Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis

Publication Date: January 30, 2024
Last Updated: February 16, 2024

Summary of Statements

1. The presenting symptoms of non-EoE EGIDs depend on the GI segment involved, the extent of eosinophilic inflammation within the GI tract and the depth of inflammation through the bowel wall (See Table 3).

2. The described symptoms and signs are not specific for non-EoE EGIDs, and detailed alternative conditions should be considered before the confirmation of the diagnosis.

3. Presently no validated symptoms severity assessment tools exist thus making correlation of symptoms with severity of eosinophilic inflammation inconclusive.

4. Studies assessing the impact of non-EoE EGIDs on quality of life of children and their families are lacking.

5. Peripheral eosinophilia may occur in patients with non-EoE EGIDs but is neither a specific nor a sensitive indicator for non-EoE EGIDs.

6. The available data do not allow conclusions to be drawn regarding the use of peripheral eosinophilia as a marker for the resolution of tissue inflammation.

7. There is lack of evidence on the usefulness of fecal calprotectin for diagnosing or monitoring non-EoE EGIDs.

8. Various non-specific endoscopic findings have been described in patients with EoG/EoN, (See Table 4).

9. In many patients with EoG/EoN, the GI mucosa looks macroscopically normal.

10. In patients with EoC, the colonoscopy findings include mucosal nodularity, oedema and mucosal friability but many patients may have normal macroscopic appearance of the colonic mucosa.

11. Imaging studies such as abdominal ultrasound, computed tomography, magnetic resonance imaging and contrast series do not directly contribute to the diagnosis of non-EoE EGIDs.

12. Imaging studies such as abdominal ultrasound, computed tomography, magnetic resonance imaging and contrast series give important additional information about the depth of inflammation through the bowel wall (muscular, serosal layers), the extent of involvement, and the presence of complications.

13. Complete blood count with differential, hemoglobin, ferritin, serum albumin, immunoglobulin G concentrations and total immunoglobulin E levels may be abnormal in selected patients with non-EoE EGIDs, but these abnormalities are not specific for non-EoE EGIDs and may be secondary to other diseases that need to be excluded.

14. Assessment of complete blood count with differential, hemoglobin, ferritin, serum albumin and immunoglobulin G as well as fecal a1-antitrypsin concentrations may be helpful to monitor non-EoE EGIDs response to treatment if they were abnormal at diagnosis.

15. When analyzing ascitic fluid, a predominance of eosinophils amongst inflammatory cells is highly suggestive of the serosal form of non-EoE EGIDs.

16. A paucity of studies have investigated the eosinophilic infiltration of the GI mucosa in children with no organic diseases reporting the area of high- power field (See Table 5).

17. Non-EoE EGIDs are clinico-pathological entities, therefore, histology alone is not enough to diagnose them without compatible symptoms and signs.

18. Some pathologic features are not normally associated with non-EoE EGIDs but do not necessarily rule out that diagnosis. Such features include acute neutrophilic inflammation, neutrophilic glandulitis/cryptitis and granulomas that are characteristic of inflammatory bowel disease but may be also seen in biopsies taken from non-EoE EGIDs-related ulcers/erosions or from patients with parasitic infection.

19. Histological features in favor of non-EoE EGIDs in the presence of eosinophilic infiltration of the GI mucosa are eosinophil glandulitis/cryptitis, eosinophils in muscularis mucosa/submucosa, fibrosis/fibroplasia of the lamina propria, degranulation of eosinophils and lymphoid aggregates (See Table 7). However, the diagnostic/prognostic value of these ancillary findings remains unclear.

20. In the presence of eosinophilic infiltration of the GI mucosa, the presence of signs of chronicity (such as atrophy, fibrosis and smooth muscle hyperplasia in the stomach and duodenum and architectural abnormalities such as villous blunting in the small intestine, and crypt elongation/branching/distortion in the small and large intestines) are helpful features to confirm the histological part of the diagnosis, especially if the endoscopic appearance is normal.

