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.     

Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft-vs-host disease

We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.     

Esophageal intra-abdominal ultrasonographic in children with gastroesophageal reflux: correlation between endoscopic and histopathologic data]

Gastroesophageal reflux disease has been very often in children and one of its most critical complications is the peptic esophagitis disease. The diagnosis of peptic esophagitis is obtained based on the endoscopic changes and the histologic features. The pressure reduction of the lower esophageal sphincter is one of the elements of the esophagitis pathogenesis. The pressure is related with the length of the esophageal abdominal segment, which can be measured by ultrasonography. The research presented in this paper aims to relate ultrasonographic measurements of esophageal abdominal segment length with endoscopic changes and with esophageal biopsy obtained from children with gastroesophagel reflux disease. We submitted 16 children with gastroesophagel reflux disease, between 10 and 156 months old (median 63.5 months old), to endoscopy and to esophageal biopsy. We verified the following results from endoscopy and biopsy: six of the 16 patients had endoscopic peptic esophagitis and, in five of these (six patients), the same diagnosis was confirmed by biopsy. Ten of the 16 patients had normal endoscopy, but the biopsy of four of these 10 patients showed histologic changes compatible with esophagitis. We observed no relationship between endoscopy and biopsy, when all degrees of histologic change were used to diagnose esophagitis. However, we found high relationship when the mild histologic changes were considered as only a consequence of the reflux. We verified the following results from ultrasonography: five of the six patients with endoscopic peptic esophagitis and all patients with esophagitis determined by biopsy (excluding those with mild histologic changes) had reduced esophageal abdominal segment length. In conclusion, we have found relationship between endoscopic changes and histologic features in the diagnosis of esophagitis and correlation between the reduced esophageal abdominal segment length and the presence of esophagitis.     

Acid reflux is a poor predictor for severity of erosive reflux esophagitis

It is unknown which factors determine the severity of mucosal damage in gastroesophageal reflux disease (GERD). Our aim was to test whether the amount of esophageal acid exposure could predict the severity of esophageal injury in erosive reflux esophagitis. A total of 644 outpatients with symptomatic GERD underwent an esophagogastroduodenoscopy followed by esophageal manometry and 24-h pH monitoring. GERD was graded according to the endoscopic severity of mucosal damage as no erosions, single erosions, confluent erosions, esophageal ulcers, and strictures. A multiple linear regression was used to assess the joint influences of demographic characteristics, social habits, endoscopic anatomy, and various parameters of esophageal function tests on the severity of erosive reflux disease. No clear-cut association between the amount of acid reflux and the severity of erosive reflux esophagitis could be established. All individual parameters of esophageal pH monitoring, such as upright or supine acid contact time, frequency of all or only long reflux episodes, and an overall summary score of pH-metry, revealed no or only a weak correlation with the severity grade of erosive reflux esophagitis. Similarly, the pressure of the lower esophageal sphincter was only slightly more decreased in patients with extensive erosive esophagitis as compared to subjects without esophageal erosions. In the multiple linear regression, the presence of hiatus hernia was a stronger predictor of disease severity than any of the other parameters. In conclusion, factors other than exposure of the esophageal mucosa to acid must contribute to the development of erosive esophagitis.     

Update in the endoscopic management of benign esophageal stenoses

Correction of dysphagia in benign esophageal stenosis without the need for surgery is a task that has been tried to be resolved for more than three centuries; in the last three decades this management has evolved with the development of pneumatic dilators and, more recently, alternative and adjuvant treatments like local steroid injection, electrocoagulation, use of argon plasma and the use of expandable stents have been added. The most common causes of benign esophageal stenosis are peptic esophagitis in first place followed by the ingestion of caustic substances; other less frequent etiologies are medication ingestion, stenosis secondary to a surgical anastomosis of the esophagus and stenosis related to mediastinal radiotherapy; the rarest causes include esophageal rings and membranes, sclerotherapy for esophageal varices, the prolonged use of a nasogastric tube, Crohn's disease, among others. A complete clinical, radiological and endoscopic evaluation of the patient is required to make the diagnosis, with the respective complimentary histopathologic study. At present, traditional esophageal dilatations, as well as pneumatic dilatations are the most common and effective treatments, the previously mentioned alternative and adjuvant treatments are used in exceptional cases, some with advantages over the others depending on each patient in particular and on the characteristics and etiology of the stenosis. The future seems to be aimed at the use of temporary expandable stents.     

