Eosinophilic esophagitis

PURPOSE OF REVIEW: Eosinophilic esophagitis is a disorder increasing in frequency that typically causes symptoms similar to those seen with gastroesophageal reflux, and is characterized by increased eosinophils isolated to the esophagus despite the use of antireflux medications. We present a review of the literature including basic science research, prevalence, clinical presentation, diagnosis, and management of eosinophilic esophagitis. RECENT FINDINGS: Over the past few years, there has been a dramatic increase in the number of publications relating to eosinophilic esophagitis in terms of case reports, cohorts of patients, familial occurrences, pathogenesis, and treatment options. Recent work confirms the role of food allergy in many patients with eosinophilic esophagitis. Several medications, including corticosteroids [topical (swallowed) or systemic], leukotriene receptor antagonists and, most recently, biologic molecules (such as anti-IL5), have been utilized. Although eosinophilic esophagitis is treatable, it is thought to be a chronic illness that requires dietary restriction or chronic medical therapy. SUMMARY: Eosinophilic esophagitis is being diagnosed in both children and adults with increasing frequency. Allergists, gastroenterologists, pathologists, internists, pediatricians, and otolaryngologists must not only be educated to be able to properly identify patients with eosinophilic esophagitis but also be informed about the current treatment and management of these patients.     

Association of Schatzki ring with eosinophilic esophagitis in children

OBJECTIVE: To describe the clinicopathologic characteristics of children with Schatzki ring and to determine if Schatzki ring is associated with eosinophilic esophagitis. METHODS: The authors report 18 adolescents with radiographically diagnosed Schatzki ring (SR). Their clinical and histologic characteristics were reviewed in a blinded fashion. RESULTS: The mean age of the patients was 15.8 +/- 0.8 years and mean duration of symptoms was 2.6 +/- 0.4 years. By histologic criteria, two groups of patients were defined. Eight had clinical and histologic criteria of eosinophilic esophagitis (EE) and 10 of peptic esophagitis. There were no differences in the symptoms or radiographic findings in the two groups. The SR was not identified by endoscopy in any EE patient and was identified in 70% of peptic esophagitis patients. Grossly apparent mucosal features associated with EE were significantly more common in those with EE. Those with peptic esophagitis had a significantly higher acid exposure than did those with EE (12.6 +/- 2.9 v 2.0 +/- 1.1%; P < 0.01) by esophageal pH probe. Patients with peptic esophagitis responded to proton pump inhibitors and/or dilatation, whereas those with EE did not have good response and required specific therapy for EE. CONCLUSIONS: EE may play a role in the pathogenesis of some patients with SR.     

Eosinophilic esophagitis—Where are we today?

ObjectiveThe objective of this review is to provide an overview of the practical diagnostic and therapeutic approaches to eosinophilic esophagitis and to increase the visibility of the disease among pediatricians.SourcesA search of the MEDLINE, Embase, and CINAHL databases and recent consensus statements and guidelines were performed.Summary of the findingsThe definition of eosinophilic esophagitis is based on symptoms and histology. It is important to rule out other diseases associated with esophageal eosinophil-predominant inflammation. It is not yet clear whether the increased prevalence is due to a real increase in incidence or a result of increased awareness of the disease. Various options for management have been used in pediatric patients, including proton pump inhibitors, dietary restriction therapies, swallowed topical steroids, and endoscopic dilations. More recently, proton pump inhibitor-responsive esophageal eosinophilia and eosinophilic esophagitis have been contemplated on the same spectrum, and proton pump inhibitors should be considered the initial step in the treatment of these patients.ConclusionsEosinophilic esophagitis is a relatively new disease with a remarkable progression of its incidence and prevalence in the past two to three decades, and diagnostic criteria that are constantly evolving. It is important to better understand the pathogenesis of the disease, the predisposing factors, the natural history, and the categorization of varying phenotypes to develop diagnostic and therapeutic strategies that meet the clinical needs of patients.     

Educational clinical case series in pediatric allergy and immunology

Eosinophilic inflammation may occur in any part of the intestinal tract from the esophagus to the rectum. Despite 70 yr having passed since the first reference to a case of eosinophilic gastroenteritis, the epidemiology and natural history of eosinophilic gastrointestinal disorders are still poorly known. Insights into their etiology and pathogenesis have revealed an important role for allergens; interleukins 4, 5, and 13; the eotaxin family of chemokines; and eosinophil-derived proteins. Diagnosis is confirmed by typical histologic features in a patient with a suggestive clinical phenotype. Treatment involves eliminating triggering allergens, making dietary restrictions the first choice of therapy in a compliant patient; corticosteroids [topical in eosinophilic esophagitis (EE)], despite the potential for serious side effects, are used with success in refractory and non-compliant patients. In this study we discuss EE and gastroduodenitis against the backdrop of clinical case presentations.     

