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Overview

Eosinophilic gastroenteritis (EG) is a rare disorder characterized by localized patchy or diffuse eosinophilic infiltration of the gastrointestinal (GI) tissue. The presentation may vary depending on the location, depth and extent of bowel wall involvement. It usually runs a chronic relapsing course.[1][2][3][4]

Historical Perspective

The first description of eosinophilic gastroenteritis was by Kaijser et al. in 1937, and it was described as an allergic disease of the gut.[5][6][7]

Classification

Eosinophilic gastroenteritis can be subdivided into three groups according to the Klein classification:[8][6][9]

  • Mucosal eosinophilic gastroenteritis
  1. Mucosal infiltration by eosinophils, and/or presence of mucosal edema on barium studies.
  2. Absent histological evidence of muscle infiltration.
  3. No evidence of gastrointestinal obstruction or eosinophilic ascites.
  • Muscular eosinophilic gastroenteritis
  1. Documentation of complete/incomplete bowel obstruction, and/or infiltration of the tunica muscularis by eosinophils.
  2. No evidence of eosinophilic ascites.
  • Subserosal eosinophilic gastroenteritis
  1. Eosinophilic infiltration of the gut
  2. Eosinophilic ascites is present

Risk Factors

  • Allergy: A study conducted in 40 patients with eosinophilic gastroenteritis demonstrated a history of allergy in half of the patients.[8] Food intolerance or allergy is more commonly seen in mucosal eosinophilic gastroenteritis, affecting over 50% of patients with mucosal disease according to a study.[8]

Pathophysiology

Eosinophilic gastroenteritis is a rare disease with poorly understood pathophysiology. Varying degrees of eosinophilic infiltration of the GIT is seen in the absence of other known causes of tissue eosinophilia.[7] It can affect any part of the GIT from the esophagus to the colon, occasionally affecting the entire GIT.[8] The etiology of the excessive eosinophilic infiltration of the GIT is not clear. Destruction of the GIT epithelium caused by the release of eosinophilic basic protein and activated degranulating eosinophils has been proposed.[8][10]





The damage to the gastrointestinal tract wall is caused by eosinophilic infiltration and degranulation.[10] As a part of thehost defense mechanism, eosinophil is normally present in gastrointestinal mucosa, though finding in deeper tissue is almost always pathologic.[11] What triggers such dense infiltration in EG is not clear. It is possible that different pathogenetic mechanisms of disease is involved in several subgroups of patients. Food allergy and variable IgE response to food substances has been observed in some patients which implies role of hypersensitive response in pathogenesis. Many patients indeed have history of other atopic conditions like eczema, asthma etc. Eosinophil recruitment into inflammatory tissue is a complex process, regulated by a number of inflammatory cytokines. In EG cytokines IL-3, IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF) may be behind the recruitement and activation. They have been observed immunohistochemically in diseased intestinal wall.[12] In addition eotaxin has been shown to have an integral role in regulating the homing of eosinophils into the lamina propria of stomach and small intestine.[13] In the allergic subtype of disease, it is thought that food allergens cross the intestinal mucosa and trigger an inflammatory response that includes mast cell degranulation and recruitment of eosinophils.[14]

Causes

The cause of eosinophilic gastroenteritis is unknown.[6]

Differentiating Sandbox:FB from Other Diseases

It is important to consider eosinophilic gastroenteritis in the differential diagnosis of unexplained gastrointestinal symptoms (even when peripheral eosinophilia is not present).

Epidemiology and Demographics

Incidence

The incidence rate differs between studies, as eosinophilic gastroenteritis is a rare disease.[6] The number of reported cases of EG are small, with approximately 300 EG cases reported in published literature. Serous membrane|Subserosal]] EG has an incidence rate of 4.5 % to 9 % in Japan, and 13 % in the USA.[15]

Age

EG can present at any age.[6] Earlier studies showed a higher incidence in the third to fifth decade of life.[1] In pediatric patients with eosinophilic gastroenteritis, the esophagus is usually the involved organ (eosinophilic esophagitis).[7] The youngest documented pediatric case of eosinophilic gastroenteritis occurred in a full-term 10month old infant.[7]

Sex

There is a slightly higher incidence in males.[16]

Race

Eosinophilic gastroenteritis has been documented in all races.[17]

Screening

Natural History, Complications, and Prognosis

Natural History

Complications

Complications of eosinophilic gastroenteritis can include the following:[8]

  • Pyloric outlet obstruction: This is more commonly seen in patients with muscular eosinophilic gastroenteritis, and surgical intervention is often required in severe cases.
  • Esophageal narrowing: This can be seen when there is esophageal involvement.

