Celiac disease (gluten enteropathy) - Diagnosis

Despite the absence of specific clinical signs pathognomonic for gluten enteropathy, it is necessary to take into account all the listed symptoms, the analysis of which, together with data from other research methods and treatment results, will allow for a correct diagnosis.

Laboratory signs of celiac disease, like clinical ones, vary depending on the extent and severity of intestinal damage and are also nonspecific.

Laboratory and instrumental data

1. Complete blood count: hypochromic iron deficiency or _B12 -deficiency macrocytic hyperchromic anemia.
2. Biochemical blood test: decreased blood levels of total protein and albumin, prothrombin, iron, sodium, chlorides, glucose, calcium, magnesium, and possibly a slight increase in bilirubin. In gluten enteropathy, a number of organs and systems are involved in the pathological process, and therefore many biochemical parameters deviate from the norm. In severe diarrhea, the body is depleted of electrolytes with a decrease in the content of sodium, potassium, chlorides, and bicarbonates in the blood serum. Sometimes significant metabolic acidosis occurs due to the loss of bicarbonates with feces. In patients with diarrhea and steatorrhea, the content of serum calcium, magnesium, and zinc decreases. In osteomalacia, the level of phosphorus in the blood serum may be decreased, and alkaline phosphatase may be increased. The content of serum albumin and, to a lesser extent, serum globulins may decrease as a result of significant release of serum protein into the intestinal lumen. In severe small bowel disease causing steatorrhea, serum cholesterol and carotene levels are usually low. Serum cholesterol levels of less than 150 mg/mL in adults should alert the clinician to the possibility of impaired gastrointestinal absorption.
3. General urine analysis: no significant changes, in severe cases - albuminuria, microhematuria.
4. Coprological analysis: polyfecalia is typical. The feces are watery, semi-formed, yellowish-brown or grayish in color, greasy (shiny). Microscopic examination reveals a large amount of fat (steatorrhea). Significantly more than 7 g of fat is excreted per day (normally, the daily excretion of fat with feces does not exceed 2-7 g). With limited damage to the proximal small intestine, steatorrhea is insignificant or even absent.
5. Study of the absorptive function of the small intestine: tests with D-xylose, glucose (after oral glucose load, a flat glycemic curve is determined), lactose (after oral administration of lactose, an increase in the concentration of exhaled hydrogen is noted) are used. The tests indicate a decrease in the absorptive function of the intestine.
6. Immunological blood test: the most typical is the appearance of antibodies to gluten in the blood, which are detected by an express method, applying the patient's blood serum to wheat grain media. Antibodies circulating in the blood can also be detected by an indirect fluorescence reaction. The detection of autoantibodies to reticulin and small intestinal epithelial cells is also typical. A decrease in the content of immunoglobulin A in the blood is possible.
7. Hormonal blood test. The blood contains reduced levels of T3 _, T4 _, cortisol, testosterone, and estradiol. These changes are observed with the development of hypofunction of the corresponding endocrine glands.
8. X-ray examination of the gastrointestinal tract. Dilation of the small intestinal loops, disappearance of its folds, and changes in the relief of the intestinal mucosa are detected. Sometimes, an excess amount of fluid is observed in the proximal part of the small intestine (due to a violation of the intestinal absorption capacity), which leads to dilution of the contrast agent and, as a result, the pattern of the mucosa in the distal parts of the small intestine seems unclear.
9. Various diagnostic tests. In malabsorption syndrome, tryptophan metabolism is impaired, possibly due to a deficiency of pyridoxine and nicotinic acid; urinary excretion of 5-hydroxyindolebutyric acid and indican increases. In severe digestive disorders that cause pituitary or adrenal insufficiency, daily urinary excretion of 17-KS and 17-OKS decreases. The LIF factor, which is formed as a result of the interaction of lymphocytes from patients with celiac disease with gluten fractions and suppresses increased leukocyte migration, is proposed as a diagnostic test. Secretion of IgA and IgM in vitro by isolated lymphocytes from the duodenum and jejunum using the enzyme-like immunosorbent technique is of certain diagnostic value.
10. For express diagnostics of gluten enteropathy, antibodies to gluten are detected in the blood serum by applying whole or diluted with buffered isotonic sodium chloride solution (pH 7.4) in a ratio of 1:11 to wheat grain media. Antibodies to gluten circulating in the blood, as well as autoantibodies to reticulin and small intestinal epithelial cells, were detected by an indirect immunofluorescence reaction.
11. Biopsy of the small intestinal mucosa. It is most appropriate to take a biopsy from the duodenal junction near the ligament of Treitz. In this place, the intestine is fixed and therefore it is easier to take biopsies here. Characteristic signs of gluten enteropathy are:
    • an increase in the number of goblet cells in the intestinal mucosa;
    • an increase in the number of interepithelial lymphocytes (more than 40 per 100 epithelial cells of the intestinal villi);
    • villous atrophy;
    • infiltration of the superficial and pit epithelium by lymphocytes, and of the lamina propria by lymphocytes and plasma cells.