21. Differential diagnosis of eosinophilic inflammation of the GI tract occurring as segmental disease or as part of more diffuse involvement of the GI tract, includes a wide range of conditions (See Table 8).


22. The initial evaluation of a patient with mucosal eosinophilia depends on the presenting symptoms, history, physical examination, laboratory findings as well as the involved GI segment(s) and may include a combination of tests (See Table 9).

23. In limited numbers of case series, systemic oral steroids have been effective in inducing clinical and histological remission in non-EoE EGIDs.

24. There are no data on the selection criteria of which patients with non-EoE EGIDs should be treated with oral steroids, nor on the optimal dose or duration of treatment.

25. Elimination diets may induce clinical improvement or remission in a proportion of children with non-EoE EGIDs but there are very limited data on histological response.

26. There is insufficient data on which foods should be eliminated, but case series suggest that avoidance of cow's milk may be effective in some children.

27. There is no evidence to support the use of IgE-based food allergy tests to guide dietary restriction therapy.

28. Evidence supporting the use of proton pump inhibitors or H2 receptor antagonists in the treatment of children with EoG/EoD is lacking.

29. Limited number of case series describe the use of endoscopic dilation to manage partial obstruction in adults with non-EoE EGIDs.

30. Surgical intervention is used for non-EoE EGIDs-related clinically significant bowel obstruction that does not respond to treatment with systemic steroids, whereas pyloromyotomy has rarely been shown to be effective in children with EoG and associated pyloric stenosis.

31. Combination therapy has been used in a proportion of patients with non-EoE EGIDs with variable effects.

32. There is lack of randomised controlled trials assessing the efficacy of the available treatment options of non-EoE EGIDs.

33. Treatment with systemic steroids at appropriate doses followed by timely tapering is an effective initial approach to the treatment of most patients with non-EoE EGIDs.

34. There are no studies that have examined the role of maintenance treatment in patients with non-EoE EGIDs.

Summary of Recommendations

1. We recommend the term Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) to describe chronic inflammatory disorders of the gastrointestinal (GI) tract beyond the esophagus characterized clinically by the presence of gastrointestinal symptoms and histologically by eosinophilic predominant inflammation of the GI tract, in the absence of an identifiable secondary cause.
SoR: Strong, Agreement: 100%

2. We conditionally recommend using the prefix “Eo” followed by the specific organ involved as a convention to name non-EoE EGIDs: EoG for eosinophilic gastritis, EoD for eosinophilic duodenitis, EoJ for eosinophilic jejunitis, EoN for eosinophilic enteritis, EoI for eosinophilic ileitis, and EoC for eosinophilic colitis.
SoR: Weak, Agreement: 100%

3. We conditionally recommend that when multiple parts of the gastrointestinal tract are affected by non-EoE EGIDs, they are referred to the segment involved; for instance, Eosinophilic gastritis and eosinophilic duodenitis: EoG and EoD and Eosinophilic gastritis and jejunitis: EoG and EoJ.
SoR: Weak, Agreement: 100%

4. We conditionally recommend that when clinically known, subclassification of the different layers of the GI tract should be also described as mucosal, muscular or serosal.
SoR: Weak, Agreement: 100%

5. We recommend that peripheral blood eosinophilia in the clinical context, not be used as the sole criterion to make the diagnosis of non-EoE EGIDs.
SoR: Strong, Agreement: 95%

6. We conditionally recommend that when consistently associated with mucosal eosinophilia in an individual patient, peripheral eosinophilia may be considered as an adjunct to monitor non-EoE EGIDs disease activity.
SoR: Weak, Agreement: 91%

7. We recommend that fecal calprotectin concentrations not be used to make the diagnosis of non-EoE EGIDs or to monitor non-EoE EGIDs disease activity.
SoR: Strong, Agreement: 95%

8. We recommend that assessment of the gross appearance of the mucosa be documented during endoscopic assessment.
SoR: Strong, Agreement: 95%.

