RU2574031C1 - Method for detecting gastric mucosa erosions in children with juvenile arthritis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves an integral assessment of patient's complaints, previous medical history and laboratory parameters, in points: absence of abdominal pain - 4 points, patient's being male - 4 points, patient's age older than 12 years - 4 points, presence of a combined anti-inflammatory therapy - 4 points, length of a combined therapy from 1 to 3 years - 3 points, systemic form of juvenile arthritis - 2 points, absence of parietal cell anti-H⁺K⁺/ATPase auto-antibodies - 4 points, positive result of the Colon View Hb/Hp test - 4 points, pepsinogen II above the norm - 3 points, pepsinogen I/pepsinogen II - 3 points, gastrin-17 above the norm - 2 points. If the total score is 27 points or more, the gastric mucosa erosions are detected in the children suffering from juvenile arthritis.

EFFECT: method enables providing the more accurate detection of the gastric mucosa erosions in the children suffering from juvenile arthritis.

2 ex, 3 tbl

Description

The invention relates to medicine, namely gastroenterology and pediatrics, and can be used to determine erosive lesions of the gastric mucosa in children with juvenile arthritis.

The “Gold Standard” for the detection of erosive lesions of the gastric mucosa in children with juvenile arthritis is fibrogastroduodenoscopy (FGDS) (Multivolume Guide to Internal Medicine. - Moscow. - T. 4. - 1965. - p. 36-39).

FGDS is the most reliable method for detecting erosive lesions of the gastric mucosa (coolant). Unfortunately, most children with erosive lesions of the gastric mucosa and with juvenile arthritis have no FGDS, which is associated with the absence of complaints of abdominal pain in children.

Recently, non-invasive methods have been used to diagnose gastritis. These include a serological test for the diagnosis and screening of stomach diseases "Biohit Gastropanel". Using the Biohit Gastropanel, an enzyme immunoassay (ELISA) can determine the content of gastrin-17, pepsinogen I, pepsinogen II in blood serum (Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacterpylori antibodies in the management of dyspeptic patients in primary care / Di Mario F., Cavallaro LG, Moussa AM, Lecis P., et al. // Digestive and Liver Disease. - 2005. - No. 3. - P. 501-508). A decrease in the concentration of pepsinogen I and pepsinogen II, gastrin-17 in the blood serum indicates a risk of developing atrophic gastritis. At the same time, an increase in the content of pepsinogen I and pepsinogen II, gastrin-17 indicates a risk of erosion and gastric ulcers (Long-term proton pump inhibitor therapy and risk of hip fracture / Yang YX, Lewis JD, Epstein S, et al. / / JAMA. - 2006.- No. 296. - P. 2947-2953). However, this test allows you to determine only the presence of inflammation in the gastric mucosa and does not provide information about the presence of erosion or ulcers.

As a prototype, we chose a non-invasive method for determining erosive lesions of the gastric mucosa - Gregersen reaction - screening diagnostics for the determination of occult blood in feces (Research technique and clinical value of occult blood in stool / L. Hirschberg // Doctor. Newspaper. - 1922. - No. 9). Determination of latent blood in feces is carried out by the method of a benzidine test for occult blood in feces. 0.025 g of benzidine and 0.1 g of barium peroxide are dissolved in 5 ml of 50% acetic acid. A few drops of the solution are applied to a smear of feces, rubbed on a glass slide. In the presence of blood, staining turns greenish-blue to dark blue. The color appears after a few seconds, usually no later than two minutes. Reagents should be used fresh, requiring certain storage conditions.

However, this technique is not specific, since a positive reaction can be to hemoglobin of animals. Therefore, when using this method, it is necessary to observe a milk-vegetable diet for several days. The reaction is evidence for bleeding from the esophagus, stomach or intestines, the possibility of an impurity to the bowel movements of the mouth and nasopharynx is not ruled out. This indicates that when carrying out this technique, it is difficult to establish the exact location of the source of bleeding.

Thus, the method does not have sufficient accuracy to determine erosive lesions of the gastric mucosa in children with juvenile arthritis.

The technical result of the invention is to increase the accuracy of determining erosive lesions of the gastric mucosa in children with juvenile arthritis, as well as simplifying the method.

