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Eosinophilic Gastroenteritis

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Last Update: July 1, 2021.

Continuing Education Activity

Eosinophilic gastroenteritis belongs to the group of eosinophilic gastrointestinal disorders, which comprise eosinophilic esophagitis and eosinophilic colitis. It predominantly affects females. The presentation is variable, based on age, anatomy (involvement of region of the GI tract), and histology (infiltration of eosinophil in different layers of the gastrointestinal tract). A detailed history, along with a physical examination, is essential, as differential diagnosis is broad. Eosinophilic gastroenteritis is a rare condition that can present with a variety of signs and symptoms. Corticosteroids are the primary medication therapy for eosinophilic gastroenteritis. This activity presents the pathophysiology of eosinophilic gastroenteritis and highlights the role of the interprofessional team in its management.

Objectives:

  • Review the pathophysiology of eosinophilic gastroenteritis.
  • Describe the presentation of eosinophilic gastroenteritis.
  • Summarize the treatment of eosinophilic gastroenteritis.
  • Outline the steps an interprofessional team plays in improving outcomes through diagnosis and management of eosinophilic gastroenteritis.
Access free multiple choice questions on this topic.

Introduction

Eosinophilic gastrointestinal disorders consist of eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis.

Eosinophilic gastroenteritis is an inflammatory disorder that presents with variable degrees of infiltration of eosinophils within the gastrointestinal tract, first described by Kaijser in 19371.[1][2] The Klein classification has its basis in the degree of eosinophilic infiltration in different gastrointestinal layers, which include mucosal, muscle, and subserosal.[3] 

Etiology

Although the data is limited, research shows that food allergies, inflammatory conditions, infections, malignancy, and some medications like gold therapy, azathioprine, enalapril, carbamazepine, and antitumor necrosis factor can trigger the inflammatory process.[4][5]

Epidemiology

Eosinophilic gastroenteritis predominantly affects females and is more prevalent in the 18 years or younger age population.[6][7] The prevalence in the United States is 5.1 per 100000,[8] Although these values are less than a previously reported estimated incidence of 28 per 100000; overall disease prevalence seems to be increasing for the past two decades.[9] Of concern are data limitations due to the rarity of the disease. 

Pathophysiology

The pathogenesis is not well understood; however, multiple studies have shown overproduction of T-helper-2 cytokines (e.g., interleukin-13) and chemokines (e.g., CCL26/eotaxin-3), eotaxin-1, interleukin-5, and interleukin-15 upregulates eosinophils. Once eosinophils get recruited in the intestinal epithelium, they become cytotoxic by producing factors major basic protein, an eosinophil-derived neurotoxin, eosinophilic cationic protein, and eosinophilic peroxidase.[10][11][12][13]

Other possible factors contributing to the pathophysiology include increased serum thymic stromal lymphopoietin (TSLP), interleukin-33 levels, and overactivation of TH17; however, it necessitates further study to define their exact roles.[14][15]

Histopathology

Normally eosinophils are present throughout the gastrointestinal tract except the esophagus. A study in the pediatric population revealed that the established eosinophilic density per high power field per mm2 showed no eosinophils in all biopsies from normal mucosa esophagus (total number=33).[16]

There is no established cutoff to make a diagnosis of eosinophilic gastroenteritis. However, the following are the proposed numbers based on reported literature[17]:

  • Stomach: greater than or equal to 30 eosinophils per high-power field in 5 HPF
  • Duodenum: greater than or equal to 30 eosinophils
  • Ileum: more than 56 per HPF in the ileum
  • Right colon: more than 100 per HPF
  • Transverse and descending colon: more than 84 per HPF
  • Rectosigmoid colon: more than 64 per HPF

History and Physical

The presentation of eosinophilic gastroenteritis depends on the extent and depth of eosinophilic infiltration. Detailed history, along with physical examination, is essential, as differential diagnosis may be broad.

Clinical features of eosinophilic gastroenteritis[18][19]

The mucosal variant can present with nausea, vomiting, abdominal pain, diarrhea, and weight loss. The muscular variant can present with intestinal obstruction and perforation. And finally, the subserosal variant is rare and can present with ascites and abdominal distention.

