bubble_chart Overview

Gluten-induced enteropathy, also known as coeliac disease or nontropical sprue, has a higher incidence in North America, Northern Europe, and Australia but is rare in China. The male-to-female ratio is 1:1.3–2.0, with females being more affected than males. It can occur at any age, with the peak incidence in children and young adults. However, the number of elderly people developing this disease has been increasing in recent years.

bubble_chart Etiology

This disease is closely related to the consumption of wheat flour. Extensive research has confirmed that gluten may be the {|###|}disease cause{|###|} of this condition. Therefore, the name of the disease has recently been directly changed to gluten-sensitive enteropathy, and it is believed that the {|###|}mechanism of disease{|###|} is the result of the interaction between genetics, immunity, and gluten consumption.

Patients with this disease are abnormally sensitive to wheat flour foods containing gluten (commonly known as wheat gluten). The gluten in barley, wheat, rye, and oats can be broken down by ethanol into gliadin, which may be the {|###|}disease cause{|###|} of this condition. Gliadin is rich in glutamic acid and proline and can be separated into four types—α, β, γ, and δ—using electrophoresis techniques. α-Gliadin is toxic to the {|###|}small intestine{|###|} mucous {|###|}membrane{|###|}. The toxicity of gliadin to the intestinal mucous {|###|}membrane{|###|} disappears after further hydrolysis. In healthy individuals, the cells of the {|###|}small intestine{|###|} mucous {|###|}membrane{|###|} contain polypeptide-degrading enzymes that can break it down into smaller, non-toxic molecules. However, in patients with active celiac disease, the enzyme activity in intestinal mucous {|###|}membrane{|###|} cells is insufficient, preventing its breakdown and leading to the disease.

Immunological studies of this disease have found that antibodies to gliadin can be detected in the blood, {|###|}small intestine{|###|} secretions, and feces of patients with active celiac disease. Recently, IgA antibodies to endomysium and reticulin have also been detected. After abstaining from gluten-containing foods for a period and then reintroducing gluten, patients experience a sharp decline in serum hemolytic complement and C₃, and immune complexes can be detected. Biopsies of the {|###|}small intestine{|###|} mucous {|###|}membrane{|###|} reveal an increase in intraepithelial lymphocytes and in situ proliferation, primarily of sensitized T cells. In vitro organ culture experiments show that T-cell activation can cause atrophy of the {|###|}small intestine{|###|} villi and hyperplasia of the glandular crypts. All of this suggests that the disease is an immune disorder triggered by gluten.

This disease has a genetic predisposition and is closely associated with MHC genes. It has been observed that multiple family members of patients may develop the condition, and asymptomatic individuals within these families may carry antibodies to gliadin, reticulin, or endomysium.

bubble_chart Pathological Changes

The main pathological changes occur in the small intestinal mucosa, with significant variations in the degree and extent of the lesions. The villi of the small intestinal mucosa atrophy, flatten, deform, or even disappear. The superficial columnar cells decrease, while the submucosal layer shows increased inflammatory cells and glandular hyperplasia. The columnar epithelial cells of the mucosa become flattened, with vacuolated cytoplasm, irregular nuclear sizes, and indistinct microvilli. In some cases, the mucosa thickens, exhibiting chronic inflammatory changes, with villi still present but disorganized, and the intestinal lumen may show varying degrees of dilation.

The enzyme secretion of intestinal mucosal cells decreases, including disaccharidases, dipeptidases, lipases, phosphatases, and dehydrogenases. The secretion of intestinal fluid and gut hormones also diminishes. Consequently, not only is the absorptive surface area of the intestinal mucosa reduced, but its absorptive function is also impaired, along with decreased enzyme activity, leading to compromised digestion of food. Patients lose large amounts of fat, protein, sugar, water, and salts daily, resulting in various corresponding clinical symptoms.

bubble_chart Clinical Manifestations

The clinical manifestations of this disease are essentially a malnutrition syndrome caused by impaired digestion and absorption of nutrients. The clinical presentations vary significantly, with many patients experiencing mild symptoms that are difficult to detect. Adult patients may exhibit atypical manifestations. Common symptoms and signs are as follows:

(1) Diarrhea and abdominal pain 80–97% of patients experience diarrhea. The typical presentation is steatorrhea, characterized by pale, voluminous, greasy, or foamy stools that often float on water and have a foul odor. Bowel movements may occur several to over a dozen times per day. Most patients have persistent or intermittent diarrhea, while a few early or mild cases may lack diarrhea or even present with constipation, often misdiagnosed as fistula disease. Abdominal pain is less common than diarrhea and is usually described as a bloating or fullness discomfort, often occurring before defecation. Grade I tenderness may be present. Some cases exhibit significant bloating, nausea, and vomiting.

