Update on basic and clinical aspects of eosinophilic oesophagitis.

The identification of a distinct syndrome, designated eosinophilic oesophagitis (EoE), with its own clinical and histopathological characteristics, was first described in the early 1990s. Meanwhile intense research has uncovered many molecular, immunological and clinical aspects of this chronic-inflammatory disorder. This article focuses exclusively on basic and clinical insights of EoE gathered during the last few years. Regarding aetiopathogenesis it has become clear that EoE is a food-triggered disease with milk and wheat as the dominant culprit food categories. However, it is still debated whether a disturbed mucosal integrity allowing allergens to cross the mucosal barrier, or changes in wheat and milk manufacturing might induce these inflammatory responses. Furthermore, basic science and clinical studies have accordingly confirmed that a chronic eosinophilic inflammation leads to a remodelling of the oesophagus with micro- and macro-morphological alterations, ending in a strictured oesophagus with impaired function. Fortunately, long-term therapeutic trials, using either topical corticosteroids or dietary allergen avoidance, have demonstrated that this sequela can be prevented or even reversed. This finding is of clinical relevance as it supports the initiation of a consistent anti-inflammatory therapy. Nevertheless, EoE is still an enigmatic disease and the long list of unanswered questions will certainly stimulate further research.

Daptomycin-associated eosinophilic pneumonia in two patients with prosthetic joint infection.

Background: Daptomycin is used increasingly to treat prosthetic joint infection (PJI). A possible side effect of this drug is eosinophilic pneumonia. We describe two patients with PJI treated with daptomycin who had this side effect with different clinical presentations. METHODS: Case reports and review of the literature. RESULTS: The first case was a 64-year-old male who received daptomycin as a part of the treatment for PJI caused by methicillin-resistant Staphylococcus epidermidis (MRSE). He developed fever without other symptoms; bronchoalveolar lavage (BAL) revealed eosinophils. The second was a 61-year-old male who also used daptomycin as part of the treatment of PJI caused by MRSE and developed severe lung symptoms. Bronchoalveolar lavage and pleural fluid showed an increased number of eosinophils. CONCLUSION: Daptomycin-induced pneumonia can present with a wide range of symptoms, from fever alone to severe lung symptoms. Surgeons should be aware of this possible side effect when prescribing daptomycin.

Activity assessment of eosinophilic esophagitis.

The activity of eosinophilic esophagitis (EoE) can be assessed with patient-reported outcomes and biologic measures. Patient-reported outcomes include symptoms and quality of life, whereas biologic measures refer to endoscopic, histologic, and biochemical activity (e.g. blood biomarkers). So far, a validated tool to assess EoE activity in the above-mentioned dimensions is lacking. Given the lack of a standardized way to assess EoE activity in the various dimensions, the results of different clinical trials may be difficult to compare. For symptom assessment in adult patients, the symptom 'dysphagia' should be evaluated according to different standardized food consistencies. Furthermore, symptom assessment should take into account the following items: avoidance of specific food categories, food modification, and time to eat a regular meal. A distinct symptom recall period (e.g. 2 weeks) has to be defined for symptom assessment. Performing an 'esophageal stress test' with ingestion of a standardized meal to measure symptom severity bears the potential risk of acute food bolus impaction and should therefore be avoided. The description of endoscopic findings in EoE has meanwhile been standardized. Histologic evaluation of EoE activity should report either the size of the high-power field used or count the eosinophils per mm(2). There is a current lack of blood biomarkers demonstrating a good correlation with histologic activity in esophageal biopsies. The development and validation of an adult and pediatric EoE activity index is urgently needed not only for clinical trials and observational studies, but also for daily practice.

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. Cite this as: A. M. Schoepfer, D. Simon and A. Straumann, Clinical & Experimental Allergy, 2011 (41) 630-639.

Development of the first disease activity index for eosinophilic esophagitis: update on the EEsAI in 2012

Background and Aims: The international E EsAI s tudy g roup is currently d eveloping the first activity index ( EEsAI) specific for E osinophilic Esophagitis (EoE). G oal: T o develop, e valuate and validate the EEsAI. Methods: T he development c omprises three p hases: 1. Selection of c andidate items ( completed); 2. Evaluation of t he activity index i n a first patient cohort (in progress, p atient recruitment completed); and 3. Validation in a s econd EoE patient cohort. F ocus group interviews with patients were used in p hase 1 to g enerate patient r eported outcomes (PRO) according to g uidelines o f regulatory authorities (FDA a nd EMA), whereas the section of biologic items was developed by Delphi rounds o f international E oE experts from E urope and North America. Results: T he EEsAI has a modular c omposition to a ssess the following components o f EoE activity: p atient r eported outcomes, e ndoscopic activity, histologic activity, laboratory activity, a nd quality of l ife (QoL). Definitions for a ll aspects o f endoscopic and histologic appearance were e stablished by consensus r ounds a mong E oE experts. S ymptom a ssessment tools were c reated that t ake into account d ifferent food consistencies as w ell as f ood avoidance and specific processing strategies. The EEsAI i s currently e valuated in a cohort of a dult EoE patients since M arch 2 011 (patient recruitment completed). Conclusions: The EEsAI standardizes outcome assessment in EoE t rials. T he collaboration with i nternational E oE e xperts a s well as f ollowing o f the guidelines f rom regulatory authorities will lead to its wide applicability.

