Eosinophilic Gastrointestinal Diseases: The Pathogenesis,Diagnosis, and Treatment

Eosinophilic gastrointestinal diseases are delayed-type chronic allergic disorders that show gastrointestinal eosinophil dense infiltration, with an exaggerated Th2-type immune reaction considered to be an important mechanism. These diseases can be roughly divided into two types: eosinophilic esophagitis, mainly found in young and middle-aged men, and eosinophilic gastroenteritis, which is found in both genders equally. A diagnosis of eosinophilic esophagitis is suspected when characteristic endoscopic findings, including longitudinal furrows and rings, are noted. However, characteristic endoscopic abnormalities are rarely found in cases with eosinophilic gastroenteritis, so multiple biopsy sampling from the apparently normal gastrointestinal mucosal surface is important for making an accurate diagnosis. The administration of systemic glucocorticoid is the standard treatment for eosinophilic gastroenteritis, while acid inhibitors and topical glucocorticoid swallowing therapy are effective for eosinophilic esophagitis. Anti-cytokine therapies for eosinophilic gastrointestinal diseases are currently under development.     

Eosinophilic gastroenteritis: A state‐of‐the‐art review

Eosinophilic gastrointestinal disorders are a series of diseases that include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes, presenting with a variety of gastrointestinal manifestations. Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear. Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal tract wall, eosinophilic gastroenteritis is classified into three different patterns including predominantly mucosal pattern, predominantly muscular pattern, and predominantly serosal pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other evidences such as laboratory results, radiological findings and endoscopy can also provide important diagnostic evidences for eosinophilic gastroenteritis. And these indirect pieces of information together with histological results will lead to a definitive diagnosis of eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered as initial treatment strategy before drug treatment. Corticosteroids are the main medication for eosinophilic gastroenteritis and have a dramatic therapeutic efficacy. Yet other medications need to further verify their effects in clinical practice, and surgery should be avoided as far as possible.     

Eosinophil function in eosinophil-associated gastrointestinal disorders

Eosinophil-associated gastrointestinal disorders (EGIDs) are characterized by a rich eosinophilic inflammation of the gastrointestinal tract in the absence of known causes for eosinophilia or other gastrointestinal disorders. These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis, and are being recognized with increasing frequency. Clinical studies suggest that eosinophils have a pathogenic role in EGID; however, the function of eosinophils in these disorders remains an enigma. In this review, we brie.y describe the clinical features of EGID of the esophagus, small bowel, and colon. We summarize recent experimental analysis examining the underlying contribution of eosinophils to disease pathogenesis and discuss possible therapeutic approaches for the treatment of these diverse diseases.     

嗜酸性粒细胞性消化道炎

原发性嗜酸性粒细胞性消化道炎（eosinophilic gastrointestinal disease,EGID）是以消化道嗜酸性粒细胞异常浸润为特征的炎症性疾病。该病可以累及消化道全长或某一部分,包括嗜酸性粒细胞性食管炎（eosinophilicesophagitis,EE）、胃炎、胃肠炎（eosinophilic gastroenteritis,EG）、小肠炎、结肠炎及直肠炎。在过去的几十年中,文献报道的发病率逐渐增高。其病因及发病机制并不清楚,大多数研究结果都提示,吸入和食物过敏反应可能诱发该病的发作。其临床主要表现为各种消化道症状,无特异性,诊断标准未得到一致公认,多强调以病理为主的综合诊断,同时要除外其他继发性消化道嗜酸性粒细胞增多疾病。治疗以控制饮食和糖皮质激素为主,近年出现针对发病机制的生物制剂治疗,但尚缺少充分的循证医学依据。     

Eosinophilic gastroenteritis with ascites and hepatic dysfunction

Eosinophilic gastroenteritis is a rare gastrointestinal disorder with eosinophilic infiltration of the gastrointestinal wall and various gastrointestinal dysfunctions. Diagnosis requires a high index of suspicion and exclusion of various disorders that are associated with peripheral eosinophilia. We report a case of eosinophilic gastroenteritis, which had features of the predominant subserosal type presenting with ascites and hepatic dysfunction, and which responded to a course of low-dose steroid.     

