Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

BACKGROUND AND AIMS: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. METHODS: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. RESULTS: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CONCLUSIONS: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Proton pump inhibitors in esophageal atresia: A systematic review and meta-analysis.

Gastroesophageal reflux disease (GERD) is frequent and prolonged in esophageal atresia (EA) pediatric patients requiring routine use of proton pump inhibitors (PPIs). However, there are still controversies on the prophylactic use of PPIs and the efficacy of PPIs on GERD and EA complications in this special condition. The aim of the study is to assess the prophylactic use of PPIs in pediatric patients with EA and its complications. We, therefore, performed a systematic review including all reports on the subject from 1980 to 2022. We conducted meta-analysis of the pooled proportion of PPI-and no PPI groups using random effect model, meta-regression, and estimate heterogeneity by heterogeneity index I2 . Thirty-eight reports on the topic met the criteria selection, representing a cumulative 6044 patients with EA. Prophylactic PPI prescription during the first year of life does not appear to prevent GERD persistence at follow-up and is not associated with a significantly reduced rate of antireflux surgical procedures (ARP). PPIs improve peptic esophagitis and induce remission of eosinophilic esophagitis at a rate of 50%. Their effect on other GERD outcomes is uncertain. Evidence suggests that PPIs do not prevent anastomotic stricture, Barrett's esophagus, or respiratory complications. PPI use in EA can improve peptic and eosinophilic esophagitis but is ineffective on the other EA complications. Side effects of PPIs in EA are almost unknown.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Benralizumab treatment in an elderly patient with eosinophilic esophagitis resulted in remission: a case report.

BACKGROUND: Interleukin-5 (IL-5) has recently been shown to play a crucial role in eosinophil-mediated diseases, implying that an IL-5 receptor alpha chain (IL-5Rα) antibody (benralizumab) can be effective against eosinophilic esophagitis (EoE). Here, we present a case in which benralizumab significantly improved the symptoms and signs of an elderly Asian woman with EoE who had inadequate response to existing treatments. Case presentation A 73-year-old woman with an 8-year history of bronchial asthma (BA) and a 7-year history of dysphagia presented to our hospital with worsening dysphagia, vomiting, chest pain, and difficulty in eating. Blood biochemical findings revealed an increase in the eosinophil fraction of white blood cells (42.2%), and a conventional chest computed tomography scan revealed esophageal wall thickening. An upper gastrointestinal endoscopy revealed mucosal edema as well as multiple esophageal rings, and esophageal biopsy specimens showed an eosinophilic infiltrate of more than 15 cells/ high power field. Based on these findings, she was diagnosed as EoE complicated by BA. We firstly administrated 20 mg/day of prednisolone, rabeprazole sodium and liquid budesonide oral suspension for 5 months; however, they were ineffective and her dysphagia worsened over time. Then, benralizumab treatment in combination with these drugs was started. Her dysphagia completely disappeared 2 weeks after starting benralizumab, and an upper endoscopy showed that the clinical findings had completely disappeared after another 6 weeks. Benralizumab was then given to her for 41 months, and her symptoms remained in remission. In addition, she had no EoE recurrence for more than 12 months after discontinuing benralizumab. CONCLUSIONS: Benralizumab in combination with other multiple drugs significantly improved the symptoms and examination findings of an elderly patients with EoE. Furthermore, she experienced no recurrence even after discontinuing benralizumab withdrawal, suggesting that benralizumab could be an appropriate therapeutic option for EoE.

Novel corticosteroid formulations in the treatment of eosinophilic esophagitis: what is the evidence?

Background and study aims: Eosinophilic esophagitis (EoE) is a food allergen-induced disease of the esophagus. Chronic, eosinophil-predominant inflammation eventually leads to fibrosis, esophageal dysfunction and severe morbidity. Swallowed topical corticosteroids (STCs) are a mainstay of anti-inflammatory therapy in the treatment of active EoE. Data on the efficacy of novel corticosteroid formulations, developed specifically for esophageal delivery, have recently become available. Methods: A comprehensive review was performed aiming to summarize evidence on the role of STCs in the treatment of EoE. Two biomedical bibliographic databases (PubMED, EMBASE) were searched for articles providing original information on the efficacy and safety of STCs in adult EoE patients. Results: Budesonide orodispersible tablet (BOT) and budesonide oral suspension (BOS) both surpassed placebo formulations regarding the efficacy of inducing and maintaining histologic, symptomatic and endoscopic remission. Overall, BOT displayed the highest grade of efficacy with clinico-histologic remission rates up to 75% after 1 year. Fluticasone propionate (APT-1011) achieved and maintained histologic and endoscopic responses in the majority of patients, whereas only a positive trend was demonstrated for symptomatic improvement. Mometasone and ciclesonide were studied in a limited number of smaller-scale trials and placebo-controlled data are required to substantiate the promising findings. All STCs displayed a similar side effects profile and were generally considered safe and well-tolerated. Conclusions: Current evidence supports long-term treatment with novel corticosteroid formulations, challenging the established treatment paradigm of EoE. BOT appears to be the most effective steroid therapy, although head-to-head comparative trials between STCs are needed.

