Eosinophilic Gastroenteritis

Article Author:
Ruba Memon
Article Editor:
Mohammedi Savliwala
Updated:
6/28/2020 11:25:23 PM
PubMed Link:
Eosinophilic Gastroenteritis

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 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 empiric elimination diet in people with malabsorption. However, empirical food-elimination in the diet warrants further studies for long-term outcome 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 is 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 outcome. 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]



  • 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
    (Move Mouse on Image to Enlarge)
    • Image 11586 Not availableImage 11586 Not available
      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

References

[1] Rothenberg ME, Eosinophilic gastrointestinal disorders (EGID). The Journal of allergy and clinical immunology. 2004 Jan;     [PubMed PMID: 14713902]
[2] Ingle SB,Hinge Ingle CR, Eosinophilic gastroenteritis: an unusual type of gastroenteritis. World journal of gastroenterology. 2013 Aug 21;     [PubMed PMID: 23964139]
[3] Pineton de Chambrun G,Desreumaux P,Cortot A, Eosinophilic enteritis. Digestive diseases (Basel, Switzerland). 2015     [PubMed PMID: 25925921]
[4] Yanagimoto Y,Taniuchi S,Ishizaki Y,Nakano K,Hosaka N,Kaneko K, Eosinophilic gastroenteritis caused by eating hens' eggs: A case report. Allergology international : official journal of the Japanese Society of Allergology. 2017 Oct;     [PubMed PMID: 28279648]
[5] Muir A,Surrey L,Kriegermeier A,Shaikhkalil A,Piccoli DA, Severe Eosinophilic Gastroenteritis in a Crohn's Disease Patient Treated With Infliximab and Adalimumab. The American journal of gastroenterology. 2016 Mar;     [PubMed PMID: 27018120]
[6] Jensen ET,Martin CF,Kappelman MD,Dellon ES, Prevalence of Eosinophilic Gastritis, Gastroenteritis, and Colitis: Estimates From a National Administrative Database. Journal of pediatric gastroenterology and nutrition. 2016 Jan     [PubMed PMID: 25988554]
[7] Alhmoud T,Hanson JA,Parasher G, Eosinophilic Gastroenteritis: An Underdiagnosed Condition. Digestive diseases and sciences. 2016 Sep;     [PubMed PMID: 27234270]
[8] Mansoor E,Saleh MA,Cooper GS, Prevalence of Eosinophilic Gastroenteritis and Colitis in a Population-Based Study, From 2012 to 2017. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2017 Nov;     [PubMed PMID: 28603057]
[9] Hui CK,Hui NK, A Prospective Study on the Prevalence, Extent of Disease and Outcome of Eosinophilic Gastroenteritis in Patients Presenting with Lower Abdominal Symptoms. Gut and liver. 2018 May 15;     [PubMed PMID: 29212311]
[10] Sherrill JD,Rothenberg ME, Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies. The Journal of allergy and clinical immunology. 2011 Jul;     [PubMed PMID: 21570716]
[11] Uppal V,Kreiger P,Kutsch E, Eosinophilic Gastroenteritis and Colitis: a Comprehensive Review. Clinical reviews in allergy     [PubMed PMID: 26054822]
[12] Kinoshita Y,Ishimura N,Oshima N,Mikami H,Okimoto E,Jiao DJ,Ishihara S, Recent Progress in the Research of Eosinophilic Esophagitis and Gastroenteritis. Digestion. 2016     [PubMed PMID: 26789117]
[13] Khan S, Eosinophilic gastroenteritis. Best practice     [PubMed PMID: 15833687]
[14] Shoda T,Matsuda A,Arai K,Shimizu H,Morita H,Orihara K,Okada N,Narita M,Ohya Y,Saito H,Matsumoto K,Nomura I, Sera of patients with infantile eosinophilic gastroenteritis showed a specific increase in both thymic stromal lymphopoietin and IL-33 levels. The Journal of allergy and clinical immunology. 2016 Jul;     [PubMed PMID: 26948075]
[15] Fujiya M,Kashima S,Sugiyama Y,Iwama T,Ijiri M,Tanaka K,Takahashi K,Ando K,Nomura Y,Ueno N,Goto T,Moriichi K,Mizukami Y,Okumura T,Sasajima J,Fujishiro D,Okamoto K,Makino Y, Takayasu's arteritis associated with eosinophilic gastroenteritis, possibly via the overactivation of Th17. Gut pathogens. 2018;     [PubMed PMID: 29942355]
[16] Silva J,Canão P,Espinheira MC,Trindade E,Carneiro F,Dias JA, Eosinophils in the gastrointestinal tract: how much is normal? Virchows Archiv : an international journal of pathology. 2018 Sep;     [PubMed PMID: 29987614]
