| disease | Idiopathic Eosinophilic Gastrointestinal Infiltration Syndrome |
| alias | Idiopathic Eosinophilic Infiltration Syndrome |
Idiopathic Eosinophilic Infiltration Syndrome is a benign eosinophilic infiltration disease primarily affecting the gastrointestinal tract. It is characterized by gastrointestinal symptoms, signs, eosinophilia, and other abnormal laboratory findings following the ingestion of certain foods, and corticosteroids are highly effective in treating this condition.
bubble_chart Etiology
The cause of the disease remains unclear to date, and it is considered to be an allergic disease. Due to the extensive infiltration of a large number of eosinophils in the affected tissue, approximately 80% of patients exhibit elevated eosinophils in peripheral blood, and about 50% have a personal or family history of allergies. Therefore, this disease may result from systemic or localized allergic reactions to endogenous or exogenous allergens. The increased levels of IgG and IgA in the serum also indicate the involvement of immune reactions.
After a specific allergen comes into contact with sensitive gastrointestinal tissue, an antigen-antibody reaction occurs within the gastrointestinal wall, releasing vasoactive substances such as histamine. This leads to gastrointestinal mucosal congestion, edema, eosinophil infiltration, as well as spasms of gastrointestinal smooth muscles and increased mucus secretion, thereby causing a series of gastrointestinal symptoms.
Ureless Classification
Type I: Diffuse eosinophilic infiltrative gastritis (referred to as eosinophilic gastroenteritis). This includes polyenteric, monoenteric, and regional forms.
Type II: Localized eosinophilic infiltrative granuloma (referred to as eosinophilic granuloma). This includes regional and polypoid forms.
This disease can extensively involve the gastrointestinal tract, ranging from the pharynx to the rectum, with the stomach and small intestine being the most commonly affected. The liver, greater omentum, and other areas may also be involved. Microscopically, a large number of eosinophilic granulocytes can be seen infiltrating, which may aggregate into clusters. The infiltration can affect the mucosa and submucosa or may predominantly involve a single layer, with the mucosa and submucosa being the most common, followed by the muscular layer, and the serosa being the least common.
Type I (eosinophilic gastroenteritis) is the characteristic type of gastroenteritis. Fibrogastroscopy reveals diffuse mucosal congestion, edema, and thickening, occasionally with superficial ulceration and erosion. Gastric lesions closely resemble general superficial gastritis, and biopsy confirms a large number of eosinophilic cell infiltrations. Intestinal lesions are mostly diffuse, with affected intestinal walls showing edema, thickening, and a loss of luster on the serosal surface, covered by fibrinous exudate. Single-organ involvement often manifests as lesions in either the stomach or small intestine. Localized lesions are confined, and when occurring in the stomach, they are often found in the pylorus or antrum. Multi-organ involvement includes lesions in the stomach, duodenum, small intestine, etc., usually presenting as extensive, non-continuous sexually transmitted disease changes.
Kleim classified the lesions into three types based on the degree of eosinophilic cell infiltration:
1. Predominant mucosal lesions: Mainly mucosal infiltration, with mucosal edema and ulceration, leading to blood loss, iron deficiency, malabsorption, and hypoproteinemia.
3. Predominant serosal lesions: Mainly serosal infiltration, with serosal thickening and edema, often involving mesenteric lymph nodes. Eosinophilic (or eosinophilic granulocyte) ascites is common.
Type II (eosinophilic granuloma) is rare. It can form single or multiple submucosal masses, often leading to pyloric obstruction. The stomach (antrum) is the most common site, with extension to surrounding areas, invading the ileum and colon. The lesions are firm or rubbery polypoid masses, sessile or pedunculated, protruding into the lumen, with a smooth surface covered by mucosa. See Table 1.
Table 1: Sites of involvement in Greenberger's series of 32 cases of eosinophilic granuloma
| Site | Number of cases | Percentage (%) |
| Pharynx | 1 | 3 |
| Stomach | 17 | 53 |
| Small intestine | 5 | 16 |
| Colon, rectum | 9 | 28 |
As seen in Table 1, eosinophilic granuloma most commonly involves the stomach (53%), followed by the colon and rectum (28%), with the small intestine being less common (16%).
bubble_chart Clinical Manifestations
The disease often begins with abdominal pain, nausea, and vomiting, with symptoms varying depending on the location of the lesion. It typically follows a chronic course, often characterized by periodic episodes and spontaneous remission.
Type I: Most commonly seen in individuals aged 30–50, with 80% experiencing gastrointestinal symptoms. Half of the patients may have other allergic conditions, such as allergic rhinitis, asthma, etc. This type primarily presents with spasmodic pain in the upper abdomen, accompanied by nausea, vomiting, diarrhea, and other symptoms. The episodes are irregular and may be related to certain foods. Severe involvement of the mucous membrane can lead to upper gastrointestinal bleeding, diarrhea, malabsorption, intestinal protein loss, iron deficiency, and weight loss. Significant involvement of the muscular layer may cause pyloric obstruction or intestinal obstruction, with corresponding symptoms and signs, sometimes misdiagnosed as Crohn's disease or tumors. Involvement of the serous membrane may result in ascites (called eosinophilic ascites) or pleural effusion containing large numbers of eosinophils. Ascites is generally exudative.
