EoE Endoscopic Reference Score and EoE Symptom Activity Index score also decreased after treatment (4.6 vs 3.0; P = 0.002; and 32.5 vs 25.0; P = 0.06, respectively).DiscussionWe successfully developed a new testing approach using CD4 T-cell proliferation and esophageal food-specific IgG4 levels, with promising accuracy rates. In clinical testing, this led to improvement in eosinophil counts, endoscopic severity, and symptoms of dysphagia, but a smaller than expected number of patients achieved histologic remission.