bubble_chart Overview

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, with corticosteroids being highly effective in its treatment.

bubble_chart Etiology

disease cause 学

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 peripheral eosinophilia, and about 50% have a personal or family history of allergies. Therefore, the disease may result from systemic or local allergic reactions to endogenous or exogenous allergens. Elevated serum levels of IgG and IgA also indicate the involvement of immune responses.

After contact with gastrointestinal-sensitive tissue, a specific allergen triggers an antigen-antibody reaction within the gastrointestinal wall, releasing histamine-like vasoactive substances. 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.

Pathological Changes

The 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 and greater omentum may also be involved. Microscopically, a large number of eosinophils can be seen infiltrating, sometimes accumulating in clusters. The infiltration may involve the mucosa and submucosa or predominantly affect 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): This is the characteristic type of gastroenteritis. Fibrogastroscopy reveals diffuse mucosal congestion, edema, and thickening, occasionally with superficial ulcerative erosions. Gastric lesions closely resemble general superficial gastritis, and biopsy confirms extensive eosinophil infiltration. Intestinal lesions are mostly diffuse, with affected intestinal walls showing edema, thickening, and a loss of serosal luster, covered by fibrinous exudate. Monoenteric cases often involve a single organ, such as the stomach or small intestine. Localized cases are confined, with gastric lesions typically occurring in the pylorus or antrum. Polyenteric cases involve multiple sites, such as the stomach, duodenum, and small intestine, often presenting as widespread, non-continuous lesions.

Kleim classified the lesions into three types based on the degree of eosinophil infiltration:

1. Predominantly mucosal type: Mainly mucosal infiltration, with mucosal edema and ulcers, leading to blood loss, iron deficiency, malabsorption, and hypoproteinemia.

2. Predominantly muscular type: Mainly muscular layer infiltration, with nodular thickening of the gastrointestinal wall protruding inward, causing pyloric or intestinal stenosis and obstruction. Clinically, this needs to be differentiated from Type II (eosinophilic granuloma).

3. Predominantly serosal type: Mainly serosal infiltration, with serosal thickening and edema, often involving mesenteric lymph nodes. Eosinophilic (or eosinophil-rich) ascites is common.

Type II (eosinophilic granuloma): This type is rare. It can form single or multiple submucosal masses, often leading to pyloric obstruction. The gastric antrum is the most common site, with extension to surrounding areas such as 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.

bubble_chart Clinical Manifestations

The disease often begins with abdominal pain, nausea, and vomiting, and the symptoms vary depending on the location of the lesion. It usually 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. If the serous membrane is affected, ascites (called eosinophilic ascites) or pleural effusion containing large amounts of eosinophils may occur. The ascites is generally exudative.

Type II: More common in individuals aged 40–60. This type often has a long history of gastric disease, with a relatively 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 due to mass formation, thickening of the intestinal wall, and edema may result in intussusception or intestinal obstruction. If the lesion occurs in the ileum, the onset is abrupt, and it 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 exhibit peripheral blood eosinophilia. In patients with predominantly mucosal lesions and those with predominantly muscular layer lesions, the average absolute eosinophil count is (1–2)×10⁹/L, while in cases with predominant serosal layer involvement, the average is 8×10⁹/L. Iron-deficiency anemia is often present, stool occult blood is frequently positive, and a large number of Charcot-Leyden crystals may 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. Findings may also include stenosis of the esophagus, gastric antrum, or small intestine, widened mucosal folds, loss of peristalsis, pyloric obstruction, thickened intestinal walls, nodular filling defects, and sometimes dilation of the stomach or small intestine.

Type II: Irregularities in the gastric antral mucosa may be observed, sometimes presenting as nodular or polypoid changes. Thickened and rigid gastric walls, gastrointestinal stenosis resembling neoplastic changes, and filling defects may also be seen.

3. Endoscopic Examination

Type I: Endoscopy may reveal coarse mucosal folds, congestion, edema, erosion, hemorrhage, or proliferative areas. Biopsy of these regions shows significant eosinophilic infiltration, which is diagnostically valuable for this condition.

