Browse the corpus

Eosinophilic gastroenteritis is a rare chronic inflammatory disorder of the gastrointestinal tract characterized by eosinophil-predominant inflammation outside the esophagus, variable clinical presentations, and frequent diagnostic delay. Symptoms may reflect mucosal, muscular, or serosal involvement and often overlap with other gastrointestinal, allergic, infectious, inflammatory, and malignant conditions, making diagnosis difficult. Current practice gaps include inconsistent recognition of clinical patterns, delayed exclusion of secondary causes, variable biopsy practices, and uncertainty regarding evidence-based dietary and pharmacologic treatment strategies in adult and pediatric populations. This educational activity addresses these deficiencies by reviewing disease classification, pathophysiology, diagnostic criteria, differential diagnosis, biopsy-based evaluation, and current treatment approaches. Participants gain skills to improve diagnostic accuracy, interpret clinical and histologic findings, select appropriate treatment strategies, prevent complications, and strengthen interprofessional coordination to support patient-centered care. Objectives: Identify the clinical, endoscopic, and histologic features of eosinophilic gastroenteritis in adult and pediatric patients. Select evidence-based dietary and pharmacologic treatment strategies based on disease severity, anatomic involvement, patient age, and treatment response. Compare the clinical implications of involvement of the mucosa, muscle, and serosa when evaluating symptoms and planning treatment. Collaborate with interprofessional team members including specialists such as allergists, hematologists, gastroenterologists to provide efficient, comprehensive, and coordinated management of eosinophilic gastroenteritis. Access free multiple choice questions on this topic.

Eosinophilic gastroenteritis consists of predominant eosinophilic inflammation of the stomach, small intestine, large intestine, or both. These disorders are chronic inflammatory disorders of the gastrointestinal tract beyond the esophagus, characterized by clinical gastrointestinal symptoms, histologic eosinophil-predominant inflammation, and the absence of an identifiable secondary cause.[1] The disorders affect both pediatric and adult patients. Because eosinophilic esophagitis (EoE) is a separate eosinophilic disease of the gastrointestinal tract, eosinophilic gastroenteritis is referred to as non-EoE eosinophilic gastrointestinal disorders and is further subdivided into eosinophilic gastritis, enteritis (duodenitis, jejunitis, ileitis, and colitis). Efforts are underway to standardize terminology for eosinophilic gastrointestinal diseases, which are currently named based on the anatomical region involved.[2] The Klein classification is based on the degree of eosinophilic infiltration across the mucosal, muscular, and subserosal layers.[3] The symptom presentation, as discussed later in this article, depends on the anatomical region and depth of the intestinal wall involved.

Because non-EoE eosinophilic gastrointestinal disorders are rare, their etiology remains unclear. Ongoing research suggests that several factors may contribute to the inflammatory process, including food allergies, systemic inflammatory conditions, infections, malignant neoplasms, and certain medications such as gold therapy, azathioprine, enalapril, carbamazepine, and anti–tumor necrosis factor agents.[4][5] Additionally, results from studies have shown a higher prevalence of coexisting atopic conditions among affected patients. For example, allergic rhinitis has been described in approximately 28% to 30% of cases, and asthma has been reported in about 16%, with overall allergic comorbidities present in up to 30.5% of patients with eosinophilic gastritis, significantly higher than that observed in the general population. A concomitant allergic condition is also more common among pediatric individuals than among adults (58.9% vs 33.6%).[6]

The overall prevalence of non-EoE eosinophilic gastrointestinal disorders (EGIDs) is variable, and according to results from a recent study of patients presenting with gastrointestinal symptoms, non-EoE EGIDs were found in 1.9%.[7] In another study by Mansoor et al, the prevalence of eosinophilic gastritis was 5.1 cases per 100,000 persons, and that of eosinophilic colitis was 2.1 cases per 100,000 persons. Results from this study also showed that non-EoE EGIDs were less common in Black and Asian patients when compared to White patients.[8] Eosinophilic gastroenteritis affects women and men equally and is more prevalent in younger persons.[6][9][10] Although these values are lower than the previously reported incidence estimate of 22 to 28 per 100,000, overall disease prevalence appears to have increased over the past 2 decades.[11]

Because non-EoE eosinophilic gastrointestinal disorders are rare, their pathogenesis is not well understood. However, results from multiple studies have shown that overproduction of T helper 2 cytokines (eg, interleukin-13) and chemokines (eg, C-C motif ligand 26, eotaxin-3, eotaxin-1, interleukin-5, and interleukin-15) upregulates eosinophils. Once eosinophils are recruited to the intestinal epithelium, they become cytotoxic by producing factors such as major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase.[12][13][14][15] Other possible factors contributing to the pathophysiology include elevated serum levels of thymic stromal lymphopoietin and interleukin-33, as well as overactivation of T-helper 17 cells. However, further studies are needed to define their exact roles.[16][17] Familial clustering and overlap with EoE, which develops in approximately 10% to 30% of patients with non-EoE EGIDs, suggest shared pathogenic mechanisms.[18] Results from studies have shown that eotaxin-3 is elevated in eosinophilic gastritis and EoE, whereas eotaxin-1 is elevated in eosinophilic colitis.[19] Multisite inflammation is also frequently present, more common in children than in adults (68% vs 37%; P < 0.001).[9]