Opportunistic Infections of the Esophagus Not Responding to Oral Systemic Antifungals in Patients with AIDS: Their Frequency and Treatment

To determine the spectrum of esophageal disease responsible for dysphagia/odynophagia in AIDS patients not responding to current oral antifungals, we studied 49 consecutive patients whose esophageal symptoms failed to improve after a minimum of 3 wk of therapy with oral ketoconazole or fluconazole. An esophageal candidiasis resistant to oral antifungals was the most frequent disease found (22 single infections and four mixed with viruses). Viral esophagitis was identified in 13 cases (eight herpes simplex virus and five cytomegalovirus), and an esophagitis of unknown origin was documented in two patients. Other causes of symptoms included peptic esophagitis (four cases), esophageal stenosis (two cases), and Kaposi's sarcoma of the esophagus (one patient). Most patients with esophageal opportunistic infection experienced prompt relief of symptoms and complete endoscopic resolution on the specific antifungal (amphotericin B or fluconazole iv) or antiviral (acyclovir or gancyclovir iv) therapy, with the exception of those with concomitant fungal and viral infection who responded poorly to treatment. We conclude that most AIDS patients with dysphagia/odynophagia who do not respond to oral antifungals have an opportunistic infection of the esophagus. Nevertheless, specific antifungal or antiviral therapy is worthwhile, because it will eradicate, at least temporarily, the causative pathogens in most such patients.     

Healing or amelioration of esophagitis does not result in increased lower esophageal sphincter or esophageal contractile pressure

There is conflicting evidence regarding whether lower esophageal sphincter and esophageal contractile pressures are affected by changes in the severity of gastroesophageal reflux disease. We compared the manometric and endoscopic findings from 30 patients before and after treatment for esophagitis. Before treatment, the grade of esophagitis (I-III) was significantly correlated (r = -0.37; p less than 0.05) with lower esophageal sphincter pressure, but not with esophageal contractile pressure. After treatment, the grade of esophagitis did not change or became worse in 15 patients, and became better in 15 patients. Of these, seven healed. The group that showed no endoscopic improvement demonstrated no change in lower esophageal sphincter or esophageal contractile pressures. The group that did show endoscopic improvement also demonstrated no increase in lower esophageal sphincter or esophageal contractile pressures, and this was particularly evident in those whose esophagitis healed. These data suggest that healing of esophagitis does not result in improvement of esophageal motor function.     

Total dysphagia after short course of systemic corticotherapy:Herpes simplex virus esophagitis

A 72 year-old female developed a herpetic esophagitis after 3 d of oral corticotherapy for an acute exacerbation of chronic obstructive pulmonary disease,presenting as odynophagia and total dysphagia.Biospies were taken during a first esophagogastroduodenoscopy(EGD) and the patient was referred to the thoracic surgery service with a presumptive diagnosis of esophageal cancer.A second EGD was planned for dilatation,but by that time the stenosis was completely resolved.The biopsies taken during the first EGD revealed multiple herpetic viral inclusions and ulcerations without any dysplasia or neoplasia.In front of a severe esophageal stenosis,one must still exclude the usual differential diagnosis peptic stenosis and cancer.Visualization of endoscopic lesions can suggest the diagnosis but must be promptly confirmed by biopsy,viral culture or polymerase chain reaction.Although immune systemic effects of corticotherapy are well known and herpetic esophagitis occurs most frequently in immunocompromised individuals,this case emphasizes the importance of clinical awareness concerning short courses of corticotherapy for immunocompetent individuals.This article discusses the reactivation process of herpetic infection in this context and addresses its diagnostic and therapeutic issues.     

Histological criteria of esophagitis in the gastroesophageal reflux disease. Reevaluation of the sensitivity of the esophageal 24-hours pHmetry]

Little change was observed in the histological criteria of reflux esophagitis since the studies of Ismail-Beiji, Pope (1970) and Weinstein (1975). The 24-hour esophageal pHmetry has been proposed as a high sensitivity method in diagnosis of gastroesophageal reflux disease patients. In this study we selected 35 patients with histological esophagitis and submitted them to 24-hour esophageal pHmetry. We determined histological differences according to reflux pattern, endoscopic esophagitis grades and age. The sensitivity of 24-hour esophageal pHmetry was 60.0% in our patients. There are higher histological alterations in patients with more severe patterns of reflux (supine and combined) and significant difference (P < 0.05) in observed quantitative exocytosis between moderate and severe endoscopic esophagitis. There are no difference between histological esophagitis criteria and age groups.     