Diagnosing Pollen-food Allergy Syndrome Allergologically in a Patient with Suspected Eosinophilic Gastroenteritis

Pollen-food allergy syndrome (PFAS) consists of type I allergy to pollen and multiple food items that are cross-reactive to the pollen. PFAS typically occurs in the oral cavity and can co-occur with eosinophilic esophagitis. However, it is infrequently reported to present with symptoms of eosinophilic gastroenteritis (EGE), such as abdominal pain and eosinophilic infiltration of the gastrointestinal tract. We herein report a patient with a condition initially suspected of being EGE based on symptoms and pathological findings that was later diagnosed as PFAS associated with birch pollen. PFAS should be considered as a differential diagnosis in patients with EGE-like symptoms.     

Eosinophilic esophagitis: A subset of eosinophilic gastroenteritis

Eosinophilic gastroenteritis (EG) was first described over 50 years ago. Despite its long history, it remains an ill-defined and poorly understood entity. EG can present in a number of ways, none of which are exclusive to the disorder. EG has features of allergy and immune dysregulation but does not clearly fit into the category of allergic or immune disorder. While EG has been reported to affect all locations and layers of the gastrointestinal tract, the vast majority of reported cases have demonstrated mucosal involvement of the gastric antrum and small intestine in addition to disease activity of other locations of the gastrointestinal tract. Recently, several reports have identified a disease consisting of an isolated esophageal eosinophilia. Eosinophilic esophagitis (EE), also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of EG with an isolated severe esophageal eosinophilia. Patients with EE present with symptoms similar to those of gastroesophageal reflux but are unresponsive to antireflux medication. Reports have demonstrated that patients with EE respond to either dietary restriction or corticosteroids.     

Eosinophilic disorders in children

Many pediatric diseases demonstrate blood or tissue eosinophilia. Included among these disorders are common atopic diatheses such as asthma as well as the rarer conditions of hypereosinophilic syndrome and eosinophilic gastrointestinal disorders. Eosinophil trafficking and activation in target organs leads to tissue damage and ongoing reparative attempts that can ultimately result in changes in organ structure and function. Recent treatment with biologic agents such as tyrosine kinase inhibitors and anti-interleukin-5 has offered new therapeutic options in certain eosinophilic disorders. Eosinophilic disorders such as eosinophilic esophagitis are increasingly being diagnosed in children, but many lessons in disease pathogenesis, diagnosis, optimal treatment, and natural history continue to be learned.     

Eosinophilic ascites. 2 new case reports]

Two new cases of eosinophilic ascites and a brief review of 40 cases found in the literature are presented. In three quarters of the cases eosinophilic ascites affects women aged 40 years on average. Because the patients present with a history of allergy (55%), blood hypereosinophilia (69%), associated pleural effusion (11%), gastrointestinal disorders and, above all, eosinophilic infiltrations in the walls of the digestive tract or the serous membranes (63%), this pathology may be regarded as a clinical form or eosinophilic gastroenteritis. The outcome is favourable in 90% of the cases; relapses occur in 26%. Is eosinophilic gastroenteritis and independent pathological entity, or should it be considered a minor clinical form of Chusid's idiopathic hypereosinophilic syndrome? The lack of decisive arguments precludes a firm conclusion.     

Idiopathic eosinophilic gastrointestinal diseases in adults

This review focuses on the latest cognitions, diagnosis and treatment strategies of the three main representatives of the eosinophilic gastrointestinal disorders (EGID): idiopathic eosinophilic oesophagitis (EE), idiopathic eosinophilic gastroenteritis (EGE) and idiopathic hypereosinophilic syndromes (HES) with gastrointestinal involvement. These disorders share important similarities: their origin is unknown and their pathogenesis is due to a histological inflammatory response characterised by eosinophilic tissue infiltration. In spite of these parallels, the courses and prognoses of the diseases differ radically: EE is restricted to the oesophagus, and though it may significantly decrease the patient's quality of life, it has a favourable long-term prognosis. In EGE, the inflammatory process involves several segments of the gastrointestinal tract but this chronic inflammation may also be considered a benign disorder. In contrast, HES is primarily a multisystem disorder that may involve several organs, including the digestive tract, and often has a fatal outcome.     