Normally, eosinophils are present throughout the gastrointestinal tract except in the esophagus. Results from a pediatric study showed that the established eosinophil density per high-power field was 0 in all biopsies of normal esophageal mucosa.[20] One of the difficulties in obtaining a cutoff estimate of eosinophils per high-power field in non-EoE EGIDs is due to the inconsistent use of the term high-power field (HPF) in the literature. Given the rarity of non-EoE EGIDs, the recommendations rely heavily on prior literature. Usually, HPF refers to 0.27 mm². Use of a consistent HPF, based on the field area studied, will help standardize guidelines in the future. Variation in the reported literature makes it difficult to establish a cutoff for diagnosing eosinophilic gastroenteritis. However, the following are the proposed numbers based on reported literature: Stomach: ≥30 eosinophils per HPF Duodenum: ≥50 eosinophils per HPF Ileum: >60 per HPF Right colon: >100 per HPF Transverse and descending colon: >80 per HPF Rectosigmoid colon: >60 per HPF [1][21]

As discussed earlier, the symptoms of non-EoE EGIDs are variable, and patients present with a wide range of symptoms. These variable presentations require a high index of suspicion for accurate diagnosis and prompt referral to a gastroenterologist for further evaluation. The symptoms depend on the anatomical area and the extent of eosinophilic involvement of the gut wall. A detailed history, along with physical examination, is essential because the differential diagnosis may be broad. Mucosal disease can present with nausea, vomiting, abdominal pain, diarrhea, and weight loss. Those who have diffuse enteritis can develop malabsorption, protein-losing enteropathy, and failure to thrive. Muscular layer disease can present with intestinal obstruction, including nausea, vomiting, gastric outlet obstruction, and perforation. Serosal disease can present with isolated ascites or with ascites accompanied by symptoms of mucosal or muscular gastritis, enteritis, or colitis. Eosinophilic pleural effusion can also be seen.[22][23] Apart from the clinical features, the history should also identify associated conditions and potential differential diagnoses, including asthma, dermatitis, blood in the stool, travel to areas endemic for parasites that cause eosinophilia, a family history of connective tissue disorders, and use of drugs associated with eosinophilia.

Eosinophilic gastroenteritis is a rare condition. Diagnosis requires exclusion of secondary causes of eosinophilia, such as intestinal tuberculosis, parasitosis, malignant neoplasms, inflammatory bowel disease, hypereosinophilic disorders, connective tissue disorders, adrenal insufficiency, graft-versus-host disease, and vasculitides (eosinophilic granulomatosis with polyangiitis and eosinophilic granulomatosis).[24][25][26] Some common laboratory findings include peripheral eosinophilia (with eosinophils >1000/μL in hypereosinophilic disorders), hypoalbuminemia, elevated immunoglobulin E levels, and iron deficiency anemia. Some cases reported positive antinuclear antibody results and Charcot-Leyden crystals in stool.[22][27][28][29] Both eosinophilia and eosinophilic infiltration in mucosal biopsy samples obtained during endoscopy are guiding factors in the diagnosis.[30] Gross endoscopic findings may vary from nonspecific findings to mucosal erythema and ulceration. In contrast, a computed tomography scan is valuable for detecting abnormalities of the gastrointestinal tract wall, including irregular narrowing, gut wall thickening, and ascites. Additionally, the ascitic fluid analysis will be significant if it shows elevated eosinophil counts.[23][31] When taking biopsies, the number of endoscopic biopsies is an important determinant. Guidelines recommend taking at least 8 biopsies in the stomach and 4 in the duodenum to accurately identify patients with non-EoE EGIDs.[32]

Goals of treatment should be directed towards symptom resolution, improvement in endoscopic and histological findings, and restoration of normal growth and function.[1] Management in Adults Results from several studies recommend an empiric 6-food elimination diet (soy, wheat, egg, milk, peanut, tree nuts, fish, and shellfish) or an elemental diet in people with malabsorption. However, empirical food elimination warrants further studies to assess long-term outcomes and efficacy in adult patients. The main limitation is patient adherence. Therapy should be pursued for at least 4 to 6 weeks with the help of a trained dietitian.[10][33][34][35] Glucocorticoids Glucocorticoids are the mainstay of treatment for eosinophilic gastroenteritis. Clinicians can begin with a trial of prednisone at 20 to 40 mg/d. The dose of corticosteroids should be tapered quickly over 2 weeks. The goal of a tapered dose of corticosteroids is to treat severe symptoms, not tissue eosinophilia, because fibrosis is comparatively less common than in eosinophilic esophagitis.[22][36][37] Other Therapies Based on findings from case reports, other therapies include: Leukotriene inhibitors (montelukast) Mast cell stabilizers (oral cromolyn) Interleukin-5 inhibitors Ketotifen Immunosuppressive drugs Biological agents include vedolizumab, mepolizumab (anti–interleukin 5 antibodies), and omalizumab (anti-IgE monoclonal antibody) [13][25][38][39][40] Treatment for Children The latest guidelines do not recommend using food allergy tests to guide restriction therapy in children. Empiric elimination of foods may be considered, and cow's milk restriction may be most effective.[41] Although proton pump inhibitors (PPIs) are one of the first-line medications for the treatment of eosinophilic esophagitis, there is insufficient evidence in children for their use. PPIs are recommended for children with non-EoE EGIDs who have ulcerations on endoscopy.[9] Endoscopic dilation may be required in cases with severe obstructive symptoms. Systemic and topical corticosteroids are often considered the first-line therapy in children, and monitoring response to treatment is essential; relapses are common. A common way to deliver topical corticosteroids is through enteric-coated budesonide capsules, which are available in different preparations to reach different areas of the gastrointestinal tract.