Eosinophilic esophagitis-like endoscopic findings in patients with erosive esophagitis

Background

Eosinophilic esophagitis (EoE) is diagnosed on the basis of the presence of dysphagia and intraepithelial eosinophilic infiltration of ≥15 cells per high-power field; nevertheless, it is important to identify the endoscopic findings of EoE in general practice. EoE should be distinguished from gastroesophageal reflux disease (GERD); however, the associations between EoE and GERD are controversial. Herein, we aimed to determine the prevalence of EoE-like endoscopic findings and associations between an EoE-like endoscopic appearance and erosive esophagitis.

Methods

Prospective endoscopic examination was performed in 804 consecutive cases. Cases with EoE-like endoscopic findings such as furrows, rings, white exudate, stricture, and mucosal tearing were examined by esophageal biopsy. Erosive esophagitis, hiatal hernia, atrophic gastritis, and gastroesophageal flap valve were assessed endoscopically, and clinical data, including age, gender, smoking and drinking habits, and presence of allergic diseases and symptoms such as dysphagia and heartburn, were analyzed.

Results

Of the 804 cases, 36 (4.5 %) showed an EoE-like endoscopic appearance, and 80 (10 %) had erosive esophagitis. Among the 36 cases with an EoE-like appearance, only 4 (0.5 %) showed significant esophageal eosinophilic infiltration with erosive esophagitis in 3 cases. Further, 28 % of the patients with erosive esophagitis had an EoE-like endoscopic appearance, while 61 % of those with an EoE-like endoscopic appearance had erosive esophagitis. There were no significant differences between the clinical characteristics and other endoscopic findings in cases of an EoE-like endoscopic appearance and erosive esophagitis.

Conclusion

Erosive esophagitis and an EoE-like endoscopic appearance frequently showed overlapping features; thus, we believe they might have common pathogenic factors.     

The Los Angeles and Savary–Miller systems for grading esophagitis: utilization and correlation with histology

The aim of the study is to determine the proportion of patients who have esophageal biopsy specimens taken for an endoscopic diagnosis of reflux esophagitis in which an endoscopic grade of esophagitis (Los Angeles [LA] or Savary–Miller [SM]) is communicated to the pathologist, and to evaluate the correlation between those endoscopic grades and histopathologic findings. We searched the database of Caris Diagnostics (a large, gastrointestinal pathology practice that receives specimens from community‐based endoscopy centers), and extracted data from all patients who had an endoscopy with esophageal biopsies submitted in a 12‐month period. There were esophageal biopsy specimens from 49 480 patients obtained during 58 986 endoscopies. The LA grade was provided in 5513 cases (27.9% of 19 778 with endoscopic esophagitis); the SM grade was stated in only 2416 cases (12.2%). A histopathologic diagnosis of erosive or ulcerative esophagitis was made significantly less often in LA grade A patients (3.2%) than in those with LA grades C (20.0%) and D (23.3%); erosive or ulcerative esophagitis was found in only 1.4% of patients with SM grade I and in 35.5% of cases with grade IV. Endoscopists who biopsy the esophagus of patients with reflux esophagitis usually do not communicate the grade of esophagitis to the pathologist. Although both the LA and SM grading systems are based on the presence of esophageal mucosal breaks (erosions or ulcers), in practice such breaks are documented in only a minority of esophageal biopsy specimens taken from patients with reflux esophagitis of any grade.     

Eosinophilic esophagitis: Update in diagnosis and management. Position paper by the Italian Society of Gastroenterology and Gastrointestinal Endoscopy (SIGE)

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized by symptoms related to esophageal dysfunction, as well as significant esophageal eosinophilia.The entity exists worldwide but has been most extensively studied in Western countries. However, a wide range of symptoms has been noticed such as chest pain or gastro-esophageal reflux disease-like symptoms. Upper gastro-intestinal endoscopy and esophageal biopsies are crucial for the diagnosis. Endoscopy might be normal or reveal typical patterns such as rings, furrows, exudates, edema, and stricture. Two to four biopsies should be performed both in the distal and in the proximal esophagus, and 15 eosinophils per high power field within the esophageal epithelium are the minimal threshold to diagnose eosinophilic esophagitis.Allergy testing is recommended, although its impact to orient treatment remains to be demonstrated. Eosinophilic esophagitis treatment includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors are the first-line therapy as up to 50% of patients respond well to proton pump inhibitors irrespective of objective evidence of GERD. Topical viscous corticosteroids or elimination diet are the treatment of choice in case of unresponsiveness to proton pump inhibitors.     