Prognosis

Diagnosis

Three diagnostic criteria are widely used for the diagnosis of eosinophilic gastroenteritis:[8]

  1. Presence of gastrointestinal symptoms
  2. Biopsy demonstrating eosinophilic infiltration of one or more areas of the GIT (from the esophagus to colon); OR characteristic radiological findings with peripheral eosinophilia (peripheral eosinophilia is not a universal finding).
  3. No evidence of parasitic or extraintestinal disease.

Hypereosinophilia, the hallmark of allergic response, may be absent in up to 20% of patients, but hypoalbuminaemia and other abnormalities suggestive of malabsorption may be present.

CT scan may show nodular and irregular thickening of the folds in the distal stomach and proximal small bowel, but these findings can also be present in other conditions like Crohn's disease and lymphoma.

The endoscopic appearance in eosinophilic gastroenteritis is nonspecific; it includes erythematous, friable, nodular, and occasional ulcerative changes.[18] Sometimes diffuse inflammation results in complete loss of villi, involvement of multiple layers, submucosal oedema and fibrosis.[19][20]

Definitive diagnosis involves histological evidence of eosinophilic infiltration in biopsy slides. Microscopy reveals >20 eosinophils per high power field.[8][6] Infiltration is often patchy , can be missed and laparoscopic full thickness biopsy may be required.

Radio isotope scan using Tc-99m HMPAO-labeled leukocyte SPECT may be useful in assessing the extent of disease and response to treatment but has little value in diagnosis, as the scan does not help differentiating EG from other causes of inflammation.[21][22]

When eosinophilic gastroenteritis is observed in association with eosinophilic infiltration of other organ systems, the diagnosis of idiopathic hypereosinophilic syndrome should be considered.[23]

History and Symptoms

History

It is important to obtain the following history from the patient:[8]

  • Presenting symptoms
  • Duration of symptoms
  • History of allergy: A history of food allergy/intolerance, drug allergy, allergy-related conditions such as atopy, asthma, allergic rhinitis and nasal polyps should be obtained.

Symptoms

The following are the gastrointestinal symptoms seen in eosinophilic gastroenteritis:[8][10][7]

Common symptoms

  • Abdominal pain
  • Nausea
  • Vomiting
  • Poor appetite
  • Weight loss
  • Diarrhea
  • Steatorrhea
  • Abdominal bloating: More often seen in patients with subserosal disease.
  • Ascites: Seen more often in patients with subserosal disease.

Uncommon symptoms

  • Dysphagia: This has been documented in patients with esophageal involvement.
  • Hematemesis


EG typically presents with a combination of chronic nonspecific GI symptoms which include abdominal pain, nausea, vomiting, diarrhea, weight loss, and abdominal distension. Approximately 80% have symptoms for several years.[24]; a high degree of clinical suspicion is often required to establish the diagnosis, as the disease is extremely rare. Occasionally, the disease may manifest itself as an acute abdomen or bowel obstruction.[25][26]

Physical Examination

Laboratory Findings

The following laboratory findings can be seen:[8]

  • CBC: Peripheral blood eosinophilia is often seen, but it may be absent in >20% of affected patients. Patients with subserosal disease often have a higher eosinophil count.
  • Elevated serum IgE is a common finding.
  • Elevated ESR: This can be moderately elevated in 25% of patients with eosinophilic gastroenteritis.

Microscopic Findings

Biopsy of the GIT[8]

  • Eosinophilic infiltration of the gastrointestinal tract is seen on histology following endoscopic/surgical biopsies. Abnormal eosinophilic infiltration of the GIT can be defined as the presence of diffuse or multifocal eosinophils ≥20 per high power field.
  • The diagnosis can occasionally be missed, especially in patients with the localized patchy infiltration.

Imaging Findings

Imaging studies such as a CT scan is essential, especially when biopsy studies are not diagnostic.[8] Radiological changes in the gastrointestinal tract such as very prominent bowel folds, in conjunction with a clinical history suggestive of eosinophilic gastroenteritis, and laboratory findings of peripheral eosinophilia, is sufficient for the diagnosis of eosinophilic gastroenteritis when biopsy findings are not diagnostic.[8]

CT scan

Spiral CT showing ascites and concentric thickening of colon and ileum in eosinophilic gastroenteritis
Spiral CT showing ascites and concentric thickening of colon and ileum in eosinophilic gastroenteritis

Treatment

Medical Therapy

  • Steroids are the mainstay of therapy for eosinophilic gastroenteritis. A dramatic response to corticosteroid therapy is commonly seen in patients with subserosal disease.[8] A 90% response rate to corticosteroid therapy has been documented in some studies.[30]
  1. Elimination of identified food allergy.