A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation, but also heterogeneous presentations involving fibrostenotic esophageal remodeling and esophageal dysmotility. We aimed to define and evaluate phenotypes of EoE using functional lumen imaging probe (FLIP) panometry (ie, a PhysioMechanical classification of EoE). METHODS: Patients with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP studies were analyzed for distensibility plateau and compliance of the esophageal body, maximum esophagogastric junction diameter, and contractile response pattern. These FLIP features were then applied to define PhysioMechanical classifications. RESULTS: A total of 215 patients with EoE (mean [standard deviation] age 38 [12] years; 31% female) were included. Seven PhysioMechanical classifications were identified that differed by various clinical characteristics, including symptom duration (P < .001) and Endoscopic EoE Reference Scores (EREFS) (P < .001). In particular, patients with "nonreactive fibrostenosis" (n = 14), had greater symptom duration (median [interquartile range] 20 [10-30] years) and more frequently had EREFS grade 2 or 3 ring scores (14 of 14 patients) than patients with a "normal" PhysioMechanical classification (symptom duration: 3 [1-8] years; 4 of 50 [8%] had EREFS grade 2 or 3 rings). In addition, among patients off treatment at cross-sectional evaluation (n = 46), there was a difference between PhysioMechanical classifications in future proton pump inhibitor (PPI) response rates (ie, achieving peak mucosal eosinophil count <15 per high-powered field after PPI treatment); P = .009. PPI response ranged from 87% (13 of 15 patients) with "isolated esophagogastric junction outflow obstruction" to 11% (1 of 9 patients) with "spastic-reactive fibrostenosis." CONCLUSIONS: Classifying PhysioMechanical esophageal function in EoE based on FLIP panometry features may facilitate defining disease severity and directing management in EoE.

An improved guideline adherence and PPI efficacy has been accompanied by a decrease in diagnostic delay, and strictures before diagnosis of eosinophilic esophagitis in the North Denmark Region - a retrospective registry study of the DanEoE cohorts.

BACKGROUND: In the North Denmark Region an increased awareness of eosinophilic esophagitis (EoE) was observed after 2011 where a regional biopsy guideline was implemented. This resulted in an increased awareness of EoE and a 50-fold increase in the incidence of EoE patients between 2007-2017. AIMS: The aims of this study were to examine the progress in diagnostic delay, complications, PPI treatment, and follow up since 2017 in Danish patients with eosinophilic esophagitis. MATERIALS AND METHODS: This was a retrospective registry- and population-based cohort study (DanEoE2 cohort) including 346 adult patients with esophageal eosinophilia diagnosed between 2018-2021 in the North Denmark Region. The DanEoE2 cohort included all possible EoE patients by using the Danish Patho-histology registry based on the SNOMED-system. The data was analyzed and compared to the DanEoE cohort (2007-2017). RESULTS: The diagnostic delay of EoE patients diagnosed between 2018-2021 in the North Denmark Region had decreased with a median of 1.5 years (5.5 (2.0;12) years versus 4.0 (1.0;12) years, p=0.03). Strictures before diagnosis had decreased 8.4 % (11.6% versus 3.2%, p=0.003). The number of patients started on high-dose PPI increased (56% versus 88%, p<0.001). An intensified awareness regarding national guidelines and follow-up was observed as an increase in the number of histological follow up (67% versus 74%, p=0.05). CONCLUSIONS: Comparisons of the DanEoE cohorts showed a decrease in diagnostic delay, a decrease in stricture formation before diagnosis, and an improved guideline adherence after 2017. Future studies are needed to assess if symptomatic or histological remission on PPI treatment is more capable of predicting a patient's risk of developing complications.

A Newly Proposed Severity Index for Eosinophilic Esophagitis is Associated With Baseline Clinical Features and Successful Treatment Response.