Type II: More common in individuals aged 40–60. This type often has a prolonged history of gastric disease, with an acute onset, and may present with spasmodic pain in the upper abdomen accompanied by nausea and vomiting. Coexistence with peptic ulcers is common (often giant ulcers). In the polypoid type, upper gastrointestinal bleeding may be the only symptom. Lesions near the pylorus can lead to pyloric obstruction. When the lesions are in the intestines, functional disturbances such as intussusception or intestinal obstruction may occur due to mass formation, thickening of the intestinal wall, and edema. If the lesion occurs in the ileum, the onset is abrupt and may be misdiagnosed as acute appendicitis due to right lower abdominal pain, tenderness, rebound tenderness, or localized muscle rigidity.bubble_chart Auxiliary Examination
1. Laboratory Tests
Most patients have peripheral blood eosinophilia. The average absolute eosinophil count is (1-2)×109/L in patients with predominant mucosal lesions or muscular layer lesions, and 8×109/L in those with predominant serosal layer lesions. Iron-deficiency anemia is often present, stool occult blood is mostly positive, and a large number of Charcot-Leyden crystals can be observed. Additionally, there is an increased erythrocyte sedimentation rate, decreased plasma albumin, and elevated blood IgE and IgG levels.
2. X-ray Examination
Type I: Approximately 40% of X-ray barium meal examinations may appear normal. It may also reveal esophageal, antral, or small intestine stenosis, widened mucosal folds, loss of peristalsis, pyloric obstruction, thickened intestinal walls, nodular filling defects, and sometimes gastric or small intestine dilation.
Type II: Irregular antral mucosa may be detected, sometimes appearing nodular or polypoid, with thickened and rigid gastric walls, gastrointestinal stenosis resembling neoplastic changes, as well as gastrointestinal filling defects.
3. Endoscopic Examination
Type I: Endoscopy may show coarse mucosal folds, congestion, edema, erosion, hemorrhage, or proliferative areas. Biopsy of these areas reveals massive eosinophilic infiltration, which is diagnostically significant for this condition.
Type II: Endoscopy demonstrates mucosal congestion and edema, with polypoid masses often mistaken for tumors or Crohn's disease.
The Leinbach diagnostic criteria mainly include: ① Peripheral blood eosinophilia; ② Gastrointestinal symptoms and signs induced by food intake; ③ Histological confirmation of eosinophilia or infiltration in the gastrointestinal tract. Given the nonspecific gastrointestinal manifestations of this disease, diagnosis should consider a history of allergies, peripheral blood (ascites or biopsy) eosinophilia, and be supported by gastrointestinal X-ray barium meal and fiber endoscopy. For early diagnosis, unexplained gastrointestinal symptoms—especially in individuals or families with a history of allergic diseases, or symptoms and signs that appear or worsen after consuming certain foods or medications, accompanied by peripheral blood eosinophilia—should raise suspicion of this condition. The presence of eosinophilia in blood or ascites, significant congestion and edema observed during fiber endoscopy, biopsy findings of multiple specimens with substantial eosinophil infiltration, or symptom relief after fasting from suspected foods or corticosteroid treatment may suggest a diagnosis of eosinophilic ascites or eosinophilic gastroenteritis.
bubble_chart Treatment Measures
The treatment principles for this disease are to remove allergens and suppress allergic reactions.
1. Actively identify and eliminate allergenic foods
Immediately stop consuming foods or medications that cause gastrointestinal allergies. For those without a history of food or drug allergies, a sequential method can be used to systematically exclude potential allergenic foods, such as milk, eggs, shrimp, meats, and sensitive medications. For patients primarily exhibiting mucosal lesions, abdominal pain and diarrhea improve rapidly after eliminating the relevant allergenic foods or drugs.
2. Adrenocortical hormones
Adrenocortical hormones are highly effective in treatment, leading to symptom relief. Most patients show improvement within 1–2 weeks of medication, and the treatment remains effective during relapses. This approach is suitable for patients with diffuse-type disease, postoperative recurrence, or those with ascites as the main symptom. During the acute phase, prednisone 30–40 mg can be administered once daily for 2 weeks. After improvement, the dose should be gradually reduced, with a maintenance dose of 5–10 mg daily for 2–4 weeks. For eosinophilic granulomas, the duration of medication may be appropriately extended. If hormonal therapy is ineffective, other immunosuppressants, such as azathioprine (50–150 mg daily), may be added. Blood counts should be monitored during treatment.
3. Sodium cromoglycate
Sodium cromoglycate (Dinatrii Cromoglycas) stabilizes mast cell membranes, inhibiting degranulation and preventing the release of mediators such as histamine, slow-reacting substances, and bradykinin, thereby exerting its anti-allergic effects. Clinically, it is used for patients who do not respond to adrenocortical hormone therapy or experience severe side effects. Dosage: 40–60 mg, three times daily, with a treatment course ranging from 6 weeks to 5 months.