儿童食管炎236例临床分析

目的探讨儿童食管炎的发病、临床特征、内镜检查、黏膜病理及其诊断与治疗。方法对236例诊断为食管炎患儿的病史、内镜检查、部分黏膜病理情况进行分析。结果8500例胃镜检查患儿中,诊断为食管炎236例（2.8%）。食管炎病例中,黏膜病理以慢性炎症为主。不同年龄儿童食管炎的临床特点为：30例0～1岁患儿表现为呕吐、厌食1.8%（30/236例）;92例～5岁患儿临床除呕吐、厌食还出现腹痛13.6%（92/236例）;114例～13岁患儿临床表现为恶心、腹痛48.3%（114/236例）。结论儿童食管炎患者黏膜病理以慢性炎症为主,不同年龄食管炎患者临床表现不同,治疗方案应个体化。     

Herpes simplex primo‐infection in an immunocompetent host with eosinophilic esophagitis

Eosinophilic esophagitis and herpes simplex esophagitis are separately well‐described entities, but their simultaneous occurrence may pose a special challenge to the clinician, especially regarding the optimal therapeutic approach. The following case report describes a patient with a history of cow's milk and dairy products intolerance, but without an underlying immunologic defect, in whom eosinophilic esophagitis was diagnosed in the course of primary herpes simplex virus 1 (HSV1) infection that clinically presented as herpes labialis and severe esophagitis. The diagnosis was confirmed by a polymerase chain reaction from cytological brush and by immunohistochemical staining that detected the presence of HSV1 DNA in esophageal mucosa, and histologically by persistent eosinophil‐predominant inflammation, typical of eosinophilic esophagitis. Despite severe clinical presentation, the HSV1 infection was self‐limited. After a directed elimination diet was introduced, the clinical course was favorable, without the need for antiviral therapy.     

Pediatric febrile urinary tract infections: the current state of play

Eosinophilic digestive disease (EDD) includes a broad spectrum of clinical presentations due to eosinophilic inflammation involving anywhere from the esophagus to the rectum. The heterogeneity in the clinical presentations of EDD is determined by the site and depth of eosinophilic infiltration. The sites of inflammation determine the nomenclature for EDD. The most well characterized of these, eosinophilic esophagitis (EE), eosinophilic gastroenteritis (EG), and eosinophilic colitis or enterocolitis. While the depth of esosinophilic infiltration through the three main layers (mucosa, musculosa and serosa) determines the prominent clinical manifestation. The recent advances in gastrointestinal endoscopy and the increasing awareness and diagnosis of EDD, in my viewpoint, can be of help to add to our understanding of the heterogeneous clinical syndrome under the broad title bronchial asthma. Here I present my viewpoint that EDD and the allergic bronchial asthma can be regarded as two clinical expressions of one disease in two different but related anatomical systems.     

Eosinophilic oesophagitis: epidemiology, clinical aspects, and association to allergy

Eosinophilic oesophagitis is characterised by age-dependent symptoms mimicking gastrooesophageal reflux disease, a distinct endoscopic appearance and a histological picture with extensive infiltration of eosinophils in the oesophageal mucosa. Eosinophilic oesophagitis is more frequently seen in males, and patients often belong to the paediatric or adolescence age groups. The exact prevalence of eosinophilic oesophagitis is unknown, but it has been suggested that the United States has a higher prevalence than Europe. Several treatment algorithms have been suggested, including elemental diets, oral steroids, inhaled (swallowed) steroids, and leucotriene receptor antagonists. Detailed information on the eosinophilic inflammatory processes in the oesophageal mucosa was initially obtained from animal models, in particular with regard to the role of interleukin-5 and the chemokine eotaxin-1 in eosinophilic recruitment. Studies have suggested a cytotoxic effect of eosinophilic degranulation products on nerve fibers in the gastric/intestinal mucosa, implicating a direct effect of allergic inflammation on gastrointestinal motility. Human studies recently have emphasized the role of eotaxin-3 and identified a single nucleotide polymorphism probably related to disease susceptibility.     