9. We recommend multiple biopsies including gastric antrum, gastric body and duodenum to be obtained in case of symptoms suggestive of EoG/EoD, taken from the involved segments of the GI tract, from normal and abnormal appearing areas of the mucosa.
SoR: Strong, Agreement: 95%

10. We conditionally recommend multiple biopsies from terminal ileum and from at least three sites (cecum/ascending colon, transverse/descending colon, and sigmoid/rectum) in case of symptoms suggestive of EoC, to be obtained from both normal and abnormal appearing areas of the mucosa.
SoR: Weak, Agreement: 100%

11. We conditionally recommend biopsies be labelled as such in separate containers to help interpret eosinophil numbers based on threshold diagnostic numbers.
SoR: Weak, Agreement: 95%

12. We recommend that imaging studies be considered in selected cases for providing information on the depth of bowel wall inflammation and disease extent.
SoR: Strong, Agreement: 95%

13. We recommend that imaging studies be considered in selected cases to localize involved areas for targeted tissue diagnosis.
SoR: Strong, Agreement: 95%

14. We conditionally recommend that blood tests not be used to make the diagnosis of non-EoE EGIDs but may be useful to monitor treatment responses in selected cases.
SoR: Weak, Agreement: 95%

15. We recommend that in the appropriate clinical context, ascitic fluid should be assessed and the finding of eosinophilic predominant inflammation will support the non-EoE EGIDs diagnosis.
SoR: Strong, Agreement: 100%

16. We recommend that GI segment specific threshold peak eosinophil counts (Table 6) be considered prior to making a non-EoE EGIDs diagnosis (expert opinion).
SoR: Strong, Agreement: 91%

17. We conditionally recommend that evaluation of acute and chronic features of mucosal inflammation should be recorded as these can be supportive of the non-EoE EGIDs diagnosis (See Table 7).
SoR: Weak, Agreement: 100%,

18. We recommend that other clinically relevant diseases associated with mucosal eosinophilia be evaluated prior to making a non-EoE EGIDs diagnosis (See Table 8).
SoR: Strong, Agreement: 100%

19. We conditionally recommend the initial evaluation of a patient with symptoms suggestive of non-EoE EGIDs be individualized based on history and clinical examination and associated laboratory testing (See Table 9).
SoR: Weak, Agreement: 100%

20. We conditionally recommend that during the initial evaluation of a patient with GI mucosal eosinophilia one should consider allergic diseases, parasite infections, drug administration (especially immunosuppressants), inflammatory bowel diseases, and malignancy as a part of the differential diagnosis (See Table 8).
SoR: Weak, Agreement: 95%

21. We recommend that the choice of endoscopic examination(s) of the gastrointestinal tract should be guided by symptoms, laboratory, and radiographic findings.
SoR: Strong, Agreement: 95%

22 We recommend that the diagnosis of non-EoE EGIDs in children and adolescents must include all three of the following: a. Symptoms and/or signs of GI dysfunction including but not limited to vomiting, abdominal pain/cramping, bloating, anorexia, weight loss, early satiety, hematemesis, heartburn, dyspepsia, tenesmus, diarrhea or constipation, hematochezia or melena, abdominal distention, ascites, iron deficiency, protein loss. b. Dense eosinophilic infiltrates found in mucosal or full thickness biopsies above organ specific threshold values (See Table 6). c. Absence of other diseases associated with GI mucosal eosinophilic inflammation (See Table 8).
SoR: Strong, Agreement: 91%

23. We conditionally recommend using an Algorithm to guide in the diagnostic approach of children and adolescents with symptoms suggestive of non-EoE EGIDs (See diagnostic Algorithm).
SoR: Weak, Agreement: 100%

24. We conditionally recommend that the goals of treatment in non-EoE EGIDs include achieving resolution of symptoms, improving gross endoscopic and histological abnormalities, promoting normal childhood growth and development, and preventing disease complications.
SoR: Weak, Agreement: 100%

25. We conditionally recommend that the timing of endoscopic and histological re-assessment should be decided on an individualized basis.
Agreement: 100%

26. We recommend that the use of oral systemic steroids be considered to induce remission in individual patients with non-EoE EGIDs and that their use should be undertaken after thorough discussion with the patient and parents about their benefits and risks (expert opinion).
SoR: Strong, Agreement: 100%