4. Surgical treatment
Surgical treatment cannot remove the infiltrated areas, and mucosal edema complicates gastrointestinal anastomosis, making postoperative recurrence likely. Therefore, since the introduction of glucocorticoids, eosinophilic gastroenteritis no longer requires surgical intervention.
For eosinophilic granulomas causing gastrointestinal obstruction that does not respond to medical treatment, surgery may be considered. Postoperatively, a low dose of prednisone (2.5 or 5 mg daily) may be administered orally for a period of time, depending on the situation.
Although the disease may recur, the prognosis is generally good, with only a few individual cases having a poorer outcome.
1. Secondary Peripheral Blood Eosinophilia
There are many causes of peripheral blood eosinophilia, such as allergies, parasitic infections, chemical drug factors, Hodgkin's disease, cysticercosis cyst rupture, etc., but each has its specific manifestations. Referencing certain laboratory tests can often confirm the diagnosis.
2. Crohn's Disease
This disease may present with nausea, vomiting, abdominal pain, diarrhea, especially when X-rays show mucosal edema and thickened intestinal walls, manifesting as ileocolitis, which should be differentiated from Crohn's disease. Peripheral blood eosinophilia suggests eosinophilic gastroenteritis; the presence of intestinal fistulas, stenosis, or secondary manifestations of inflammatory bowel disease (stomatitis, arthritis, etc.) suggests Crohn's disease.
3. Hypereosinophilic Syndrome
Hypereosinophilic syndrome is characterized not only by elevated peripheral blood eosinophils but also by multi-system and multi-organ involvement, such as the heart, brain, kidneys, lungs, and skin, and may also affect the gastrointestinal tract, leading to extensive eosinophilic infiltration. The disease has a short course and poor prognosis. Therefore, if there are obvious clinical manifestations of extra-gastrointestinal organ involvement, this syndrome should be considered.
4. Gastrointestinal Malignancy, Cervical Malignancy with Cachexia
When eosinophilic granuloma occurs in the stomach, it should be differentiated from stomach cancer and gastric cervical malignancy with cachexia. See Table 2.
Table 2: Key Points for Differentiating Gastric Eosinophilic Granuloma, Stomach Cancer, and Gastric Cervical Malignancy with Cachexia
| Differentiation Points | Gastric Eosinophilic Granuloma | Stomach Cancer | Gastric Cervical Malignancy with Cachexia |
| Age | Middle-aged | Middle-aged and elderly | Young |
| Medical History | Often has a history of peptic ulcer for many years | May have a history of gastric disease, shorter duration | No specific history |
| Systemic Symptoms | Mild | Varies from mild to severe | Mild |
| Abdominal Pain | Paroxysmal, varying severity | Persistent, with paroxysmal exacerbations | Indeterminate |
| Superficial Lymph Nodes | Not enlarged | Enlarged locally if metastasis occurs | May be enlarged in multiple areas |
| Cachexia | Not obvious | Significant | Significant |
| Blood Test | May show eosinophilia | No specific findings | Increased immature lymphocytes if leukemia is present |
| Barium Meal | Smooth filling defect, mucosa uninterrupted | Irregular filling defect, mucosal interruption | Protruding filling defect, possible mucosal changes |
| Biopsy | Shows eosinophilic granuloma cells | Cancer cell infiltration | malignant lymphocytes |
In the eosinophilic granuloma type of this disease, when there is hepatosplenomegaly and lymphadenopathy, it must be differentiated from histiocytic basophilic leukemia. The latter, also known as mast cell leukemia, is relatively rare and is a malignant proliferative disorder of mast cells. The clinical manifestations occur in three stages: ① pigmented urticaria, ② systemic histiocytic basophilia, and ③ histiocytic basophilic leukemia. The course of the disease can last for several years, but once it enters the third stage, survival is limited to ~9 months. Diagnosis primarily relies on biopsy, with histiocytic basophilic cell infiltration observed in the skin, liver, spleen, and lymph nodes, or a large number of histiocytic basophilic cells detected in peripheral blood and bone marrow.
Additionally, eosinophilic granuloma must also be differentiated from eosinophilic hyperplastic lymphogranuloma. In the latter, eosinophils in the blood are increased, and even the affected skin and subcutaneous tissues show grade I eosinophilic infiltration. The differences are as follows: eosinophilic hyperplastic lymphogranuloma is often accompanied by localized or generalized rubbery swelling of superficial lymph nodes; it frequently presents with skin dryness, pigmentation, desquamation, atrophy, and other lesions; apart from eosinophilia, the blood profile shows relative lymphocytosis; the pathological features include a significant increase in eosinophils, along with lymphocyte proliferation and mononuclear cell infiltration; it is relatively sensitive to deep X-ray radiation therapy.
Since this disease can cause gastrointestinal obstruction, the possibility of this condition should be considered in any case of obstruction caused by gastrointestinal disorders.
