Embracing Diversity, Equity, Inclusion, and Accessibility in Eosinophilic Gastrointestinal Diseases.

Eosinophilic gastrointestinal diseases (EGIDs) including eosinophilic esophagitis (EoE) are rare diseases in which eosinophils abnormally infiltrate the gastrointestinal tract. Because these are rare diseases, there is limited information regarding race and ethnicity in EGIDs and even less is known about the impact of socioeconomic factors. There is some evidence that access to care in rural settings may be affecting epidemiologic understanding of EGIDs in the pediatric populations. Future work should try to evaluate bias in research and strive for representation in clinical trials and medicine.

Esophageal dysmotility in patients with eosinophilic esophagitis: pathogenesis, assessment tools, manometric characteristics, and clinical implications.

Eosinophilic esophagitis (EoE) represents a growing cause of chronic esophageal morbidity whose incidence and prevalence are increasing rapidly. The disease is characterized by eosinophilic infiltrates of the esophagus and organ dysfunction. Typical symptoms include dysphagia, chest pain, and bolus impaction, which are associated to mechanical obstructions in most patients. However, up to one in three EoE patients has no visible obstruction, suggesting that a motor disorder of the esophagus may underlie symptoms. Although potentially relevant for treatment refractoriness and symptomatic burden, esophageal dysmotility is often neglected when assessing EoE patients. The first systematic review investigating esophageal motility patterns in patients with EoE was published only recently. Accordingly, we reviewed the pathogenesis, assessment tools, manometric characteristics, and clinical implications of dysmotility in patients with EoE to highlight its clinical relevance. In summary, eosinophils can influence the amplitude of esophageal contractions via different mechanisms. The prevalence of dysmotility may increase with disease duration, possibly representing a late feature of EoE. Patients with EoE may display a wide range of motility disorders and possible disease-specific manometric pressurization patterns may be useful for raising a clinical suspicion. Intermittent dysmotility events have been found to correlate with symptoms on prolonged esophageal manometry, although high-resolution manometry studies have reported inconsistent results, possibly due to the suboptimal sensitivity of current manometry protocols. Motor abnormalities may recover following EoE treatment in a subset of patients, but invasive management of the motor disorder is required in some instances. In conclusion, esophageal motor abnormalities may have a role in eliciting symptoms, raising clinical suspicion, and influencing treatment outcome in EoE. The assessment of esophageal motility appears valuable in the EoE setting.

Disease Burden and Unmet Need in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of increasing prevalence, characterized by symptoms of dysphagia and reduced quality of life. A dysregulated type 2 immune response to food and aeroallergen leads to barrier dysfunction, chronic esophageal inflammation, remodeling, and fibrosis. Patients with EoE have impaired quality of life because of dysphagia and other symptoms. They may also suffer social and psychological implications of food-related illness and expensive out-of-pocket costs associated with treatment. Disease burden in EoE is often compounded by the presence of comorbid type 2 inflammatory diseases. Current conventional treatments include elimination diet, proton pump inhibitors, and swallowed topical corticosteroids, as well as esophageal dilation in patients who have developed strictures. These treatments demonstrate variable response rates and may not always provide long-term disease control. There is an unmet need for long-term histologic, endoscopic, and symptomatic disease control; for targeted therapies that can normalize the immune response to triggers, reduce chronic inflammation, and limit or prevent remodeling and fibrosis; and for earlier diagnosis, defined treatment outcomes, and a greater understanding of patient perspectives on treatment. In addition, healthcare professionals need a better understanding of the patient perspective on disease burden, the disconnect between symptoms and disease activity, and the progressive nature of EoE and the need for continuous monitoring and maintenance treatment. In this review, we explore the progression of disease over the patient's lifespan, highlight the patient perspective on disease, and discuss the unmet need for effective long-term treatments.

Disease Burden and Treatment Patterns Associated With Eosinophilic Esophagitis in the United States: A Retrospective Claims Study.

GOALS: This US-based, retrospective claims study aimed to investigate disease burden and treatment patterns in patients with eosinophilic esophagitis (EoE), and to compare health care resource use (HCRU) in patients with EoE and matched controls without EoE. MATERIALS AND METHODS: Patients with a diagnosis of EoE and ≥12 months of prediagnosis data were identified from the Truven Health MarketScan Research databases (January 2008 to September 2016) and followed up from the diagnosis date until termination of eligibility for a health plan. Patient clinical characteristics and HCRU were recorded in the 12 months before diagnosis; HCRU and treatment patterns were recorded during follow-up. HCRU in patients with EoE and matched controls was compared during the 12-month postdiagnosis period. RESULTS: Among the 23,003 patients with EoE (mean age: 34.3 y; 64.8% male), gastroesophageal reflux disease was the most common prediagnosis condition (34.6%). After diagnosis, the most common off-label, first-line treatments were proton pump inhibitor monotherapy (52.8%) and topical corticosteroid monotherapy (21.5%). Overall, 3336 patients (14.5%) received at least 3 lines of off-label pharmacotherapy. Outpatient visits (recorded in 99.9% of patients on and postdiagnosis) were most frequently to gastroenterologists/pediatric gastroenterologists (49.5% prediagnosis, 72.6% on and postdiagnosis). Inpatient admissions and outpatient and emergency room visits were more likely in patients with EoE than in matched controls (P<0.0001). CONCLUSIONS: Patients with EoE in the USA experience a high disease burden both before and after diagnosis, which requires significant HCRU. Our findings highlight the unmet need for adequate control of EoE-related symptoms.