The technical result is achieved by conducting a comprehensive assessment of complaints, medical history, laboratory parameters, in which each indicator is assigned an appropriate number of points, namely: no abdominal pain - 4 points, male patient gender - 4 points, patient age over 12 years - 4 points, the presence of a combined anti-inflammatory therapy - 4 points, the duration of the combination therapy of 1 to 3 years - 3 points, systemic juvenile arthritis embodiment - 2 points, absence of autoantibodies to the H ⁺ K ⁺ / ATPase in the parietal etok stomach - 4 points, positive test «Colon View Hb / Hp» - 4 points, the level of pepsinogen II overweight - 3 points, the reduction ratio of pepsinogen I to pepsinogen II - 3 points, the gastrin-17 above normal - 2 points. With a total of 27 points and above, erosive lesions of the gastric mucosa in children with juvenile arthritis are determined.

The method is carried out in two stages.

The first stage is preparatory.

At this stage, the complaints and anamnesis of children with a verified diagnosis of juvenile arthritis, as well as the results of clinical and laboratory studies, are assessed. When evaluating complaints, pay attention to the presence or absence of complaints of abdominal pain. When collecting an anamnesis, indicators such as the patient’s gender, age, form of juvenile arthritis, the presence of combination therapy and its duration are noted. From laboratory studies, an immunochromatographic rapid test for occult blood in feces is performed using Colon View Hb and Hb / Hp (Finland), serum levels of gastrin-17, pepsinogen I, pepsinogen II and the ratio of pepsinogen I to pepsinogen II are determined. the presence of autoantibodies to H ⁺ K ⁺ / ATPase of the parietal cells of the stomach in blood serum.

The second stage is diagnostic.

At this stage, a score is assigned to each of the following symptoms: absence of abdominal pain - 4 points, male patient gender - 4 points, patient age over 12 years old - 4 points, the presence of combined anti-inflammatory therapy - 4 points, the duration of combination therapy from 1 to 3 years - 3 points, a systemic version of juvenile arthritis - 2 points, the absence of autoantibodies to H ⁺ K ⁺ / ATPase of parietal cells of the stomach - 4 points, a positive test "Colon View Hb / Hp" - 4 points, the level of pepsinogen II is higher than normal - 3 points, reduction in pepsinogen ratio I to pepsinogen II - 3 points, the level of gastrin-17 is higher than normal - 2 points. With a total of 27 points and above, erosive lesions of the gastric mucosa in children with juvenile arthritis are determined.

Salient features of the proposed method are:

- clinical and medical history indicators (history indicators);

For the first time, diagnostic criteria were used for determining erosive lesions of the gastric mucosa in children with juvenile arthritis: patient age (patients older than 12 years), gender (boys), clinical variant of juvenile arthritis (systemic version), the presence of combination therapy and its duration (from 1 years to 3 years) in the absence of gastritic complaints.

- as laboratory tests in blood serum, the levels of gastrin-17, pepsinogen I, pepsinogen II and the ratio of pepsinogen I to pepsinogen II, the presence of autoantibodies to H ⁺ K ⁺ / ATPase of the parietal cells of the stomach in the blood serum are determined, an express test is performed for occult blood in feces ("Colon View Hb and Hb / Hp").

- each indicator is assigned a score: no abdominal pain - 4 points, male patient gender - 4 points, patient age over 12 years old - 4 points, the presence of combined anti-inflammatory therapy - 4 points, duration of combination therapy from 1 to 3 years - 3 score, systemic version of juvenile arthritis - 2 points, the absence of autoantibodies to H ⁺ K ⁺ / ATPase of parietal cells of the stomach - 4 points, the positive test "Colon View Hb / Hp" - 4 points, the level of pepsinogen II is higher than normal - 3 points, a decrease in the ratio of pepsinogen I to pepsinogen II - 3 b lla, the level of G-17 more than the norm - 2 points, and the sum of 27 points and above determine the erosive lesions of the gastric mucosa in children with juvenile arthritis.

With a total of 27 points and above, erosive lesions of the gastric mucosa in children with juvenile arthritis are determined.

A causal relationship between the salient features and the result:

Colon View Hb and Hb / Hp is a visual immunochromatographic rapid test. The main purpose of these tests is screening for colorectal cancer or large bleeding adenomas. The Colon View Hb test identifies intact human hemoglobin. The hemoglobin molecule breaks up when passing through the gastrointestinal tract, so the Colon View Hb test is specific for the diagnosis of bleeding from the colon, including rectum. To detect a source of bleeding from the upper gastrointestinal tract, Colon View Hb / Hp is used. Dissociated hemoglobin molecules bind to the haptoglobin protein to form a hemoglobin / haptoglobin complex. It is proved that this complex is more stable compared to hemoglobin, therefore the use of the Colon View Hb / Hp rapid test is suitable for the diagnosis of bleeding from the gastrointestinal tract above the level of the colon. The advantage of this method is its availability. (Cost-effective analysis of immunochemical occult blood screening for colorectal cancer among three fecal sampling methods / Yamamoto M, et al. // Hepatogastroenterology. - 2000. - Vol. 47, No. 32. - P. 396-399).