  • Corticosteroids are the mainstay of therapy with a 90% response rate in some studies. Appropriate duration of steroid treatment is unknown and relapse often necessitates long term treatment. Various steroid sparing agents e.g. sodium cromoglycate (a stabilizer of mast cell membranes), ketotifen (an antihistamine), and montelukast (a selective, competitive leukotriene receptor antagonist) have been proposed, centering around an allergic hypothesis, with mixed results.[30] An elimination diet may be successful if a limited number of food allergies are identified.[31][18]

Surgery

Prevention

Other gastrointestinal conditions associated with allergy

See also

Allergy
Gastroenteritis
Malabsorption

References

  1. 1.0 1.1 Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH (1970). "Eosinophilic gastroenteritis". Medicine (Baltimore). 49 (4): 299–319. PMID 5426746.
  2. Treiber GG, Weidner S (2007). "Eosinophilic gastroenteritis". Clin Gastroenterol Hepatol. 5 (5): e16. doi:10.1016/j.cgh.2007.01.011. PMID 17428742.
  3. Christopher V, Thompson MH, Hughes S (2002). "Eosinophilic gastroenteritis mimicking pancreatic cancer". Postgrad Med J. 78 (922): 498–9. PMC 1742453. PMID 12185230.
  4. Jimenez-Saenz M, Villar-Rodriguez JL, Torres Y, Carmona I, Salas-Herrero E, Gonzalez-Vilches J; et al. (2003). "Biliary tract disease: a rare manifestation of eosinophilic gastroenteritis". Dig Dis Sci. 48 (3): 624–7. PMID 12757181.
  5. Whitaker IS, Gulati A, McDaid JO, Bugajska-Carr U, Arends MJ (2004). "Eosinophilic gastroenteritis presenting as obstructive jaundice". Eur J Gastroenterol Hepatol. 16 (4): 407–9. PMID 15028974.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Whitaker IS, Gulati A, McDaid JO, Bugajska-Carr U, Arends MJ (2004). "Eosinophilic gastroenteritis presenting as obstructive jaundice". Eur J Gastroenterol Hepatol. 16 (4): 407–9. PMID 15028974.
  7. 7.0 7.1 7.2 7.3 7.4 Shetty V, Daniel KE, Kesavan A (2017). "Hematemesis as Initial Presentation in a 10-Week-Old Infant with Eosinophilic Gastroenteritis". Case Rep Pediatr. 2017: 2391417. doi:10.1155/2017/2391417. PMC 5337357. PMID 28299223.
  8. 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR (1990). "Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues". Gut. 31 (1): 54–8. PMC 1378340. PMID 2318432  2318432 Check |pmid= value (help).
  9. Lee CM, Changchien CS, Chen PC, Lin DY, Sheen IS, Wang CS; et al. (1993). "Eosinophilic gastroenteritis: 10 years experience". Am J Gastroenterol. 88 (1): 70–4. PMID 8420276.
  10. 10.0 10.1 10.2 Tan AC, Kruimel JW, Naber TH (2001). "Eosinophilic gastroenteritis treated with non-enteric-coated budesonide tablets". Eur J Gastroenterol Hepatol. 13 (4): 425–7. PMID 11338074  11338074 Check |pmid= value (help).
  11. Blackshaw AJ, Levison DA (1986). "Eosinophilic infiltrates of the gastrointestinal tract". J Clin Pathol. 39 (1): 1–7. PMC 499605. PMID 2869055  2869055 Check |pmid= value (help).
  12. Desreumaux P, Bloget F, Seguy D, Capron M, Cortot A, Colombel J, Janin A (1996). "Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis". Gastroenterology. 110 (3): 768–74. PMID 8608886.
  13. Mishra A, Hogan S, Brandt E, Rothenberg M (2001). "An etiological role for aeroallergens and eosinophils in experimental esophagitis". J. Clin. Invest. 107 (1): 83–90. PMID 11134183.
