Primary Eosinophilic Gastrointestinal Disorders Research Articles

Clinical and atopic features of patients with primary eosinophilic colitis: an Italian multicentre study

Eosinophilic colitis (EC) is the rarest among primary eosinophilic gastrointestinal disorders (EGID). EC is underdiagnosed due to its blurred and proteiform clinical manifestations. To explore the clinical and atopic characteristic of EC adult patients, the diagnostic delay, and relapse-associated factors, by comparison with patients with eosinophilic esophagitis (EoE) and irritable bowel syndrome (IBS). EC patients followed-up at four clinics were included, and clinical, histopathological, and laboratory data were retrieved. As control groups, age-matched patients with EoE and IBS were recruited. Allergy tests included skin prick test and serum specific IgE. Diagnostic delay was assessed. Overall, data from 73 patients were retrieved, including 40 with EC (median age 39 years IQR 22.5–59, F:M 2.1:1), 12 with EoE (F:M ratio: 1:5), and 21 with IBS (F:M ratio: 1:0.9). The most common features in EC patients were female sex (67.5%), atopy (77.5%), abdominal pain/distention (70%), diarrhoea (77.5%), and faecal calprotectin elevation (22.5%). Blood eosinophils were elevated in EoE, but not in EC (p < 0.001), while ECP did not differ across the three groups (p = 0.4). The frequency of allergen sensitization reached 25% of patients. Several frequent pan-allergens for this region were present. The overall diagnostic delay was 10 months (IQR 4–15). Factors contributing to a greater diagnostic delay were atopy, weight loss, and a previous misdiagnosis. EC is mostly a diagnosis of exclusion, burdened by a substantial diagnostic delay. In female patients the presence of allergen sensitization, abdominal symptoms and faecal calprotectin elevation should raise the suspicion of EC.

Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract: in search of a definition for "abnormally increased eosinophils".

Primary eosinophilic gastrointestinal disorders (EGIDs) constitute chronic allergic inflammation. The number of eosinophils is one of the diagnostic criteria; more than 20 eosinophils per high-power field (HPF) in the gastrointestinal (GI) tract are considered abnormal in Japan. However, the quantity of eosinophils considered normal varies according to anatomical location and geographical region; such values have not been reported in Japanese pediatric patients, nor have the numbers of lymphocytes in the normal pediatric stomach. To establish a reference for defining diagnostic criteria for EGIDs, we evaluated the number of eosinophils in the normal Japanese pediatric GI tract. We examined 131 biopsy cases without significant clinical history, endoscopic abnormality, or histological abnormality. Immunohistochemical analysis of CD3 and CD20 was performed. The mean eosinophil density was highest in the cecum (49.5 ± 22.4 per HPF). Counts of more than 20 eosinophils per HPF were observed in the duodenum [bulb (20.0 ± 9.6) and second portion (30.0 ± 15.8)], terminal ileum (38.3 ± 22.7), cecum (49.5 ± 22.4), ascending colon (42.3 ± 25.3), transverse colon (29.4 ± 17.0), and descending colon (32.2 ± 17.9). Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum; a count of fewer than one eosinophil per HPF was observed in the esophagus. More than 100 CD3-positive T cells per HPF were observed in the stomach. The mean numbers of eosinophils in the bowel were greater than 20 per HPF. For Japanese pediatrics, the current threshold eosinophil count should be revised.

Eosinophilic Disorders of the Gastrointestinal Tract and Associated Abdominal Viscera: Imaging Findings and Diagnosis.

Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions of the gastrointestinal tract that are characterized by tissue eosinophilia and end-organ dysfunction or damage. Primary EGIDs are associated with atopy and other allergic conditions, whereas secondary EGIDs are associated with underlying systemic diseases or hypereosinophilic syndrome. Within the spectrum of EGIDs, eosinophilic esophagitis is the most prevalent. Eosinophilic gastroenteritis and eosinophilic colitis are relatively uncommon. Eosinophilic infiltration of the liver, biliary tree, and/or pancreas also can occur and mimic other inflammatory and malignant conditions. Although endoscopic evaluation is the method of choice for eosinophilic esophagitis, radiologic evaluation of the esophagus plays an important role in the assessment of disease severity. CT and MR enterography are the modalities of choice for demonstrating specific forms of eosinophilic gastroenteritis. CT and MRI are important in the detection of abdominal visceral involvement in EGIDs. Diagnosis is often challenging and relies on symptoms, imaging findings, histologic confirmation of tissue eosinophilia, and correlation with peripheral eosinophilia. Imaging is crucial for identifying characteristic organ-specific findings, although imaging findings are not specific. When promptly treated, EGIDs usually have a benign clinical course. However, a delayed diagnosis and associated surgical interventions have been associated with morbidity. Therefore, a radiologist's knowledge of the imaging findings of EGIDs in the appropriate clinical settings may aid in early diagnosis and thereby improve patient care. An overview of the clinical features and imaging findings of EGIDs and the eosinophilic disorders of associated abdominal viscera is provided. Online supplemental material is available for this article. ©RSNA, 2022.