2007 E. Mead Johnson award: scientific pursuit of the allergy problem

My research has focused on elucidating the allergy problem over the past two decades. The primary approach has been to uncover critical mechanisms of allergic inflammation, with particular focus on eosinophils, a hallmark cellular constituent of allergic responses. Molecular processes that bridge T helper cell type 2 (TH2) immunity with eosinophilia and key checkpoints for regulating eosinophilia have been uncovered. Notably, interleukin (IL)-5 (derived from TH2 cells) has been identified as the chief hematopoietin responsible for eosinophil expansion in the circulation. Pathways for selective eosinophil mobilization from the blood stream to the tissue have been uncovered by defining the role of the eotaxin subfamily of chemokines in eosinophil chemoattraction and activation. Finally, TH2 cell derived IL-4 and IL-13 have been defined as chief inducers of the eotaxins, and upstream orchestrators of eosinophilic inflammation. These translational studies have formulated novel therapeutic strategies (currently being tested) for a variety of eosinophilic conditions, with particular attention on hypereosinophilic syndromes and eosinophil-associated gastrointestinal disorders such as eosinophilic esophagitis.     

Eosinophilic esophagitis in children and adults

Children with eosinophilic esophagitis, an isolated, severe esophageal eosinophilia, present with symptoms similar to gastroesophageal reflux but do not experience response to aggressive antireflux therapy. Increasingly, eosinophilic esophagitis is considered to be a separate entity from reflux disease. Current theory suggests that the former may be caused by cell-mediated food hypersensitivity or may be a subset of eosinophilic gastroenteritis. Reports support the efficacy of dietary restriction or corticosteroid therapy. Additional research is needed to determine etiology, allow earlier clinical recognition, and improve treatment.     

Reflux Esophagitis: Sequelae and Differential Diagnosis in Infants and Children Including Eosinophilic Esophagitis

Gastroesophageal reflux disease (GERD) is a common condition in infants and children and has many clinical mimics. Most pediatric pathology departments process many mucosal biopsies from the proximal gastrointestinal tract to evaluate the presence or absence of reflux esophagitis. Since this subject was last reviewed in the 1997 edition of Perspectives in Pediatric Pathology devoted to gastrointestinal diseases in children (Dahms BB. Reflux esophagitis and sequelae in infants and children. In: Dahms BB, Qualman SJ, eds. Gastrointestinal Disease. Perspectives in Pediatric Pathology, vol. 20. Basel: Karger, 1997;14–34), progress in the field has allowed recognition of additional presenting symptoms and treatments of GERD. Histologic criteria for diagnosing reflux esophagitis have not changed. However, the entity of eosinophilic esophagitis has emerged since 1997 and has been defined well enough to allow it to be distinguished from reflux esophagitis, with which it was probably previously confused. Refinements (though not simplification!) in the definition of Barrett esophagus are still in evolution. This review will summarize these newer concepts and briefly review the standards of diagnosis of reflux esophagitis.     

Omalizumab in the treatment of eosinophilic esophagitis and food allergy

Omalizumab is currently used in severe asthma and has been tried in other allergic disorders. The authors report two patients with multiple food allergies and eosinophilic esophagitis on a very restrictive diet who have been treated with omalizumab, in order to improve food intolerance—the major distressing factor in their lives. The patients significantly improved in the reported symptoms. However, no improvement was seen regarding esophageal endoscopy and histology. Given the poor histological and endoscopy response, eosinophilic esophagitis persistence is unlikely to be IgE dependent. Omalizumab may improve the quality of life of patients with severe food allergy by improving symptoms, but it does not appear to change endoscopic and histological features of eosinophilic esophagitis in a short follow-up.     

Intra- and interobserver agreement of histopathological findings in pediatric patients with eosinophilic esophagitis

ObjectiveTo assess intra- and interobserver agreement among non-expert pathologists in identifying features of the eosinophilic esophagitis histologic scoring system (EoEHSS) in pediatric patients.Patients and methodsThe authors used 50 slides from patients (aged 1-15 years; 72% male) with EoE. EoEHSS evaluates eosinophilic inflammation and other features including epithelial basal zone hyperplasia, eosinophilic abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Grade and stage of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Four pathologists determined EoEHSS findings on two occasions. Intra- and interobserver agreement was assessed using Kappa (κ) statistics and intra-class correlation coefficients.ResultsIntra- and interobserver agreement for the identification of eosinophil counts ≥ 15/high power field (HPF) was excellent, however varied when assessing additional features of the EoEHSS. For the more experienced pathologist, agreement for most EoEHSS items and the composite scores was substantial to excellent. For the less experienced pathologists, intraobserver agreement ranged from absent to substantial for individual features and ranged from moderate to substantial for the composite scores.ConclusionMost items of the EoEHSS had substantial to excellent reliability when assessed by a pathologist experienced in the diagnosis of EoE but presented lower repeatability among less experienced pathologists. These findings suggest that specific training of pathologists is required for the identification of EoEHSS characteristics beyond eosinophil count, as these features are considered useful in the evaluation of response to treatment and correlation with clinical manifestations and endoscopic findings.     