27. We conditionally recommend that topical steroids may be considered in selected patients with non-EoE EGIDs (expert opinion). See General approach to treatment.
SoR: Weak, Agreement: 96%

28. We conditionally recommend that empiric elimination diets may be considered in selected patients with non-EoE EGIDs (expert opinion). See General approach to treatment.
SoR: Weak, Agreement: 100%

29. We conditionally recommend not using food allergy tests to guide dietary restriction therapy for the treatment of non-EoE EGIDs.
SoR: Weak, Agreement: 100%

30. There is insufficient data to make a recommendation for or against the use of proton pump inhibitors or H2 receptor antagonists for treating childhood EoG/EoD.
Agreement: 100%

31. We conditionally recommend that proton pump inhibitors may be considered for treating upper GI ulcerations in children with EoG/EoD.
SoR: Weak, Agreement: 90%

32. There is insufficient data to make a recommendation for or against the use of antihistamines, leukotriene inhibitors or mast cell stabilizers as a sole treatment of non-EoE EGIDs.
Agreement: 90%

33. There is insufficient data to make a recommendation for or against the use of immunomodulating drugs for the treatment of non-EoE EGIDs.
Agreement: 100%

34. There is insufficient data to make a recommendation for or against the use of biological drugs in treating childhood non-EoE EGIDs.
Agreement: 90%

35. We conditionally recommend that in addition to medical/dietary treatment, endoscopic dilation may be considered in selected cases with significant objective signs of obstruction.
SoR: Weak, Agreement: 91%

36. We conditionally recommend that surgical treatment of non-EoE EGIDs may be useful for patients with refractory ulcers, intestinal perforation or bowel obstruction which cannot be controlled otherwise.
SoR: Weak, Agreement: 100%

37. There is insufficient data to make a recommendation for or against the use of combination therapy for treating non-EoE EGIDs.
Agreement: 90%

38. We conditionally recommend that combination therapy may be useful for treating concomitant allergic diseases.
SoR: Weak, Agreement: 85%

39. We conditionally recommend that the initial treatment of children with non-EoE EGIDs be individualized based on the symptoms, impact on growth and development and other co-morbid features with an attempt to involve patients and parents/caregivers in shared decision making.
SoR: Weak, Agreement: 95%

40. We conditionally recommend that changes in symptoms and histology should be monitored, preferably with objective tools to allow meaningful conclusions on treatment effects.
SoR: Weak, Agreement: 100%

41. Since the natural history of non-EoE EGIDs is uncertain, we conditionally recommend that the long-term treatment should be discussed with patients and parents/caregivers and include the benefits and risks of long- term treatments as well as their impact on health-related quality of life and financial costs.
SoR: Weak, Agreement: 100%

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis

Authoring Organization

Publication Month/Year

January 30, 2024

Last Updated Month/Year

February 19, 2024

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Document Objectives

Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs.

Inclusion Criteria

Male, Female, Adolescent, Child, Infant

Health Care Settings

Ambulatory

Intended Users

Dietician nutritionist, nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Assessment and screening, Management

Diseases/Conditions (MeSH)

D004802 - Eosinophilia, D057765 - Eosinophilic Esophagitis, D004804 - Eosinophils

Keywords

eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic colitis, eosinophilic duodenitis, eosinophilic gastritis, eosinophilic gastrointestinal disorders

Source Citation

Papadopoulou A, Amil-Dias J, Auth MK, Chehade M, Collins MH, Gupta SK, Gutiérrez-Junquera C, Orel R, Vieira MC, Zevit N, Atkins D, Bredenoord AJ, Carneiro F, Dellon ES, Gonsalves N, Menard-Katcher C, Koletzko S, Liacouras C, Marderfeld L, Oliva S, Ohtsuka Y, Rothenberg ME, Strauman A, Thapar N, Yang GY, Furuta GT. Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2024 Jan;78(1):122-152. doi: 10.1097/MPG.0000000000003877. Epub 2023 Jul 4. PMID: 38291684.