Bleeding and stenosis caused by reflux esophagitis was not common in emergency endoscopic examinations: a retrospective patient chart review at a single institution in Japan

Background Bleeding and stenosis are serious complications of reflux esophagitis, although few studies have been performed in Japan regarding these complications. This study aimed to indicate the characteristics of reflux esophagitis observed during emergency endoscopic examination in Japan. Methods All subjects who had emergency endoscopic examination performed between 1990 and 2004 at Saga Medical School Hospital were evaluated. Patients with endoscopic reflux esophagitis were evaluated with a retrospective patient chart review. Results A total of 1621 subjects underwent emergency endoscopy; 1420 of the endoscopies were because of hematemesis or melena. Endoscopic examination revealed that 19 cases with bleeding were caused by reflux esophagitis (19/1621, 1.2%). The 19 patients with bleeding and the four patients with stenosis (0.2%) had emergency endoscopy performed for complications of reflux esophagitis. The Los Angeles classification of these 23 cases showed that most were severe esophagitis (grade A, 0; B, 2; C, 8; and D, 13). The frequency of comorbidity with diabetes mellitus and collagen disease and the proportion of heavy drinkers were higher in patients who received emergency endoscopy because of reflux esophagitis than in those diagnosed with reflux esophagitis but who received emergency endoscopy because of other diseases. Conclusions Relatively small numbers of patients with reflux esophagitis undergo emergency endoscopy in Japan, and most such patients have underlying diseases, including diabetes mellitus and collagen disease. This finding is supported by a previous report that severe esophagitis is not common in Japan.     

Œsophagite à éosinophiles : rôle du pathologiste. A propos d’une observation pédiatrique

Eosinophilic esophagitis is a chronic allergic disease, recently described. The first reports date from 1977. Since, several other reports have been published. Eosinophilic esophagitis affects patients of all ages. In adults, the most characteristic symptom is intermittent dysphagia. In children, the symptoms can be similar to those of gastroesophageal reflux disease. The diagnosis of eosinophilic esophagitis is made when characteristic histological features are found in a setting of esophageal symptoms combined with endoscopic findings seen on the esophageal mucosa. The histological diagnosis requires multiples biopsies of the esophagus and remains mandatory to rule out other differential diagnosis and to order a specific treatment of this disease. We report a case of a 2 — year- old child with history of dysphagia. The diagnosis of eosinophilic esophagitis was established with the demonstration of a dense eosinophilic infiltrate of the esophageal mucosa at the histopathologic examination of esophageal biopsies. In this report, we present pathologists, gastroenterologists and pediatricians with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis.     

Efficacy of Endoscopic Prosthesis in T4 Cancer of the Intrathoracic Esophagus

No remarkable improvement has yet been achieved in the survival of patients with advanced intrathoracic esophageal cancer. In particular, patients with complications such as esophago-bronchial fistula or invasion into the mediastinum have an especially miserable prognosis, even with surgical treatment. To improve the quality of life (QOL) of such patients, extensive palliative therapy should be provided. Thus, we have introduced an endoscopic esophageal intubation technique for the treatment of stenosis or perforation in patients with T4 esophageal cancer. Nine patients with unresectable intrathoracic esophageal cancer, complicated by stenosis or perforation, were treated with an endoscopic esophageal prosthesis. Four cases had an esophago-bronchial fistula, and in three the tumor had perforated the mediastinum. The prosthesis was successfully placed under endoscopic guidance in all nine cases. Six patients (66.7%) subsequently resumed oral intake without discomfort, while two had reasonably good outcomes in this regard (efficacy rate; 88.9%). Complications were seen in three patients: mainly chest discomfort, reflux esophagitis and migration of the prosthesis in one patient each. Six patients required prolonged administration of chemotherapeutic agents following prosthesis placement. Mean survival was 123.4±77.0 days. Four of the nine patients died in the hospital. Palliative endoscopic esophageal prosthesis was considered to be useful for patients with advanced esophageal cancer. With this technique, an improvement in QOL was achieved, as sufficient oral intake was facilitated and pulmonary and mediastinal complications due to perforation were diminished.     

Eosinophilic esophagitis in adults, an emerging cause of dysphagia. Description of 9 cases.