Endoscopic dilation may be required in cases with severe obstructive symptoms. Systemic and topical corticosteroids are often considered the first-line therapy in children, and monitoring response to treatment is essential; relapses are common. A common way to deliver topical corticosteroids is through enteric-coated budesonide capsules, which are available in different preparations to reach different areas of the gastrointestinal tract. If left intact, the capsules can reach the colon and ileum. If the capsules are opened and placed in a vehicle, they can reach the stomach and proximal small intestine. Budesonide can be started at 9 mg/d and then tapered gradually to 3 mg/d for maintenance therapy.[9][42][43][44]

Some common diseases associated with eosinophilia include celiac disease, inflammatory bowel disease, infections (including parasitic, amebic, and fungal infections), connective tissue disorders, vasculitis, and hypereosinophilic syndrome. Radiographically, inflammatory bowel disease and lymphoma can mimic eosinophilic gastroenteritis.[23][45][46][47] In the pediatric group, non–immunoglobulin E-mediated food allergy and infantile hypertrophic pyloric stenosis should be excluded, along with the differential diagnoses mentioned above.[16][48]

Diagnosis in non–EoE EGIDs is frequently delayed, with a mean diagnostic delay of 3.6 years, a 38.2% missed-diagnosis rate, and a 44.3% misdiagnosis rate. Despite the chronic nature of the disease, it is not life-threatening. Infants have better prognoses than children if treated appropriately.[49] However, the disease course is variable. Some patients respond positively to treatment, while others can progress to malabsorption.[25][50]

Complications are poorly defined, and long-term studies are necessary to understand the disease's clinical course. Results from case reports on acute calculus eosinophilic cholecystitis and respiratory distress in neonates with transient eosinophilic colitis report complications related to management, including adverse effects of long-term steroids and ulceration as a rare complication of endoscopic biopsies.[51][52][53] Other severe complications include gastric ulcer perforation, gastric outlet obstruction, small bowel obstruction, dysmotility, and intussusception. Results from one review identified fewer than 15 case reports published from 1977 to 2023 describing perforation, and 3 of these reported gastric perforation.[54]

Dietary Therapy Use of allergen-free foods, education on proper nutrition, and appropriate follow-up are essential. The main limitation of dietary therapy is patient adherence. The chronic nature of the disease and unclear natural progression warrant extensive counseling of patients to ensure adherence. Study results have shown low health care transition knowledge among young patients with eosinophilic gastroenteritis, making education for parents and young patients crucial.[55]

Based on results from case reports, eosinophilic gastroenteritis is associated with certain diseases, including immunoglobulin A nephropathy, minimal change disease, allergic bronchopulmonary aspergillosis, Sjogren disease, eosinophilic cystitis, occurrence after allogeneic bone marrow transplant, and ingestion of the Rhus tree.[56][57][58][59][60][61][62] Future studies may help clarify the pathophysiology of these associations. Results from a study showed that anti–cysteine-cysteine receptor-3 reduces eosinophilic inflammation, mucosal injury, and diarrhea. Targeting these receptors could be the future of treatment for eosinophilic gastroenteritis.[63]

Research suggests that comparative analyses of patients with tissue eosinophilia, using a baseline control from retrospective studies of healthy individuals, will improve outcomes. Overall, the clinical course of eosinophilic gastroenteritis remains unknown, underscoring the urgent need for long-term follow-up studies.[23] The Consortium of Eosinophilic Gastrointestinal Disease Researchers is a collaborative effort, made possible by National Institutes of Health awards, dedicated to advancing understanding of this rare entity.[64] An interprofessional team plays a crucial role in managing eosinophilic gastroenteritis, which includes gastroenterologists, allergists, pathologists, gastroenterology specialty-trained nurses, pharmacists, and dietitians.[65] Clinicians will diagnose the condition, and they can then enlist the help of pharmacists for drug selection and medication reconciliation, nursing for patient and parent counseling, assessment of adherence, and monitoring for adverse reactions to treatment, and the dietitian to monitor the patient's food intake, especially for empiric diet elimination, as well as for allergens and monitoring food intake. All these ancillary disciplines need to maintain open communication channels with the treating clinicians, so everyone is operating from the same place. This type of interprofessional health care team model will lead to optimal patient outcomes.