(2) Weight loss and fatigue/lack of strength These symptoms vary in severity but are almost universal. Emaciation and weakness primarily result from impaired absorption of proteins, fats, etc., with dehydration, hypokalemia, and loss of appetite also contributing factors. Severe cases may present with cachexia.

(3) Manifestations of vitamin deficiencies and electrolyte imbalances Calcium and vitamin D deficiency may lead to convulsions, paresthesia, osteoporosis, osteomalacia, and bone pain. Vitamin K deficiency can cause bleeding tendencies. Vitamin B complex deficiency may result in tongue coating, stomatitis, angular cheilitis, beriberi, and pellagra-like pigmentation. Vitamin A deficiency can lead to follicular hyperkeratosis, dry conjunctiva, and night blindness. Over half of patients exhibit anemia, often accompanied by koilonychia. A few may experience muscle tenderness and clubbing of fingers or toes.

(4) Edema, fever, and nocturia Edema is common, while fever is often due to concurrent infections. During the active phase, nocturnal urine output exceeds daytime output. IgA nephropathy, infertility, and bleeding tendencies may also occur.

bubble_chart Auxiliary Examination

(1) Blood Tests Most cases present with macrocytic anemia, though normocytic or mixed anemia can also occur. Serum levels of potassium, calcium, sodium, and magnesium may all decrease. Plasma albumin, cholesterol, phospholipids, and prothrombin may also be reduced. In severe cases, serum levels of folate, carotene, and vitamin B₁₂ may also be low. (2) Quantitative Fecal Fat Measurement and Fat Absorption Test The Van de Kamer method is commonly used. When a normal individual consumes 50–100g of fat per day, fecal fat excretion is <5g/d, and the fat absorption rate exceeds 95%. The fat absorption rate is calculated as:

Test method: Consume a standardized test meal (containing 60–100g/d of fat) for 3 consecutive days while measuring fecal fat excretion over the same 3 days, then take the daily average. If fecal fat excretion exceeds 6g/d or the fat absorption rate is <95%, fat malabsorption can be diagnosed.

The quantitative fecal fat test is simple and can diagnose the majority of cases of steatorrhea. However, it is not highly sensitive; in mild cases or when fat intake is <60g/d, fecal fat levels may not necessarily increase. The fat absorption test provides a more precise reflection of fat absorption status. (3) ¹³¹I-Triolein and ¹³¹I-Oleic Acid Absorption Test Before the test, oral compound formula iodine solution (Lugol solution) is administered to block thyroid uptake of ¹³¹I. After ingesting ¹³¹I-triolein (or ¹³¹I-oleic acid) along with peanut oil and water (0.5ml/kg each), feces are collected for 72 hours, and the percentage of excreted radioactivity relative to the ingested dose is calculated. Fecal excretion rates exceeding 5% for ¹³¹I-triolein or 3% for ¹³¹I-oleic acid indicate lipid malabsorption. This test is simple but less accurate than chemical fecal fat measurement. (4) Serum Carotene Concentration Measurement This is a valuable screening test, with a normal value >100 IU/dl. Levels are often below normal in malabsorption due to small intestine disorders, while in pancreatic steatorrhea, they may be normal or mildly reduced. Levels may also decrease in malnutrition, inadequate dietary intake, fever, or certain liver diseases. (5) Other Small Intestine Absorption Function Tests Water-soluble substances such as xylose, glucose, lactose, and folate can be used to assess upper small intestine absorption function. Patients with primary malabsorption syndromes typically show impaired absorption, whereas those with pancreatic or secondary steatorrhea may exhibit normal results.

1. D-xylose Absorption Test D-xylose is passively absorbed in the jejunum after oral administration, is not metabolized in the body, and is primarily excreted through the kidneys. When renal function is normal, the D-xylose test best reflects the absorptive function of the jejunum. The method involves fasting and orally administering 25g of D-xylose (dissolved in 250ml of water), followed by drinking an additional 250ml of water to promote urination. Normally, 4.5–5g of D-xylose is excreted in the urine within 5 hours. If the excretion is 3–4.5g, it is considered suspiciously abnormal, while an excretion of <3g definitively indicates small intestine malabsorption. Alternatively, blood concentration can be measured 2 hours after oral administration, with a normal level being >20mg/dl. In cases of renal insufficiency, urinary excretion of D-xylose decreases, resulting in a false-negative result, although blood concentration remains normal. In patients with extensive bacterial overgrowth in the intestines, gastric retention, or ascites, renal excretion of D-xylose may also decrease, affecting test results. Because some patients experience adverse reactions such as upper abdominal discomfort, vomiting, and diarrhea after ingesting 25g of D-xylose, an alternative method using 5g of oral D-xylose has been adopted. In healthy individuals, the urinary excretion within 5 hours should be >1.0–1.2g. The diagnostic value is similar to the 25g method, but adverse reactions are reduced. In recent years, the D-xylose hydrogen breath test has been introduced, which is unaffected by renal function and is as effective as the urinary D-xylose excretion test.

