Acute Eosinophilic Pneumonia (AEP) Due to Daptomycin: Is Autoimmunity a Clinico-Pathophysiologic Bridge to AEP?

Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophilic pneumonia include smoking, environmental irritants or inhalants and certain medications such as Daptomycin [1]. In this review of literature, we aim to explore the potential triggers for developing acute eosinophilic pneumonia in patients exposed to Daptomycin. The exact immune mechanism for daptomycin induced AEP is unknown, however the current proposed mechanism describes a T helper 2 lymphocyte response to inactivated daptomycin in the pulmonary surfactant, which leads to eosinophilia. Disordered T regulatory cell function is seen in patients with certain cancers, allergies and autoimmune conditions. We propose that patients with these underlying risk factors may be at increased risk of developing AEP after becoming exposed to Daptomycin. Understanding potential risk factors is crucial for health care workers as it allows them to identify susceptible populations, explore preventative measures and treat accordingly.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.

Unusual presentations of eosinophilic gastroenteritis:Case series and review of literature

Eosinophilic gastroenteritis (EG) is an uncommon disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, and is usually associated with dyspepsia, diarrhea and peripheral eosinophilia. Diffuse gastrointestinal tract and colonic involvement are uncommon. The endoscopic appearance may vary from normal to mucosal nodularity and ulceration. Gastrointestinal obstruction is unusual and is associated with predominantly muscular disease. We present five unusual cases of EG associated with gastric outlet and duodenal obstruction. Two cases presented with acute pancreatitis and one had a history of pancreatitis. Four cases responded well to medical therapy and one had recurrent gastric outlet obstruction that required surgery. Four out of the five cases had endoscopic and histological evidence of esophagitis and two had colitis. Two patients had ascites. These cases reaffirm that EG is a disorder with protean manifestations and may involve the entire gastrointestinal tract. Gastric outlet and/or small bowel obstruction is an important though uncommon presentation of EG. It may also present as esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.

Adult eosinophilic gastroenteritis and hypereosinophilic syndromes

Eosinophilic gastroenteritis (EGE) in the adult is a distinctive pathologically-based disorder characterized by an eosinophil-predominant mucosal inflammatory process. Most often,the disorder is detected during endoscopic investigation for abdominal pain or diarrhea. Other causes of gastric and intestinal mucosal eosinophilia require exclusion,including parasitic infections and drug-induced causes. Occasionally,the muscle wall or serosal surface may be involved. EGE appears to be more readily recognized,in large part,due to an evolution in the imaging methods used to evaluate abdominal pain and diarrhea,in particular,endoscopic imaging and mucosal biopsies. Def inition of EGE,however,may be diffi cult,as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not well standardized. Also,the eosinophilic inflammatory process may be either patchy or diffuse and the detection of the eosinophilic infiltrates may vary depending on the method of biopsy fixation. Treatment has traditionally focused on resolution of symptoms,and,in some instances,eosinophil quantification in pre-treatment and post-treatment biopsies. Future evaluation and treatment of EGE may depend on precise serological biomarkers to aid in defi nition of the long-term natural history of the disorder and its response to pharmacological or biological forms of therapy.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease:Correlations with blood eosinophil level

Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LD grade 4,middle lobe of right lung WT grade 5,upper lobe of right lung WA grade 4,middle lobe of right lung WA grade 5 and lower lobe of left lung WA grade 3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LD grade 4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

Human Eosinophil Cell Manipulation by Optical Tweezers

In this work, lateral deformation of human eosinophil cell during the lateral indentation by an optically trapped microbead of diameter 4.5 µm is studied. The images were captured using a CCD camera and the Boltzmann statistics method was used for force calibration. Using the Hertz model, we calculated and compared the elastic moduli resulting from the lateral force, showing that the differences are important and the force should be considered. Besides the lateral component, the setup also allows us to examine the lateral cell-bead interaction. The mean values of the properties obtained, in particular the elastic stiffness and the shear stiffness, were Eh = (37.76 ± 2.85) µN/m and Gh = (12.57 ± 0.32) µN/m. These results show that the lateral indentation can therefore be used as a routine method for cell study, because it enabled us to manipulate the cell without contact with the laser.

Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago.The definition,diagnosis,and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians,enabling a better understanding of this disease and more targeted treatment for patients.We describe the definition,presentation,and diagnosis of eosinophilic esophagitis including management,challenges,and future directions in children.The definition,diagnosis,and management of eosinophilic esophagitis have evolved over the last 50 years.Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients.We describe the definition,presentation,diagnosis,management,and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.

Clinical Research Progress of Peripheral Blood Eosinophils in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD)accounts for one of the major health and economic burdens worldwide.As a heterogeneous disease,the underlying inflammatory pattern of COPD differs from the previously thought neutrophil-dominated inflammation,with eosinophilic inflammation occupying approximately one third of stable COPD.Although the eosinophil(EOS)threshold associated with clinical relevance in patients with COPD is currently debated,eosinophil count can be used as a biomarker to guide treatment and to assess the risk of acute exacerbations of COPD,the efficacy of inhaled corticosteroids,and clinical outcomes.The purpose of this review is to describe the biological characteristics of eosinophils and the related research progress as clinical biomarkers.

