Eosinophilic esophagitis: unclear roles of IgE and eosinophils.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the oesophagus. Recognized as a distinct entity only two decades ago, the emergence of the disease along with the availability of new technologies has rapidly opened new research avenues and outlined the main features of the pathogenesis of EoE. Yet, each advance in our understanding of the disease has raised new questions about the previous consensus. Currently, new subsets of the disease challenge our diagnostic criteria. For instance, it was believed that EoE did not respond to proton pump inhibitor (PPI) therapy; however, it has now been shown that a substantial proportion of EoE patients indeed respond to PPIs. In addition, a new subset of patients not even presenting eosinophil infiltrates in the oesophagus has also been described. Moreover, approaches for better understanding the heritability of the disease bring into question the dogma of predominant genetic involvement. Furthermore, the specificity and sensitivity of allergy testing for targeted food avoidance is highly controversial, and the production of specific antibodies in EoE now includes IgG4 in addition to IgE. In conclusion, EoE is perceived as 'a moving target' and the aim of this review was to summarize the current understanding of EoE pathogenesis.

A new eosinophilic esophagitis (EoE)-like disease without tissue eosinophilia found in EoE families.

BACKGROUND: Eosinophilic esophagitis (EoE) is a rapidly emerging, chronic inflammatory, genetically impacted disease of the esophagus, defined clinically by symptoms of esophageal dysfunction and, pathologically, by an eosinophil-predominant tissue infiltration. However, in four EoE families, we have identified patients presenting with EoE-typical and corticosteroid-responsive symptoms, but without tissue eosinophilia. The aim of this study was to clinically and immunologically characterize these patients with EoE-like disease. METHODS: Five patients suffering from an EoE-like disease were evaluated with endoscopic, histologic, functional, and quantitative immunohistological examinations, and mRNA expression determination. RESULTS: The frequency of first-generation offspring of patients affected by EoE or EoE-like disease was 40%. Immunofluorescence analysis confirmed an almost complete absence of eosinophils in the esophageal tissues of patients with EoE-like disease, but revealed a considerable T-cell infiltration, comparable to EoE. In contrast to EoE, eotaxin-3 mRNA and protein were markedly reduced in EoE-like disease (P < 0.05). The mRNA expression levels of three selected EoE genes (eotaxin-3, MUC4, and CDH26) allowed to discriminate between EoE-like disease, EoE, and normal epithelium. CONCLUSIONS: Patients suffering from 'EoE without eosinophilia' do not fulfill formally the diagnostic criteria for EoE. However, their clinical manifestation, immunohistology, and gene expression pattern, plus the fact that they bequeath EoE to their offspring, suggest a uniform underlying pathogenesis. Conventional EoE, with its prominent eosinophilia, therefore appears to be only one phenotype of a broader 'inflammatory dysphagia syndrome' spectrum. In this light, the role of the eosinophils, the definition of EoE, and its diagnostic criteria must likely be reconsidered.

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures.

How to measure disease activity in eosinophilic esophagitis.

Activity of Eosinophilic Esophagitis (EoE) can be measured by patient reported outcomes (symptoms and quality of life) and clinician-reported outcomes (endoscopic, histologic, or biochemical alterations). Over the last years efforts have been underway to develop and validate instruments to assess EoE activity in the different domains. Such instruments are urgently needed to standardize the language of EoE activity assessment and, in so doing, to facilitate communication among various stakeholders. Such standardization will ultimately allow EoE researchers to define meaningful endpoints for use in clinical trials and observational studies, to compare the efficacy of different therapeutic modalities, and to develop algorithms in order to provide patients with the appropriate therapy. This review provides an overview of the current status of instruments that assess EoE activity in the different domains.