BACKGROUND: Eosinophilic esophagitis is a rare condition mainly affecting children, although the number of cases reported in adults is on the increase. It is characterized by intense infiltration of eosinophilic leukocytes in the esophageal mucosa, without involvement of other sections of the alimentary canal. MATERIAL AND METHODS: Over the past year, following the performance of endoscopies and biopsies, our service identified nine patients who were diagnosed with suffering from this disorder. Each patient sought medical help for episodes of long-term, self-limited dysphagia or food impaction in the alimentary canal. RESULTS: Endoscopy revealed esophageal stenosis in the form of simultaneous contraction rings or regular stenosis. In six cases, the manometric study showed a nonspecific motor disorder of severe intensity affecting the esophageal body, and another patient had a disorder characterized by the presence of simultaneous waves and secondary peristaltic waves in the three thirds of the organ. These disorders are presumably due to eosinophilic infiltration of the muscular layer or ganglionar cells of the esophagus, and account for symptoms in these patients. Although the etiopathogenesis of this illness is uncertain, it is clearly an immunoallergic manifestation. CONCLUSIONS: As the number of diagnosed cases is on the increase, eosinophilic esophagitis is in adults a specific entity within the differential diagnosis of dysphagia in young males with a history of allergies. Eosiniphilic esophagitis responds in a different number of ways to therapies used. We successfully used fluticasone propionate, a synthetic corticoid applied topically, which proved to be efficient in the treatment of this illness by acting on the pathophysiological basis of the process. It does not have any adverse effects, thus offering advantages over other therapies such as systematic corticoids or endoscopic dilations.     

Unusual endoscopic findings of CMV esophagitis after liver transplantation

Cytomegalovirus infections are associated with a high mortality rate after liver transplantation, but they are treated successfully by administration of the combination of ganciclovir plus intravenous immunoglobulin. We herein describe cytomegalovirus esophagitis in a patient having gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia after liver transplantation was detected by performing the surveillance of endoscopy. At first, the findings of endoscopy that were segmental erosive areas but no ulcerative areas on the esophageal lumen were unusual in this case of cytomegalovirus infections, but cytomegalovirus esophagitis was confirmed by cytomegalovirus immunohistochemical stain using biopsies. The patient was treated by ganciclovir at an oral dosage of 5mg/kg twice a day for 2 weeks. Our experience suggests that cytomegalovirus esophagitis should be taken into consideration when a patient has gastrointestinal symptoms such as dysphagia, retrosternal pain and epigastralgia and has endoscopic findings such as segmental erosions on the esophageal lumen despite having no cytomegalovirus-specific endoscopic findings such as ulcerative lesions.     

TWELVE CASES OF ACUTE ESOPHAGEAL MUCOSAL LESION

Background and Aims: The incidence of erosive esophagitis in emergent endoscopy for upper gastrointestinal bleeding is not rare but the clinical and endoscopic findings have not been fully investigated. The aim of the present study was to clarify features of acute esophagitis cases showing acute onset and severe endoscopic findings. Methods: We defined severe esophagitis that endoscopically showed circumferential diffuse mucosal lesion involving at least the entire lower third of the esophagus as acute esophageal mucosal lesion and investigated the clinical and endoscopic characteristics. Results: We experienced six cases of black or dark esophagitis and six cases of non‐black esophagitis. Both groups showed common clinical features. Patients were predominantly males older than middle age. The presenting symptoms were upper gastrointestinal bleeding such as coffee‐ground‐like vomit, hematemesis or tarry stool. Seven cases had a history of taking non‐steroidal anti‐inflammatory drugs. Endoscopically, both types of case showed diffuse circumferential erosion in the lower esophagus, which continuously extended, and worsened towards the esophagogastric junction. All had esophageal sliding hernia and five cases had duodenal mucosal lesion. All cases rapidly improved with a proton pump inhibitor except one case. Conclusion: Black and non‐black esophagitis was considered to belong to the same disease entity, acute esophageal mucosal lesion, which should be recognized as a differential diagnosis on emergency endoscopy for upper gastrointestinal bleeding.     

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.     

Endoscopic atlas of motility disorders

Upper endoscopy is generally indicated to evaluate for mechanical obstruction and eosinophilic esophagitis in patients with dysphagia. However, a good exam can be a valuable tool in stratifying patients with nonobstructive dysphagia by identifying those with findings suggestive of achalasia or other esophageal motility disorders. Assessing the esophageal body and the esophagogastric junction are the key facets of a diagnostic endoscopic evaluation of motility and can often yield a diagnosis in experienced hands. Recognizing anatomical variables such as hiatal hernia that can affect motor pattern and findings specific to disease states such as in treated achalasia can guide management.