Primary eosinophilic gastrointestinal disorders and allergy: Clinical and therapeutic implications

Primary eosinophilic gastrointestinal disorders (EGID) are increasingly prevalent, immune‐mediated, chronic conditions which primarily affect pediatric and young adult patients, leading to substantial disease burden, and poor quality of life. EGID may either involve single portions of the gastrointestinal tract (i.e., esophagus, stomach, small bowel, and colon) or a combination. Their strong association with allergic disorders has been recently recognized, and although their shared pathophysiological basis remains partly elusive, this feature greatly impacts the diagnostic and treatment work‐up. We herein critically discuss the current knowledge on the association of EGID and allergic disorders, including atopic dermatitis, allergic rhinitis, allergic asthma, and food or drug allergy. In particular, we reviewed the literature focusing on their epidemiology, pathophysiological basis and mechanisms, and diagnostic strategies. Finally, we discuss the currently ongoing clinical trials targeting EGID and allergic diseases, including, among others the monoclonal antibodies dupilumab, mepolizumab, benralizumab, and lirentelimab.

The need for a reliable non-invasive diagnostic biomarker for eosinophilic oesophagitis

Eosinophilic oesophagitis is part of the spectrum of primary eosinophilic gastrointestinal disorders and is characterised by a chronic, Th2-mediated, inflammatory process within the oesophageal mucosa, leading to prominent eosinophilic infiltration (≥15 eosinophils per high-power field).1 The most common view of the pathogenesis of eosinophilic oesophagitis is that it marks the endpoint of an atopic progression, moving from atopic dermatitis, food allergy, asthma, allergic rhinitis, and, eventually, eosinophilic oesophagitis, although its pathogenesis remains largely elusive.

Pathologist’s approach to paediatric and neonatal eosinophilic gastrointestinal disorders

SummaryChildren are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach.Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist’s ability in identifying an abnormal number of eosinophils in this setting of patients.When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis.Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like “with eosinophilic pattern” should be favoured over a specific diagnosis of “eosinophilic disorder” in order to avoid potential confusion between different entities.

Malnutrition in Eosinophilic Gastrointestinal Disorders.

Primary eosinophilic gastrointestinal disorders (EGIDs) are emerging chronic/remittent inflammatory diseases of unknown etiology, which may involve any part of the gastrointestinal (GI) tract, in the absence of secondary causes of GI eosinophilia. Eosinophilic esophagitis is the prototype of eosinophilic gastrointestinal disorders and is clinically characterized by symptoms related to esophageal inflammation and dysfunction. A few studies have assessed the nutritional status of patients with eosinophilic gastrointestinal disorders, showing conflicting results. This review summarizes the current evidence on the nutritional status of patients with EGIDs, focusing on the pediatric point of view and also speculating potential etiological mechanisms.

Association between defective spleen function and primary eosinophilic gastrointestinal disorders

Association between defective spleen function and primary eosinophilic gastrointestinal disorders

The pathology and causes of tissue eosinophilia in the gastrointestinal tract

Eosinophilic inflammation in the gastrointestinal tract may occur as a primary eosinophilic disorder or as a secondary response with other causes. Primary eosinophilic gastrointestinal disorders (EGIDs) are Th2-mediated allergic diseases that overlap pathogenetically with atopic conditions involving other organs. The pathological diagnosis of primary EGIDs can be challenging, as the quantity of eosinophils considered to be 'abnormal' is difficult to define, and the diagnosis, by definition, requires exclusion of the far more common secondary causes. Our understanding of the basic biology and natural history of eosinophilic oesophagitis has advanced considerably over the last decade, whereas other EGIDs have proven more difficult to characterize; nonetheless, some recent advances have been made. This review summarizes current knowledge regarding the clinical presentation, diagnosis, natural history and treatment of EGIDs, including eosinophilic oesophagitis. We also draw attention to the numerous secondary causes of tissue eosinophilia in the gastrointestinal tract, and suggest a practical approach to the histological assessment, diagnosis and reporting of EGIDs.

