Eosinophilic esophagitis: Current concepts in diagnosis and treatment

Eosinophilic esophagitis is an immune-allergic pathology of multifactorial etiology(genetic and environmental) that affects both pediatric and adult patients. Its symptoms, which include heartburn, regurgitation, and esophageal stenosis(with dysphagia being more frequent in eosinophilic esophagitis in young adults and children), are similar to those of gastroesophageal reflux disease, causing delays in diagnosis and treatment. Although endoscopic findings such as furrows, esophageal mucosa trachealization, and whitish exudates may suggest its presence, this diagnosis should be confirmed histologically based on the presence of more than 15 eosinophils per high-power field and the exclusion of other causes of eosinophilia(parasitic infections,hypereosinophilic syndrome, inflammatory bowel disease, among others) for which treatment could be initiated. Currently, the 3 "D"s("Drugs, Diet, and Dilation") are considered the fundamental components of treatment. The first 2 components, which involve the use of proton pump inhibitors, corticosteroids,immunosuppressants and empirical diets or guided food elimination based on allergy tests, are more useful in the initial phases, whereas endoscopic dilation is reserved for esophageal strictures. Herein, the most important aspects of eosinophilic esophagitis pathophysiology will be reviewed, in addition to evidence for the various treatments.     

Eosinophilic esophagitis: a practical approach to diagnosis and management

Eosinophilic esophagitis (EoE) has emerged as a common cause of dysphagia and food impaction in children and adults. A trial of proton pump inhibitor (PPI) therapy is a mandatory diagnostic first step, given that at least one third of patients with suspected EoE will have PPI-responsive esophageal eosinophilia. Once EoE is diagnosed, short-and long-term therapeutic decision making may rely on patient symptoms, phenotype (inflammatory vs fibrostenotic) and preferences. Currently, the most reliable therapeutic targets are mucosal healing and caliber abnormalities resolution. Topical steroids followed by endoscopic dilation are recommended in symptomatic narrow caliber esophagus/strictures, whereas either topical steroids or dietary therapy are good short-term options for mucosal inflammation. Maintenance anti-inflammatory therapy is necessary to prevent esophageal fibrotic remodeling and stricture formation.     

Rifaximin and diverticular disease: Position paper of the Italian Society of Gastroenterology (SIGE)

Management of diverticular disease has significantly improved in the last decade. Antibiotic treatment is used for symptom relief and prevention of complications. In Italy, the non-absorbable antibiotic rifaximin is one of the most frequently used drugs, and it is perceived as the reference drug to treat symptomatic diverticular disease. Its non-systemic absorption and high faecal concentrations have oriented rifaximin use to the gastrointestinal tract, where rifaximin exerts eubiotic effects representing an additional value to its antibiotic activity. This position paper was commissioned by the Italian Society of Gastroenterology governing board for a panel of experts (RC, GB, BA) to highlight the indications for treatment of diverticular disease. There is a lack of rationale for drug use for the primary prevention of diverticulitis in patients with diverticulosis; thus, rifaximin use should be avoided. The cyclic use of rifaximin, in association with high-fibre intake, is safe and useful for the treatment of symptomatic uncomplicated diverticular disease, even if the cost-efficacy of long-term treatment remains to be determined. The use of rifaximin in the prevention of diverticulitis recurrence is promising, but the low therapeutic advantage needs to be verified. No evidence is available on the efficacy of rifaximin treatment on acute uncomplicated diverticulitis.     

Update on endoscopic diagnosis, management and surveillance strategies of esophageal diseases

In the last few decades, upper gastrointestinal endoscopy has become the most complementary test for investigation of esophageal diseases. Its accessibility and safety guarantee wide clinical utilization in patients with suspected benign and malignant diseases of the esophagus. Recent technological advances in endoscopic imaging and tissue analysis obtained from the esophagus have been useful to better understand and manage highly relevant diseases such as gastroesophageal reflux disease, eosinophilic esophagitis and esophageal cancer. Using endoscopy to elucidate esophageal disorders in children has been another field of intensive and challenging research. This editorial highlights the latest advances in the endoscopic management of esophageal diseases, and focuses on Barrett’s esophagus, esophageal cancer, eosinophilic esophagitis, as well as esophageal disorders in the pediatric population.     

