Esofagitis disecante supeEsofagitis disecante superficial: dos casos de una misma entidad poco frecuente / Esophagitis dissecans superficialis: two cases of the same rare entity

La esofagitis disecante superficial (EDS) es una entidad infrecuente que se caracteriza endoscópicamente por el desprendimiento de las capas superficiales del epitelio esofágico e, histológicamente, por el aspecto bitonal del epitelio escamoso esofágico secundario a la necrosis de los estratos más superficiales. La etiología es desconocida, aunque se ha asociado con la ingesta de determinados fármacos, enfermedades autoinmunes, estasis esofágica y procedimientos endoscópicos. Presentamos dos casos: uno de ellos acontece en una mujer tras un episodio de disfagia abrupta y el segundo en un varón con comorbilidades y clínica de dolor epigástrico. La EDS es una patología que hay que considerar en su adecuado contexto clínico y endoscópico, ya que su curso es autolimitado en comparación con otras entidades de evolución tórpida o que precisan un tratamiento específico. (AU)

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment. (AU)

Monitoring and modulating the trajectory of eosinophilic esophagitis.

Current treatments of eosinophilic esophagitis (EoE) aim to eliminate esophageal mucosal inflammation and attenuate, stabilize, or reverse stricture formation. However, our ability to study the long-term course of esophageal strictures in patients with EoE is hampered by the short-term existence of this disease. It is unclear to what degree of control of inflammation is needed to prevent stricture formation. Additionally, identified phenotypes of EoE may ultimately dictate different levels of concern and time intervals for developing fibrosis. Currently, multiple methods are used to monitor patients' disease progression to fibrosis, as symptoms alone do not correlate with disease activity. Endoscopic findings and mucosal histology are used to monitor disease activity, but these focus on improvements in inflammation with inconsistent evaluation of underlying fibrosis. The use of functional lumen impedance planimetry, barium esophagraphy, and endoscopic ultrasound continues to expand in EoE. The rapid advancements in EoE have led to an armamentarium of measuring tools and therapies that holistically characterize disease severity and response to therapy. Nevertheless, our ability to evaluate gross esophageal fibrosis and stricture formation from a transmural rather than mucosal view should be a focus of future investigations because it is essential to monitoring and modulating the trajectory of EoE.

Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients.

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago. The definition, diagnosis, and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians, enabling a better understanding of this disease and more targeted treatment for patients. We describe the definition, presentation, and diagnosis of eosinophilic esophagitis including management, challenges, and future directions in children. The definition, diagnosis, and management of eosinophilic esophagitis have evolved over the last 50 years. Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients. We describe the definition, presentation, diagnosis, management, and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.

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.

High prevalence of response to PPI treatment in children and adolescents with eosinophilic esophagitis in southern Brazil.

Introduction: Eosinophilic esophagitis is a newly recognized entity, in which there is significant evidence available that clearly demonstrates the positive impact of PPIs on reducing esophageal eosinophilia in individuals across different age groups, including children, adolescents, and adults. Multiple mechanisms have been proposed to explain how this treatment effect occurs. In Brazil, there seems to be a lack of studies that have prospectively assessed the clinical and therapeutic response rate in pediatric patients with EoE. The objective of this study was to prospectively evaluate the clinical and therapeutic response of pediatric patients with EoE in a medical center located in southern Brazil, by investigating the effectiveness of PPI treatment. Methods: This study is a clinical, prospective, open trial that took place in a pediatric hospital located in southern Brazil. The focus of the study was on patients diagnosed with Eosinophilic Esophagitis (EoE) who were given treatment using omeprazole/esomeprazole at a dosage of 1 mg.kg per dose, twice daily, for a period of 8-12 weeks. Following the treatment period, the patients underwent another endoscopy. Patients who exhibited 15 or less eosinophils in the biopsy conducted after the treatment were considered as responders. Results: A total of 27 patients was evaluated (74.1% boys). The average age (± standard deviation) was 8 years (±4). Nineteen patients (70.3%) were considered as responders to PPI treatment: 6 patients-22.2%-exhibited a complete response (defined as having 5 or fewer eosinophil per high power field. Additionally, 13 patients-48.1%-demonstrated a partial response, characterized by eosinophil counts exceeding 5 but less than 15 eos/hpf. When comparing the responder and non-responder groups at presentation, a statistical difference was observed in the prevalence of food refusal as a presenting symptom. Food refusal was found to be more prevalent in the non-responder group (87.5% vs. 26.3%, P = 0.008). No differences were observed in terms of atopy history and endoscopic scores. Upon comparing the histological findings from the post-treatment endoscopy of the two groups, it was observed that PPI responders exhibited a greater tendency to decrease basal cell hyperplasia (P = 0.06) and intercellular edema (P = 0.08). Conclusion: In this group of pediatric patients with EoE in Southern Brazil most patients showed a high prevalence of histological, endoscopic, and clinical response to PPI treatment. PPIs showed efficacy in Brazilian patients with EoE, most of whom would probably not be able to adequately undergo other treatments. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-2ntbth9, identifier (U1111-1301-1842).