We use the Colon View Hb and Hb / Hp occult blood test for the first time to determine erosive lesions of the coolant in children with juvenile arthritis.

In order to identify clinical diagnostic criteria for the non-invasive diagnosis of erosive gastritis in children with juvenile arthritis, we studied the clinical, laboratory, medical history of 92 children aged 9 to 16 years (mean age 13.9 ± 2.3 years) with a verified diagnosis of juvenile arthritis.

The first, main group included 10 patients with juvenile arthritis with endoscopically verified erosive gastritis.

The second, control group consisted of 82 children with juvenile arthritis without erosion in the gastric mucosa.

The comparison was carried out according to 23 features provided by the research protocol using the method of analysis of contingency tables.

We were able to identify the following differences between the main and control groups:

- Among the patients of the main group, boys (80% and 65.8%, p <0.05) older than 12 years old (80% and 51.2%, p <0.05) were significantly more common, mainly with a systemic version of juvenile arthritis (20% and 0%, p <0.001).

- All patients of the main group significantly more often did not complain of abdominal pain (100% and 87.9%, p <0.05).

- In the main group, combination therapy of juvenile arthritis dominated (80% and 58.5%, p <0.05), while the duration of combination therapy was mainly from 1 year to 3 years (60% and 36.6%, p <0.05).

- In patients of the main group, significantly increased serum levels of gastrin-17 (40% and 25.2%, p <0.001), pepsinogen II (60% and 12.1%, p <0.01) and a decrease in the ratio pepsinogen I to pepsinogen II (60% and 21.9%, p <0.01).

- A positive rapid test “Colon View Hb / Hp” was detected only in the main group (80% and 0%, p <0.001).

- In patients of the main group, the absence of autoantibodies to H ⁺ K ⁺ / ATPase of the parietal cells of the stomach was significantly more frequent (100% and 75.6%, p <0.05).

The typicality of non-invasive signs for erosive gastritis, characteristic of patients of the main group, allowed us to create a diagnostic algorithm for determining erosive lesions of the gastric mucosa in children with juvenile arthritis. According to the probability of occurrence of each of the signs in the main and control groups, we calculated a diagnostic score for each symptom. Based on multivariate correlation and regression analysis, the most significant criteria for determining erosive lesions of the gastric mucosa in children with juvenile arthritis were determined. The significance of the constructed mathematical model and statistical reliability were determined by the Fisher criterion. The model is compiled as follows: we determined 11 discrete diagnostic features (X1, X2, ..., X11) that take values 1 or 0 and a response function y that takes values 1 or 0 (1-unit of erosion in the coolant, 0-no erosion in coolant). The obtained regression model reflects the dependence of the values of the function y on the values of the attributes (X1, X2, ..., X11). Since the function of y is discrete, probit regression is chosen as the model of dependence:

; $$y_i^{*}=b_{\mathrm{one}}{x}_{\mathrm{one}i}+b_2{x}_{2i}+b_3{x}_{3i}+b_{\mathrm{four}}{x}_{\mathrm{four}i}+b_5{x}_{5i}+b_6{x}_{6i}+b_7{x}_{7i}+b_8{x}_{8i}+b_9{x}_{9i}+b_{\mathrm{one}0}{x}_{\mathrm{one}0i}+b_{\mathrm{one}\mathrm{one}}{x}_{\mathrm{one}\mathrm{one}i}$$

;

Based on the sample, the coefficients b are determined:

B = [- 11.8141; 34.0214; -8.6128; -9.7796; -1.4425; -1.5535; -1.2398; 7.6973; -1.7162; 49.1146; -2.1143].

P (y _i = 1) = Ф (B ^T X _i ),

Where $$F(x)=\frac{\mathrm{one}}{\sqrt{2\pi }}{\displaystyle \underset{0}{\overset{x}{\int }}{e}^{-\frac{t^2}{2}}}dt$$

Based on the obtained probability values, a table was compiled.