Escalating incidence of eosinophilic esophagitis in Canton of Vaud, Switzerland, 1993-2013: a population-based study.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus with a rapidly increasing incidence. However, population-based epidemiologic data on EoE are rare and limited to regions with less than 200,000 inhabitants. We evaluated the incidence and prevalence of EoE over time in Canton of Vaud, Switzerland. MATERIALS AND METHODS: Canton of Vaud lies in the French-speaking, Western part of Switzerland. As of December 2013, it had a population of 743,317 inhabitants. We contacted all pathology institutes (n = 6) in this canton to identify patients that have been diagnosed with esophageal eosinophilia between 1993 and 2013. We then performed a chart review in all adult and pediatric gastroenterology practices to identify patients with EoE. RESULTS: Of 263 patients with esophageal eosinophilia, a total of 179 fulfilled the diagnostic criteria for EoE. Median diagnostic delay was 4 (IQR 1-9) years. No patient was diagnosed with EoE prior to 2003. Incidence of EoE increased from 0.16/100,000 inhabitants in 2004 to 6.3/100,000 inhabitants in 2013 (P < 0.001). The cumulative EoE prevalence in 2013 was 24.1/100,000. The incidence in males was 2.8 times higher (95% CI 2.01-3.88, P < 0.001) when compared to that in females. The annual EoE incidence was 10.6 times higher (95%-CI 7.61-14.87, P < 0.001) in the period from 2010 to 2013 when compared to that in the period from 1993 to 2009. CONCLUSIONS: The incidence and cumulative prevalence of EoE in Canton of Vaud, Switzerland, has rapidly increased in the past 10 years.

Swallowed topical corticosteroids reduce the risk for long-lasting bolus impactions in eosinophilic esophagitis.

BACKGROUND: Long-lasting food impactions requiring endoscopic bolus removal occur frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for severe esophageal injuries. We evaluated whether treatment with swallowed topical corticosteroids is able to reduce the risk of occurrence of this complication. METHODS: We analyzed data from the Swiss EoE Cohort Study. Patients with yearly clinic visits, during which standardized assessment of symptoms, endoscopic, histologic, and laboratory findings was carried out, were included. RESULTS: A total of 206 patients (157 males) were analyzed. The median follow-up time was 5 years with a total of 703 visits (mean 3.41 visits/patient). During the follow-up period, 33 patients (16 % of the cohort) experienced 42 impactions requiring endoscopic bolus removal. We evaluated the following factors regarding the outcome 'bolus impaction' by univariate logistic regression modeling: swallowed topical corticosteroid therapy (OR 0.503, 95%-CI 0.255-0.993, P = 0.048), presence of EoE symptoms (OR 1.150, 95%-CI 0.4668-2.835, P = 0.761), esophageal stricture (OR 2.832, 95%-CI 1.508-5.321, P = 0.001), peak eosinophil count >10 eosinophils/HPF (OR 0.724, 95%-CI 0.324-1.621, P = 0.433), blood eosinophilia (OR 1.532, 95%-CI 0.569-4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%-CI 1.034-3.755, P = 0.017). In the multivariate model, the following factors were significantly associated with bolus impaction: swallowed topical corticosteroid therapy (OR 0.411, 95%-CI 0.203-0.835, P = 0.014) and esophageal stricture (OR 2.666, 95%-CI 1.259-5.645, P = 0.01). Increasing frequency of use of swallowed topical steroids was associated with a lower risk for bolus impactions. CONCLUSIONS: Treatment of EoE with swallowed topical corticosteroids significantly reduces the risk for long-lasting bolus impactions.

EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

[An update on celiac disease]. / Maladie coeliaque: état des lieux.

Celiac disease is a well-known entity in pediatrics and pediatric gastroenterology that is now also frequently encountered in the adult population. Apart from typical symptoms, celiac disease can present with a wide range of manifestations that are sometimes atypical, scarce or purely extraintestinal. Serologic and genetic testing are useful tools in case of low clinical probability in the early diagnostic algorithm. Upper gastrointestinal endoscopy remains the mainstay to confirm the diagnosis especially in atypical clinical presentations. Complications are rare but can be severe. Although gluten-free diet often leads to complete recovery, compliance is not universal and alternative treatment strategies are under investigation.

Pediatric and adult eosinophilic esophagitis: similarities and differences.

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.

Colorectal polypectomy during insertion and withdrawal or only during withdrawal? A randomized controlled trial.