Eosinophilic aseptic arachnoiditis. A neurological complication in HIV-negative drug-addicts.

The finding of an eosinophilic aseptic meningitis in IV drug abuse is usually suggestive of an opportunistic infection or an allergic reaction. However, HIV-negative patients are at lower risk for developing these complications. Two young HIV-negative patients, with previous intravenous polytoxicomany, developed cystic arachnoiditis over the spinal cord associated with eosinophilic meningitis. Histology of the meningeal spinal cord lesions revealed a vasculocentric mixed inflammatory reaction. In one patient prednisone led to marked clinical improvement. Since infection, vasculitis, sarcoidosis and previous myelography were ruled out, we believe that the syndrome of eosinophilic aseptic arachnoiditis may be related to an hyperergic reaction in the meniges toward drug-adulterants inoculated through the intravenous route.

Eosinophilic esophagitis: overview of clinical management.

A validated disease-specific symptom-assessment tool for eosinophilic esophagitis (EoE) has yet to be approved by regulatory authorities for use in clinical trials. Relevant end points for daily practice include EoE-related symptoms and esophageal eosinophilic inflammation. Endoscopic features should also be taken into account when establishing a therapy plan. A reasonable clinical goal is to achieve a reduction in EoE-related symptoms and esophageal eosinophilic inflammation. Evidence is increasing to support an anti-inflammatory maintenance therapy, as this can reduce esophageal remodeling. In EoE patients in clinical remission, annual disease monitoring with symptom, endoscopic, and histologic assessments of sustained treatment response is recommended.

Long-term treatment of eosinophilic esophagitis esophagitis with budesonide

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease of the esophagus, characterized by esophagus-related symptoms and a dense tissue eosinophilia, both refractory to proton pump inhibitors. Topical corticosteroids have proven effective in inducing clinical and histologic remission. However, a long-term strategy for the management of this chronic disease is not yet defined. METHODS: In a randomized, double-blind, placebocontrolled, long-term trial, we evaluated the efficacy of twice-daily 0.25 mg swallowed budesonide in maintaining a remission in adult EoE with prior response to induction therapy. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically, by immunofluorescence and by high-resolution endosonography. The primary end point was the ability to maintain histologic remission (<5 eos/hpf) of EoE in. Secondary end points were the efficacy on symptom control and on tissue remodeling as well as the determination of the safety of long-term esophageal administration of topical corticosteroids. RESULTS: During a 50-week therapy of quiescent EoE with low-dose budesonide the esophageal eosinophil load (ECP staining) increased from 1.1 to 29.9 eos/hpf, but under placebo the increase was significantly larger (0.5 to 51.1 eos/hpf; p=0.01). At the end of the studyperiod, 35.7% (5/14) of the budesonide patients were in complete and 14.3% (2/14) in partial histologic remission; with placebo no patient was in complete and 28.6% (4/14) were in partial remission (p=0.0647). The increase of the symptom score was markedly lower in budesonide- (0.79 to 2.29 points) than in placebo-patients (0.71 to 4.00 points; p=0.0875). The median time to relapse of symptoms was >125 days in the budesonide and 95 days in the placebo group (p = 0.14). Measured by high-resolution endosonography, all EoE patients had pre-treatment a highly thickened esophageal wall compared with healthy controls (3.05±1.08 mm vs. 2.18±0.35 mm; p<0.0001). Long-term topical budesonide reduced mainly the thickness of the superficial wall layers (mucosa, 0.75 mm to 0.45 mm; p=0.025) whereas the response of the deeper layers was less pronounced (submucosa 1.31 to 1.08 mm; p=0.19 and muscularis 0.82 to 0.76 mm; p=0.72). Budesonide did not evoke any mucosal atrophy. CONCLUSIONS: This study clearly demonstrates that 1) Untreated eosinophil inflammation results in an impressive remodeling of the esophagus; 2) A therapy is therefore needed; 3) The high relapse rate after short-term therapy requires a long-term management and 4) Maintenance treatment with budesonide is well tolerated and keeps half of the patients in remission.