Eosinophilic Esophagitis: Incidence, Diagnosis, Management, and Future Directions.

Eosinophilic esophagitis (EoE) is an antigen-mediated esophageal disease defined by the presence of esophageal eosinophilia and symptoms of esophageal dysfunction. The pathophysiology involves an allergen-driven Th2 T cell response that triggers infiltration of eosinophils into the esophagus leading to inflammation, remodeling, and fibrosis. This results in disruption of esophageal function and accompanying symptoms - most notably dysphagia. Effective therapies target inflammation or fibrostenotic complications and include proton pump inhibitors, swallowed topical steroids, dietary exclusion, and dilation. Clinical trials testing promising biologic therapies are ongoing.

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases.

OBJECTIVES: Clinical features of eosinophilic esophagitis (EoE) have been well-described in the literature, however, characterization of features experienced by patients with other eosinophilic gastrointestinal diseases (EGIDs) is lacking. Using data collected from a patient contact registry, we sought to characterize and contrast patient-reported gastrointestinal and extragastrointestinal symptoms and comorbidities in non-EoE EGIDs, including eosinophilic gastritis, gastroenteritis and colitis, relative to EoE. METHODS: We conducted a cross-sectional study of contact registry data collected from 2015 to 2018. Statistical comparisons were made using chi-square (categorical measures) and the Mann-Whitney U test (continuous measures). Multivariable analyses were used to evaluate associations between treatment and feelings of isolation. RESULTS: Of the 715 reporting an EGID diagnosis (n = 525 EoE; n = 190 non-EoE EGID), a higher proportion of those with a non-EoE EGID reported more frequent specific and nonspecific gastrointestinal symptoms, including nausea, abdominal pain, diarrhea, constipation, and bloating (P < 0.01 for all). Participants with a non-EoE EGID were more likely to report higher frequency of fatigue, isolation, and deep muscle or joint pain (P < 0.01 for all). Specific food elimination and elemental formula treatments were associated with increased odds of more frequent (at least weekly) feelings of isolation for participants with EoE (adjusted odds rtaio [aOR]: 2.4; 95% confidence interval [CI]: 1.5--4.1 for specific food elimination and adjusted OR: 1.9; 95% CI: 1.2--3.3 for elemental formula). CONCLUSIONS: Significant differences exist in the symptoms and comorbidities experienced between those with EoE versus non-EoE EGIDs. Additional investigation is needed to elucidate the factors that may contribute to the high disease burden of these poorly understood conditions.

Differences in Management of Eosinophilic Esophagitis in Europe: An Assessment of Current Practice.

OBJECTIVES: The aim of the study was to assess differences in the diagnosis and management of eosinophilic esophagitis (EoE) by European pediatric (PG) and adult gastroenterologists (AG), and their self-reported adherence to guidelines. METHODS: A multiple-choice questionnaire gauged the diagnostic and management strategies of gastroenterologists treating children or adults in 14 European countries and the United Arab Emirates (UAE). RESULTS: Questionnaires were completed by 465 PG and 743 AG. PG were significantly more likely to take biopsies in patients with symptoms of esophageal dysfunction (86.2% PG vs 75.4% AG, P < 0.001) and to perform endoscopic follow-up (86.3% PG vs 80.6% AG, P < 0.001). After failure of proton-pump inhibitors (PPIs), topical steroids were the preferred second-line therapy; however, PG opted more frequently for elimination diets (47.5% PG vs 13.7% AG, P < 0.001). More PG than AG indicated having read recent guidelines (89.4% PG vs 58.2% AG, P < 0.001). Geographic differences in practice were reported, with respondents from the United Kingdom, Portugal, and Spain more often adhering to recommended biopsy protocols. Physicians in the UAE, France, Lithuania, and Poland tended to opt for steroid therapy or elimination diets as first-line therapy, in contrast to most other countries. CONCLUSIONS: Significant differences in general practice between PG and AG were demonstrated with notable divergence from consensus guidelines. International practice variations are also apparent. Among other strategies, educational activities to highlight current recommendations may help harmonize and optimize clinical practice.