An Incidental Finding of Eosinophilic Colitis

Eosinophilic colitis (EC) is an exceptionally rare inflammatory gastrointestinal disorder in which eosinophils infiltrate the colonic gut. Of the primary eosinophilic gastrointestinal disorders, EC is the most rare manifestation, following eosinophilic esophagitis and eosinophilic gastroenteritis. Eosinophils are essential components of the immune system that protect against various infectious pathogens and, when activated, promote a cascade of events that leads to local inflammation and tissue damage. Clinical manifestations are non-specific and not always accompanied by peripheral eosinophilia. Symptoms vary upon which intestinal layer is most affected by the eosinophilic infiltration. Endoscopic findings may appear normal or show non-specific inflammatory features. Diagnosis requires presence of gastrointestinal symptoms, biopsy consistent with colonic eosinophilia, and exclusion of secondary causes of gastrointestinal eosinophilia. Pathogenesis still remains unclear. Moreover, there is no consensus regarding treatment, due to the lack of randomized controlled trials, given the rarity of this condition. We present a case of a 44-year-old male with recent blood on tissue noted after bowel movements, but otherwise asymptomatic. He endorsed a history of gastroesophageal reflux well-controlled with ranitidine and no significant family history. The patient was not taking any other medications. Vital signs were stable and laboratory studies were unremarkable, with no drop in hemoglobin and no eosinophilia. Physical and rectal exam were normal. Further, an EGD was unremarkable. However, a colonoscopy revealed medium-sized hemorrhoids with a streak of blood, mild diverticulosis in the sigmoid colon, a single polyp at 50 cm from entry site removed with cold biopsy polypectomy, as well as diffuse cobblestone-like edema in the cecum with a raised area, which was biopsied. Pathology studies from the single polyp and cecal edematous area revealed colonic mucosa with prominent infiltration of eosinophils in the lamina propria (similar to Figure 1), consistent with a diagnosis of EC that did not require immediate treatment, given lack of symptoms or other secondary causes. The patient's rectal bleeding was secondary to the hemorrhoids, and this resolved. This case illustrates that rare conditions like EC could be found incidentally even in the absence of peripheral eosinophilia and may require close follow up for development of symptoms.Figure 1

Primary eosinophilic gastrointestinal disorders in children who have received food oral immunotherapy

BackgroundFood oral immunotherapy (OIT) involves the administration of the food allergen causing the symptoms, in order to induce tolerance. Primary eosinophilic gastrointestinal disorders (PEGDs) are characterised by an eosinophil-rich inflammation affecting different locations of the digestive tract. We present a series of patients with PEGDs in a group of children following OIT with milk and/or egg. Material and methodsA prospective study during the period 2006–2014 was performed in paediatric patients subjected to OIT with milk and/or egg. When these children present persistent gastrointestinal symptoms, they are referred to the Paediatric Gastroenterology Unit for evaluation. ResultsPrimary eosinophilic gastrointestinal disorders were diagnosed in eight of the 128 cases of OIT (6.25%). The time to PEGDs development was variable: two cases showed symptoms during OIT, and the rest with a median time of 29 months (15–48 months). Food treatment discontinuation was not required in four of the five cases of eosinophilic oesophagitis, although food removal was necessary in patients with eosinophilic gastroenteritis. ConclusionsWe report the highest prevalence of PEGDs in children subjected to OIT, and the first cases of eosinophilic gastroenteritis following food OIT.The monitoring of new digestive signs and symptoms after OIT is crucial for the diagnosis of these disorders, and prolonged follow-up is required. The management of such patients and the need or not to eliminate the food should be assessed on an individualised basis, according to the severity of the condition, its evolution and response to different treatment alternatives.

Eosinophilic Gastrointestinal Disorders: an Experience in a tertiary Care Rural Hospital

Background:- Primary Eosinophilic Gastrointestinal Disorders are a rare entity with an obscure etiology. As simple as they sound, however, they require high degree of clinical suspicion as they can mimic various disorders of gastrointestinal tract. Here in we present our experience in a rural tertiary care hospital. Materials and Method:-All diagnosed cases of Eosinophilic gastrointestinal disorders from June 2009 to May 2014 were included in the study. The cases were studied according to the criteria led down by Talley et. al. Klein’s classification was used to segregate and study the cases. Result:- We received four endoscopic biopsies; one from stomach and jejunum each; and two from ileum. Eleven appendicectomy and two hemicolectomy specimens respectively were also received by the Department of Pathology of our hospital. Majority of the cases showed mucosal involvement. Appendix was the most commonly affected organ. The overall response to treatment was better with a few exceptions. Conclusion:- Primary Eosinophilic Gastrointestinal Disorders is a diagnosis of exclusion. Proper diagnostic modalities and high degree of suspicion is needed for precise diagnosis. Treatment

Roles and regulation of gastrointestinal eosinophils in immunity and disease.