[17] Collins MH, Histopathologic features of eosinophilic esophagitis and eosinophilic gastrointestinal diseases. Gastroenterology clinics of North America. 2014 Jun     [PubMed PMID: 24813514]
[18] Gonsalves N, Eosinophilic Gastrointestinal Disorders. Clinical reviews in allergy & immunology. 2019 Mar 22     [PubMed PMID: 30903439]
[19] Koutri E,Papadopoulou A, Eosinophilic Gastrointestinal Diseases in Childhood. Annals of nutrition & metabolism. 2018     [PubMed PMID: 30783041]
[20] Santos C,Morgado F,Blanco C,Parreira J,Costa J,Rodrigues L,Marfull L,Cardoso P, Ascites in a Young Woman: A Rare Presentation of Eosinophilic Gastroenteritis. Case reports in gastrointestinal medicine. 2018;     [PubMed PMID: 29862093]
[21] Walker MM,Potter M,Talley NJ, Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus. The lancet. Gastroenterology     [PubMed PMID: 29533199]
[22] Imaeda H,Yamaoka M,Ohgo H,Yoneno K,Kobayashi T,Noguchi T,Uchida Y,Soma T,Kayano H,Kanazawa M,Nakamoto H,Nagata M, Eosinophil infiltration in the upper gastrointestinal tract of patients with bronchial asthma. Allergology international : official journal of the Japanese Society of Allergology. 2016 Sep     [PubMed PMID: 27118436]
[23] Kelly KJ, Eosinophilic gastroenteritis. Journal of pediatric gastroenterology and nutrition. 2000;     [PubMed PMID: 10634296]
[24] Kodan P,Shetty MA,Pavan MR,Kariappa A,Mahabala C, Acute eosinophilic ascites: an unusual form of an unusual case. Tropical doctor. 2015 Jan     [PubMed PMID: 25315240]
[25] Siddique SM,Gilotra NA, Crystal clear: a unique clue to diagnosis in a patient with recurrent nausea and vomiting. Gastroenterology. 2014 Aug     [PubMed PMID: 24973673]
[26] Furuta GT,Atkins FD,Lee NA,Lee JJ, Changing roles of eosinophils in health and disease. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2014 Jul     [PubMed PMID: 24795292]
[27] Shimamoto Y,Harima Y, A Case of Eosinophilic Gastroenteritis Forming a Rigid Chamber Mimicking Giant Duodenal Ulcer on Computed Tomography Imaging. The American journal of case reports. 2016 Apr 18;     [PubMed PMID: 27086704]
[28] Okimoto E,Ishimura N,Okada M,Mikami H,Sonoyama H,Ishikawa N,Araki A,Oshima N,Hirai J,Ishihara S,Maruyama R,Kinoshita Y, Successful Food-Elimination Diet in an Adult with Eosinophilic Gastroenteritis. ACG case reports journal. 2018;     [PubMed PMID: 29850645]
[29] Elliott JA,McCormack O,Tchrakian N,Conlon N,Ryan CE,Lim KT,Ullah N,Mahmud N,Ravi N,McKiernan S,Feighery C,Reynolds JV, Eosinophilic ascites with marked peripheral eosinophilia: a diagnostic challenge. European journal of gastroenterology & hepatology. 2014 Apr     [PubMed PMID: 24535594]
[30] Lucendo AJ,Serrano-Montalbán B,Arias Á,Redondo O,Tenias JM, Efficacy of Dietary Treatment for Inducing Disease Remission in Eosinophilic Gastroenteritis. Journal of pediatric gastroenterology and nutrition. 2015 Jul;     [PubMed PMID: 25699593]
[31] Zhang M,Li Y, Eosinophilic gastroenteritis: A state-of-the-art review. Journal of gastroenterology and hepatology. 2017 Jan;     [PubMed PMID: 27253425]
[32] Wong GW,Lim KH,Wan WK,Low SC,Kong SC, Eosinophilic gastroenteritis: Clinical profiles and treatment outcomes, a retrospective study of 18 adult patients in a Singapore Tertiary Hospital. The Medical journal of Malaysia. 2015 Aug;     [PubMed PMID: 26358020]
[33] Abou Rached A,El Hajj W, Eosinophilic gastroenteritis: Approach to diagnosis and management. World journal of gastrointestinal pharmacology and therapeutics. 2016 Nov 6;     [PubMed PMID: 27867684]
[34] Kim HP,Reed CC,Herfarth HH,Dellon ES, Vedolizumab Treatment May Reduce Steroid Burden and Improve Histology in Patients With Eosinophilic Gastroenteritis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Dec;     [PubMed PMID: 29596982]
[35] Han D,Lee JK, Severe asthma with eosinophilic gastroenteritis effectively managed by mepolizumab and omalizumab. Annals of allergy, asthma     [PubMed PMID: 30056148]
[36] Costa C,Pinto Pais I,Rios E,Costa C, Milk-sensitive eosinophilic gastroenteritis in a 2-month-old boy. BMJ case reports. 2015 Aug 13;     [PubMed PMID: 26272958]
[37] Choi JS,Choi SJ,Lee KJ,Kim A,Yoo JK,Yang HR,Moon JS,Chang JY,Ko JS,Kang GH, Clinical Manifestations and Treatment Outcomes of Eosinophilic Gastroenteritis in Children. Pediatric gastroenterology, hepatology     [PubMed PMID: 26770900]