BACKGROUND AND AIMS: The Index of Severity for EoE (I-SEE) was recently developed. We aimed to determine the relationship between features of eosinophilic esophagitis and disease severity, and assess change in disease severity with topical corticosteroid treatment, using I-SEE. METHODS: We performed a post hoc analysis of an 8-week randomized trial comparing 2 topical corticosteroid formulations in newly diagnosed patients with eosinophilic esophagitis. I-SEE was calculated at baseline and posttreatment, and patients were classified as mild (1-6 points), moderate (7-14 points), severe (≥15 points), or inactive (0 points). We analyzed clinical, endoscopic, and histologic features at baseline by disease severity, and examined the change in severity before and after treatment, and by histologic response (<15 eosinophils per high-power field). RESULTS: Of 111 subjects randomized, 20 (18%) were classified as mild, 75 (68%) as moderate, and 16 (14%) as severe at baseline. Increasing severity was associated with lower body mass index (30 for mild, 27 for moderate, 24 for severe; P = .01), longer duration of dysphagia symptoms before diagnosis (9 years for mild, 9 for moderate, and 20 for severe; P < .001), and decreasing esophageal diameter (15 mm for mild, 13 for moderate, and 10 for severe; P < .001). Mean severity score decreased after treatment (11 vs 4; P < .001), with lower scores in histologic responders compared with nonresponders (2 vs 9; P < .001). The severity score at baseline predicted need for dilation at follow-up (C statistic, 0.81). CONCLUSIONS: The newly developed I-SEE correlates with many clinical features at diagnosis, and severity improves with successful topical corticosteroid treatment. Additional investigations in other populations can further confirm its utility.

Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice - International Expert Recommendations.

BACKGROUND & AIMS: There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor patients with EoE in routine clinical practice, on the basis of available clinical evidence and expert opinion. METHODS: A multidisciplinary, international group of EoE experts identified the following important 3 questions during several consensus meetings: why, by what means, and when to monitor patients with EoE. A steering committee was named, and 3 teams were formed to review literature and to formulate statements for each topic. In a Delphi survey, a level of agreement of ≥75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed, and statements were rephrased/rewritten if necessary. RESULTS: Eighteen EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university-based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring patients with EoE. Each statement attained ≥75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. CONCLUSIONS: It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured, and, under certain conditions, individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side effects, adjusting therapy, and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.

Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.

Odynophagia in a young adult: revisiting herpetic esophagitis and eosinophilic esophagitis.

An immunocompetent man in his 20s presented with a 24-hour history of severe odynophagia, nausea, vomiting and throat pain. Esophagogastroduodenoscopy (EGD) revealed severe esophagitis with ulcerated mucosa, exudative debris, haemorrhage and multiple erosions. Biopsy of the oesophageal tissue demonstrated marginated chromatin, multinucleated giant cells and molding of nuclei, consistent with herpes simplex virus esophagitis (HSE). Treatment with oral acyclovir led to the complete resolution of symptoms. The patient subsequently developed dysphagia again, 8 months later. EGD showed furrowing and concentric rings typical of eosinophilic esophagitis (EoE), a diagnosis confirmed by biopsy. Treatment with a proton pump inhibitor and swallowed topical corticosteroids led to symptomatic improvement. Thus, HSE can occur in immunocompetent hosts and on occasion, HSE may be a harbinger of EoE, as evidenced by our extensive literature review. Mechanical disruption of the mucosal barrier by viruses, facilitating food allergen penetration, and associated immunological signaling abnormalities may be responsible phenomena requiring further elucidation.

Overlapping Transcriptional Profile in Proton Pump Inhibitor Responsive and Nonresponsive Eosinophilic Esophagitis.

INTRODUCTION: We compared esophageal mucosal gene transcript expression in proton pump inhibitor (PPI) responsive (PPI-R) eosinophilic esophagitis (EoE), PPI nonresponsive (PPI-NR) EoE, and healthy controls. METHODS: Transcript expression in midesophagus biopsies was determined using NanoString and a custom panel of EoE-specific genes. The top upregulated and downregulated genes with ≥2-fold difference in expression and statistically significant ( P < 0.05) were identified. RESULTS: Nearly all the top upregulated (17 of 20) and downregulated (5 of 5) genes in EoE, compared with healthy controls, were shared between the PPI-R and PPI-NR groups. DISCUSSION: Esophageal mucosal transcript expressions are remarkably similar in PPI-R EoE and PPI-NR EoE compared with healthy controls.

The new indications for biologicals in type 2 diseases: perspectives.

PURPOSE OF REVIEW: To provide a literature review of what is on the market and under study for some diseases treated with drugs targeting type 2 (T2) inflammation. RECENT FINDINGS: Literature data have shown that drugs targeting type 2 inflammation are effective in asthma and nasal polyposis, conditions for which they are on the market, and have promising expectations in the case of eosinophilic esophagitis, especially using anti-IL-5/IL-5 receptor and IL-4 receptor antibodies, while concerning eosinophilic granulomatosis with polyangitis (EGPA), mepolizumab (MEP) was approved by FDA and EMA as a drug for the treatment of this condition because of the promising results obtained in trials and in real life. SUMMARY: The use of these drugs is certainly an important achievement in the treatment of complex diseases such as those mentioned above, which are too often orphaned from innovative treatments and limited to the use of immunosuppressants and systemic corticosteroid for their control.