Systematic Assessment of Adult Patients' Satisfaction with Various Eosinophilic Esophagitis Therapies.

BACKGROUND AND AIMS: The treatment options for eosinophilic esophagitis (EoE) patients include drugs (proton pump inhibitors [PPIs], swallowed topical corticosteroids [STCs]), elimination diets, and dilation. Given the lack of data, we aimed to assess adult EoE patients' satisfaction with different EoE-specific treatment modalities. PATIENTS AND METHODS: We evaluated therapy satisfaction recalled over a 12-month period using the validated Treatment Satisfaction Questionnaire for Medication that assesses effectiveness, side effects, convenience, and overall satisfaction. The score for each scale ranges from 0 (dissatisfied) to 100 (satisfied). To evaluate satisfaction with nonpharmacologic therapies, the questionnaire was modified and debriefed into three focus groups. The final questionnaire was sent to 147 patients. RESULTS: The patient response rate was 74%. In the last 12 months, 24, 75, 19, and 9% were treated with PPIs, STCs, elimination diet, and dilation, respectively. Patients identified the following considerations as important for therapy choice: effect on symptoms (89%), effect on esophageal inflammation (76%), side effects (69%), and ease of use (58%). Patients found STCs to be effective (83 points), convenient (83 points), and experienced no side effects when using this therapy. When using STCs alone (43%), overall patient satisfaction was high (86 points). Patients judged PPIs to be most convenient (89 points), STCs to be a bit less convenient (83 points), and diet to be most inconvenient (46 points) of the three therapies examined. CONCLUSIONS: Adult EoE patients consider both therapy effect on symptoms and esophageal inflammation as important criteria when choosing EoE therapy and appear to be satisfied with STC use.

Cost of chronic inflammatory disease: The impact of eosinophilic esophagitis in Nevada.

OBJECTIVES: The cost of treating the rare eosinophilic esophagitis (EoE) disease and its impact on patients' quality of life have not been well documented in the literature. This study seeks to fill this gap by comparing the cost of EoE with other well-known inflammatory diseases, including Crohn's disease (CD) and celiac disease (CeD). METHODS: A Mann-Whitney U test and multiple logistic regression were used to examine the cost of EoE in the state of Nevada across all hospital settings and its impact on quality of life compared with CD and CeD. RESULTS: Several factors were associated with the overall cost of EoE in Nevada, including patients' age, sex and region (P < 0.001). EoE was significantly more expensive to treat in the pediatric group ($4001 EoE; $985 CD; $856 CeD), among men ($2532 EoE; $1500 CD; $1724 CeD), among those residing in the southern region of Nevada ($4501 EoE; $2538 CD; $1888 CeD), and among patients seeking medical care from outpatient clinics ($3298 EoE; $741 CD; $1686 CeD) (P < 0.001). Age, sex, region and hospital setting were all associated with having a positive EoE record compared with CeD or CD (P < 0.001). CONCLUSIONS: Data from this study indicate that the EoE burden is significantly higher in cost for certain demographics and regions compared with CD and CeD in the state of Nevada, specifically among pediatric and male patients. These differences suggest that clinicians may encounter similar issues when treating EoE.

Sensitivity and Specificity of Administrative Medical Coding for Pediatric Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a delayed-type hypersensitivity with increasing rates among pediatric populations. Although studies have used International Classification of Diseases (ICD) coding to define local cohorts and report disease epidemiology, the accuracy of the EoE ICD code for pediatric EoE is unknown. METHODS: We searched the Intermountain Healthcare Database for pediatric cases with the EoE ICD code over a 5-year period. We cross-referenced these results with a recently published pediatric EoE cohort from the same region and period, where incident cases were identified via retrospective review of pathology reports and medical records. Using the retrospective review cohort as the reference standard, we evaluated the accuracy of the EoE ICD code. RESULTS: Via retrospective review, we identified 1129 new pediatric EoE cases in the Intermountain Healthcare system over 5 years. Six hundred ten of these had the EoE ICD code associated with their chart. Out of 878,872 unique pediatric records in the Intermountain Healthcare system, 219 had the EoE ICD code incorrectly applied. The specificity of the EoE ICD code in children was 99%, but sensitivity and positive predictive value were 61% and 79%, respectively. CONCLUSIONS: The EoE ICD code has strengths and weaknesses in pediatrics. The EoE ICD code is specific, with few false positives across a large population, but not sensitive. The low sensitivity is likely multifactorial and requires further evaluation. Compared to retrospective chart review, which allows for application of clinicopathologic EoE diagnostic criteria, sole use of ICD codes results in underascertainment of EoE cases and key misclassifications.