  14. Pérez-Millán A, Martín-Lorente J, López-Morante A, Yuguero L, Sáez-Royuela F (1997). "Subserosal eosinophilic gastroenteritis treated efficaciously with sodium cromoglycate". Dig. Dis. Sci. 42 (2): 342–4. PMID 9052516.
  15. Miyamoto T, Shibata T, Matsuura S, Kagesawa M, Ishizawa Y, Tamiya K (1996). "Eosinophilic gastroenteritis with ileus and ascites". Intern. Med. 35 (10): 779–82. PMID 8933185.)
  16. Guandalini, Stefano (2004). Essential Pediatric Gastroenterology and Nutrition. City: McGraw-Hill Professional. ISBN 0071416307. Page 210.
  17. Guandalini, Stefano (2004). Essential Pediatric Gastroenterology and Nutrition. City: McGraw-Hill Professional. ISBN 0071416307. Page 210.
  18. 18.0 18.1 18.2 Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE (2003). "Eosinophilic gastroenteritis: clinical experience with 15 patients". World J Gastroenterol. 9 (12): 2813–6. PMC 4612059. PMID 14669340.
  19. Johnstone J, Morson B (1978). "Eosinophilic gastroenteritis". Histopathology. 2 (5): 335–48. PMID 363591.
  20. Katz A, Goldman H, Grand R (1977). "Gastric mucosal biopsy in eosinophilic (allergic) gastroenteritis". Gastroenterology. 73 (4 Pt 1): 705–9. PMID 892374.
  21. Lee K, Hahm K, Kim Y, Kim J, Cho S, Jie H, Park C, Yim H (1997). "The usefulness of Tc-99m HMPAO labeled WBC SPECT in eosinophilic gastroenteritis". Clinical nuclear medicine. 22 (8): 536–41. PMID 9262899.
  22. Imai E, Kaminaga T, Kawasugi K, Yokokawa T, Furui S (2003). "The usefulness of 99mTc-hexamethylpropyleneamineoxime white blood cell scintigraphy in a patient with eosinophilic gastroenteritis". Annals of nuclear medicine. 17 (7): 601–3. PMID 14651361.
  23. Matsushita M, Hajiro K, Morita Y, Takakuwa H, Suzaki T (1995). "Eosinophilic gastroenteritis involving the entire digestive tract". Am. J. Gastroenterol. 90 (10): 1868–70. PMID 7572911.
  24. Christopher V, Thompson M, Hughes S (2002). "Eosinophilic gastroenteritis mimicking pancreatic cancer". Postgraduate medical journal. 78 (922): 498–9. PMID 12185230.
  25. Shweiki E, West J, Klena J, Kelley S, Colley A, Bross R, Tyler W (1999). "Eosinophilic gastroenteritis presenting as an obstructing cecal mass--a case report and review of the literature". Am. J. Gastroenterol. 94 (12): 3644–5. PMID 10606337.
  26. Tran D, Salloum L, Tshibaka C, Moser R (2000). "Eosinophilic gastroenteritis mimicking acute appendicitis". The American surgeon. 66 (10): 990–2. PMID 11261632.
  27. Lee C, Changchien C, Chen P, Lin D, Sheen I, Wang C, Tai D, Sheen-Chen S, Chen W, Wu C (1993). "Eosinophilic gastroenteritis: 10 years experience". Am. J. Gastroenterol. 88 (1): 70–4. PMID 8420276.
  28. Miyamoto T, Shibata T, Matsuura S, Kagesawa M, Ishizawa Y, Tamiya K (1996). "Eosinophilic gastroenteritis with ileus and ascites". Intern. Med. 35 (10): 779–82. PMID 8933185.)
  29. Lyngbaek S, Adamsen S, Aru A, Bergenfeldt M (2006). "Recurrent acute pancreatitis due to eosinophilic gastroenteritis. Case report and literature review". JOP. 7 (2): 211–7. PMID 16525206.
  30. 30.0 30.1 30.2 Barbie DA, Mangi AA, Lauwers GY (2004). "Eosinophilic gastroenteritis associated with systemic lupus erythematosus". J Clin Gastroenterol. 38 (10): 883–6. PMID 15492606.
  31. 31.0 31.1 Katz AJ, Twarog FJ, Zeiger RS, Falchuk ZM (1984). "Milk-sensitive and eosinophilic gastroenteropathy: similar clinical features with contrasting mechanisms and clinical course". J Allergy Clin Immunol. 74 (1): 72–8. PMID 6547462.


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