Role of mast cells in eosinophilic esophagitis.

PURPOSE OF REVIEW: This review will present what is known from recent research on the involvement of mast cells in eosinophilic esophagitis and identify questions requiring further investigation. RECENT FINDINGS: In the adults and children with eosinophilic esophagitis, there is increasing evidence that mastocytosis can persist, despite resolution of eosinophilia and is associated with persistent mucosal abnormalities and symptoms. Despite, treatment mast cells have an activated transcriptome. Mast cells likely contribute to epithelial barrier dysfunction, smooth muscle hypertrophy and contraction, and subepithelial fibrosis. It remains unclear whether targeting MCs alone has therapeutic efficacy to improve tissue damage. SUMMARY: Mast cells appear to play a key role in eosinophilic esophagitis and serve as a biomarker of mucosal healing in conjunction with eosinophils. Excessive mast cell activation likely contributes to tissue damage in eosinophilic esophagitis and need to be considered as a target of therapy along with eosinophils.

Current treatment options and long-term outcomes in patients with eosinophilic esophagitis.

INTRODUCTION: Dietary and pharmacological (proton pump inhibitors, swallowed topical corticosteroids) therapies are effective for induction of clinical and histological remission of eosinophilic esophagitis. However, data evaluating their long-term efficacy and safety is limited. AREAS COVERED: Since eosinophilic esophagitis is chronic, clinical, endoscopic, and histological features usually recur when successful treatments are stopped. In untreated patients, persistent esophageal eosinophilic inflammation may progress to fibrostenosis over time, giving place to strictures and narrow-caliber esophagi. This article comprehensively reviews available data on long-term maintenance of eosinophilic esophagitis with pharmacological and dietary treatment. It also discusses limitations re: available literature and outlines data gaps on adherence to therapy and monitoring disease activity in the long-term. EXPERT OPINION: Evidence indicates that long-term maintenance therapy may decrease the risk of esophageal stricture, food bolus impaction, and need for dilation in patients with eosinophilic esophagitis. Further knowledge on eosinophilic esophagitis phenotypes is needed to ascertain who will benefit best from sustained therapy. Unanswered questions include an adequate definition for sustained remission, best strategies for maintenance drugs and diets, enhancement of treatment adherence, and proper monitoring for long-term surveillance.

Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer with Esophageal Involvement: A Pediatric Case.

Eosinophilic gastrointestinal disorders are diseases that cause inflammation and dysfunction due to infiltration of eosinophils into various regions of the gastrointestinal tract. Symptoms and treatment vary depending on lesion severity. We describe the first pediatric case of an eosinophilic duodenal ulcer with esophageal involvement that was effectively treated using proton pump inhibitor monotherapy. A 12-year-old boy with no relevant family or medical history presented with a one-month history of epigastric pain. Laboratory test results were as follows: white blood cell count, 4,700/µL; eosinophil count, 150/µL (3.2%); and total IgE, 151.6 IU/L; and IgG antibodies for Helicobacter pylori were absent. Esophagogastroduodenoscopy revealed longitudinal linear furrows in the esophagus, indicating eosinophilic esophagitis with an A1 ulcer from the duodenal bulb to the descending duodenum. The patient was diagnosed with an eosinophilic duodenal ulcer with esophageal involvement based on pathological findings. Esomeprazole, a common proton pump inhibitor, was orally administered, after which the symptoms promptly improved. After two months, the esophagogastroduodenoscopy and pathological examination results showed improvement in both the esophagus and duodenum. There have been no previous reports of an eosinophilic duodenal ulcer with esophageal involvement without post-duodenal involvement at the time of diagnosis. The possibility of eosinophilic gastrointestinal disorders should be investigated in patients with duodenal ulcers by means of active biopsy, and patients should be investigated for other types of gastrointestinal lesions. Proton pump inhibitor monotherapy may be considered a first-line treatment for eosinophilic duodenal ulcers with esophageal involvement, depending on lesion severity.

Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis.

BACKGROUND: Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials. OBJECTIVE: To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis. METHODS: Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (>1,500 cells/µL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented. RESULTS: Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/µL; week 4: 515-578 cells/µL), CRSwNP (baseline: 440-448 cells/µL; week 16: 595 cells/µL), and atopic dermatitis (baseline: 434-600 cells/µL; week 4: 410-710 cells/µL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/µL; week 4: 230 cells/µL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy. CONCLUSIONS: Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.