Eosinophilic esophagitis. The North against the South? A bio-economic-social mechanistic approach and clinical implications. / La esofagitis eosinofílica. ¿El Norte contra el Sur? Enfoque mecanicista bio-económico-social e implicaciones clínicas.

Eosinophilic esophagitis is a chronic antigen-mediated disease characterized by esophageal symptoms, esophageal eosinophilia, and the absence of response to proton pump inhibitors. It is the most frequent cause of dysphagia and food impaction in adults. Its incidence and prevalence is very high in the developed countries (USA, Europe, Australia), where its connotation is that of an emerging epidemic. While studies have been published with large case series in the developed countries, those published in Latin America are small or consist of isolated case reports. The differences in the prevalence of the disease between the developed and developing regions are unknown. Genetic or racial causes have been cited. Nevertheless, the epidemic nature of the disease suggests that environmental causes are the most powerful. Based on the published hypotheses, as well as on epidemiologic studies, the present review discusses some of the possible causes of the disparity in the prevalence of eosinophilic esophagitis between the two types of countries. The 'hygiene hypothesis' is reviewed, together with the possible relation of Helicobacter pylori, intestinal parasites, and modifications of the esophageal microbiota in patients with eosinophilic esophagitis. In reference to studies conducted in the United States, the clinical behavior and progression of eosinophilic esophagitis in Hispanics is reviewed and a possible predominant phenotype in Mexican and other Latin American patients is discussed. Finally, based on the above, an algorithm for studying the disease in the Latin American countries is proposed.

Eosinophilic oesophagitis: epidemiology, pathogenesis and management.

Eosinophilic oesophagitis (EE) is a clinico-pathological entity recognized with increased frequency in children and adults. It is an atopic disease involving ingested and inhaled allergens. A pathological eosinophilic infiltrate is diagnosed by finding ≥ 15 eosinophils per high-powered field on oesophageal mucosal biopsies. This infiltrate may result in a narrowed oesophageal lumen. It does not involve the stomach or duodenum. Children commonly present with abdominal pain, vomiting and dysphagia. Presentation in adults is with dysphagia, heartburn, chest pain or impaction of a food bolus in the oesophagus. There is often a history of allergy (asthma, hay fever, eczema). A male predominance (70% in adults) is unexplained. Distinctive endoscopic features are linear furrows, mucosal rings and white papules, and the narrowed lumen may be appreciated. Although EE and gastro-oesophageal reflux disease are separate entities, there is a significant overlap of the conditions. Treatment options include nonpharmacological approaches including an elimination or elemental diet, and/ or medications, chiefly with corticosteroids. The topical administration of fluticasone propionate has been demonstrated to improve symptoms and mobilize the pathological infiltrate of eosinophils. There has been a variable effect with the leukotriene receptor antagonist montelukast and promising early results with mepolizumab, a monoclonal antibody against interleukin-5. The long-term efficacy of topical corticosteroids has not been well studied and most patients experience recurrent symptoms when treatment is completed. Currently, repeated short courses of topical corticosteroids are utilized. Acid suppression by a proton pump inhibitor may be considered in view of the overlap between EE and gastro-oesophageal reflux disease.

Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States.

OBJECTIVES: Variation in the prevalence of eosinophilic gastrointestinal diseases in different geographical regions has not been extensively studied. The aim of the present study was to define the regional and national prevalence of eosinophilic gastrointestinal diseases, and differences in practice approaches. PATIENTS AND METHODS: We administered a survey electronically to members of the American College of Gastroenterology, the American Academy of Allergy, Asthma, and Immunology, and the North American Society Pediatric Gastroenterology, Hepatology, and Nutrition. Questions pertained to the number and proportion of patients seen with eosinophilic gastroenteritis or colitis and eosinophilic esophagitis (EoE), and methods used to diagnose and treat these conditions. RESULTS: A total of 1836 physicians responded from 10,874 requests (17% response). Extrapolating responses from our US sample, we estimated an overall prevalence of 52 and 28/100,000 for EoE and eosinophilic gastroenteritis or colitis. The patient burden of EoE is higher in urban (0.58) and suburban (0.44) compared with rural settings (0.36, P < 0.0065), observations consistent with other allergic disorders. There was also increased prevalence in northeast region when calculated by prevalence per 100,000. There was considerable variability in criteria and initial treatment options used to diagnose EoE. Only one-third of respondents reported using diagnostic criteria proposed in a 2007 consensus document. Seventy-one and 35% of respondents reported treating some patients with EoE with a food elimination or elemental diet, respectively. CONCLUSIONS: EoE is diagnosed more often in northeastern states and urban areas. There is considerable variability in diagnostic criteria and initial treatment approach supporting the need for additional clinical trials and consensus development.