Oesophagite a eosinophiles: mise a jour 2011 [Eosinophilic esophagitis: update 2011].

Eosinophilic esophagitis (EoE) shows an increasing incidence and prevalence in western countries and is currently the main cause of dysphagia in adults. This disease is more prevalent in males and is frequently associated with allergies. Diagnosis is based on the presence of esophageal symptoms, dense eosinophilic esophageal infiltration, and the exclusion of other conditions associated with esophageal eosinophilia. Topical corticosteroids lead to a rapid clinical and histological improvement of active EoE. Especially in children, elimination diets can have similar efficacy as topical corticosteroids. Esophageal dilation of EoE-induced strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Long-term therapeutic strategies have yet to be defined.

The Visual Dysphagia Questionnaire: Evaluating the first Tool for Assessing Food Consistency-Dependent Dysphagia in Eosinophilic Esophagitis

Background and Aims: The international EEsAI study group iscurrently developing the first a ctivity index specific forEosinophilic Esophagitis (EoE). None of the existing dysphagiaquestionnaires take into account the consistency of theingested food t hat considerably impacts the symptompresentation. Goal: To d evelop and evaluate an E oE-specificquestionnaire assessing dysphagia caused by foods of differentconsistencies.Methods: B ased on patient interviews and chart reviews, a nexpert panel ( EEsAI study g roup) identified internationallystandardizedfood prototypes t ypically a ssociated with EoErelateddysphagia. Food consistencies were c orrelated withEoE-related d ysphagia, t aking into account p otential f oodavoidance and f ood processing. This V isual D ysphagiaQuestionnaire (VDQ) was piloted in 20 patients and is currentlyevaluated in a cohort of 150 adult EoE patients.Results: T he following 8 food c onsistency prototypes w ereidentified: soft foods (pudding, jelly), grits, toast bread, Frenchfries, dry rice, ground meat, raw fibrous f oods (eg. apple,carrot), s olid m eat. Dysphagia was r anked o n a 4-point Likertscale (0=no difficulties; 3= severe difficulties, food will not pass).First analysis demonstrated that severity of dysphagia is relatedto the eosinophil load and presence of esophageal strictures.Conclusions: T he VDQ i s the first EoE-specific tool f orassessing dysphagia caused by i nternationally-standardizedfoods of different consistencies. This instrument also addressesfood avoidance behaviour and food processing habits. This toolperformed well in a p ilot study a nd is currently evaluated in acohort of 150 adult EoE patients.

Oesophagite à éosinophiles [Eosinophilic esophagitis].

Eosinophilic esophagitis is a recent diagnosis, of growing interest and prevalence. It has to be considered by every physician when facing any adult or pediatric case of dysphagia, food impaction, and symptoms of GERD (gastroesophageal reflux disease) resistant to proton-pump inhibitor treatment. The diagnosis is made by combining clinical symptoms and endoscopic signs, supported by biopsies of the mucosa, which should show more than 15 eosinophils per high power field. The etiology seems to be of allergic origin, and a full immuno-allergic testing should be made. Recommendations for the treatment are to calm down the inflammatory process by proton-pump inhibitors, and to give topical steroids, keeping the systemic treatment for acute severe cases. In cases of esophageal stenoses, dilations can be undertaken, but with a high risk of recurrence.

The Patientʼs Perception of Eosinophilic Esophagitis Related Symptoms: a Qualitative Content Analysis

Background and Aims: The international EEsAI study group is currently developing an activity index for Eosinophilic Esophagitis (EoE). A potential discrepancy between patient and physician reported EoE symptoms has not been assessed yet. Therefore, we aimed to evaluate patient reported items describing their EoE activity and to compare these with the physicianʼs perception. Methods: A questionnaire was sent to 100 EoE patients in Switzerland. EoE-related symptoms dependent and independent of food intake were reported by patients. Results were analyzed using a qualitative content analysis and compared with symptoms reported by international EoE experts in Delphi rounds. Results: The questionnaire response rate was 64/100. The following items were developed by combining categories based on patients answers: food-consistency related dysphagia, frequency and severity of dysphagia, food impaction, strategies to avoid food impaction, food allergy, drinking-related retrosternal pain. The following food categories associated with dysphagia were identified: meat, rice, dry bread, French fries, raw, fibrous foods, others. Sports and psychological stress were identified as triggers for non-food intake related EoE symptoms. A good correlation was found between patient and physicianʼs reported EoE related symptoms. Conclusions: There is a good correlation between patient reported symptoms and the physicianʼs perception of clinical items as reported by international EoE experts. These patient reported outcomes will now be incorporated into the EEsAI questionnaire that measures EoE activity.