Idiopathic hypereosinophilic syndrome with predominant digestive manifestations or eosinophilic gastroenteritis? Apropos of 2 cases

We report two cases of hypereosinophilic syndrome with predominant gastrointestinal signs, which could have been mistaken for eosinophilic gastroenteritis. In the first case, the patient presented with eosinophilic ascites; documentation of pulmonary involvement allowed to easily establish the diagnosis. In the second case, the patient presented with diarrhea and malabsorption; gastrointestinal and pancreatic involvement seemed isolated. Cases reported as eosinophilic gastroenteritis in the literature with polyvisceral involvement raise the possibility of hypereosinophilic syndrome. We suggest that diffuse eosinophilic gastroenteritis could in fact be an isolated manifestation of the idiopathic hypereosinophilic syndrome.     

Eosinophilic gastroenteritis presenting in an adolescent with isolated colonic involvement.

Eosinophilic gastroenteritis most commonly involves the stomach and proximal small intestine with eosinophilic inflammation of either the mucosa, submucosa or serosa. The patient reported here had isolated eosinophilic colitis. The initial presentation with iron deficiency anaemia owing to occult gastrointestinal blood loss emphasises the need to evaluate the entire gastrointestinal tract in patients with eosinophilic gastroenteritis.     

A new case of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa The hallmark of this condition is intermittent and often painful dysphagia that may become constant as the disease progresses. It was initially included within the more general condition known as eosinophilic gastroenteritis but it is now considered an independent entity. Attwood et al. called attention to eosinophilic esophagitis as a distinct clinical condition in 1993. Although eosinophilic esophagitis was thought to occur primarily in children, a significant body of evidence suggests that it affects adults as well. We describe a clinical case of a young woman with a long-standing history of dysphagia affected of this rare entity.     

Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis

Recent data suggest that the interaction between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis can be complex, and that the notion of establishing a clear distinction between the two disorders may be too simplistic. There are at least four situations in which GERD might be associated with esophageal eosinophils: (a) GERD causes esophageal injury that results in a mild eosinophilic infiltration, (b) GERD and eosinophilic esophagitis coexist but are unrelated, (c) eosinophilic esophagitis contributes to or causes GERD, or (d) GERD contributes to or causes eosinophilic esophagitis. The high frequency of GERD described in adult patients with eosinophilic esophagitis suggests that there may be more than a chance association between the two disorders. This report discusses potential mechanisms for the complex interaction between GERD and eosinophilic esophagitis. We hope that this information will serve as a conceptual basis for future studies on the relationship between the two disorders. Whereas there are a number of plausible mechanisms whereby GERD might contribute to the accumulation of eosinophils in the esophageal epithelium, it seems prudent to recommend a clinical trial of proton pump inhibitor (PPI) therapy even when the diagnosis of eosinophilic esophagitis seems clear-cut. Furthermore, we suggest that a favorable response to PPI therapy does not preclude a diagnosis of eosinophilic esophagitis.     

Eosinophilic colitis

Eosinophilic colitis （EC） is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions, inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination. Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics.     

Eosinophilic gastroenteritis presenting as obstructive jaundice

Eosinophilic gastroenteritis is a rare condition of unknown aetiology, first described by Kaijser in 1937. It is manifest by eosinophilic infiltration of the gastrointestinal tract and peripheral eosinophilia. Patients have various clinical presentations depending on the region of the gastrointestinal tract involved and the depth and extent of the bowel wall involvement. Whereas gastrointestinal obstruction associated with this condition is not uncommon, isolated biliary obstruction has only been reported twice. We present a case of eosinophilic gastroenteritis with involvement of the biliary tract causing ulceration, fibrosis and obstruction. Although a rare condition, we believe the diagnosis of eosinophilic gastroenteritis should be entertained in patients with gastrointestinal symptoms and a peripheral eosinophilia who have no evidence of parasitic infection, vasculitis or neoplasms.     