To build a model of correlation and regression analysis, the following names were adopted: R - coefficient of multiple correlation; R ² is the coefficient of determination; adR ² is the adjusted coefficient of determination; F is the Fisher test; Df is the number of degrees of freedom for the F-criterion; t-criteria for the coefficients of the regression equation; SS is the sum of the squared deviations; MS is the sum of mathematical expectations. The results of analysis of variance are presented in table 1.

Names for analysis of variance are presented in table 2.

When analyzing the results, a diagnostic table 3 was compiled, including 11 signs. The sum of scores of 27 and higher makes it possible to determine with high probability erosive lesions of the gastric mucosa in children with juvenile arthritis.

We give examples from clinical practice:

Example 1. And / b No. 1-25., Patient S., 14 years old.

The diagnosis is basic: juvenile arthritis, oligoarthritic variant.

Entered the rheumatology department, without presenting gastritic complaints. From the anamnesis, it is known that a girl receives combination therapy with sulfasalazine, methotrexate and prednisolone for 3 years. The patient underwent a laboratory study: “Biohit Gastropanel”: an increase in gastrin-17, pepsinogen 2 levels and a decrease in the ratio of pepsinogen I to pepsinogen II, a positive test “Colon View Hb / Hp”, autoantibodies to H ⁺ K ⁺ / ATPase of parietal cells stomach - neg. The diagnostic table scored 30 points, which according to the claimed method indicates the presence of erosive lesions of the gastric mucosa, which was confirmed by the results of FGDS.

Both diagnostic methods coincided.

Example 2. And / b No. 17. Patient K., 14 years old.

The diagnosis is basic: juvenile arthritis, a systemic version.

The patient is observed in the rheumatology department, at the time of admission does not have gastritic complaints. From the anamnesis, it is known that the boy receives combination therapy with sulfasalazine, prednisolone, non-steroidal anti-inflammatory drugs for 3 years.

The patient underwent a laboratory study: “Biohit Gastropanel”: an increase in the level of gastrin-17, a positive test “Colon View Hb / Hp” was noted. The diagnostic table scored 27 points, which according to the claimed method indicates the presence of erosive lesions of the gastric mucosa, which was confirmed by the results of FGDS. Both diagnostic methods coincided.

The proposed method was examined 92 children with juvenile arthritis. Among 92 examined children in 8 patients, the sum of diagnostic points was 27 or more, which made it possible to diagnose the presence of erosive lesions of the gastric mucosa. When conducting FGDS, the presence of erosive lesions of the gastric mucosa was detected in 10 patients, that is, the accuracy of the method developed by us was 80%. The differences are due to the fact that in two patients, erosion was detected at the stage of completion of epithelization and was not accompanied by bleeding. When using the prototype method in 3 patients, a positive reaction to occult blood in the stool was detected, that is, the accuracy of the method was only 30%.

Thus, the developed method improves the accuracy of determining erosive lesions of the gastric mucosa in children with juvenile arthritis by 50%, compared with the prototype method, against the background of therapy for the underlying disease without the presence of abdominal pain syndrome. The method allows a differentiated approach to the appointment of FGDS and does not require a milk-vegetable diet for several days when conducting a test for occult blood, which greatly simplifies the implementation of the method.

Claims (1)

A method for determining erosive lesions of the gastric mucosa in children with juvenile arthritis, which consists in determining the latent blood in the feces, characterized in that they further evaluate the patient’s complaints, anamnesis, and also determine the levels of gastrin-17, pepsinogen I, pepsinogen II and the ratio of pepsinogen I to pepsinogen II, the presence of autoantibodies to H ⁺ K ⁺ / ATPase of the parietal cells of the stomach in blood serum, each of the indicators is assigned the corresponding number of points, namely: the absence of abdominal pain - 4 points la, male patient gender - 4 points, patient age over 12 years old - 4 points, the presence of combined anti-inflammatory therapy - 4 points, duration of combination therapy from 1 to 3 years - 3 points, systemic version of juvenile arthritis - 2 points, lack of autoantibodies to H ⁺ K ⁺ / ATPase of the parietal cells of the stomach - 4 points, positive test “Colon View Hb / Hp” for occult blood in the feces - 4 points, the level of pepsinogen II is higher than normal - 3 points, a decrease in the ratio of pepsinogen I to pepsinogen II - 3 point, the level of gastrin-17 is more than the norm - 2 points, and with a total of 27 points s and above determine the erosive lesions of the gastric mucosa in children with juvenile arthritis.