Improved Outcomes in Eosinophilic Esophagitis with Higher Medication Possession Ratio.

Eosinophilic esophagitis (EoE) disease activity can be caused by treatment non-adherence. Medication possession ratio (MPR) is an established metric of medication adherence. A higher MPR correlates with better outcomes in several chronic diseases, but MPR has not been investigated with respect to EoE. A retrospective cohort study was performed using an established EoE registry for the years 2005 to 2020. Treatment periods were identified, MPRs were calculated, and medical records were assessed for histologic remission (<15 eos/hpf), dysphagia, food impaction, stricture occurrence, and esophageal dilation that corresponded to each treatment period. In total, 275 treatment periods were included for analysis. The MPR in the histologic remission treatment period group was 0.91 (IQR 0.63-1) vs. 0.63 (IQR 0.31-0.95) for the non-remission treatment period group (p < 0.001). The optimal MPR cut-point for histologic remission was 0.7 (Sen 0.66, Spec 0.62, AUC 0.63). With MPRs ≥ 0.7, there were significantly increased odds of histologic remission (odds ratio 3.05, 95% confidence interval 1.79-5.30) and significantly decreased odds of dysphagia (OR 0.27, 95% CI 0.15-0.45), food impaction (OR 0.26, 95% CI 0.11-0.55), stricture occurrence (OR 0.52 95% CI 0.29-0.92), and esophageal dilation (OR 0.29, 95% CI 0.15-0.54). Assessing MPR before repeating an esophagogastroduodenoscopy may decrease unnecessary procedures in the clinical management of eosinophilic esophagitis.

The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review.

Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.

Antacids and reflux esophagitis as a risk factor for gastric neoplasm of fundic-gland type: A retrospective, matched case-control study.

BACKGROUND AND AIM: Since the first report of gastric adenocarcinoma of the fundic-gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic-gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. METHODS: We conducted a single-center, retrospective, matched case-control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39 240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values < 0.1 and antacid use. RESULTS: A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P = 0.036). Factors antacids and duodenitis had P values < 0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio = 3.68 [95% confidence interval: 1.04-11.91] and 3.25 [95% confidence interval: 1.11-9.35]). CONCLUSIONS: Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG.

Prevalence and Costs of Esophageal Strictures in the United States.

BACKGROUND AND AIMS: Esophageal strictures are a leading cause of dysphagia, but data regarding the epidemiology of esophageal strictures are limited. This study aimed to investigate the prevalence, healthcare utilization, and financial burden of esophageal strictures in the United States. METHODS: We performed a retrospective cohort study utilizing two large national insurance claims databases (MarketScan and Medicare). Using ICD-9 and -10 diagnostic codes, annual prevalence was calculated for both cohorts overall, as well as stratified by age and sex strata. Most common diagnostic and procedural codes associated with esophageal strictures were extracted and analyzed to estimate healthcare utilization. Direct annual medical costs of esophageal strictures were calculated. RESULTS: The annual prevalence of esophageal strictures in MarketScan in 2021 was 203.14 cases/100,000 people while the annual prevalence in Medicare cohort in 2017 was 1123.47 cases/100,000. While rates were relatively stable over time, esophageal stricture prevalence increased with advancing age. No prevalence differences were noticed between males and females. GERD/erosive esophagitis was the top diagnostic code associated with esophageal strictures, though an increase in the proportion of eosinophilic esophagitis codes was noted over time. Esophageal dilation codes were present in ∼50% of stricture cases. The total healthcare costs associated with esophageal strictures were estimated at $1.39 billion in 2017. CONCLUSIONS: Esophageal strictures are common, affecting between 1/100 to 1/1000 patients in the United States, with the highest rates seen in patients aged 75y and older. Accordingly, strictures have a significant financial burden on the healthcare system, with costs above $1 billion annually.