Eosinophilic gastrointestinal diseases – Pathogenesis,diagnosis, and treatment

Eosinophilic gastrointestinal diseases (EGIDs) are divided into eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), depending on the involved gastrointestinal tract, though both are considered to be chronic Th2-type allergic diseases caused by food or environmental allergens. In development of EoE, refluxed gastric acid may also have an important role. For diagnosis of EGIDs, the presence of symptoms possibly originating from the involved gastrointestinal tract and dense eosinophil infiltration are important factors. Imaging studies, including endoscopy and computed tomography, along with histopathological examinations of biopsy specimens are useful for diagnosis, whereas laboratory testing of blood, urine, and stool samples has limited value. Three useful options for treating EoE patients are acid inhibitors, swallowed topical corticosteroids, and an elimination diet, while systemic administration of glucocorticoids is the standard treatment of EGE, though information is limited. Since the prevalence of EGIDs is increasing in Western countries as well as Japan, development of effective treatments based on sufficient evidence is becoming an urgent need.     

Eosinophilic gastroenteritis

Eosinophilic gastroenteritis despite its uncommon occurrence is one of the most important primary eosinophilic gastrointestinal disorders, and most commonly presents with abdominal pain. The terminology is, however, misleading because all levels of the gastrointestinal tract from the esophagus to the rectum may be affected. A history of atopy and allergies is present in 25-75% cases. The heterogeneity in the clinical presentations of EG is determined by the site and depth of eosinophilic infiltration. Eosinophilic intestinal inflammation also occurs secondarily in the gastrointestinal tract in inflammatory bowel disease, autoimmune diseases, as reactions to medications, infections, hypereosinophilia syndrome, and after solid organ transplantation. Recent investigations providing an insight into the pathogenesis of eosinophilic gastroenteritis support a critical role for allergens, eosinophils, Th-2 type cytokines, and eotaxin in mediating eosinophilic inflammation. The diagnosis is confirmed by demonstrating prominent tissue eosinophilia on histopathology. Treatment recommendations based on data extrapolated from retrospective, uncontrolled studies, and expert opinion support the use of restricted diets, corticosteroids, leukotriene receptor antagonists, and mast cell stabilizers. Many unanswered questions remain with regard to the natural history, optimal duration of therapy, safer steroid-sparing long-term treatment agents, and the means of reliable and non-invasive follow-up.     

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 onehad 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 outletand/or small bowel obstruction is an important though uncommon presentation of EG. It may also presentas esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.     

Gastroentérite à éosinophiles

Purpose

Eosinophilic gastroenteritis is a rare and heterogeneous disorder characterized by eosinophilic infiltration of one or more layers of the gastrointestinal tract. Although it can involve any part of the gastrointestinal tract, the stomach and the proximal small bowel are the most common sites of involvement. Clinical features depend on which layer and site are involved. We report eight cases of eosinophilic gastroenteritis.

Methods

We conducted a retrospective review of consecutive adult cases diagnosed with eosinophilic gastroenteritis from 1990 to 2010. The diagnosis was established by histologic examination of endoscopic biopsy or operative specimen or by the presence of eosinophilic ascites.

Results

Eight patients (three men, five women) were diagnosed with eosinophilic gastroenteritis during the study period. Three out of the eight patients had a history of allergy. All patients had gastrointestinal symptoms. The most common symptoms were abdominal pain, vomiting, weight loss and ascites. Seven patients (87.5%) had hypereosinophilia. Seven patients had involvement of the subserosa and one of the mucosa. Four patients were treated with oral prednisolone. The symptoms in all the patients subsided within one month. The remaining four patients improved spontaneously. Four of our patients were followed-up for at least 2 months (11 to 68 months). A single patient presented a relapse.

Conclusion

Eosinophilic gastroenteritis should be suspected in patients having gastrointestinal discomfort along with peripheral eosinophilia. Definitive diagnosis requires histological demonstrations of eosinophilic infiltration of the gastrointestinal wall or high eosinophilic count in ascites fluid.