Management of Helicobacter pylori infection: Guidelines of the Italian Society of Gastroenterology (SIGE) and the Italian Society of Digestive Endoscopy (SIED)

Helicobacter pylori infection is very common and affects more than one-third of adults in Italy. Helicobacter pylori causes several gastro-duodenal diseases, such as gastritis, peptic ulcer and gastric malignancy, and extra-gastric diseases. The eradication of the bacteria is becoming complex to achieve due to increasing antimicrobial resistance. To address clinical questions related to the diagnosis and treatment of Helicobacter pylori infection, three working groups examined the following topics: (1) non-invasive and invasive diagnostic tests, (2) first-line treatment, and (3) rescue therapies for Helicobacter pylori infection. Recommendations are based on the best available evidence to help physicians manage Helicobacter pylori infection in Italy, and have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.     

Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitis

Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 ± 2.2/HPF, EoE 19.8 ± 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 ± 0.7 and 74.9 ± 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 ± 0.16/HPF) and EoE (0.09 ± 0.04; P = 0.07). Eight of the 39 RE specimens had ≥50 lymphocytes in ≥1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = ?0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 ± 1.3 vs 22.2 ± 2.3/HPF; P = 0.030) and eosinophils (55.6 ± 5.2 vs 76.0 ± 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE.     

嗜酸细胞性食管炎临床资料回顾性分析

[目的]了解嗜酸细胞性食管炎(EoE)的临床表现、内镜表现、病理学特点和诊治经验。[方法]回顾性分析2006-01—2016-01期间武汉第一医院收治的6例EoE患者的临床资料。[结果]EoE以吞咽困难、烧心等症状为主要表现;胃镜下可见食管黏膜糜烂、溃疡、水肿、狭窄,部分可见食管环;食管黏膜组织学检查可见大量嗜酸性粒细胞和肥大细胞浸润,细胞水肿和固有层纤维化。5例经脱敏和使用糖皮质激素治疗后均明显好转,1例经内镜下食管球囊扩张术联合糖皮质激素治疗效果满意,均随访1年以上无复发。[结论]EoE临床表现和内镜下表现无特异性,病理组织学检查对诊断EoE有重要价值,糖皮质激素是一线治疗用药。     

Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment

During the last decade, clinical practice saw a rapid increase of patients with esophageal eosinophilia who were thought to have gastroesophageal reflux disease (GERD) but who did not respond to medical and/or surgical GERD management. Subsequent studies demonstrated that these patients had a "new" disease termed eosinophilic esophagitis (EE). As recognition of EE grew, so did confusion surrounding diagnostic criteria and treatment. To address these issues, a multidisciplinary task force of 31 physicians assembled with the goal of determining diagnostic criteria and making recommendations for evaluation and treatment of children and adults with suspected EE. Consensus recommendations were based upon a systematic review of the literature and expert opinion. EE is a clinicopathological disease characterized by (1) Symptoms including but not restricted to food impaction and dysphagia in adults, and feeding intolerance and GERD symptoms in children; (2) > or = 15 eosinophils/HPF; (3) Exclusion of other disorders associated with similar clinical, histological, or endoscopic features, especially GERD. (Use of high dose proton pump inhibitor treatment or normal pH monitoring). Appropriate treatments include dietary approaches based upon eliminating exposure to food allergens, or topical corticosteroids. Since EE is a relatively new disease, the intent of this report is to provide current recommendations for care of affected patients and defining gaps in knowledge for future research studies.     

Recent advances in the recognition and management of eosinophilic esophagitis

The incidence and recognition of eosinophilic esophagitis is increasing. Pathophysiological understanding of eosinophilic esophagitis is improving and an immunological reaction to ingested food is likely to play a significant role. Patients present with dysphagia and food bolus obstruction. Both histological and endoscopic criteria have been developed and validated. Dietary therapy, topical steroid therapy, proton pump inhibitors and endoscopic dilation are the main approaches to therapy; however, novel targeted therapies are being developed. Among the food items commonly implicated are wheat, dairy, nuts, soy, shellfish and eggs. A multidisciplinary approach to management in dedicated clinics may yield the best results.     

