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Gastroesophageal reflux disease is the most frequent gastroente-rological diagnosis, with a high prevalence of symptoms impacting patients' quality of life and causing high economic costs. It has a -complex pathophysiology that encompasses different mechanisms and an overlap with functional disorders that cause similar symptoms. Hence, an accurate diagnosis and phenotyping of patients is crucial to individualize therapy and limit health costs. Nowadays, therapy is personalized and encompasses lifestyle interventions, proton pump inhibitors, surgery, neuromodulation, diaphragmatic breathing as well as, in the future, new drugs and endoscopic interventions.
La maladie de reflux gastro-Åsophagien est le diagnostic le plus fréquent en gastroentérologie, avec une prévalence élevée des symptômes, impactant la qualité de vie des patients et engendrant des coûts sanitaires élevés. Sa physiopathologie est complexe et englobe plusieurs mécanismes, ainsi un chevauchement est possible avec des troubles fonctionnels pouvant se présenter avec des symptômes similaires. D'où l'importance d'un diagnostic précis et d'une prise en charge individualisée incluant, entre autres, les mesures hygiénodiététiques, les inhibiteurs de la pompe à protons, la chirurgie, la neuromodulation, la respiration diaphragmatique ainsi que, dans le futur, de nouvelles thérapies médicamenteuses et endoscopiques.
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Reflujo Gastroesofágico , Inhibidores de la Bomba de Protones , Calidad de Vida , Humanos , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/epidemiología , Inhibidores de la Bomba de Protones/uso terapéutico , Prevalencia , Estilo de VidaRESUMEN
Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.
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Edema, rings, exudates, furrows, and strictures (EREFS) represent the major endoscopic features of eosinophilic esophagitis (EoE). The Endoscopic Reference System (EREFS) grading system is easy to learn and apply during daily clinical practice in the diagnosis and follow-up of EoE patients. When endoscopy is performed by an EoE-experienced physician, the EREFS criteria will identify the majority of EoE patients. The EREFS score from the area of greatest involvement of the esophagus should be reported. The EREFS grading system was formally validated as an endoscopy score and several randomized placebo-controlled trials have shown responsiveness of the EREFS score to therapeutic interventions.
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Esofagitis Eosinofílica , Humanos , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/terapia , Esofagoscopía , Índice de Severidad de la Enfermedad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. METHODS: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. RESULTS: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). CONCLUSION: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited.
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Esofagitis Eosinofílica , Padres , Calidad de Vida , Humanos , Esofagitis Eosinofílica/terapia , Esofagitis Eosinofílica/diagnóstico , Padres/psicología , Niño , Encuestas y Cuestionarios , Masculino , Femenino , Resultado del Tratamiento , Adolescente , PreescolarRESUMEN
INTRODUCTION: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined. METHODS: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls. RESULTS: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months). DISCUSSION: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.
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Progresión de la Enfermedad , Esofagitis Eosinofílica , Esófago , Humanos , Esofagitis Eosinofílica/genética , Esofagitis Eosinofílica/patología , Esofagitis Eosinofílica/diagnóstico , Femenino , Masculino , Adulto , Esófago/patología , Araquidonato 15-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/metabolismo , Adolescente , Eosinófilos/patología , Eosinófilos/inmunología , Adulto Joven , Factor de Transcripción GATA3/genética , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Niño , Biopsia , Células Th2/inmunología , Persona de Mediana Edad , Estudios de Casos y Controles , Recuento de LeucocitosRESUMEN
INTRODUCTION: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. METHODS: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. RESULTS: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. CONCLUSION: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Masculino , Femenino , Humanos , Adulto , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/terapia , Endoscopía , FenotipoRESUMEN
Although mostly accentuated in the distal esophagus, distribution of esophageal eosinophilia in eosinophilic esophagitis (EoE) seems to be nonuniform.1 Disease extent has been associated with disease severity and disease progression in inflammatory bowel disease.2,3 Whether the same holds true for EoE remains largely unknown. One recent EoE study looked at the distribution of eosinophilia, but without analyzing its potential association with treatment outcomes.4 Here, we characterize the different inflammatory patterns of EoE and investigate their impact on disease presentation and disease outcome, with a particular focus on therapeutic response.
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Esofagitis Eosinofílica , Eosinófilos , Esofagitis Eosinofílica/terapia , Humanos , Resultado del Tratamiento , MasculinoRESUMEN
Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis.
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Enteritis , Esofagitis Eosinofílica , Gastritis , Humanos , Esofagitis Eosinofílica/diagnóstico , Eosinófilos/patología , Enteritis/complicaciones , Enteritis/patología , Gastritis/complicacionesRESUMEN
Introduction: Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years). Methods: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). Results: A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p < 0.001), and more specifically arthritis/arthralgias (p < 0.001) and ankylosing spondylitis/sacroiliitis (p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. Conclusions: As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients.
