Eosinophilic gastroenteritis

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Eosinophilic gastroenteritis
Eos gastroen.jpg
H&E Stain: Dense Eosinophilic infiltration of gastro-duodenal wall
ICD-10 K52.8
ICD-9 558.3
DiseasesDB 32555
eMedicine med/688 

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Fatimo Biobaku M.B.B.S [2]

Synonyms and Keywords: Eosinophilic esophagitis; eosinophilic gastritis; Eosinophilic enteritis; Eosinophilic colitis; Eosinophilic proctocolitis, Eosinophilic gastrointestinal disorders

Overview

Eosinophilic gastroenteritis is a rare, heterogenous disorder characterized by localized patchy or diffuse eosinophilic infiltration of the gastrointestinal tract.[1] Most of the data available in the literature are based on few documented case reports/case series. The presentation of eosinophilic gastroenteritis may vary depending on the location, depth and extent of bowel wall involvement.[2][1][3] The cause of eosinophilic gastroenteritis is idiopathic although there is a significant association with allergy.[2][1] Non-specific gastrointestinal symptoms such as episodic abdominal pain, vomiting and diarrhea are common. Eosinophilic gastroenteritis is a diagnosis of exclusion and other causes of GIT symptoms with gastrointestinal tissue eosinophilia must be ruled out.[2] Biopsy of the GIT is the primary diagnostic modality. The mainstay of treatment is corticosteroid therapy. Majority of patients respond well to treatment but the disease may run a chronic relapsing course.[4][2]

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] Klein et al. subsequently classified it into three types (predominant mucosal, muscular, and subserosal layer disease) based on the depth of eosinophilic infiltration.[7]

Classification

Eosinophilic gastroenteritis can be subdivided into three groups according to the Klein classification:[4][8][1][3][2]

  • Mucosal eosinophilic gastroenteritis
  1. Most common subtype of eosinophilic gastroenteritis.
  2. Mucosal infiltration by eosinophils, and/or presence of mucosal edema on barium studies.
  3. Absent histological evidence of muscle infiltration.
  4. 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. Presence of eosinophilic ascites (may occasionally progress to an eosinophilic pleural effusion)

Causes

The cause of eosinophilic gastroenteritis is unknown.[1]

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

Pathogenesis

  • Eosinophilic gastroenteritis is a rare disease with poorly understood pathophysiology.
  • Eosinophils are normally seen in the entire GIT (except in the esophagus) of healthy individuals.[2]
  • In patients with eosinophilic gastroenteritis, there is varying degrees of increased eosinophilic infiltration of the GIT (in the absence of other known causes of tissue eosinophilia).[6][2]
  • Any part of the GIT from the esophagus to the colon can be affected. Occasionally, eosinophilic gastroenteritis affects the entire gastrointestinal tract.[8] The stomach and proximal small intestine are most commonly affected, while the colon is usually the least affected part of the GIT.[6][8][2]
  • 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][9]
  • Inflammatory mediators such as Th-2 cytokines (IL-3, IL-5, GM-CSF and IL-13), monocyte generating chemokines such as IL-8, monocyte chemotactic proteins, mast cells, granulocytes, eosinophils, and eosinophilic mediators such as eotaxin have been strongly implicated.[6][2][1]
  • The inflammatory mediators associated with the pathogenesis of eosinophilic gastroenteritis have well established roles in the pathogenesis of allergy and asthma. A significant number of patients with eosinophilic gastroenteritis have also been documented to have allergies/allergy-related disorders, suggesting a hypersensitivity reaction is involved in the pathogenesis of eosinophilic gastroenteritis.[6][1]

Differentiating Eosinophilic gastroenteritis from Other Diseases

Diseases with peripheral eosinophilia and gastrointestinal symptoms should be differentiated from eosinophilic gastroenteritis. It is also important to consider eosinophilic gastroenteritis in the differential diagnosis of unexplained gastrointestinal symptoms (even when peripheral eosinophilia is not present). Most diseases that can manifest with gastrointestinal symptoms and peripheral eosinophilia are easily differentiated from eosinophilic gastroenteritis via detailed history taking, laboratory investigations, and histologic examination of endoscopic biopsies.[1][2] Some of these diseases include:[1][2][10][11]

Epidemiology and Demographics

Incidence

The estimated incidence of eosinophilic gastroenteritis is approximately 1-20 per 100,000 patients.[6][2] It is a rare disease with approximately 300 reported cases in published literature.[1]

Age

Eosinophilic gastroenteritis can present at any age.[1] However, a higher incidence has been observed in the third to fifth decade of life.[2][4] In pediatric patients with eosinophilic gastroenteritis, the esophagus is usually the involved organ (eosinophilic esophagitis).[6] The youngest documented pediatric case of eosinophilic gastroenteritis occurred in a full-term 10month old infant.[6]

Sex

There is a slightly higher incidence in adult males.[1]

Race

Eosinophilic gastroenteritis has been documented in all races.[21] However, most of the cases reported occurred in Caucasians.[1]

Screening

There is no screening guideline for eosinophilic gastroenteritis.