泮托拉唑治疗老年人反流性食管炎的长期疗效观察

目的探讨泮托拉唑治疗老年人反流性食管炎及预防复发的临床疗效。方法 70例反流性食管炎老年患者随机分为两组,每组35例,A组服用泮托拉唑40 mg,2次/d,B组服用泮托拉唑40 mg,1次/d。8周后,治疗有效的患者共61例,其中26例继续口服泮托拉唑40 mg,1次/d,维持治疗48周,另外35例未继续服用泮托拉唑但同时给予随访,并在8周、24周及48周时分别评价临床症状并复查胃镜。结果治疗8周后A组、B组的症状缓解有效率分别为91.4%、82.9%,内镜下食管炎改善有效率分别为97.1%、91.4%。维持治疗患者,24周后临床症状和内镜下食管炎缓解的有效率均为84.6%;48周后临床症状缓解的有效率为88.5%,内镜下食管炎改善有效率为84.6%。未维持治疗组24周及48周时临床症状缓解的有效率分别为48.6%、37.1%。结论泮托拉唑能有效地治疗老年人反流性食管炎及减少复发,维持48周的用药安全、有效。     

Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches

Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US$ 1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation.     

Prevalence, clinical manifestations and endoscopic features of eosinophilic esophagitis: a pathological review in China

OBJECTIVE: We aimed to determine the prevalence of eosinophilic esophagitis (EoE) and define its clinical and endoscopic characteristics in Chinese patients. METHODS: Esophageal specimens obtained from January 2006 to December 2010 in the First Affiliated Hospital of Sun Yat‐sen University were reviewed, and the data on clinical characteristics and endoscopic findings of patients were obtained. Patients with eosinophils ≥15 per high power field (HPF) were identified as having EoE. RESULTS: A total of 12 patients met the criteria for EoE, establishing a prevalence of 0.34%. These patients presented with dysphagia (4/12, 33.3%), gastroesophageal reflux disease (GERD)‐like symptoms (3/12, 25.0%), abdominal pain (3/12, 25.0%) and others (2/12, 16.7%). The most common endoscopic finding was plaques (5/12, 41.7%), and other findings were irregular Z‐line (2/12, 16.7%), erosive esophagitis (2/12, 16.7%), white exudates (1/12, 8.3%), linear furrows (1/12, 8.3%), Schatzki ring (1/12, 8.3%), ulcers (1/12, 8.3%) and erythema (1/12, 8.3%). CONCLUSIONS: The prevalence of EoE was 0.34% in our patients. Clinicians should pay attention to patients manifested with dysphagia and GERD‐like symptomes with endosopic findings of white exudates, plaques, Schatzki ring and linear furrows.     

Cholangiocarcinoma: A position paper by the Italian Society of Gastroenterology (SIGE), the Italian Association of Hospital Gastroenterology (AIGO), the Italian Association of Medical Oncology (AIOM) and the Italian Association of Oncological Radiotherapy (AIRO)

The incidence of Cholangiocellular carcinoma (CCA) is increasing, due to a sharp increase of the intra-hepatic form. Evidence-ascertained risk factors for CCA are primary sclerosing cholangitis, Opistorchis viverrini infection, Caroli disease, congenital choledocal cist, Vater ampulla adenoma, bile duct adenoma and intra-hepatic lithiasis. Obesity, diabetes, smoking, abnormal biliary-pancreatic junction, bilio-enteric surgery, and viral cirrhosis are emerging risk factors, but their role still needs to be validated. Patients with primary sclerosing cholangitis should undergo surveillance, even though a survival benefit has not been clearly demonstrated.     

Routine management of gastro-oesophageal reflux disease by gastroenterologists in France: A prospective observational study

AIMS: To obtain data on routine care of gastro-oesophageal reflux disease by French gastroenterologists. PATIENTS: Five thousand and forty-five adults with gastro-oesophageal reflux disease. METHODS: Patients were recruited by a representative sample of 598 French gastroenterologists. A full disease history, with treatments given/investigations undertaken, was obtained from all patients. The patients' expectations with regard to the improvement of the symptoms' control and the corresponding assessments made by the gastroenterologists were recorded on a 4-point scale. RESULTS: The mean time since diagnosis was approximately 4 years. The most commonly presented symptom was heartburn (79% of patients). A total of 3735 patients (74%) underwent endoscopy because of gastro-oesophageal reflux disease. Erosive oesophagitis was present in 38% and Barrett's oesophagus in 8%. Medical therapy for gastro-oesophageal reflux disease was prescribed in 92% of patients, of whom 86% received proton pump inhibitors. Lifestyle advice was given to 73% of patients. Overall, 84% of patients and 72% of physicians expected 'highly' or 'moderately' improved control of gastro-oesophageal reflux disease. Gastroenterologists underrated the need for improvement of the symptoms' control as expressed by 'de novo' as well as 'previously diagnosed' patients. CONCLUSIONS: This study provides cross-sectional data on the management of gastro-oesophageal reflux disease by gastroenterologists in France. Most patients have high expectations of an improvement in their management, but gastroenterologists generally underrate these expectations.     