Update on pediatric vasculitis

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the recent research and progress made in the field of pediatric vasculitis. RECENT FINDINGS: Over the past year, researchers have described several polymorphisms in Henoch-Schonlein purpura and Kawasaki Disease as well as the association between various vasculitides and infections. International and multidisciplinary efforts in Kawasaki Disease have resulted in recommendations for its diagnosis, treatment, and long-term management to improve patient care and further increase global collaboration. Researchers are investigating the role of inflammation and its role in endothelial health and atherosclerosis. Treatment regimens continue to improve, with the use of different immunosuppressive medications; however, we continue to have incomplete treatment successes. SUMMARY: Vasculitides are rare conditions with significant morbidity and mortality whose prognosis has improved with newer diagnostic modalities and treatments; however, we continue to have insufficient knowledge of vasculitides and lack unambiguous diagnostic criteria. As technology continues to progress it is clear that a single cause of these diseases may be an oversimplification: the genetic makeup of individuals, as well as various environmental exposures, are of vital importance in the pathophysiology and evolution of disease processes, as well as response to therapy. Efforts should continue to improve international multicenter collaboration and interdisciplinary efforts to help solve this ever-growing puzzle.     

Diagnosis of tuberous sclerosis complex in the fetus

Tuberous sclerosis complex is a dominantly inherited genetic disorder of striking clinical variability. It is caused by mutations in either TSC1 or TSC2 gene, which regulate cell growth and proliferation by inhibition of mTORC1 signaling. TS is characterized by the development of benign tumors in many tissues and organs and its neurological manifestations include epilepsy, autism, cognitive and behavioral dysfunction, and giant cell tumors. With mechanism-based mTOR inhibitors therapy now available for many of its manifestations, early diagnosis of TSC is very important in order to offer appropriate care, long-term surveillance and parental counseling. Fetal ultrasound and MRI imaging techniques have evolved and may capture even earlier the following TSC-associated lesions: cardiac rhabdomyomas, subependymal nodules, cortical tubers and renal cysts. Often these represent an incidental finding during a routine ultrasound. Furthermore, in the past decades prenatal molecular diagnosis of TSC has emerged as an important option for families with a known affected member; however, the existing evidence with regards to the clinical characteristics and long-term outcome of babies diagnosed prenatally with TSC is yet limited and the path that follows early TSC detection merits further research.     

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??Objective??To investigate the clinical features??diagnosis??treatment and prognosis of eosinophilic cystitis in pediatric population. Methods??The records of four patients who had been diagnosed and treated for eosinophilic cystitis from January 2012 to May 2015 in Shengjing Hospital were retrospectively reviewed. Results??All the four patients were boys whose age ranged from 6 to 8 years. The main symptoms of the 4 cases were frequent micturition??odynuria??dysuria??suprapubic pain and hematuria.All of the 4 cases had significant peripheral eosinophilia and increased bladder wall thickness. All of the patients were diagnosed with biopsy. Bladder interstitial eosinophil infiltration was revealed by histopathology. The clinical symptoms??peripheral eosinophilia and bladder imaging changes were relieved after steroids and antihistamines treatment. Three cases developed recurrence. Total course of oral corticosteroids ranged from 3 months to 18 months. One case remained persistent remission for 2 years??two cases had are recurrence and one case had two recurrences. Conclusion??Bladder biopsy is essential to establishing the diagnosis of eosinophilic cystitis. Patients with peripheral eosinophilia and the increased bladder wall thickness should be considered with eosinophilic cystitis. Steroids is effective as medical therapy for eosinophilic cystitis and close long-term follow-up is necessary.     