Natural History, Complications, and Prognosis

Natural History

Eosinophilic gastroenteritis is an idiopathic disease. A history of allergy/allergy-related disorders have been documented in a significant number of patients with the disease.[1]

Complications

Complications of eosinophilic gastroenteritis can include the following:[8][5][22][3][2][23]

Prognosis

The prognosis is good with treatment but relapses are common, which may necessitate chronic low dose steroid therapy for maintenance of remission.[2][3] If eosinophilic gastroenteritis is left untreated, patients may develop severe malabsorption and malnutrition. Spontaneous remission can also occur.[1]

Diagnosis

History and Symptoms

History

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

Symptoms

Eosinophilic gastroenteritis can present with several nonspecific gastrointestinal symptoms. The manifestations often depend on the site affected in the GIT, and the involved layer of the gastrointestinal wall.[2][1][3] The following are the gastrointestinal symptoms seen in eosinophilic gastroenteritis:[8][9][6][1][3][24][5]

Common symptoms


Uncommon symptoms

Physical Examination

The physical examination findings in eosinophilic gastroenteritis are non-specific, and are mostly dependent on the site and depth of bowel involvement. The following findings may be present:[2][24]

HEENT

Gastrointestinal system

Skin

Eczema may be seen in patients with atopy.

Laboratory Findings

The following laboratory findings can be seen:[8][2]

  • 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. Anemia can also be present (iron deficiency anemia is a frequent finding).
  • Elevated serum IgE is a common finding.
  • Elevated ESR: This can be moderately elevated in 25% of patients with eosinophilic gastroenteritis.
  • Hypoalbuminemia: This can occur as a result of severe malabsorption and protein losing enteropathy.
  • Fecal fat test: Mild-moderate steatorrhea is sometimes seen.
  • Stool α-1 antitrypsin clearance: For assessment of fecal protein loss.
  • Allergy testing: Tests such as skin-prick and RAST testing may be done when specific food and environmental allergies are strongly suspected as triggers for the disease.

Microscopic Findings

Eosinophilic gastroenteritis is a diagnosis of exclusion. There are no well standardized pathologic criteria for making a diagnosis of eosinophilic gastroenteritis. There are three widely utilized diagnostic criteria:[2][8]

  1. Presence of gastrointestinal symptoms
  2. Biopsy demonstrating eosinophilic infiltration of one or more areas of the GIT (from the esophagus to colon)
  3. Exclusion of other causes of tissue eosinophilia.

Biopsy

  • Biopsy is widely used for making a diagnosis. In the absence of other causes of tissue eosinophilia, eosinophilic infiltration of the GIT on biopsy and/or the presence of eosinophilic ascitic fluid in a patient with gastrointestinal symptoms is diagnostic for eosinophilic gastroenteritis.[6]
  • The diagnosis can occasionally be missed, especially in patients with the localized patchy infiltration. Multiple biopsy samples throughout the GIT (including visually normal areas) should be taken.[2]
Endoscopic biopsy of ileum showing distinct eosinophilic infiltration

Paracentesis

  • In cases of suspected eosinophilic ascites, it is important to perform a diagnostic paracentesis.[2]

Imaging Findings

Radiological studies are of limited diagnostic value in patients with eosinophilic gastroenteritis. The findings on imaging are often variable and non-specific. Imaging studies may reveal the following:[6][25][8][26][27]

Ultrasonography

CT scan

Barium studies

Endoscopy

  • Normal appearance of the GIT.
  • Gross findings such as gastric pseudopolyps.
  • Other non-specific findings such as mucosal erythema, friability, and fine granularity in the stomach may be seen. Mucosal ulcerations/erosions, thickening of gastric mucosal folds and mucosal nodules or whitish specks are sometimes seen.

Tc-99m hexamethylpropyleneamine oxime(HMPAO) scintigraphy scanning

  • Radionuclide scan using Tc-99m HMPAO-labeled leukocyte SPECT may be useful for assessing the extent of disease and the response to treatment
  • It cannot differentiate eosinophilic gastroenteritis from other causes of GIT inflammation, hence, it is not a diagnostic test.

Treatment

There are no guidelines/definitive consensus for the management of eosinophilic gastroenteritis, and the treatment is usually based on the severity of the disease. Steroids are widely recognized as the mainstay of treatment for eosinophilic gastroenteritis. Chronic relapses frequently occur and continued maintenance on low dose steroid therapy may be necessary.[2][3]

Medical Therapy

The medical management of eosinophilic gastroenteritis entails the following:[8][2][28][25][6][29]

Preferred therapy

  1. Elimination of identified food allergies from the diet.
  2. Introduction of elemental diets.

Alternate therapy

These medications can be used alone or in combination with steroids for treatment and/or maintenance therapy.

Surgical Therapy

There are no indications for surgery in the primary management of eosinophilic gastroenteritis. However, surgical management may be required when complications such as intestinal perforation or severe gastric outlet obstruction occurs.