    Diagnostic criteria for celiac disease

    1. The appearance of diarrhea, malabsorption syndrome in early childhood, delayed growth and physical development in childhood and adolescence.
    2. Typical results of a biopsy of the mucous membrane of the duodenum or jejunum.
    3. Detection of circulating antibodies to gluten in the blood, as well as autoantibodies to reticulin and small intestinal epithelial cells.
    4. Clear clinical and morphological (according to the results of a repeat biopsy) improvement after eliminating gluten (products made from wheat, barley, rye, oats) from the diet.
    5. Positive results of gliadin loading (rapid increase in blood glutamine levels after oral administration of 350 mg gliadin per 1 kg of body weight).

    Differential diagnosis of celiac disease. The first stage of diagnosis is to establish the intestinal absorption disorder and the underlying cause. Steatorrhea and decreased serum cholesterol, carotene, calcium and prothrombin levels alone do not allow differentiating gluten enteropathy from other diseases that may be caused by insufficient absorption. They are also observed in cases of cavity digestion disorder caused by prior resection of the stomach and ileum or pancreatic insufficiency.

    In the differential diagnosis of primary disease of the small intestinal mucosa, the xylose tolerance test is of certain importance, since its normal absorption in the case of impaired cavity digestion is maintained for quite a long time - until the structure of the mucosa changes. Radiographs of the small intestine after taking a contrast agent also help differentiate absorption disorders caused either by damage to the mucosa or by other reasons. "Abnormal" relief of the mucosa, intestinal dilatation, liquefaction of the barium sulfate suspension are highly suspicious of a disease of the mucosa.

    Normal biopsies obtained from the proximal small intestine reliably exclude the diagnosis of clinically expressed untreated celiac enteropathy. At the same time, biopsies demonstrating a lesion typical of celiac enteropathy reliably confirm this diagnosis. Its detection is excluded by examining the biopsy of histological signs characteristic of Whipple's disease and Crohn's disease. Hypogammaglobulinemia, in which changes in the small intestinal mucosa resemble the picture observed in celiac enteropathy, is characterized by the absence or significant decrease in the number of plasma cells.

    The absence of absolutely specific histological signs pathognomonic for celiac disease indicates the need to consider biopsy results in combination with other manifestations of the disease.

    Mucosal involvement identical or similar to that seen in celiac disease occurs in tropical sprue, diffuse small intestinal lymphoma, Zollinger-Ellison syndrome with significant hypersecretion, unclassifiable sprue, and viral gastroenteritis in young children.

    The detection of circulating antibodies to gluten in the blood, as well as autoantibodies to reticulin and epithelial cells of the small intestine, simultaneously with an assessment of the histological structure of the mucous membrane of its initial section, makes diagnostics and differential diagnostics reliable.

    Clinical and morphological improvement after treatment with a diet completely free of toxic gluten confirms the diagnosis of celiac enteropathy. It should be noted that clinical improvement occurs after several weeks, and normalization of the histological picture requires adherence to a gluten-free diet for several months or even years, although some morphological improvement may be observed in the early stages of clinical remission.

    In young children suffering from gastroenteritis, diagnosis is complicated not only by the similarity of histological changes in the small intestinal mucosa with celiac enteropathy, but also by a positive reaction to a gluten-free diet.

    The following help differentiate gluten enteropathy from other diseases of the small intestine, in particular from chronic enteritis: a gliadin load test (a rapid increase in the level of glutamine in the blood after oral administration of 350 mg of gliadin per 1 kg of body weight); a long history of the disease, starting in childhood; an exacerbation of the disease due to the use of products made from wheat, rye, barley, oats; a good effect of a gluten-free diet.

    The diagnosis of celiac disease is based on the following signs: dysfunction of the small intestinal mucosa; documented most characteristic signs of its damage; the presence of circulating antibodies to gluten; clear clinical and morphological improvement after eliminating toxic gluten from the diet.

    [1], [2], [3], [4]