Eosinophilic esophagitis improved by the discontinuation of sublingual immunotherapy for aeroallergens: a case report.

Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammation of the esophagus, characterized by symptoms related to esophageal dysfunction, resulting from severe eosinophilic infiltration of the esophageal mucosa. It is common in atopic subjects and food antigens have been identified as the most common triggers. However, a seasonal variation in EoE prevalence, correlated with air pollen levels, is reported, suggesting that also aeroallergens may play a role. Little is known about the interplay between EoE and concomitant atopy treatment for aeroallergens. Case presentation: We describe the case of an 11-year-old boy who presented dysphagia, vomiting, drooling, and chest pain while eating meat, developed 15 months after receiving sublingual immunotherapy (SLIT) for Alternaria (SUBLIVAC®). He underwent esophagogastroduodenoscopy (EGD) revealing severe eosinophilic predominant inflammation (100 eos/HPF), consistent with the diagnosis of EoE, not improving at the EGDs performed after both omeprazole and topical corticosteroids treatment, despite symptom improvement. Afterward, immunotherapy was switched from sublingual to injective form. At the EGD performed 1 month later, macroscopic examination of the esophageal mucosa was normal and eosinophilic infiltration was significantly decreased (5-10 eos/HPF). Conclusions: SLIT may induce EoE by chronic antigenic exposure of oral mucosa in patients with a robust allergic susceptibility: while attenuating the IgE-mediated immune reactions, the progressive contact with the causative allergen might induce a chronic stimulation of the immune system with the consequent activation of tissue eosinophils. Our data suggest monitoring patients receiving SLIT for EoE symptoms and to discontinue SLIT on their earlier appearance, possibly as a first-line treatment.

Novel Endoscopic Findings of Lesions with a Short White Hair-like Appearance in the Lower Esophagus.

Objective The presence of a short white hair-like appearance in the lower esophagus has recently been noted during esophagogastroduodenoscopy (EGD) at our institution. Histological findings showed that this formation was a spiked protrusion of the esophageal papilla. The results regarding the prevalence of such lesions in individuals who underwent EGD examinations as part of medical checkup procedures are herein presented. Methods The EGD results of 14,338 individuals (9,225 males, 5,113 females; mean age 54.0±9.8 years) were examined. The findings related to the presence of multiple lesions with a short white hair-like appearance in the lower esophagus of patients with reflux esophagitis, esophageal squamous papilloma, or gastric mucosal atrophy (GMA), as well as the hiatal hernia width, were investigated. Results Endoscopic findings indicating short white hair-like appendages in the lower esophagus were noted in 167 patients, with a prevalence rate of 1.2%. A female sex, younger age, lower body mass index, lower percentages of habitual smoking and drinking, and the presence of esophageal squamous papilloma were characteristic features of cases with such findings. In addition, a significantly lower prevalence of reflux esophagitis and a smaller diaphragmatic hiatus size were observed. A multiple logistic regression analysis indicated that a female sex, absence of reflux esophagitis, presence of esophageal squamous papilloma, and a smaller diaphragmatic hiatus were factors significantly related to the presence of these short white hair-like appendages. An analysis of circumferential localization revealed the main location to be the left-posterior wall. Conclusion This study is the first to report the prevalence of multiple short white hair-like appendages in the lower esophagus. The occurrence of such lesions is inversely associated with the presence of reflux esophagitis.

Pathophysiology and Clinical Impact of Esophageal Remodeling and Fibrosis in Eosinophilic Esophagitis.