[38] Shih HM,Bair MJ,Chen HL,Lin IT, Eosinophilic Gastroenteritis : Brief Review. Acta gastro-enterologica Belgica. 2016 Apr-Jun;     [PubMed PMID: 27382945]
[39] Mehta P,Furuta GT, Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections. Immunology and allergy clinics of North America. 2015 Aug     [PubMed PMID: 26209893]
[40] Saraiva N,Filipe C,Simão A,Carvalho A, A 22-year-old male patient with ascites. BMJ case reports. 2015 Jun 8     [PubMed PMID: 26055595]
[41] Choi SJ,Jang YJ,Choe BH,Cho SH,Ryeom H,Hong SJ,Lee D, Eosinophilic gastritis with gastric outlet obstruction mimicking infantile hypertrophic pyloric stenosis. Journal of pediatric gastroenterology and nutrition. 2014 Jul     [PubMed PMID: 25222812]
[42] Choi BS,Hong SJ,Park SH,Kim HM,Choe BH, Differences in Features and Course of Mucosal Type Eosinophilic Gastroenteritis between Korean Infants and Children. Journal of Korean medical science. 2015 Aug;     [PubMed PMID: 26240491]
[43] Hui CK, Eosinophilic gastroenteritis complicating acute calculus eosinophilic cholecystitis 6 months after cholecystectomy. Journal of digestive diseases. 2018 Nov;     [PubMed PMID: 30370999]
[44] Tanaka K,Koshida S,Yanagi T,Tsutsui H,Nakahara S,Furukawa O,Tsuji S, Suspected fetal onset of neonatal transient eosinophilic colitis and development of respiratory distress. Pediatrics international : official journal of the Japan Pediatric Society. 2015 Aug     [PubMed PMID: 25809522]
[45] Chen B,Yang Z,Lu H,Wei C,Wang F,Liu C, Eosinophilic gastroenteritis presenting as upper gastrointestinal hematoma and ulcers after endoscopic biopsy: A case report and literature review. Medicine. 2017 Sep;     [PubMed PMID: 28906408]
[46] Eluri S,Book WM,Kodroff E,Strobel MJ,Gebhart JH,Jones PD,Menard-Katcher P,Ferris ME,Dellon ES, Lack of Knowledge and Low Readiness for Health Care Transition in Eosinophilic Esophagitis and Eosinophilic Gastroenteritis. Journal of pediatric gastroenterology and nutrition. 2017 Jul;     [PubMed PMID: 28644350]
[47] Panchangam V,Manjunath SM, Rare association of IgA nephropathy with nephrotic syndrome in a patient with eosinophilic gastritis. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. 2014 Jul     [PubMed PMID: 24969211]
[48] Choi DM,Pyun JE,Yim HE,Yoo KH,Shim JO,Lee EJ,Won NH, Eosinophilic gastroenteritis in an 18-year-old male with prolonged nephrotic syndrome. Korean journal of pediatrics. 2016 Nov;     [PubMed PMID: 28018451]
[49] Bumbacea RS,Balea MI,Ghiordanescu IM,Popp C,Bumbacea D, Allergic Bronchopulmonary Aspergillosis Associated With Eosinophilic Gastroenteritis. Journal of investigational allergology     [PubMed PMID: 26727774]
[50] Ishii H,Konuma T,Kato S,Ota Y,Tojo A,Takahashi S, Eosinophilic gastroenteritis after allogeneic bone marrow transplantation. Annals of hematology. 2015 Aug;     [PubMed PMID: 25913480]
[51] Choi W,Park SY,Choi C,Cho K,Park CH,Kim HS,Choi SK,Rew JS, Eosinophilic gastroenteritis due to rhus ingestion presenting with gastrointestinal hemorrhage. Clinical endoscopy. 2015 Mar;     [PubMed PMID: 25844348]
[52] Lecouffe-Desprets M,Groh M,Bour B,Le Jeunne C,Puéchal X, Eosinophilic gastrointestinal disorder preceding Sjögren's syndrome. Joint, bone, spine : revue du rhumatisme. 2017 Jan     [PubMed PMID: 27131745]
[53] Han SG,Chen Y,Qian ZH,Yang L,Yu RS,Zhu XL,Li QH,Chen Q, Eosinophilic gastroenteritis associated with eosinophilic cystitis: Computed tomography and magnetic resonance imaging findings. World journal of gastroenterology. 2015 Mar 14;     [PubMed PMID: 25780317]
[54] Song DJ,Shim MH,Lee N,Yoo Y,Choung JT, CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in a Mouse Model of Eosinophilic Gastroenteritis. Allergy, asthma     [PubMed PMID: 28497923]
[55] Zevit N,Furuta GT, Eosinophilic Gastroenteritis and Colitis: Not Yet Ready for the Big Leagues. Journal of pediatric gastroenterology and nutrition. 2018 Jul;     [PubMed PMID: 29620603]
[56] Steinbach EC,Hernandez M,Dellon ES, Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach to Diagnosis and Management. The journal of allergy and clinical immunology. In practice. 2018 Sep - Oct     [PubMed PMID: 30201096]