Prevention

There are no guidelines for the prevention of eosinophilic gastroenteritis. Elimination of identified triggers such as food allergies may be beneficial.[29]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 Baig MA, Qadir A, Rasheed J (2006). "A review of eosinophilic gastroenteritis". J Natl Med Assoc. 98 (10): 1616–9. PMC 2569760. PMID 17052051.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 Uppal V, Kreiger P, Kutsch E (2016). "Eosinophilic Gastroenteritis and Colitis: a Comprehensive Review". Clin Rev Allergy Immunol. 50 (2): 175–88. doi:10.1007/s12016-015-8489-4. PMID 26054822.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 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.
  4. 4.0 4.1 4.2 Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH (1970). "Eosinophilic gastroenteritis". Medicine (Baltimore). 49 (4): 299–319. PMID 5426746.
  5. 5.0 5.1 5.2 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. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 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.
  7. Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH (1970). "Eosinophilic gastroenteritis". Medicine (Baltimore). 49 (4): 299–319. PMID 5426746.
  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 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. 9.0 9.1 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).
  10. 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.
  11. Barbie DA, Mangi AA, Lauwers GY (2004). "Eosinophilic gastroenteritis associated with systemic lupus erythematosus". J Clin Gastroenterol. 38 (10): 883–6. PMID 15492606.
  12. Shakeer VK, Devi SR, Chettupuzha AP, Mustafa CP, Sandesh K, Kumar SK; et al. (2002). "Carbamazepine-induced eosinophilic enteritis". Indian J Gastroenterol. 21 (3): 114–5. PMID 12118924.
  13. Lange P, Oun H, Fuller S, Turney JH (1994). "Eosinophilic colitis due to rifampicin". Lancet. 344 (8932): 1296–7. PMID 7968003.
  14. Jiménez-Sáenz M, González-Cámpora R, Linares-Santiago E, Herrerías-Gutiérrez JM (2006). "Bleeding colonic ulcer and eosinophilic colitis: a rare complication of nonsteroidal anti-inflammatory drugs". J Clin Gastroenterol. 40 (1): 84–5. PMID 16340639.
  15. Bridges AJ, Marshall JB, Diaz-Arias AA (1990). "Acute eosinophilic colitis and hypersensitivity reaction associated with naproxen therapy". Am J Med. 89 (4): 526–7. PMID 2220886.
  16. Kakumitsu S, Shijo H, Akiyoshi N, Seo M, Okada M (2000). "Eosinophilic enteritis observed during alpha-interferon therapy for chronic hepatitis C." J Gastroenterol. 35 (7): 548–51. PMID 10905364.
  17. Lee JY, Medellin MV, Tumpkin C (2000). "Allergic reaction to gemfibrozil manifesting as eosinophilic gastroenteritis". South Med J. 93 (8): 807–8. PMID 10963515.
  18. Ravi S, Holubka J, Veneri R, Youn K, Khatib R (1993). "Clofazimine-induced eosinophilic gastroenteritis in AIDS". Am J Gastroenterol. 88 (4): 612–3. PMID 8470652.
  19. Barak N, Hart J, Sitrin MD (2001). "Enalapril-induced eosinophilic gastroenteritis". J Clin Gastroenterol. 33 (2): 157–8. PMID 11468446.
  20. Saeed SA, Integlia MJ, Pleskow RG, Calenda KA, Rohrer RJ, Dayal Y; et al. (2006). "Tacrolimus-associated eosinophilic gastroenterocolitis in pediatric liver transplant recipients: role of potential food allergies in pathogenesis". Pediatr Transplant. 10 (6): 730–5. doi:10.1111/j.1399-3046.2006.00538.x. PMID 16911498.
  21. Guandalini, Stefano (2004). Essential Pediatric Gastroenterology and Nutrition. City: McGraw-Hill Professional. ISBN 0071416307. Page 210.
  22. 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  12757181 Check |pmid= value (help).
  23. 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.
  24. 24.0 24.1 24.2 Tien FM, Wu JF, Jeng YM, Hsu HY, Ni YH, Chang MH; et al. (2011). "Clinical features and treatment responses of children with eosinophilic gastroenteritis". Pediatr Neonatol. 52 (5): 272–8. doi:10.1016/j.pedneo.2011.06.006. PMID 22036223.
  25. 25.0 25.1 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.
  26. 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". Ann Nucl Med. 17 (7): 601–3. PMID 14651361.
  27. Lee KJ, Hahm KB, Kim YS, Kim JH, Cho SW, Jie H; et al. (1997). "The usefulness of Tc-99m HMPAO labeled WBC SPECT in eosinophilic gastroenteritis". Clin Nucl Med. 22 (8): 536–41. PMID 9262899.
  28. 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.
  29. 29.0 29.1 Yanagimoto Y, Taniuchi S, Ishizaki Y, Nakano K, Hosaka N, Kaneko K (2017). "Eosinophilic gastroenteritis caused by eating hens' eggs: A case report". Allergol Int. doi:10.1016/j.alit.2017.02.007. PMID 28279648.
  30. Shirai T, Hashimoto D, Suzuki K, Osawa S, Aonahata M, Chida K; et al. (2001). "Successful treatment of eosinophilic gastroenteritis with suplatast tosilate". J Allergy Clin Immunol. 107 (5): 924–5. PMID 11344364.




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