Most of the major clinical signs and consequences of eosinophilic esophagitis seem to be related to tissue remodeling. Important data on remodeling activity in patients with eosinophilic esophagitis are provided by a range of current and new biologic markers and diagnostics. To completely clarify the possible advantages and restrictions of therapeutic approaches, clinical studies should take into consideration the existence and reversibility of esophageal remodeling. The degree of mucosal or submucosal disease activity may not be reflected by epithelial eosinophilic inflammation, which is used to define one criterion of disease activity".

Clinical Evaluation of the Child with Eosinophilic Esophagitis.

The diagnosis of eosinophilic esophagitis (EoE) is based on clinical symptoms of esophageal dysfunction and eosinophil predominant esophageal inflammation. Clinical symptoms in children with EoE vary based on age and may be nonspecific. EoE has a male predominance with the majority having comorbid atopic disorders. At present, treatment options include medications (proton pump inhibition, swallowed topical steroids), dietary therapy or biologic therapy (dupilumab, approved for those ≥12 years of age). Outside of EoE in the context of oral immunotherapy, EoE is typically chronic requiring lifelong therapy. Long-term complications including feeding difficulties, malnutrition, and fibrostenotic disease.

Pathophysiology of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, progressive immune-mediated disease associated with antigen-driven type 2 inflammation and symptoms of esophageal dysfunction. Research over the last 2 decades has dramatically furthered our understanding of the complex interplay between genetics, environmental exposures, and cellular and molecular interactions involved in EoE. This review provides an overview of our current understanding of EoE pathogenesis.

Clinical Evaluation of the Adult with Eosinophilic Esophagitis.

Adult patients with eosinophilic esophagitis (EoE) typically present with a history of dysphagia for solids, sometimes with additional reflux-like pain and a history of prior food impactions. In contrast to these alarming symptoms, the general appearance and physical examination of adult patients with EoE is in line with apparently healthy individuals. Therefore, the diagnosis is based on a history of solid-food dysphagia and eosinophilic tissue infiltration. Importantly, the increasing prevalence of EoE variants, that is, typical EoE symptoms in the absence of a relevant eosinophilia, and several studies with eosinophil-targeting drugs, call the pathogenic role of eosinophils into question.

Endoscopic Features of Eosinophilic Esophagitis.

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.

Dietary Management of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated food allergy-driven disease characterized by eosinophilic inflammation of the esophagus leading to symptoms of esophageal dysfunction. Prior studies have supported the key role of food allergen exposure as the main driver behind the etiopathogenesis showing that removal of food antigens can result in disease remission in both children and adults. These landmark studies serve as the basis for the rising interest and evolution of dietary therapy in EoE. This article will focus on the rationale for dietary therapy in EoE and provide helpful tools for the implementation of dietary therapy in practice.

Recognition and Management of Feeding Dysfunction in the Pediatric Patient with Eosinophilic Esophagitis.

Feeding is a complex skill requiring coordination of multiple body systems. Multiple factors are considered in feeding dysfunction in pediatric patients with eosinophilic gastrointestinal disorders, including overall development, nutritional status, mealtime behaviors, and medical comorbidities. Symptoms of feeding dysfunction vary by age, with maladaptive learned feeding behaviors spanning all age ranges. Knowledge of the normal acquisition of feeding skills is critical to interpret the impact of the disease and plan appropriate intervention. Assessment and treatment from a feeding and swallowing disorders specialist can dramatically impact successful outcomes in nutrition, growth, mealtime dynamics and ultimatly quality of life for children and their caregivers in home and social settings.

Role of Mast Cells in Eosinophilic Gastrointestinal Diseases.

Mast cells play a central role in the pathogenesis of eosinophilic gastrointestinal disorders (EGIDs), including eosinophilic esophagitis. Their interactions with immune and structural cells, involvement in tissue remodeling, and contribution to symptoms make them attractive targets for therapeutic intervention. More is being discovered regarding the intricate interplay of mast cells and eosinophils. Recent studies demonstrating that depletion of eosinophils is insufficient to improve symptoms of EGIDs have raised the question of whether other cells may play a role in symptomatology and pathogenesis of EGIDs.