2. Vitamin B₁₂ Absorption Test The absorption function of the distal ileum can be measured using radioactive cobalt-labeled vitamin B₁₂. First, 1mg of vitamin B₁₂ is injected intramuscularly to saturate the body's reserves, then 2μg of orally administered ⁶⁰cobalt or ⁵⁷cobalt-labeled vitamin B₁₂ is given, and the urinary radioactivity is measured within 48 hours. The normal value should be >8–10%. In cases of ileal dysfunction or resection, or excessive bacterial growth in the intestine (such as in blind loop syndrome), urinary excretion is lower than normal.

3. ¹⁴C-Glycocholic Acid Breath Test After oral administration of 10 microcuries of ¹⁴C-glycocholic acid, most of it is absorbed in the ileum in healthy individuals, circulates to the liver, and is then excreted into the bile. Only a very small portion is excreted into the colon and eliminated in feces; another portion is metabolized into ¹⁴CO₂ and exhaled through the lungs. In healthy individuals, the amount of ¹⁴CO₂ excreted in feces within 4 hours after oral administration of ¹⁴C-glycocholic acid is <1% of the total dose, and <8% within 24 hours. In cases of excessive bacterial growth in the small intestine, ileal resection, or dysfunction, the amount of ¹⁴CO₂ exhaled through the lungs and ¹⁴C excreted in feces increases significantly, up to 10 times the normal level.

(6) Pancreatic Function Tests Abnormal results can be observed in chronic pancreatitis, pancreatic cancer, and cystic fibrosis of the pancreas, aiding in the diagnosis of pancreatic malabsorption.

(7) Gastrointestinal X-ray Examination Functional changes are often observed in the small intestine, particularly in the mid and distal jejunum. These changes mainly include dilation of the intestinal lumen, fluid accumulation, and barium deposition; segmentation of intestinal loops with a snowflake-like distribution; thickening of mucosal folds or smooth intestinal walls resembling a "wax tube" sign; and delayed barium transit time. Gastrointestinal X-ray examination can also rule out other organic sexually transmitted diseases in the gastrointestinal tract.

(8) Endoscopic Examination Insertion-type small intestine endoscopes can reach 60–100 cm beyond the ligament of Treitz. Probe-type small intestine endoscopes are 256 cm long with a tip diameter of about 5 mm. After insertion into the jejunum, they are gradually advanced into the distal ileum with the help of peristalsis, sometimes even reaching the colon. The procedure takes 6–8 hours and typically allows visualization of 50–70% of the small intestine mucosa. Direct biopsy under visualization improves the diagnostic accuracy of small intestine lesions, largely replacing blind suction biopsy. Colonoscopy can sometimes pass through the ileocecal valve to observe lesions in the terminal ileum.

The appearance of normal small intestine mucosa resembles that of the duodenal mucosa. The proximal jejunal mucosa has circular folds and a villous surface, while the folds gradually diminish and almost disappear toward the terminal ileum, with short, blunt villi. In cases of small intestine malabsorption, the basic features of the mucosa include atrophy, such as shortened, thickened, flattened, or denuded villi.

Additionally, testing for antibodies against gliadin, endomysium, and reticulin (IgA) can aid in the diagnosis of this condition.

bubble_chart Diagnosis

For cases of chronic diarrhea and weight loss, the presence of small intestine malabsorption should be suspected. Diagnosing celiac disease first requires differentiation from other intestinal organic diseases and pancreatic disorders causing malabsorption. A preliminary diagnosis can be made based on fecal fat, gastrointestinal X-ray examinations, various small intestine absorption tests, gliadin antibody measurements, endoscopy, and small intestine mucosal biopsy. The diagnosis is then confirmed through a therapeutic trial demonstrating a correlation with gluten.

bubble_chart Treatment Measures

After a definitive diagnosis, comprehensive replacement therapy targeting the disease cause is implemented, with dietary therapeutics being the most important.

(1) Dietary therapy: Avoid consuming gluten-containing foods (such as various types of wheat). For example, if the gluten is removed from flour, the remaining starch can be consumed. The principle is to focus on a high-protein, high-calorie, low-fat, non-irritating, and easily digestible diet.

(2) Symptomatic treatment and supportive therapy: Supplement with various vitamins A, B complex, C, D, K, and folic acid. Correct typical edema and electrolyte imbalances. If necessary, human albumin or blood transfusions may be administered.

(3) Adrenocortical hormones: For severe cases, ACTH can be administered intravenously, or oral prednisone or prednisolone may be used. Sometimes, this can improve small intestine absorption function and alleviate clinical symptoms, but relapses often occur after discontinuation. Long-term use may also lead to water and sodium retention, exacerbating hypokalemia and osteoporosis.