BACKGROUND AND STUDY AIMS: Removal of colorectal polyps is routinely performed during withdrawal of the endoscope. However, polyps detected during insertion of the colonoscope may be missed at withdrawal. We aimed to evaluate whether polypectomy during both insertion and withdrawal increases polyp detection and removal rates compared with polypectomy at withdrawal only, and to assess the duration of both approaches. PATIENTS AND METHODS: Patients were included into the study when the first polyp was detected, and randomized into two groups; in group A, polyps ≤ 10 mm in diameter were removed during insertion and withdrawal of the colonoscope, while in group B, these polyps were removed at withdrawal only. Main outcome measures were duration of colonoscopy, number of polyps detected during insertion but not recovered during withdrawal, technical ease, patient discomfort, and complications. RESULTS: 150 patients were randomized to group A and 151 to group B. Mean (± standard deviation [SD]) duration of colonoscopy did not differ between the groups (30.8 ± 15.6 min [A] vs. 28.5 ± 13.8 min [B], P = 0.176). In group A 387 polyps (mean 2.58 per colonoscopy) were detected and removed compared with 389 polyps detected (mean 2.58 per colonoscopy) in group B of which 376 were removed (13 polyps were missed, mean size [SD] 3.2 [1.3] mm; 7.3 % of patients). Patient tolerance was similar in the two groups. CONCLUSIONS: Removal of polyps ≤ 10 mm during withdrawal only is associated with a considerable polyp miss rate. We therefore recommend that these polyps are removed during both insertion and withdrawal.

Quality of life: a potentially useful measure to indicate subclinical flares in Crohn disease.

BACKGROUND: While quality of life (QoL) is a well-recognised outcome measure of Crohn disease (CD) activity, its influence on other outcome measures, including exacerbation of CD is poorly understood. If QoL measures were to be associated with intestinal inflammatory activity, they might be useful for early detection of subclinical flares. AIMS: We hypothesised that low QoL might be associated with subsequent CD flares. METHODS: A cohort of 318 adult CD patients was observed for 1 year after assessment of baseline characteristics. Data were collected in Swiss university hospitals, regional hospitals and private practices. At inclusion, patients completed the Inflammatory Bowel Disease QoL Questionnaire (gastrointestinal QoL; range: 32 to 224 points) and the Short Form-36 Health Survey (general QoL; range: 35 to 145 points). During follow up, flares were recorded. Binary logistic regression was performed to estimate the relation between QoL and the odds of subsequent flares. RESULTS: A twofold decrease in the odds of flares (99% CI: 1.1; 4.0) per standard deviation of gastrointestinal QoL and a threefold decrease (99% CI: 1.5; 6.2) per standard deviation of general QoL were observed. CONCLUSIONS: The close association between QoL and subsequent flares suggests that QoL measures might be useful in detecting upcoming flares before they become clinically apparent.

[Eosinophilic esophagitis. The gastroenterologist's perspective]. / Eosinophile Ösophagitis. Die Sicht des Gastroenterologen.

Eosinophilic esophagitis is characterized by symptoms of esophageal dysfunction and eosinophil-predominant esophageal inflammation. Eosinophilic inflammation in other parts of the gastrointestinal tract is absent and several differential diagnoses for esophageal eosinophilia have to be excluded before diagnosing eosinophilic esophagitis. Most patients are male and have concomitant atopic disorders. Therapeutic options are based on drugs, diet and dilation.

[Fecal calprotectin: a diagnostic tool for inflammatory bowel disease]. / Calprotectine fecale: outil diagnostique dans les maladies inflammatoires chroniques de l'intestin.

Fecal calprotectin (FC) is a valid biomarker to discriminate with a good sensitivity and specificity the presence of mucosal lesions of the gastrointestinal tube (e.g. ulcers in the context of inflammatory bowel disease (IBD)) from functional disorders (e.g. irritable bowel syndrome). FC is not specific for IBD and can be elevated also in gastrointestinal infections, ischemic colitis or neoplasia. An elevated FC should stimulate further investigations, notably an endoscopic workup. The level of FC correlates with the endoscopic score in Crohn's disease and ulcerative colitis. The correlation of FC and the endoscopic severity is better than the one of CRP or blood leukocytes. Thus, FC can also be used in the follow-up of IBD patients.

Eosinophilic oesophagitis: latest intelligence.

Eosinophilic oesophagitis (EoE), first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory oesophageal disease with increasing incidence and prevalence in the westernized countries. Currently, EoE represents the main cause of dysphagia in adult patients. This disease is more prevalent in males and is frequently associated with allergies. The diagnosis is established based on the presence of oesophageal symptoms and dense eosinophilic oesophageal infiltration once other conditions leading to oesophageal eosinophilia are excluded. It is currently under discussion to what extent and by which methods allergic testing should be performed. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically. Especially in children, elimination diets can have similar efficacy as topical corticosteroids. Oesophageal dilation of EoE-induced oesophageal strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies are as yet defined.

[Highlights in gastroenterology and hepatology 2010]. / Actualités en gastroentérologie et hépatologie.