Eosinophils have historically been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergic reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract, where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system.

Eosinophilic gastroenteritis: a case report and a review of eosinophilic gastrointestinal disorders

Background: Despite its uncommon occurrence, eosinophilic gastroenteritis is one of the most important primary eosinophilic gastrointestinal disorders. These are defined as disorders that selectively affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia. The disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis and eosinophilic colitis. Aim of the study: This review focuses on the epidemiology, pathophysiology, clinical features and treatment of primary eosinophilic gastrointestinal disorders with particular attention to primary eosinophilic gastroenteritis. Clinical case: We report a case of a 32-years-old woman that was admitted to our Hospital complaining of abdominal pain, ascites and diarrhea. Laboratory investigations showed a white cell count of 15.1 thousands/mm3 with eosinophilia; other laboratory studies were within the normal limits. Abdominal ultrasonography demonstrated peritoneal effusion and cytological analysis revealed a prevalence of eosinophils in the ascites. The multiple endoscopic biopsies were normal. However, the clinical history, and the laboratory, radiological and endoscopic findings gave a firm diagnosis of the serosal form of primary eosinophilic gastroenteritis. Discussion: This is a rare, benign condition, pathologically characterized by an important eosinophilic infiltration of the wall of the digestive tract and presents a constellation of symptoms that are related to the degree and area of the gastrointestinal tract affected. Primary eosinophilic gastroenteritis encompasses multiple disease entities subcategorized into three types on the basis of the level of histologic involvement: mucosal, muscolaris and serosal forms. Every layer of the gastrointestinal tract can be involved, so that endoscopic biopsy can be normal in patients with the muscolaris subtype, serosal subtype, or both.

Eosinophilic colitis: an update on pathophysiology and treatment

Primary eosinophilic gastrointestinal disorders, a spectrum of inflammatory conditions, occurs when eosinophils selectively infiltrate the gut in the absence of known causes for such tissue eosinophilia. These may be classified into eosinophilic esophagitis, eosinophilic gastroenteritis and eosinophilic colitis (EC). This review focuses on EC: its pathogenesis, epidemiology, clinical presentation, diagnosis and current approach to treatment. A literature review published in English was performed using Pubmed, Ovid, Google scholar search engines with the following keywords: eosinophilic gastrointestinal disorder, EC, eosinophils, colitis and gastrointestinal. The basis for primary EC appears related to increased sensitivity to allergens, principally as a food allergy in infants and a T lymphocyte-mediated event in adults. Endoscopic changes are generally modest, featuring edema and patchy granularity. Clear clinical and pathological diagnostic criteria of EC and its management strategy. Intestinal involvement of EC is primarily mucosal, presenting as a mild self-limited proctitis in infants and self-limited colitis in young adults. Therapeutic approaches based on case reports tend to use either elimination diets to avoid a presumed allergen; agents traditionally used in inflammatory disease or targeted drugs like anti-histamines or leukotriene receptor antagonists. Prospective randomized controlled trials addressing the disease natural history, possible preventive methods and effective medical approach and long-term prognosis are required.

Eosinophilic Gastrointestinal Disorders (EGID) with Peripheral Eosinophilia: A Retrospective Review at Mayo Clinic

Hypereosinophilic syndrome (HES) is defined by significant eosinophilia (>1,500eos/μl), which often leads to end-organ damage/dysfunction. It is unclear if the presence of significant peripheral eosinophilia (>1,500eos/μl) indicates a more aggressive form of eosinophilic gastrointestinal disorder (EGID). A database query of the Mayo Clinic Rochester electronic records (1995-2008) was performed using several search terms for eosinophilic gastrointestinal disease, and 161 records were reviewed. Patients under 18years age, those without Mayo-reviewed pathology specimens, those with eosinophilic esophagitis only, and/or those with evidence of secondary etiologies for GI eosinophilia were excluded. A total of 39 were found to have primary EGID. We compared individuals with biopsy-proven primary EGID based on whether they had significant peripheral eosinophilia (≥1,500eos/μl) (group A) or not (group B). Group A tended to have more atopy (A: 12/15; B: 11/24; p=0.03) and more extensive segmental involvement of the GI tract (p=0.001). None with available studies had evidence of cardiac (A: 7/15; B: 6/24) or bone marrow (A: 10/15; B: 6/24) involvement. The two thromboembolic events in group A after diagnosis did not translate to significantly greater risk (HR=infinity, p=0.13; group A vs. B). Doses of initial (A: 40mg/day; B: 55mg/day; p=0.17) and maintenance prednisone (A; 8.75mg/day; B: 7.5mg/day; p>0.90) were similar. Group A was significantly more likely to need maintenance prednisone (77 vs. 8%, p=0.001), with a median treatment duration of 52weeks. Recurrence of symptoms (and peripheral eosinophilia) during prednisone taper was common in both groups. Prednisone-sparing agents (hydroxyurea, imatinib mesylate, interferon (IFN)-α2b, anti-interleukin (IL-5) monoclonal antibody) were more commonly used in group A (73 vs. 8%; p<0.0001). EGID with peripheral eosinophilia ≥1,500/μl is associated with atopy, greater GI segmental involvement, and uncertain risk of thrombosis. The common use of long-term steroids and variable responsiveness to nonsteroidal agents, particularly in group A, underscores the need for targeted therapies.