Esophagitis: a frequent consequence of gastroesophageal reflux in infancy

A control group of infants was evaluated to determine criteria for the diagnosis of histologic esophagitis. Based on our observations, histologic esophagitis was defined as four or more intraepithelial neutrophils or one eosinophil per high power field or both. Esophageal biopsy specimens from 33 consecutive infants younger than 2 years who had been examined for clinically significant gastroesophageal reflux (GER) were reviewed for histologic esophagitis. Endoscopy had been performed in each patient, and 4.1 +/- 1.1 (mean +/- SD) biopsy specimens had been obtained above the distal 20% of the esophagus. Twenty (61%) infants had histologic esophagitis, including 15 with intraepithelial eosinophils alone, one with intraepithelial neutrophils alone, and four with both. Older infants (7 to 24 months) with histologic esophagitis were more likely to have moderate to severe inflammation than were infants younger than 7 months of age (P = 0.01). Endoscopic evidence for gross esophagitis was found in six (18%) infants; of these, five had abnormal biopsies, including four with moderate to severe inflammation. Among the 27 infants with a grossly normal esophagus, 14 (52%) had histologic esophagitis, including nine (33%) with moderate to severe inflammation. We conclude that in infants with clinically significant GER: (1) esophagitis is common, (2) histologic esophagitis frequently occurs in the absence of gross endoscopic findings, (3) the likelihood of moderate to severe inflammation increases after 6 months of age, and (4) intraepithelial eosinophils are a sensitive marker for acute inflammation in association with GER.     

Clinical,endoscopic, and histologic features of eosinophilic inflammation of the gastrointestinal tract in pediatric liver transplant patients

Immunosuppression during the post‐transplantation period has led to dramatic outcome improvements in PLTR patients. There have been reports describing the development of food allergies and an increased predilection for development of EGI in PLTR. We aimed to identify the clinical, endoscopic and histologic features of EGI in PLTR patients. In this retrospective case series we analyzed medical record of all PLTR who underwent EGD and/or colonoscopy at our institution from 2000 to 2006. From 2000 to 2006, 32 PLTR patients underwent endoscopic evaluation. Seventeen (53%) of 32 patients were diagnosed with EGI. Endoscopic abnormalities were seen in the esophagus, stomach, and small intestine in 11 (65%), 11 (65%), and four (24%) patients, respectively. Eosinophilic inflammation was seen in the esophagus, stomach, and small intestine in 13 (76%), 10 (59%), and five (29%) patients, respectively. Nine of 17 patients underwent colonoscopy and endoscopic abnormalities were seen in four (44%) patients. Five patients (56%) had eosinophilic inflammation. In conclusion, we have characterized the clinical, endoscopic, and histologic features of EGI. Histologic and endoscopic examination reveals that, when present, EGI is often found at multiple segments along the gastrointestinal tract.     

新生儿惊厥

惊厥是新生儿中枢神经系统功能异常最常见的临床表现.由于新生儿脑发育的阶段性,惊厥多见于新生儿,其表现和对药物治疗的反应有其自身特点.惊厥可使脑损伤加重,甚至留下神经系统后遗症.因此,新生儿期的惊厥应及时的诊断和处理.该文主要介绍新生儿惊厥的病因和病理生理、临床表现、治疗和预后几个方面的选展.     

Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia.

AIM: To assess the prevalence of eosinophilic oesophagitis in a tertiary paediatric gastroenterology clinic population. METHODS: A retrospective audit of Western Australian children investigated for oesophageal disease by paediatric gastroenterologists in the years 1995, 1999 and 2004. Macroscopic appearance of the oesophagus at endoscopy, original histological findings and diagnosis were recorded for each child. Biopsy specimens were blindly re-evaluated, with re-coded histological diagnoses compared with original reports. Age, sex and socioeconomic status were identified for each child. RESULTS: The prevalence of eosinophilic oesophagitis in Western Australia increased over the decade 1995-2004, rising from 0.05 to 0.89 per 10 000 children, with a concomitant increase in the severity of oesophagitis as determined by inflammatory cell numbers and associated features of inflammation. Children diagnosed with eosinophilic oesophagitis had a median age of 78.9 months (6.58 years), with no associated predisposition by sex or socioeconomic status trend. Almost one third of cases were macroscopically normal at endoscopy. All children with an original diagnosis of eosinophilic oesophagitis had > or =40 eosinophils per high-power field. CONCLUSION: Over the decade 1995-2004, a true increase was seen in the prevalence of eosinophilic oesophagitis, not accounted for by diagnostic shift. Histological samples should be taken at endoscopy to confirm or exclude the diagnosis of eosinophilic oesophagitis.