This review highlights recent advances in gastroenterology and hepatology, including the treatment of Crohn's disease, of eosinophilic esophagitis, of chronic hepatitis C, and of hepatic encephalopathy as well as the role of high resolution manometry in the investigation of esophageal motility disorders. These new developments will be summarized and discussed critically, with a particular emphasis on their potential implications for current and future clinical practice.

Management of blunt injuries to the spleen.

BACKGROUND: Non-operative management (NOM) of blunt splenic injuries is nowadays considered the standard treatment. The present study identified selection criteria for primary operative management (OM) and planned NOM. METHODS: All adult patients with blunt splenic injuries treated at Berne University Hospital, Switzerland, between 2000 and 2008 were reviewed. RESULTS: There were 206 patients (146 men) with a mean(s.d.) age of 38.2(19.1) years and an Injury Severity Score of 30.9(11.6). The American Association for the Surgery of Trauma classification of the splenic injury was grade 1 in 43 patients (20.9 per cent), grade 2 in 52 (25.2 per cent), grade 3 in 60 (29.1 per cent), grade 4 in 42 (20.4 per cent) and grade 5 in nine (4.4 per cent). Forty-seven patients (22.8 per cent) required immediate surgery. Transfusion of at least 5 units of red cells (odds ratio (OR) 13.72, 95 per cent confidence interval 5.08 to 37.01), Glasgow Coma Scale score below 11 (OR 9.88, 1.77 to 55.16) and age 55 years or more (OR 3.29, 1.07 to 10.08) were associated with primary OM. The rate of primary OM decreased from 33.3 to 11.9 per cent after the introduction of transcatheter arterial embolization in 2005. Overall, 159 patients (77.2 per cent) qualified for NOM, which was successful in 143 (89.9 per cent). The splenic salvage rate was 69.4 per cent. In multivariable analysis age at least 40 years was the only factor independently related to failure of NOM (OR 13.58, 2.76 to 66.71). CONCLUSION: NOM of blunt splenic injuries has a low failure rate. Advanced age is independently associated with an increased failure rate.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite.

BACKGROUND AND STUDY AIMS: Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination. PATIENTS AND METHODS: This was a prospective single-blinded trial involving 50 patients who were undergoing elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the biopsy forceps first without and then with suctioning following contact with the sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds at 30-cm distance from the biopsy channel valve of the colonoscope, with time starting at forceps removal. Airborne bacteria were collected by an impactor air sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy room air. RESULTS: At the beginning and end of the daily colonoscopy program, the median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air suctioning during removal of the biopsy forceps reduced the bioaerosol burden from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 - 16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates. CONCLUSION: The bacterial aerosol burden during handling of biopsy forceps can be reduced by applying air suction while removing the forceps. This simple method may reduce transmission of infectious agents during gastrointestinal endoscopies.

Systematic review of atraumatic splenic rupture.

BACKGROUND: Atraumatic splenic rupture (ASR) is an ill defined clinicopathological entity. METHODS: The aim was to characterize aetiological and risk factors for ASR-related mortality in order to aid disease classification and treatment. A systematic literature review (1980-2008) was undertaken and logistic regression analysis employed. RESULTS: Some 632 publications reporting 845 patients were identified. The spleen was normal in 7.0 per cent (atraumatic-idiopathic rupture). One, two or three aetiological factors were found in 84.1, 8.2 and 0.7 per cent respectively (atraumatic-pathological rupture). Six major aetiological groups were defined: neoplastic (30.3 per cent), infectious (27.3 per cent), inflammatory, non-infectious (20.0 per cent), drug- and treatment-related (9.2 per cent) and mechanical (6.8 per cent) disorders, and normal spleen (6.4 per cent). Treatment comprised total splenectomy (84.1 per cent), organ-preserving surgery (1.2 per cent) or conservative measures (14.7 per cent). The ASR-related mortality rate was 12.2 per cent. Splenomegaly (P = 0.040), age above 40 years (P = 0.007) and neoplastic disorders (P = 0.008) were associated with increased ASR-related mortality on multivariable analysis. CONCLUSION: The condition can be classified simply into atraumatic-idiopathic (7.0 per cent) and atraumatic-pathological (93.0 per cent) splenic rupture. Splenomegaly, advanced age and neoplastic disorders are associated with increased ASR-related mortality.

The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy.

This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.

Esophageal strictures in adult eosinophilic esophagitis: dilation is an effective and safe alternative after failure of topical corticosteroids.

Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.