Eosinophilic colitis: epidemiology, clinical features, and current management

Primary eosinophilic gastrointestinal disorders (EGIDs) represent a spectrum of inflammatory gastrointestinal disorders in which eosinophils infiltrate the gut in the absence of known causes for such tissue eosinophilia. EGIDs can be subgrouped as eosinophilic esophagitis (EE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC). The least frequent manifestation of EGIDs is EC. EC is a heterogeneous entity with a bimodal age distribution, presenting with either an acute self-limited bloody diarrhea in otherwise healthy infants or as a more chronic relapsing colitis in young adults. The pathophysiology of primary EC appears related to altered hypersensitivity, principally as a food allergy in infants and T lymphocyte-mediated (i.e. non-IgE associated) in young adults. In adults, symptoms include diarrhea, abdominal pain, and weight loss. Endoscopic changes are generally modest, featuring edema and patchy granularity. Although standardized criteria are not yet established, the diagnosis of EC depends on histopathology that identifies an excess of eosinophils. Therapeutic approaches are based on case reports and small case series, as prospective randomized controlled trials are lacking. Eosinophilic colitis in infants is a rather benign, frequently food-related entity and dietary elimination of the aggressor often resolves the disorder within days. Adolescent or older patients require more aggressive medical management including: glucocorticoids, anti-histamines, leukotriene receptors antagonists as well as novel approaches employing biologics that target interleukin-5 (IL-5) and IgE. This review article summarizes the current knowledge of EC, its epidemiology, clinical manifestations, diagnosis, and treatment.

Gastroenterite eosinofila: un caso clinico con revisione della letteratura sui disordini intestinali associati agli eosinofili

Despite its uncommon occurrence, eosinophilic gastroenteritis is one of the most important primary eosinophilic gastrointestinal disorders. These are defined as disorders that selectively affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia. The disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis and eosinophilic colitis. This review focuses on the epidemiology, pathophysiology, clinical features and treatment of primary eosinophilic gastrointestinal disorders with particular attention to primary eosinophilic gastroenteritis. We report a case of a 32-years-old woman that was admitted to our Hospital complaining of abdominal pain, ascites and diarrhea. Laboratory investigations showed a white cell count of 15.1 thousands/mm 3 with eosinophilia; other laboratory studies were within the normal limits. Abdominal ultrasonography demonstrated peritoneal effusion and cytological analysis revealed a prevalence of eosinophils in the ascites. The multiple endoscopic biopsies were normal. However, the clinical history, and the laboratory, radiological and endoscopic findings gave a firm diagnosis of the serosal form of primary eosinophilic gastroenteritis. This is a rare, benign condition, pathologically characterized by an important eosinophilic infiltration of the wall of the digestive tract and presents a constellation of symptoms that are related to the degree and area of the gastrointestinal tract affected. Primary eosinophilic gastroenteritis encompasses multiple disease entities subcategorized into three types on the basis of the level of histologic involvement: mucosal, muscolaris and serosal forms. Every layer of the gastrointestinal tract can be involved, so that endoscopic biopsy can be normal in patients with the muscolaris subtype, serosal subtype, or both.

Eosinophilic Esophagogastritis In A Child With Atopy And Abdominal Pain

RATIONALE: Primary eosinophilic gastrointestinal disorders (EGID) are defined by eosinophil-rich GI tract inflammation in the absence of malignancy, parasitic infection, or collagen vascular disease. An estimated 75% of patients with EGID have atopic conditions. Here we report a case of eosinophilic esophagogastritis in a child with a history of atopy and recurrent abdominal pain.

Responses of Treatment Primary Eosinophilic Gastrointestinal Disorders with Corticosteroid, Montelukast and Ketotifen, 3 Cases Report

Responses of Treatment Primary Eosinophilic Gastrointestinal Disorders with Corticosteroid, Montelukast and Ketotifen, 3 Cases Report