Endoscopic Classification of Esophagic Eosinophilia

Introduction： EoE （eosinophilic esophagitis） is an inflammatory condition characterized by a dense eosinophilic infiltrate in the esophageal epithelium. In Brazil, it remains a poorly diagnosed disease due to the lack of interaction between the clinician, the endoscopist, and the pathologist. The diagnosis is performed by histological study of esophageal biopsies, with at least fifteen eosinophils per high-power field （EOS/HPF）. Some doubts remain with respect to patients with a clinical picture and symptoms compatible with the disease （EoE）, but who have a lower number of eosinophils than established. The main objective of this study was to create an endoscopic classification for EsEo （esophageal eosinophilia）, which pointed the way to the endoscopist towards the diagnosis. Methods： This study was a prospective, two-year study, at a gastrointestinal endoscopy center where all patients with endoscopic symptoms and/or endoscopic findings suggestive of EsEo were biopsied for histological examination of EOS/HPF. After the study and compilation of the results, a retrospective study was performed, based on a review of electronic medical records, where the same diagnosis was searched, although at a period when this classification was not adopted. Results： A total of 4,251 endoscopies were performed between September 2011 and September 2013. Two biopsies were performed, aimed at lesions, in 133 patients with clinical picture or imaging suggestive of EsEo. Eosinophils were found in 55 patients, corresponding to an incidence of 1.29% of the total population studied and 41.35% of the suspected cases of the disease. EoE was diagnosed in 24 patients during the period of this study. In the two-year retrospective study, only two cases of EoE were found. Conclusions： The results of this study demonstrate that the endoscopic standardization of esophageal lesions, suggestive of eosinophilia, in this case by classification, alerts the endoscopist for the diagnosis of EoE, prompting him to perform targeted biopsies. Further, it was observed that two samples of esophageal tissue were sufficient for the diagnosis. The relationship between the clinical picture, endoscopy, and histology was not evident in this study.

A Fatal Case of Chronic Eosinophilic Leukemia Not Otherwise Specified (CEL-NOS) in a 19-Year-Old Male with Acute Transformation into Blast Crisis

Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndrome (HES) by the presence of eosinophilic clonality. Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) diagnosis is made when no fusion genes are detected by most modern molecular testing, particularly the most common fusion gene FIP1L-1/PDGFRA (Factor Interacting with PAP like-1/Platelet-Derived Growth Factor Receptor Alpha). This disease is very rare, and its description in the literature is not well characterized. We report a fetal case of severe CEL-NOS in a 19-year-old male who presented with a plethora of clinical features consists of constitutional symptoms, pancytopenia, intravascular thrombosis, acute stroke and endomyocardial infiltrates. The course of his disease was aggressive and resistant to conventional treatment. After a short period of improvement, an acute transformation into blast crisis (BC) had occurred. The diagnosis was confirmed by morphology and immunophenotyping of bone marrow biopsy. The patient eventually died of heart failure and sepsis. To our knowledge this is the first case report of fatal CEL-NOS transforming into severe blast crisis.

Eosinophilic chronic rhinosinusitis in East Asians

Chronic rhinosinusitis(CRS) is a common disease worldwide, with a prevalence rate of 5%-15% in the general population. CRS is currently classified into two types: CRS with and without nasal polyps. CRS may also be divided into eosinophilic CRS(ECRS) and non-ECRS subtypes based on the presence of tissue eosinophilic infiltration or not. There are significant geographic and ethnic differences in the tissue eosinophilic infiltration, which is predominant in Western white patients and less common in East Asians, despite an increasing tendency for its prevalence in East Asia countries. ECRS differs significantly from non-ECRS in clinical characteristics, treatment outcomes and strategies, and underlying pathogenic mechanisms. ECRS commonly demonstrates more severe symptoms, polyp diseases with a higher incidence of bilateral polyps and sinonasal diseases on computed tomography, and the increase in blood eosinophils. ECRS is considered a special and recalcitrant subtype of CRS, commonly with poor treatment outcomes compared to non-ECRS. The differentiation of specific subtypes and clinical features of CRS will be important for developing novel treatment strategies and improving treatment outcomes for individual phenotypes of CRS. This review discusses clinical features, diagnosis, treatment and prognosis of ECRS in East Asians.