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis： A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.     

Chronic atrophic gastritis: Natural history,diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the Italian Society of Internal Medicine [SIMI]

Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may manifest itself by a variable spectrum of gastric and extra-gastric symptoms and signs. It is relatively common among older adults in different parts of the world, but large variations exist. Helicobacter pylori-related CAG [multifocal] and autoimmune CAG (corpus-restricted) are apparently two different diseases, but they display overlapping features. Patients with cobalamin and/or iron deficiency anaemia or autoimmune disorders, including autoimmune thyroiditis and type 1 diabetes mellitus, should be offered screening for CAG. Pepsinogens, gastrin-17, and anti-H. pylori antibodies serum assays seem to be reliable non-invasive screening tools for the presence of CAG, helpful to identify individuals to refer to gastroscopy with five standard gastric biopsies in order to obtain histological confirmation of diagnosis. Patients with CAG are at increased risk of developing gastric cancer, and they should be estimated with histological staging systems (OLGA or OLGIM). H. pylori eradication may be beneficial by modifying the natural history of atrophy, but not that of intestinal metaplasia. Patients with advanced stages of CAG (Stage III/IV OLGA or OLGIM) should undergo endoscopic surveillance every three years, those with autoimmune CAG every three-five years. In patients with CAG, a screening for autoimmune thyroid disease and micronutrient deficiencies, including iron and vitamin B₁₂, should be performed. The optimal treatment for dyspeptic symptoms in patients with CAG remains to be defined. Proton pump inhibitors are not indicated in hypochlorhydric CAG patients.     

Digestive neuroendocrine tumours: diagnosis and treatment in Italy. A survey by the Oncology study Section of the Italian Society of Gastroenterology (SIGE)

BACKGROUND: New insights in the diagnosis and treatment of digestive neuroendocrine tumours have prompted a renewed interest in these rare and complex diseases. AIM: To establish how many new cases of digestive neuroendocrine tumours were diagnosed, and how they were treated, at gastroenterological centres across Italy during a two-year period (1997-1998). METHODS: The 12 centres taking part filled in a data collection form reporting type of tumour, methods of diagnosis and therapeutic strategies adopted in each case. Data were collected and analysed by the authors of the present report. RESULTS: Data refer to 98 patients, 22 with functioning and 76 with non-functioning digestive neuroendocrine tumours [50 carcinoids, 48 pancreatic endocrine tumour syndromes]. Primary tumours were localised in 96% (38% with metastases) of non-functioning and 81% (50% with metastases) of functioning tumours. These were surgically removed in >80% of patients in both groups. Somatostatin analogue treatment, with or without interferon, was administered in 35% of patients, while chemotherapy was used in 9% and 23% of functioning and non-functioning tumours, respectively. The imaging study always included a computed tomography scan (20% helical computed tomography). Magnetic resonance and somatostatin receptor scintigraphy were also performed, the former in 41% and 21% of the two (functioning and non-functioning tumour) groups, the latter in 45% and 30%. CONCLUSIONS: The number of functioning digestive neuroendocrine tumours reported was lower than expected. Surgery plays a major role in the treatment of these tumours in all centres. Overall, in only a small number of patients was a multidisciplinary approach applied.     

Italian Society of Digestive Endoscopy (SIED) position paper on the non-anaesthesiologist administration of propofol for gastrointestinal endoscopy

Propofol sedation by non-anesthesiologists in GI endoscopy, despite generally considered a safe procedure, is still a matter of debate. Benefits of propofol sedation include rapid onset of action, greater patient comfort and fast recovery with prompt discharge from the endoscopy unit.The use of propofol for sedation in GI endoscopy, preceded by dedicated training courses, has been approved by several anaesthesiologist and gastroenterologist societies but an Italian position paper taking into account the Italian law is lacking.In the present document, the Italian Society of Digestive Endoscopy (SIED) Sedation Group, on behalf of the SIED, presents a series of updated position statements concerning propofol sedation in GI endoscopy. The paper summarizes the advantages of propofol, how it should be administered and how patients should be monitored. Moreover, details concerning proper training of non-anaesthesiologist personnel involved in its use are provided. Protocols concerning propofol use s must be shared with the hospital's anaesthesiology staff and approved by the hospital’s Executive Director.