Evaluation

Eosinophilic gastroenteritis is a rare condition that can present with a variety of signs and symptoms. It is a diagnosis of exclusion and calls for ruling out secondary causes of eosinophilia like intestinal tuberculosis, parasitosis, and malignant neoplasm.[20][21][22] 

Some of the common laboratory findings include eosinophilia, hypoalbuminemia, elevated IgE levels, iron deficiency anemia. Some cases reported positive antinuclear antibodies, Charcot Leyden crystals in the stool.[18][23][24][25] Both eosinophilia and eosinophilic infiltration on mucosal biopsy samples during endoscopy are guiding steps towards diagnosis.[26] Gross endoscopic findings may vary from nonspecific to mucosal erythema and ulceration. In contrast, CT scan is valuable in detecting GI wall abnormalities, including irregular narrowing, gut wall thickening, and ascites. Of note, the ascitic fluid analysis will be significant for elevated eosinophilic counts.[19][27]

Treatment / Management

Management in Adults

Some studies recommend an empiric elimination diet in people with malabsorption. However, empirical food elimination in the diet warrants further studies for long-term outcomes and efficacy in adult patients.[7][28][29][30]

Glucocorticoids

Glucocorticoids are the mainstay treatment for eosinophilic gastroenteritis. The dose of steroids should be tapered quickly over two weeks. The goal of the tapering dose of steroids is to treat severe symptoms, not tissue eosinophilia because fibrosis is comparatively less common than eosinophilic esophagitis.[18][31][32] 

Other Therapies

Based on the case reports, other therapies include[11][33][21][34][35]:

  • 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).

Management in the pediatric population

The first line is food restriction and then steroids, however, one has to monitor the response to treatment as some cases can relapse or develop resistance to steroids.[36][37]  

Differential Diagnosis

Some of the common diseases associated with eosinophilia are celiac disease, inflammatory bowel disease, infections (parasitic, amebic, fungal), connective tissue disorders, vasculitis, and hypereosinophilic syndrome, for instance. Radiographically, inflammatory bowel disease and lymphoma can mimic eosinophilic gastroenteritis.[19][38][39][40]

In the pediatric group, non-IgE mediated food allergy and infantile hypertrophic pyloric stenosis require exclusion, along with differential diagnoses mentioned above.[14][41]

Prognosis

Infants have better prognoses than children if treated appropriately.[42] However, the disease course is variable. Some patients respond positively to treatment, while others can progress to malabsorption.[21]

Complications

Complications are not well defined, and long-term studies are necessary to understand the clinical course of the disease. There are case reports on acute calculus eosinophilic cholecystitis and respiratory distress in neonates with transient eosinophilic colitis.[43][44] Complications related to management include adverse effects of long-term steroids and ulceration as a rare complication of endoscopic biopsies.[45]

Deterrence and Patient Education

Dietary therapy: Use of allergen-free food, education about proper nutrition, and proper follow-up are essential. The main limitation of dietary therapy is patient compliance.

There is low health care transition knowledge in young patients with eosinophilic gastroenteritis; which makes it crucial to educate parents and young patients.[46]

Pearls and Other Issues

Based on case reports, eosinophilic gastroenteritis has correlations with certain diseases, for instance, with IgA nephropathy, minimal change disease, allergic bronchopulmonary aspergillosis, Sjogren syndrome, eosinophilic cystitis, after allogeneic bone marrow transplantation, and ingestion of Rhus tree.[47][48][49][50][51][52][53]. Future studies may answer the question of the pathophysiology between associations.

Study shows that anti-cysteine-cysteine receptor-3 (anti- CCR3) reduces eosinophilic inflammation, mucosal injury, and diarrhea; targeting these receptors can be the future of treatment of eosinophilic gastroenteritis.[54]

Enhancing Healthcare Team Outcomes

Research suggests that comparative analyses of cases on tissue eosinophilia against a baseline control from retroactive studies from healthy individuals will improve outcomes. Overall the clinical course of eosinophilic gastroenteritis is unknown, therefore warrants an urgent need for long-term follow-up studies.[19] The Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) is a collaborative effort made possible through awards by the National Institutes of Health (NIH), dedicated to discovering more about this rare entity.[55]

An interprofessional team plays a crucial role in managing eosinophilic gastroenteritis, which includes gastroenterologists, allergists, pathologists, gastroenterology specialty-trained nurses, pharmacists, and dieticians.[56] Clinicians will diagnose the condition, but then they can enlist the help of pharmacists for drug selection and medication reconciliation, nursing for patient/parent counsel, assessing compliance, and monitoring for adverse reaction to treatment, and the dietitian to monitor the patient's food intake, especially for empiric diet elimination, but also for allergens and monitoring food intake. All these ancillary disciplines need to have an open communication channel to the treating clinicians, so everyone is operating from the same place. This type of interprofessional healthcare team model will lead to optimal patient outcomes [Level 5]

Review Questions

Eosinophilic gastroenteritis

Figure

Eosinophilic gastroenteritis. Contributed by Michael Bonert, (CC By-S.A. https://creativecommons.org/licenses/by-sa/3.0/deed.en) Image courtesy: https://commons.wikimedia.org/wiki/File:Eosinophilic_esophagitis_-_very_high_mag.jpg

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