Diagnosis of eosinophilic gastroenteritis is easily missed

AIM To analyze the clinical characteristics of eosinophilic gastroenteritis(EGE)and to investigate the situations of missed diagnosis of EGE.METHODS First,the clinical characteristics of 20 EGE patients who were treated at our hospital were retrospectively summarized.Second,159 patients who underwent gastroscopy and 211 patients who underwent colonoscopy were enrolled.The pathological diagnosis showed only chronic inflammation in their medical records.The biopsy slides of these patients were reevaluated to determine the number of infiltrating eosinophils in order to assess the probability of a missed diagnosis of EGE.Finally,122 patients who experienced refractory upper gastrointestinal symptoms for at least one month were recruited.At least 6biopsy specimens were obtained by gastroscopy,and the number of eosinophils that had infiltrated was evaluated.Those who met the pathological diagnostic criteria of EGE underwent further examination to confirm the diagnosis of EGE.The probability of a missed diagnosis of EGE was prospectively investigated.RESULTS Among the 20 patients with EGE,mucosal EGE was found in 15 patients,muscular EGE was found in 3patients and serosal EGE was found in 2 patients.Abdominal pain was the most common symptom.The number of peripheral blood eosinophils was elevated in all 20 patients,all of whom were sensitive to corticosteroids.Second,among the 159 patients who underwent gastroscopy,7(4.40%)patients met the criteria for pathological EGE(eosinophil count≥25/HPF).Among the 211 patients who underwent colonoscopy,9(4.27%)patients met the criteria for pathological EGE(eosinophil count≥30/HPF).No patients with eosinophil infiltration were diagnosed with EGE in clinical practice before or after endoscopy.Although these patients did not undergo further examination to exclude other diseases that can also lead to gastrointestinal eosinophil infiltration,these might be the cases where the diagnosis of EGE was missed.Finally,among the 122 patients with refractory upper gastrointestinal symptoms,eosinophil infiltration was seen in 7 patients(5.74%).The diagnosis of EGE was confirmed in all 7 patients after the exclusion of other diseases that can also lead to gastrointestinal eosinophil infiltration.A positive correlation was observed between the duration of the symptoms and the risk of EGE(r=0.18,P<0.01).The patients whose symptoms persisted longer than 6 mo more readily developed EGE.None of the patients were considered to have EGE by their physicians before endoscopy.CONCLUSION Although EGE is a rare inflammatory disorder,it is easily misdiagnosed.When a long history of abdominal symptoms fails to improve after conventional therapy,EGE should be considered.

Eosinophilic gastroenteritis presenting as small bowel obstruction: A case report and review of the literature

Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by eosinophilic infiltration of the bowel wall to a variable depth and symptoms associated with gastrointestinal tract. Recently, the authors experienced a case of eosinophilic gastroenteritis presenting as small bowel obstruction. A 51-year old woman was admitted to our hospital complaining of abdominal pain and vomiting. Physical examination revealed a distended abdomen with diffuse tenderness. Complete blood count showed mild leukocytosis without eosinophilia. Computed tomography confirmed a dilatation of the small intestine with ascites. An emergency laparotomy was performed for a diagnosis of peritonitis due to intestinal obstruction. Segmental resection of the ileum and end to end anastomosis were performed. Histologically, there was a dense infiltration of eosinophils throughout the entire thickness of ileal wall and eosinophilic enteritis was diagnosed. The patient recovered well, and was free from gastrointestinal symptoms at the time when we reported her disease.

Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

Eosinophilic enteritis presenting as a rare cause for ileo-ileal intussusception

Eosinophilic enteritis,a relatively rare entity,usually involves gastric antrum or proximal small bowel. Our case is rarer in its involvement of the distal small bowel and presents unusually as intussusception. The disease if diagnosed in the initial stages responds well to medical treatment but if associated with complications or misdiagnosed,surgical modality is the treatment of choice. In our case,the patient presented with acute intestinal obstruction due to intussusception and emergency laparotomy with ileoileal anastomosis was done. Histopathology confirmed the diagnosis as eosinophilic enteritis. This case with such a presentation is discussed here.

Recent discoveries and emerging therapeutics in eosinophilic esophagitis

Eosinophilic esophagitis(Eo E) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease(GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor- responsive esophageal eosinophilia(PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for Eo E rather than a diagnostic screen to differentiate GERD, PPIREE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics.

Overlap of reflux and eosinophilic esophagitis in two patients requiring different therapies:A review of the literature

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis(Eo E), subepithelial eosinophilic esophagitis(s Eo E) and eosinophilic esophageal myositis(Eo EM), identified by endoscopy, manometry and serum immunoglobulin E levels(s-Ig E), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples.RESULTS In five patients with Eo E, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with s Eo E and four with Eo EM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with Eo E and s Eo E with some variation, while Eo EM was associated with hypercontractile or hypertensive peristalsis, with elevated s-Ig E. Histology revealed the following eosinophils per high-power field values. Eo E = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; s Eo E = 3 in the epithelium and 35 in the subepithelium(conventional biopsy); Eo EM = none in the epithelium, 10.7 ± 11.7 in the subepithelium(conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria(peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to Eo E. Eotaxin-3, IL-5 and IL-13 were overexpressed in Eo E.CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between Eo E, s Eo E and Eo EM, and reflected a different pathogenesis between these esophageal Eo GDs.