Type II: Endoscopy demonstrates mucosal congestion and edema, with polypoid masses often mistaken for tumors or Crohn’s disease.

bubble_chart Diagnosis

According to the Leinbach diagnostic criteria, the main points are: (1) Peripheral blood eosinophilia; (2) Gastrointestinal symptoms and signs appearing after 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 should be supported by gastrointestinal X-ray barium meal and fiber endoscopy. For early diagnosis, the possibility of this disease should be considered in cases of unexplained gastrointestinal symptoms, especially in individuals or families with a history of allergic diseases, or when gastrointestinal symptoms and signs appear or worsen after consuming certain foods or medications, accompanied by peripheral blood eosinophilia. The presence of eosinophilia in blood or ascites, significant congestion and edema observed during fiber endoscopy, biopsy findings of multiple specimens with substantial eosinophilic infiltration, or symptom relief after fasting from suspected foods or glucocorticoid 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 search for 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, meat, and sensitive medications. For patients with primarily mucosal lesions, abdominal pain and diarrhea rapidly improve after excluding the relevant allergenic foods or medications.

2. Adrenocortical hormones

   Adrenocortical hormones have a good therapeutic effect, leading to symptom relief. Most patients show improvement within 1–2 weeks of medication, and the treatment remains effective during recurrence. This is suitable for patients with diffuse types, postoperative recurrence, or those with ascites as the main symptom. During the acute phase, prednisone 30–40mg can be administered once daily for 2 weeks. After efficacy is observed, the dose should be gradually reduced, with a maintenance dose of 5–10mg daily for 2–4 weeks. For eosinophilic granulomas, the medication duration can be appropriately extended. If hormonal therapy is ineffective, other immunosuppressants such as azathioprine (50–150mg daily) may be added. Blood tests should be monitored during medication.

3. Sodium cromoglicate

   Sodium cromoglicate (Dinatrii Cromoglycas) stabilizes mast cell membranes, inhibits degranulation, and prevents the release of mediators such as histamine, slow-reacting substances, and bradykinin, thereby exerting its anti-allergic effects. Clinically, it can be used for patients who do not respond to adrenocortical hormone therapy or experience severe side effects. Dosage: 40–60mg, three times daily, for a course of 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 do not respond to medical treatment, surgical intervention may be considered. Depending on the situation, a low dose of prednisone (2.5 or 5mg daily) can be administered postoperatively for a period of time.

bubble_chart Prognosis

Although the disease may recur repeatedly, the vast majority of cases have a good prognosis, with only a few individuals experiencing a poorer outcome.

bubble_chart Differentiation

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. Reference to 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 fistulas, strictures, or secondary manifestations of inflammatory bowel disease (stomatitis, arthritis, etc.) suggests Crohn's disease.

3. Hypereosinophilic Syndrome

Hypereosinophilic syndrome, in addition to elevated peripheral blood eosinophils, is also accompanied 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 gastrointestinal eosinophilic infiltration. The disease has a short course and poor prognosis. Therefore, if there are obvious clinical manifestations of involvement of organs outside the gastrointestinal tract, this syndrome should be considered.

4. Gastrointestinal Malignancies, Cervical Malignancy with Cachexia

When eosinophilic granuloma occurs in the stomach, it must be differentiated from stomach cancer and cervical malignancy with cachexia.

The eosinophilic granuloma type of this disease, when accompanied by hepatosplenomegaly and lymphadenopathy, must be differentiated from histiocytic basophilic leukemia. The latter, also known as mast cell leukemia, is relatively rare and is a malignant proliferative disease of mast cells. The clinical manifestations have three stages: (1) Pigmented urticaria. (2) Systemic histiocytic basophilia. (3) Histiocytic basophilic leukemia. The course can last for several years, but once it enters the third stage, survival is only about 9 months. Diagnosis mainly relies on biopsy, with histiocytic basophilic infiltration in the skin, liver, spleen, and lymph nodes, or the discovery of large numbers of histiocytic basophils in the peripheral blood and bone marrow.

In addition, eosinophilic granuloma must also be differentiated from eosinophilic hyperplastic lymphogranuloma. The latter is characterized by increased eosinophils in the blood, and even grade I eosinophilic infiltration in the affected skin and subcutaneous tissues. The differences are: eosinophilic hyperplastic lymphogranuloma is often accompanied by rubbery enlargement of local or systemic superficial lymph nodes; it often presents with dry skin, pigmentation, desquamation, atrophy, and other lesions; in addition to eosinophilia, the blood picture shows relative lymphocytosis; the pathological features include a large 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, any gastrointestinal disease leading to obstruction should consider the possibility of this condition.