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Introduction: Medical care and surveillance of inflammatory bowel disease (IBD) patients have been shown to be far from satisfactory. Data on therapy patterns and surveillance measures in IBD patients are scarce. We, therefore, aimed to compare the therapy patterns and surveillance management of IBD patients in the year before and after IBD-related hospitalization. Methods: We examined medical therapy, surveillance management (influenza vaccination, dermatologist visits, Pap smear screening, creatinine measurements, iron measurements, and ophthalmologist visits) and healthcare utilization in 214 ulcerative colitis (UC) and 259 Crohn's disease (CD) patients who underwent IBD-related hospitalization from 2012 to 2014. Results: IBD-related drug classes changed in 64.5% of IBD patients following hospitalization. During the 1-year follow-up period, biological treatment increased in UC and CD patients, while steroid use decreased. Following hospitalization, 63.1% of UC and 27.0% of CD patients received 5-ASA. Only 21.6% of all IBD patients had a flu shot, and 19.6% of immunosuppressed IBD patients were seen by a dermatologist in the follow-up; other surveillance measures were more frequent. Surveillance before hospital admission and consultations by gastroenterologists were strongly correlated with surveillance during the postoperative follow-up, while gender and diagnosis (UC vs. CD) were not. During the 1-year follow-up, 20.5% of all IBD patients had no diagnostic or disease-monitoring procedure. Discussion/Conclusion: Surveillance measures for IBD patients are underused in Switzerland. Further research is needed to examine the impact of annual screenings and surveillance on patient outcomes.
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INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS: We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS: Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P < 0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION: DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.
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Trastornos de Deglución , Esofagitis Eosinofílica , Estenosis Esofágica , Adulto , Humanos , Masculino , Enfermedad Crónica , Trastornos de Deglución/diagnóstico , Diagnóstico Tardío , Esofagitis Eosinofílica/complicaciones , Estenosis Esofágica/complicaciones , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.
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Esofagitis Eosinofílica , Estenosis Esofágica , Dilatación , Endoscopía Gastrointestinal , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/patología , Estenosis Esofágica/terapia , HumanosRESUMEN
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.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
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.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND AIMS: No recommendations exist regarding optimal follow-up schedule in patients with eosinophilic esophagitis (EoE) under maintenance treatment. METHODS: We retrospectively evaluated a long-term surveillance concept at the Swiss EoE clinic, where clinical, endoscopic and histological disease activity is assessed annually regardless of EoE symptoms. Data on 159 adult patients under maintenance steroid treatment with available follow-up were analyzed. Patients were classified as having close (duration between visits <18 months) or non-close follow-up (≥18 months). RESULTS: We analyzed a total of 309 follow-up visits of 159 patients (123 males, age at diagnosis 38.9 ± 15.4 years). 157 (51%) visits were within a close follow-up schedule (median duration between visits of 1.0 years (interquartile range (IQR) 0.9-1.2)), while 152 visits (49%) were not (median duration between visits 2.9 years (IQR 2.0-4.1)). There was no difference regarding ongoing clinical, endoscopic, and histological disease activity, and adherence to prescribed steroid treatment between the two groups. However, stricture formation was significantly less frequently observed at visits within a close follow-up schedule (22.9 vs. 33.6%, p = 0.038). Absence of close follow-up was a significant risk factor for stricture development in a multivariate regression model. Patients who achieved histological remission and were followed within a close-follow-up schedule had significantly earlier detection of histological relapse compared to patients not within such close follow-up. CONCLUSION: Close follow-up is associated with fewer stricture formation and appears to result in earlier detection of histological relapse in patients with eosinophilic esophagitis. We advocate for regular assessment of disease activity (every 12-18 months) in order to detect relapsing disease as early as possible, and therefore potentially minimize the risk for EoE complications.
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Esofagitis Eosinofílica , Adulto , Enfermedad Crónica , Constricción Patológica , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/terapia , Estudios de Seguimiento , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
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.
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Trastornos de Deglución , Esofagitis Eosinofílica , Costo de Enfermedad , Trastornos de Deglución/complicaciones , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/terapia , Fibrosis , Humanos , Inflamación/complicaciones , Inhibidores de la Bomba de Protones/uso terapéutico , Calidad de VidaRESUMEN
BACKGROUND AND AIMS: Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. METHODS: Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). RESULTS: The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. CONCLUSIONS: EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.
Asunto(s)
Esofagitis Eosinofílica , Esofagitis Eosinofílica/diagnóstico , Esofagoscopía/métodos , Humanos , Inhibidores de la Bomba de Protones , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE. METHODS: In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency. RESULTS: Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses. CONCLUSION: APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile. CLINICALTRIALS: gov, Number: NCT03191864.
Asunto(s)
Trastornos de Deglución , Esofagitis Eosinofílica , Adulto , Humanos , Esofagitis Eosinofílica/patología , Trastornos de Deglución/etiología , Esofagoscopía , Fluticasona , Comprimidos/uso terapéutico , Método Doble Ciego , Resultado del TratamientoRESUMEN
OBJECTIVE: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants. DESIGN: Patients from six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro-esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)-histological, and molecular features were determined and compared with EoE, GERD, and healthy controls. RESULTS: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE-like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non-specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed-in contrast to EoE-no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE-typical Th2-response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE-like (characterized by eotaxin-3 expression), non-specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression). CONCLUSION: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype.