Gastritis and duodenitis in children: clinical guidelines

List of Abbreviations

AI — autoimmune gastritis

AMO** — amoxicillin**

B** — bismuth tripotassium dicitrate**

EBV — Epstein-Barr virus

GER – gastroesophageal reflux

Du – duodenum

DGR — duodenogastric reflux

IHC – immunohistochemistry

PPI – proton pump inhibitors

CLA** — clarithromycin**

PT — physical therapy (Physical therapy for diseases of the esophagus, stomach, and duodenum)

MET** — metronidazole**

NSAIDs – nonsteroidal anti-inflammatory drugs

DMS — duodenal mucosa

GM — gastric mucosa

T — #tetracycline

FD – functional dyspepsia

CG — chronic gastritis

CD — chronic duodenitis

EGD – esophagogastroduodenoscopy

H. pylori – Helicobacter pylori

OLGA system — Operative Link for Gastritis Assessment

OLGIM system — Operating Link For Gastric Intestinal Metaplasia

Terms and Definitions

Gastritis is an inflammatory disease of the gastric mucosa.

Duodenitis is an inflammatory disease of the duodenal mucosa.

Chronic gastritis is a chronic inflammation of the gastric mucosa characterized by its cellular infiltration, impaired physiological regeneration, and consequently, atrophy of the glandular epithelium, intestinal metaplasia, and dysfunction of the secretory, motor, and frequently incretory functions of the stomach.

Chronic duodenitis is a disease characterized by chronic inflammatory infiltration of the duodenal mucosa, gastric epithelial metaplasia, and histoarchitectural abnormalities in the form of villous shortening and crypt deepening.

Helicobacter pylori (H. pylori) is a motile, spiral or S-shaped Gram-negative bacterium capable of colonizing the gastric mucosa and, in some cases, the duodenal mucosa, causing inflammation.

Eradication is a comprehensive treatment aimed at eliminating Helicobacter pylori (H. pylori) infection.

Autoimmune gastritis is an organ-specific chronic progressive disease involving the body and fundus of the stomach, with the development of glandular atrophy and hypochlorhydria, culminating in pernicious anemia.

Functional dyspepsia is a symptom complex including pain, burning, and epigastric fullness after meals, and early satiety, which have been present for the last 3 months (with a total duration of at least 6 months) and cannot be explained by organic diseases (peptic ulcer disease, tumors, etc.).

OLGA system (Operative Link for Gastritis Assessment) determines the stage of atrophy (%) and the grade of inflammation (mild, moderate, severe).

OLGIM system (Operating Link For Gastric Intestinal Metaplasia) determines the stage, form, and degree of intestinal metaplasia involvement. Both systems together assess the risk of gastric cancer development.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Gastritis (gastritis; Greek gaster stomach + -itis inflammation) is a lesion of the gastric mucosa characterized predominantly by inflammatory changes in acute processes and phenomena of dysregeneration and structural remodeling with progressive atrophy in chronic courses, accompanied by impaired functions of the stomach and other body systems [1]. Acute and chronic gastritis are distinguished. Chronic gastritis accounts for the majority of gastric diseases [1].

Chronic gastritis (CG) is a chronic inflammation of the gastric mucosa (GM) of various etiologies, manifesting as cellular infiltration of the GM, impaired physiological regeneration, and consequent atrophy of the glandular epithelium, intestinal metaplasia, and dysfunction of the secretory, motor, and frequently incretory functions of the stomach [2].

Duodenitis (duodenitis; Latin duodenum duodenum + -itis inflammation) is an inflammatory-dystrophic process involving all layers of the duodenal wall or confined to its mucosa. Bulbitis (inflammation of the duodenal bulb) and odditis (inflammation of the sphincter of the common bile duct [Oddi], a ring muscle surrounding the common bile duct before it opens into the duodenal lumen) are also distinguished [3].

Chronic duodenitis (CD) is a disease characterized by chronic inflammatory infiltration of the duodenal mucosa, gastric epithelial metaplasia, and histoarchitectural abnormalities in the form of villous shortening and crypt deepening [2].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Causes contributing to the development of gastritis are divided into exogenous and endogenous. Exogenous gastritis develops against the background of dietary errors, smoking, alcohol consumption, H. pylori infection, as well as other infectious diseases affecting the stomach, foodborne toxicoinfections, the irritating effect of certain medications (salicylates, nonsteroidal anti-inflammatory drugs [NSAIDs], prednisolone, digitalis preparations, potassium chloride, certain antibiotics, antituberculous drugs, etc.) that have an adverse effect on the gastric mucosa, and food allergies (to strawberries, mushrooms, etc.). The role of the allergic factor in the etiology of chronic gastritis remains controversial. The involvement of food allergy is currently considered proven only with respect to a specific form of chronic gastritis—eosinophilic gastritis.

Endogenous gastritis, depending on the cause, is subdivided into neuro-reflex (pathological reflex effects from other affected organs—intestines, gallbladder, pancreas), gastritis associated with autonomic nervous system disorders and endocrine organ pathology (pituitary, adrenal glands, thyroid gland), hematogenous gastritis (in chronic infections, metabolic disorders), hypoxemic gastritis (against the background of reduced blood flow in the gastric mucosa, e.g., in coronary heart disease and vascular disease), and elimination gastritis (associated with the excretion of various toxic substances through the gastric mucosa. This group includes, for example, uremic gastritis arising from the excretion of nitrogenous metabolic end products through the gastric wall in patients with advanced chronic kidney disease).

Hereditary factors also occupy a certain place in the etiology of chronic gastritis, although their specific role in the onset of the disease has not been sufficiently studied yet.

The pathogenesis of changes in gastritis is primarily associated with an imbalance between protective and aggressive factors in the gastric mucosa, which leads not only to an inflammatory process, but subsequently to dysmetabolic, dysregeneratory, dystrophic, and atrophic processes in the gastric mucosa, ultimately contributing to the development of organ functional insufficiency. Regardless of the cause of gastric mucosal inflammation, the pathological process develops through the stages of the well-known Correa cascade: normal mucosa – superficial gastritis – chronic atrophic gastritis – small intestinal-type metaplasia – colonic-type metaplasia – dysplasia – adenocarcinoma [4]. H. pylori is considered one of the main etiological factors of chronic gastritis and is recognized as a Group 1 carcinogen by the International Agency for Research on Cancer [5]. The microorganism possesses more than 40 pathogenicity genes gathered in one of its segments, the "pathogenicity island." The high-molecular-weight CagA protein is considered the main pathogenicity factor, the production of which increases the risk of gastric mucosal atrophy by 3 times [6, 7]. In addition to the presence of CagA, the risk of gastric cancer increases with infection by vacA, iceA, and babA-positive strains [8]. However, even with successful eradication of the pathogen in patients with chronic gastritis, complete restoration of the gastric mucosa morphology does not always occur. The Maastricht III Consensus introduced the term "point of no return," after which H. pylori eradication no longer provides a significant preventive effect regarding the development of gastric cancer [9]. This "point of no return" is considered to be the presence of pronounced atrophy and intestinal metaplasia. The Maastricht VI Consensus states that after successful H. pylori eradication, patients with high-stage (OLGA/OLGIM III–IV) gastritis and/rextensive endoscopic atrophy remain at risk for gastric cancer [10]. Chronic gastritis in children is characterized in 68% of cases by moderately severe superficial inflammation with minor infiltration, not accompanied by the development of atrophy [11]. Atrophic changes in the gastric mucosa are more common in adulthood [12].

Upon H. pylori invasion of the gastric mucosa, a specific inflammatory process develops (gastritis, duodenitis) involving local and humoral immune mechanisms (phagocytosis, lymphocyte blast transformation, synthesis of immunoglobulins, etc.), and a local immune response is induced, manifested not only by changes in sIgA levels but also accompanied by alterations in the cytokine (interleukin) status [13, 14]. The detection of H.pylori in the duodenum is explained by the fact that in gastritis with increased acidity, approximately 30% of adult patients experience duodenal epithelial metaplasia—specifically, its replacement with epithelium characteristic of the stomach, which creates conditions for H.pylori colonization of the duodenum [15]. The frequency of gastric metaplasia increases with age: up to 8 years, the frequency of gastric metaplasia was 8%; from 8–12 years, 25%; and in children over 12 years old, 38% [16].

Pathomorphological data, as well as studies using the sucrose permeability test, prove that in gastritis and duodenitis, as in any chronic inflammation of the digestive tract, an increased epithelial permeability syndrome occurs, the severity of which correlates with the activity of the inflammatory process in the gastric mucosa. H.pylori contributes to the occurrence of this syndrome by exerting a negative effect on the structural components of epithelial tight junctions [17].

More than 90% of the population harbors another infection—the Epstein-Barr virus (EBV). Studies show the triggering role of this virus in the development of upper gastrointestinal tract diseases [18].

An important etiological factor of chronic gastritis, besides H. pylori, is autoimmune damage to the gastric mucosa [19]. It accounts for 15–18% of cases in the population. Autoimmune gastritis in children is a rare phenomenon, most commonly found in elderly European women. Nevertheless, cases of autoimmune gastritis in young people have been described in the literature [20]. Insufficient knowledge regarding autoimmune gastritis in children leads to a delayed diagnosis [19].

The etiology of autoimmune gastritis is still not fully understood. Among the infectious factors acting as triggers for autoimmune gastritis, Helicobacter pylori undoubtedly occupies a leading place; its genome contains cytotoxin-associated genes capable of causing various severe pathological processes in the gastric mucosa, including the activation of oncogenic proteins [21].

The pathogenesis of autoimmune gastritis is associated with the formation of antibodies to the H+/K+-ATPase of gastric mucosal parietal cells and to Castle's intrinsic factor, as well as impaired epithelial differentiation and the destruction of parietal cells. There is convincing evidence supporting the mechanism of molecular mimicry between H. pylori antigens and the H+/K+-ATPase of parietal cells [22].

Nevertheless, a consensus regarding the role of H. pylori in the development of autoimmune gastritis has not yet been reached. However, most researchers acknowledge that the role of H.pylori in the development of autoimmune gastritis is very minor. In adults, parietal cell antibodies were detected only among H. pylori-negative patients [22, 23]. It has been shown that in children, H. pylori infection may not play a role in the development of autoimmune gastritis [24, 25].

An EBV infection and its combination with H. pylori can also play a triggering role in autoimmune gastritis [26].

In some cases, autoimmune gastritis is combined with other autoimmune diseases (autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo, etc.) [27, 28, 29]. H. pylori may precede autoimmune gastritis and play a leading role in triggering autoimmune mechanisms through cross-reactivity between microorganism antigens and parietal cell H+/K+-ATPase [30].

Due to the destruction of parietal cells, the production of both hydrochloric acid and Castle's intrinsic factor is impaired, leading to impaired iron absorption with the development of iron deficiency anemia, and impaired vitamin B12 absorption followed by disordered erythropoiesis and the development of pernicious anemia. Pernicious anemia is not the only symptom of the disease. Vitamin B12 is also crucial for myelin production, a deficiency of which leads to neurological disorders such as numbness, paresthesias, weakness, and ataxia, which may precede anemia, as well as subacute combined degeneration of the spinal cord [25, 31].

It is necessary to focus on the fact that the disease develops slowly over many years. Antibodies must be persistent and present in sufficient concentrations to induce a local reaction together with autoreactive gastric CD4+ T cells, contributing to mucosal atrophy and the destruction of parietal cells [25]. To date, the dynamics of parietal cell antibody concentrations in relation to time and disease pathology have not been clearly defined. However, in patients with severe autoimmune gastritis, the disappearance of the antigen source due to pronounced mucosal atrophy leads to a decrease in antibody titers. Notably, gastric parietal cell antibodies are also present in 2.5–9% of healthy adults [32].

Special forms of gastritis are less common, characterized by specific etiological factors or accompanying other diseases. Lymphocytic gastritis may be associated with celiac disease, eosinophilic gastritis occurs within the framework of eosinophilic gastroenteritis, and granulomatous gastritis is associated with Crohn's disease, sarcoidosis, and vasculitis [34].

Duodenitis is a heterogeneous disease caused by infectious agents (H. pylori, mycobacteria, Tropheryma whipplei, Candida fungi, parasites: giardia, hookworm, anisakiasis; Strongyloides, viruses including cytomegaloviruses and herpesviruses), exogenous influences (alcohol, chemical agents, radiation, medications), and other diseases (Crohn's disease, sarcoidosis, vasculitis, Henoch-Schönlein purpura, celiac disease) [35, 36].

Risk factors for chronic duodenitis also include irregular dietary habits, eating dry food, consumption of coarse, spicy, or mucosa-irritating foods, and food intolerance. Among medications, the most adverse effects are caused by long-term use of aspirin, prednisolone, and nonsteroidal anti-inflammatory drugs [37]. The consumption of alcoholic beverages, especially strong ones, and tobacco smoking have both a direct negative impact on the duodenal mucosa and disrupt the neurohumoral mechanisms regulating repair processes. These factors are most typical for adults, but also occur in adolescents [38]. The significance of chronic psychoemotional stress, which disrupts the mechanisms regulating the morphofunctional state of the gastroduodenal zone, cannot be ruled out [37]. Patients often exhibit a combination of several etiological factors [39]. Determining the etiological factor in each specific case is quite difficult, as duodenitis and concomitant diseases often share common risk factors and mutually exacerbate each other during the course of the disease [37].

Chronic duodenitis is subdivided into primary (isolated), which is rare, and secondary, which is considered a concomitant pathology or a complication of an underlying disease. Chronic secondary duodenitis is observed in peptic ulcer disease, gastritis, and pathologies of the pancreas, biliary tract, and liver. The pathogenesis of primary chronic duodenitis is unknown. In secondary CD, a diverse etiology logically implies differences in the pathogenesis of the disease; however, it has been established that the action of etiological factors in the duodenal mucosa often causes uniform morphofunctional changes [40]. The pathogenesis distinguishes a triggering mechanism, general and local pathogenetic reactions. The triggering mechanism is associated with the direct effect of aggressive factors on the duodenal mucosa (DM). One of the main etiological factors of secondary chronic duodenitis is H. pylori. Chronic duodenitis typically develops against the background of chronic gastritis associated with H. pylori and metaplasia of the gastric epithelium in the duodenum. Foci of metaplastic epithelium are easily damaged by acidic gastric contents, and erosions develop in the areas of metaplasia. Duodenitis caused by H. pylori is typically localized in the duodenal bulb [41]. In chronic hepatitis and chronic pancreatitis, the development of chronic duodenitis is caused by increased absorption of pancreatic enzymes; decreased bicarbonate secretion, which promotes acidification of duodenal contents and the action of aggressive factors of gastric juice; reduced resistance of the duodenal mucosa; in pulmonary and cardiovascular diseases, hypoxia of the duodenal mucosa contributes to the development of chronic duodenitis [41]. In the development of chronic duodenitis during biliary tract diseases, intestinal microflora plays an important role. This factor plays an especially large role in gastric achylia. Under these conditions, dysbiosis easily develops; the proximal small intestine, including the duodenum, is colonized by a bacterial flora unusual for these segments [42, 43, 44].

Local mechanisms of the pathogenesis of chronic duodenitis include impaired regional microcirculation, which leads to dystrophic, necrotic, and inflammatory-erosive lesions of the duodenal mucosa, impaired repair processes—including the differentiation of glandular structures—and the development of atrophy and secretory insufficiency. In the area of microcirculatory disorders in the affected tissue, neutrophilic and lymphoplasmacytic infiltration appears, triggering an immuno-inflammatory reaction that, during a chronic disease course, can acquire an autoimmune character.

1.3 Epidemiology of the Disease or Condition

The prevalence of CG and CD in the pediatric population has not been precisely established, given the lack of epidemiological morphological studies. Data provided in the literature are based on the examination of children with chronic gastritis or functional dyspepsia. According to available data, the proportion of CG among young school-age children is 45%, among middle school-age children 73%, and 65% among older schoolchildren; CG is frequently combined with duodenitis, whereas in an isolated form it occurs in only 10-15% of children [45, 46].

Studies on the prevalence of H. pylori infection as one of the important etiological factors in the development of CG among children show a fairly high prevalence of H. pylori in children in the 1990s and its significant decline in recent times. Over nearly two decades—from 1996 to 2014—a population of 14-17-year-old schoolchildren was studied in Siberia. During this period, 684 children were examined, revealing a decrease in the prevalence of infection: in 1996 – 62.5%, in 1999 – 56.2%, in 2009 – 50%, in 2014 – 45.1% [47, 48]. In the late 1990s and early 2000s in Saint Petersburg, children were screened for H. pylori using serological methods. In 1995, in a group of 307 children aged 2-19 years, the prevalence of infection was 44%, while in 2005 among children of the same age group it was 31% [49].

In 2007-2011, also in Saint Petersburg, 860 children aged 0-17 years were examined using DRG ELISA test systems (Germany) and the Biohit GastroPanel (Finland). Antibodies were detected in 48.95% of cases [50]. In 2017-2018 in Ryazan, 24 children aged 4-16 years were examined: 20.8% of the examinees proved to be seropositive [51].

Duodenitis is one of the most common, if not the most common, diseases of the duodenum, and together with gastritis, of the entire gastrointestinal tract. Histological studies have established that an inflammatory process of varying degrees in the duodenal mucosa is registered in 100% of children with clinical signs of functional dyspepsia [52]. Among patients with dyspeptic syndrome, morphological signs of acute duodenitis are detected in 1.5% of examinees, and chronic duodenitis in 25.6% [45, 53]. According to some data, the frequency of chronic duodenitis in chronic gastritis (CG) is also high, ranging from 75% to 100% [55].

1.4 Features of Coding the Disease or Condition

K29 Gastritis and duodenitis

K29.0 – Acute hemorrhagic gastritis

K29.1 – Other acute gastritides

K29.3 – Chronic superficial gastritis

K29.4 – Chronic atrophic gastritis

K29.5 – Chronic gastritis, unspecified

K29.6 – Other gastritides (hypertrophic giant, granulomatous, Ménétrier's disease)

K29.7 – Gastritis, unspecified

K29.8 – Duodenitis

K29.9 – Gastroduodenitis, unspecified

K31.8 – Other specified diseases of stomach and duodenum

1.5 Classification of the disease or condition

There are several classifications of CG and CD. In 1984, A.V. Mazurin and co-authors developed a classification of CG that was adopted as a basis and has been used in Russian pediatric practice to the present day. Constantly updated data, driven by the large number of studies conducted since the discovery of H. pylori in 1983, require updating recommendations for the practical work of general practitioners, gastroenterologists, pediatricians, and primary care physicians. Both Russian and international classifications are undergoing changes in accordance with the obtained results. A.V. Mazurin's classification was revised and supplemented by the Union of Pediatricians of Russia in 2002 (Table 1) [45, 54, 55].

Table 1

Classification of chronic gastritis and duodenitis [45, 54, 55]

In foreign practice, the Sydney System of classification, modified in 1996, has been used since 1990.

Since 2006, the diagnosis of chronic gastritis has been considered exclusively morphological. In this regard, in 2008, to complement the Sydney system, a histological grading system for gastritis was developed based on the evaluation of histological signs of inflammation severity and atrophy in the antrum (3 biopsy specimens) and gastric body (2 biopsy specimens), named OLGA (Operative Link for Gastritis Assessment), with grading (severity of inflammatory infiltration) and staging (severity of atrophy) of chronic gastritis, which is currently used for adults. There is no universally accepted separate histological classification of chronic gastritis in international pediatric practice [57].

In 2015, the Kyoto Global Consensus on the management of H. pylori-associated gastritis was adopted, which updated existing information and reviewed it through the prism of gastric cancer risk for adult patients [34].

In 2010, A.I. Khavkin and G.V. Volynets proposed a working classification of chronic gastritis in children, supplementing the existing classification by A.V. Mazurin (Table 4) [45, 54, 55]. This classification is currently undergoing scientific validation and discussion. Given the expanded etiological characteristics of chronic gastritis presented in this classification, it may potentially become the leading classification of chronic gastritis in the future.

Currently, for practical use, one should apply the classification of A.V. Mazurin, revised and supplemented by the Union of Pediatricians of Russia in 2002.

The etiological diversity of chronic duodenitis is presented in the classification proposed by the Kyoto Consensus expert panel [34] (Table 5).

Table 5

Classification of duodenitis forms based on the etiological principle (Kyoto Consensus)

In pediatric literature, duodenitis is most frequently described in chronic gastritis associated with H. pylori [58-61], which is due to the leading role of Helicobacter pylori infection in the etiology of chronic duodenitis; in giardiasis [62, 63] and the combination of these two etiological factors [60]; and duodenitis associated with herpesvirus infections [64].

Aside from the etiological approach, there are several other approaches to classifying duodenitis. Acute and chronic duodenitis are distinguished [65]. In the Sydney system of chronic gastritis classification, adopted in 1990 at the 9th World Congress of Gastroenterology, the diagnosis of chronic duodenitis is reflected in the endoscopic examination section [66].

The endoscopic examination section includes the following variants:

- erythematous duodenitis (based on the presence of duodenal mucosal hyperemia);

- erosive duodenitis (based on the presence of superficial mucosal defects);

- hemorrhagic duodenitis (in the presence of hemorrhagic manifestations);

- atrophic duodenitis (signs of mucosal atrophy);

- nodular duodenitis (with visually detectable follicular formations) [67, 68].

A more detailed classification of duodenitis based on endoscopic presentation is presented in Table 6 [55, 68].

Table 6

Classification of duodenitis based on endoscopic presentation

Chronic duodenitis is a morphological diagnosis. M.R. Konorev et al. (2003) propose distinguishing the following morphological types of chronic duodenitis [68]:

• non-atrophic;

• atrophic;

• Helicobacter-associated;

• nodular;

• granulomatous;

• eosinophilic;

• lymphocytic.

1.6 Clinical presentation of the disease or condition

Chronic gastritis as a morphological diagnosis has no specific clinical equivalent; most children are asymptomatic.

The Kyoto Consensus noted that H. pylori infection itself can lead to symptoms in a subset of patients with dyspepsia. Therefore, if an H. pylori-infected patient with dyspepsia and no morphological changes in the gastric mucosa shows persistent symptom improvement (for 6–12 months) following eradication therapy, such patients are considered to have H. pylori-associated dyspepsia. In other cases, they are managed as patients with functional dyspepsia requiring alternative treatment [34].

General manifestations of chronic gastritis in children include weakness, irritability, cardiovascular disorders such as cardialgia and arrhythmia; patients with atrophic chronic gastritis may develop a symptom complex similar to dumping syndrome (sudden weakness, pallor, diaphoresis, drowsiness occurring shortly after eating), sometimes combined with bowel disorders and an imperative urge to defecate. There is a specific category of symptoms known as «red flag» (alarm) symptoms. In children, attention should be paid to the onset of dysphagia, recurrent vomiting, hematemesis, melena, recurrent diarrhea, stunted physical and sexual development, and prolonged fever. If these signs are identified, an expanded workup is required to rule out severe organic gastrointestinal pathology, including erosive gastritis and duodenitis.

Complications of chronic gastritis include hypovitaminosis, anemias, and pancreatitis. Erosive lesions may cause bleeding. Since in most cases chronic gastritis and chronic duodenitis occur in combination, it is difficult to isolate clear diagnostic symptoms of isolated duodenitis [59]. The most typical symptoms of chronic duodenitis are aching epigastric and periumbilical pain accompanied by a sensation of heaviness, fullness in the upper abdomen, nausea, and salivation. Vegetovascular disorders—weakness, diaphoresis, headaches, and dizziness—frequently appear during puberty [71].

Complications of chronic duodenitis are quite diverse. They include [72]:

• Pathological duodenogastric reflux: occurs as a result of dyskinesia and duodenostasis, pyloric sphincter incompetence, and contributes to the development of chronic antral gastritis.

• Duodenostasis: caused by dystrophic processes in the intestinal wall and impaired function of the enteric nervous system. It leads to stasis and fermentation of food masses entering from the stomach, as well as the development of intoxication.

• Small intestinal bacterial overgrowth syndrome: associated with inflammatory and erosive changes in the duodenal mucosa, duodenostasis, and impaired gastric and duodenal digestion.

• Intestinal bleeding: most commonly occurs in erosive-hemorrhagic duodenitis, is rarely massive, and leads to pronounced anemia. It is observed at various times in 19–25% of patients with chronic duodenitis.

• Papillitis: occurs as a result of a pronounced inflammatory process in the area of the major duodenal papilla, which can lead to its stenosis, the development of obstructive jaundice, and cholangitis.

• Periduodenitis: characterized by a pronounced inflammatory process affecting the entire duodenal wall, frequently extending to adjacent tissues. It occurs in widespread erosive processes and papillitis.

• Duodenal deformity: a consequence of a pronounced inflammatory-erosive process and papillitis.

• Dumping syndrome: most commonly occurs when duodenitis is combined with peptic ulcer disease and chronic gastritis, in patients with vagotonia, accelerated evacuation of food masses into the small intestine, inadequate insulin secretion, insufficient starch digestion by pancreatic amylase alpha-amylase, hypoglycemia, and parasympathetic-type vegetovascular paroxysms.

In infants and young children, chronic gastritis and chronic duodenitis are rare and primarily associated with other diseases: celiac disease, infectious enteritis, etc. The frequency of detecting atrophic processes in the gastric mucosa and duodenal mucosa directly depends on the patients' age [73].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition:

The diagnosis of chronic gastritis and chronic duodenitis is a morphological diagnosis based on the detection of histological signs of inflammation of the gastric and/or duodenal mucosa (lymphocytic and neutrophil infiltration, as well as atrophy, intestinal metaplasia, and dysplasia). Additional diagnostic criteria include objective changes characteristic of gastric mucosal inflammation identified during endoscopic examination (nodular hyperplasia and erosive changes). Positive test results for H. pylori help establish the etiology of gastritis, as this microorganism is an important etiological factor in the development of gastric mucosal inflammation [57].

2.1 Complaints and Anamnesis

Potential complaints in patients with gastritis and duodenitis and their interpretation are presented in subsection 1.6. Attention must be paid to the presence or absence of alarm symptoms: persistent pain in the right upper or right lower quadrant, dysphagia, odynophagia, persistent vomiting, signs of gastrointestinal bleeding, involuntary weight loss, growth deceleration, delayed puberty, unexplained fever, and a family history of inflammatory bowel disease, celiac disease, or peptic ulcer disease [74].

When taking the history, it should be clarified whether the patient has previously undergone an EGD with biopsy; whether there were indications of inflammatory changes in the gastric and duodenal mucosa, as well as atrophy, intestinal metaplasia, or epithelial dysplasia. It is important to ascertain whether H. pylori infection was previously detected, whether eradication therapy was previously administered, what treatment regimen was used, and whether the efficacy of eradication therapy was verified.

When autoimmune gastritis is suspected, a history of other autoimmune diseases, previously detected atrophy of the gastric body mucosa with a relatively preserved antral mucosa, and the presence of anti-gastric parietal cell antibodies and intrinsic factor antibodies are important.

Clinically, autoimmune gastritis is frequently associated with other autoimmune conditions, such as autoimmune thyroiditis, Sjögren's syndrome, and type 1 diabetes mellitus, and can therefore be considered a systemic disease. In particular, complications of autoimmune thyroiditis classified under type 3B autoimmune polyglandular syndrome are well known [25]. However, autoimmune gastritis can also be an independent disease not associated with other immunopathological processes.

The clinical presentation of autoimmune gastritis in children is not associated with any specific signs or symptoms characteristic of gastrointestinal diseases [25, 32].

In children, as in adults, abdominal pain is more characteristic of non-autoimmune gastritis. Pain syndrome in autoimmune gastritis (if present) is characterized by prolonged, aching abdominal pain without a definite localization. Among dyspeptic manifestations, heartburn, a feeling of bitterness and/or acidity in the mouth (which are specific for gastroesophageal reflux), and flatulence (indicating impaired digestion) are more characteristic of autoimmune gastritis compared to non-autoimmune gastritis. However, compared to children with non-autoimmune gastritis, children with autoimmune gastritis more frequently exhibit chronic nonspecific intoxication syndrome, characterized by low-grade fever and/or episodic, short-term, unmotivated spikes in body temperature to febrile levels, as well as lymphadenopathy with predominant enlargement of the anterior and/or posterior cervical lymph node groups; hepatosplenomegaly may also be present (Table 1) [75]. Red blood cell parameters in 86.2% of children with autoimmune gastritis remain within age-appropriate reference ranges. Mild iron deficiency anemia is observed in 13.8% of patients. Another symptom of autoimmune gastritis characteristic of adults—vitamin B12-deficiency anemia—is practically absent in children [32]. This is likely due to the fact that pernicious anemia develops predominantly in atrophic gastritis appearing at an older age, often in the elderly, whereas autoimmune gastritis in children is in the pre-atrophic stage [75].

2.2 Physical Examination

Physical examination includes superficial and deep palpation of the abdomen (palpation in diseases of the esophagus, stomach, duodenum), which may reveal tenderness in the epigastric region; assessment of peritoneal irritation signs (palpation in diseases of the esophagus, stomach, duodenum), which is important in severe abdominal pain syndrome; liver percussion (percussion in diseases of the liver and biliary tract) to rule out concomitant hepatomegaly; and auscultation (auscultation in diseases of the esophagus, stomach, duodenum) to assess the peristalsis of the digestive tract.

There are no pathognomonic physical examination findings for gastritis and duodenitis.

2.3 Laboratory Diagnostics

There are no pathognomonic laboratory markers for gastritis and duodenitis. Laboratory tests are performed in children to rule out or confirm complications, as well as for cancer prevention purposes in older adolescents.

• Patients with gastritis and duodenitis are recommended to undergo a complete blood count (CBC) with determination of hemoglobin, hematocrit, erythrocytes, color index, platelets, and leukocytes with differential, in order to confirm/exclude anemia due to bleeding from erosive lesions of the gastroduodenal mucosa, as well as anemia as a consequence of autoimmune gastritis [76-80].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: leukocytosis may indicate an infectious etiology of the disease, microcytic anemia indicates occult blood loss or iron malabsorption, and macrocytic anemia develops due to vitamin B12 deficiency in autoimmune gastric involvement [76-80]. The test is performed during dynamic follow-up; the frequency of administration is determined by the clinical situation and detected changes.

If anemia is detected, diagnosis and treatment are carried out in accordance with the relevant clinical guidelines.

• All patients with suspected autoimmune gastritis are recommended to have blood levels of antibodies to gastric antigens determined (gastric parietal cell antibodies) to confirm or exclude the diagnosis [81-85].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Parietal cell antibodies are an effective tool for screening for autoimmune atrophic gastritis and malignant pernicious anemia. The target for parietal cell antibodies is H+/K+ ATPase, with this type of antibody targeting both the alpha and beta subunits of the proton pump, although the main antigen is the alpha subunit. Parietal cell antibodies can be detected in 85-90% of patients with pernicious anemia, as well as in 20.7% of patients with Helicobacter pylori infection, which is considered one of the possible causes of autoimmune gastritis. The sensitivity of parietal cell antibody testing for the diagnosis of autoimmune gastritis is ~80%, with low specificity (they are detected in individuals without autoimmune gastritis: found in the serum of patients with type 1 diabetes mellitus, autoimmune thyroid diseases, vitiligo, and celiac disease). Intrinsic factor blocking antibodies block the binding of cobalamin to intrinsic factor. Sensitivity for the diagnosis of autoimmune gastritis is ~50%, but specificity reaches 99% [81-86].

Cases of autoimmune gastritis combined with autoimmune thyroiditis, type 1 diabetes, rheumatological diseases, and immunodeficiency states have been published; therefore, patients with autoimmune gastritis should be referred for specialist consultations and examinations in accordance with the relevant clinical guidelines [20, 188, 189].

• Pediatric patients with gastritis and duodenitis in whom anemia/iron deficiency has been detected are recommended to undergo selective fecal occult blood testing to diagnose occult bleeding and subsequently determine the scope of endoscopic examination in case of a positive result [93, 94].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: when evaluating the results of the fecal occult blood test, it must be taken into account that a positive reaction may occur in many other diseases, the use of certain medications (bismuth subcitrate dicitrate**, iron preparations, ascorbic acid**), and non-compliance with dietary recommendations prior to testing (consumption of meat, beets, etc.).

The test generally can be used when EGDS is not feasible and/or when searching for sources of occult bleeding in the lower gastrointestinal tract.

2.4 Instrumental Diagnostics

• Pediatric patients with suspected gastritis and duodenitis are recommended to undergo upper gastrointestinal endoscopy (esophagogastroduodenoscopy (EGD)) according to indications and "alarm" symptoms, which include: dysphagia, odynophagia, medically refractory gastroesophageal reflux, vomiting, signs of gastrointestinal bleeding, chronic persistent or stereotyped abdominal pain, anorexia, weight loss and/or growth retardation, anemia, chronic diarrhea, and a family history of peptic ulcer disease or gastric cancer, in order to confirm the diagnosis, detect upper GI mucosal changes, and perform gastric and duodenal biopsies [95, 96].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: performing an endoscopic examination in all pediatric patients with suspected gastritis and duodenitis is not feasible in routine medical practice; a differentiated approach and determination of indications for this procedure are essential, taking into account modern concepts of upper GI pathology [95, 96]. Endoscopic signs of gastritis in children in the vast majority of cases directly correlate with histological findings (confirmed gastritis). Modern endoscopic imaging techniques, in particular high-definition videoendoscopy with multimodal imaging and magnification, provide additional highly informative capabilities for the diagnosis of gastritis and duodenitis, as they can be used to increase the detection rate of atrophy/metaplasia at the endoscopic stage and to enhance targeted biopsy capabilities (EGD with improved image quality, including chromoendoscopy) [95].

The endoscopic presentation of chronic gastritis and duodenitis is provided in Appendix A3.

• Pediatric patients with suspected gastritis and duodenitis who have indications for EGD are recommended to undergo endoscopic gastric biopsy and endoscopic duodenal biopsy (from the body and antrum of the stomach, duodenal bulb, and post-bulbar area) followed by pathomorphological (histological) examination of the gastric biopsy (surgical) material (including gastric biopsy material analysis using histochemical and immunohistochemical methods, and microscopic examination of the gastric material for Helicobacter pylori) and pathomorphological examination of the duodenal biopsy (surgical) material (including duodenal biopsy material analysis using histochemical and immunohistochemical methods) to rule out malignant ulceration, diagnose H. pylori and other infectious agents, and detect inflammatory changes, atrophy, and metaplasia to determine the severity of gastritis and duodenitis [97-104].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: pathomorphological (histological) examination is indispensable for clarifying the features of the inflammatory process in the gastric mucosa (atrophic vs. non-atrophic), its degree of activity (active vs. inactive), and for detecting H. pylori itself [98]. Unlike in adults, there is no single uniform protocol regarding the number of biopsies in children; targeted biopsies are taken from affected areas of the gastroduodenal mucosa. Biopsy specimens from different parts of the stomach and duodenum must be clearly labeled and placed in separate containers. When ulcers or erosions are detected, as well as in suspected H. pylori-associated gastritis, gastric mucosal biopsy should be performed to verify H. pylori using available methods. Biopsies should be taken during any diagnostic endoscopy in children, even from unchanged areas [96, 106]. For the diagnosis of special forms of gastritis (autoimmune atrophic gastritis, atrophic-hyperplastic gastritis, hypertrophic gastritis, polypoid gastritis, lymphocytic gastritis, granulomatous gastritis, eosinophilic gastritis, rigid (antral) gastritis), the results of histological examination are decisive.

The pathomorphological (histological) presentation of chronic gastritis and duodenitis is provided in Appendix A3.

• Pediatric patients with suspected gastritis and duodenitis are recommended to undergo a comprehensive ultrasound examination of the abdominal organs (including water-siphon test) to exclude or confirm pathology of other abdominal organs, especially the biliary tract [54, 107].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: biliary tract pathology is quite common in children and may accompany gastritis and duodenitis. The sensitivity and specificity of ultrasound diagnostics are somewhat lower compared to computed tomography and largely depend on the qualification of the ultrasound specialist; however, this method is non-invasive, carries no radiation burden, and can be repeated, therefore, it can be used for screening examinations [54, 107, 108].

It is also useful to perform a gastric ultrasound with a water-siphon test due to the need to exclude/confirm motility disorders: GER and DER.

2.5 Other Procedures

Special attention should be paid to the diagnosis of H. pylori infection in childhood because, unlike the adult population, the "test and treat" strategy is not applied to children, where eradication therapy is prescribed to all patients regardless of the presence or absence of complaints upon detection of H. pylori. In pediatric practice, a more differentiated approach is important, especially when the microorganism is detected in a patient without dyspepsia symptoms, when the issue of treatment can be considered after a thorough discussion with the patient/parents [109].

• Patients with gastritis and duodenitis are recommended to be tested for H. pylori infection to determine the etiology of the disease and treatment tactics [10, 15, 34].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: H. pylori infection is an important etiological factor in gastritis [10, 15, 34]; therefore, if inflammatory changes in the gastroduodenal mucosa are detected, the presence of this microbial etiological agent must be ruled out or confirmed [10, 15, 34].

• In patients with gastritis and duodenitis, testing for H. pylori is recommended to be performed no earlier than 2 weeks after the cessation of antisecretory drugs, especially proton pump inhibitors, and/or 4 weeks after the cessation of systemic antimicrobial drugs and bismuth tripotassium dicitrate**, in order to avoid distorted results [10].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Therapy with proton pump inhibitors and systemic antibacterial drugs can yield false-negative results in diagnostic tests for H. pylori infection due to the suppression of microorganism replication [110].

The specified time intervals apply to cases of primary H. pylori diagnosis as well as for monitoring treatment efficacy. They concern both invasive and non-invasive tests, namely, bacteriological, pathomorphological (histological) methods, the 13C-urea breath test for Helicobacter pylori (rapid urease test), and rapid immunochromatographic stool testing for Helicobacter pylori [10, 109, 110, 111].

• For the primary diagnosis of H. pylori infection in patients with gastritis and duodenitis, it is recommended to use high-sensitivity invasive methods: the 13C-urea breath test for Helicobacter pylori (rapid urease test) or microscopic examination of gastric material for Helicobacter pylori, as well as (if available) bacteriological examination of biopsy specimens (microbiological (cultural) examination of gastric wall biopsy specimens for Helicobacter pylori, microbiological (cultural) examination of gastric mucosa biopsy specimens for Helicobacter pylori) [10].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: currently, the main "gold standard" for investigating H. pylori-associated diseases in children remains upper gastrointestinal endoscopy with biopsy for bacteriological and histological examination, and the 13C-urea breath test for Helicobacter pylori (rapid urease test) [112]. A feature of modern dry rapid urease tests is the ability to test the same biopsy specimen first directly with the urease test and then pathomorphologically (histologically), which reduces the number of biopsies required, thereby shortening the procedure time and accelerating and facilitating diagnostics [114]. When using gel or liquid urease tests where re-testing the same biopsy specimen is impossible, it is necessary to take 2 biopsy specimens from each section, and if a bacteriological examination is also performed—an additional 2 biopsy specimens. In such cases, it is advisable to perform EGD under anesthesia if technical capabilities exist and there are no contraindications, taking at least 4 (maximum 6) biopsy specimens from the body and antrum of the stomach [115].

In a review by Seo et al. [116] examining 255 children using the 13C-urea breath test for Helicobacter pylori (rapid urease test), it was found that the sensitivity of this method increased with age (it was lowest in the 0-4 years age group) and with the number of biopsies [116]. The authors attribute their findings to a lower bacterial density in children compared to adolescents and adults.

The use of microbiological (cultural) examination of gastric wall/mucosa biopsy specimens for Helicobacter pylori with antimicrobial susceptibility testing (using methods such as E-test (gradient diffusion method for antimicrobial susceptibility testing), disk diffusion method, real-time PCR (detection of Helicobacter pylori DNA in gastric mucosa biopsy specimens by PCR), FISH test (fluorescence in situ hybridization (FISH) method)) and PCR to determine mutations encoding resistance to clarithromycin**, metronidazole**, #tetracycline, is desirable, if possible, even when prescribing first-line therapy in children, and is absolutely indicated in case of failure of first- and second-line therapy for personalized treatment selection [10, 54, 109].

In the absence of technical capabilities to perform bacteriological examination, PCR (detection of Helicobacter pylori DNA in gastric mucosa biopsy specimens by PCR), or the FISH test (fluorescence in situ hybridization (FISH) method), the choice of treatment regimen must be based on data regarding the prevalence of resistant H. pylori strains in the specific region.

Primary diagnosis of H. pylori infection using non-invasive tests (e.g., the 13C-urea breath test for Helicobacter pylori (rapid urease test), ammonia breath test) is of a screening nature; the "test and treat" approach is not applied in pediatrics [109]. If a non-invasive test yields a positive result, EGD is indicated for a definitive diagnosis using a rapid urease test and histology, as described above. The combination of the 13C-urea breath test for Helicobacter pylori (rapid urease test) and pathomorphological examination (histology) increases the sensitivity and specificity of primary diagnosis to nearly 100%. Using only the 13C-urea breath test for Helicobacter pylori (rapid urease test) or only pathomorphological examination (histology) reduces diagnostic accuracy by approximately 10–15% [117].

Comments: The clinical utility of the test is limited by its inability to differentiate between past and current H. pylori infection or to monitor eradication efficacy. Not all serological tests are equivalent. ESPGHAN (2018) guidelines state that the determination of IgA and IgG antibodies to H. pylori in serum, whole blood, urine, and saliva should not be used in clinical practice. Testing for H. pylori antibodies (via ELISA) is acceptable for population-based research purposes and when no other diagnostic modalities for H. pylori are available [109].

Thus, serological tests should not be used for diagnosis, nor are they used to monitor H. pylori eradication, as IgG antibodies can persist in the blood for a prolonged period [109, 117].

• To verify successful H. pylori eradication 4–6 weeks post-treatment, it is recommended to use the 13C-urea breath test for Helicobacter pylori (rapid urease test) (using urea of natural isotopic abundance) or fecal H. pylori antigen testing (using monoclonal antibodies) [10, 118].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: The sensitivity of the 13C-urea breath test for Helicobacter pylori (rapid urease test) is 94–96%, the ammonia breath test (not included in the approved Nomenclature of Medical Services) is 90–92%, and the fecal H. pylori antigen test is 83–92%, with specificities of 90–93%, 86–93%, and 90–100%, respectively [118–120]. It should be borne in mind that the 13C-urea breath test for Helicobacter pylori (rapid urease test) may yield false-positive results in children under 6 years of age due to a smaller volume of distribution and different CO₂ production rates [113]. If a follow-up endoscopic examination is required after treatment, preference should be given to invasive tests for H. pylori verification: histological examination of gastric and duodenal biopsy (surgical) specimens or the 13C-urea breath test for Helicobacter pylori (rapid urease test).

Comment: EGD is not indicated for suspected functional gastrointestinal disorders (if the clinical presentation meets their criteria) [74, 121–126]. In the absence of "alarm" symptoms, current guidelines suggest presuming functional dyspepsia or another functional disorder, prescribing treatment, and proceeding to a more in-depth workup—specifically EGD—only if treatment is ineffective or "alarm" symptoms appear. The decision to perform an EGD also takes into account the family history and genetic predisposition to peptic ulcer disease or gastric cancer. If organic lesions, including gastritis and duodenitis, are not suspected clinically or detected via EGD, invasive diagnostic testing solely to detect H. pylori infection should not be performed. Diagnostic testing for H. pylori in children is justified only when the expected benefits outweigh the costs and risks associated with testing and subsequent treatment. H. pylori-associated gastritis in children without peptic ulcer disease rarely causes symptoms or progresses to more severe disease complications during childhood [127]. The lower risk of complications in children may be partially explained by a different immune response to the infection. Compared to adults, gastric biopsies from H. pylori-infected children show less pronounced inflammation. Furthermore, an increased number of immunosuppressive T regulatory cells (Treg) has been found, along with an anti-inflammatory IL-10 cytokine response rather than a pro-inflammatory IL-17 response [128–129]. Based on available data, treatment aimed at eradicating H. pylori infection is not expected to improve symptoms in children, except in cases of peptic ulcer disease [127].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

3.1.1 Diet Therapy

• Patients with acute gastritis and duodenitis are recommended dietary therapy to minimize trauma to the inflamed gastroduodenal mucosa [95, 130, 131].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: chemical, mechanical, and thermal dietary restrictions are indicated; fractional meals up to 5–6 times a day for 1 month, after which the number of meals is reduced to 4 times a day, and after 2–3 months, upon achieving sustained clinical and endoscopic remission, the patient returns to a normal diet. During the acute phase of gastritis and duodenitis, fried, smoked, salted, and pickled foods, as well as products containing extractive substances (pepper, mustard, spices, onion, garlic), should be excluded; steamed, boiled, or stewed foods are preferred. Porridges, sweet berry kissels, mousses, jellies, and baked apples are also recommended [95, 130, 131].

3.1.2 H. pylori eradication

• Pediatric patients with gastritis and duodenitis who test positive for H. pylori are recommended to undergo eradication therapy based on absolute indications (presence of erosive and/or atrophic changes in the gastroduodenal mucosa, history of a family predisposition to peptic ulcer disease or gastric cancer in relatives) and relative indications (any H. pylori-associated variants of chronic gastroduodenitis presenting with prominent clinical symptoms and/or high H. pylori mucosal colonization density according to histological data, any H. pylori-associated variants of gastroduodenal pathology in relatives who wish to undergo a course of eradication therapy [after evaluation]) to ensure a personalized approach considering the benefits and risks of the administered treatment [54, 95, 109].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: unlike adults, for whom H. pylori eradication is required in all cases regardless of symptoms or gastroduodenal mucosal damage [10, 95, 120], a differentiated approach to determining the need for anti-H. pylori therapy is applied in the pediatric population. This is particularly relevant for young children, given the limitations on the use of antisecretory and systemic antibacterial drugs, as well as the high risk of H. pylori reinfection. In populations with a high infection prevalence, the rate of reinfection among young children following successful eradication can be substantial. A study conducted in Bolivia among a high-prevalence, low-income population showed that the reinfection rate 1 year after successful treatment is 20% in children under 10 years of age and 8% in older children and adolescents [133]. In Latin America, the 1-year reinfection rate is 11% [134], while in Germany (a low-prevalence country for H. pylori), it is 2.3% per year [135]. The risk of developing H. pylori-associated cancer or mucosa-associated lymphoid tissue (MALT) lymphoma during childhood in Europe and North America is extremely low. The risk-benefit ratio of eradication therapy may vary across different regions. In regions with a high incidence of gastric cancer, such as China or Japan, the benefit of treatment aimed at reducing gastric cancer risk may outweigh the risks associated with treatment [137]. In Western countries, epidemiological data indicate that H. pylori infection, particularly in early childhood, may be associated with a lower prevalence of allergic diseases, specifically bronchial asthma [138–141]. Therefore, the decision to treat H. pylori-associated gastritis and duodenitis discovered incidentally during EGD, in the absence of erosive and ulcerative gastroduodenal mucosal lesions, should be carefully discussed with the patient and their family, taking into account the potential risks and benefits of treatment for each individual patient.

• Patients with gastritis and duodenitis infected with H. pylori are recommended preliminary microbiological (culture) testing of gastric mucosal biopsies for Helicobacter pylori with antimicrobial susceptibility testing to select an individualized treatment regimen and improve H. pylori eradication efficacy (Table 1) [109].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: The use of microbiological (culture) examination of gastric mucosa biopsy specimens for Helicobacter pylori with determination of susceptibility to antibacterial drugs (by dilution method or E-test) and PCR to determine mutations encoding resistance to clarithromycin**, metronidazole**, and #tetracycline is desirable when prescribing even first-line therapy in children and is strictly indicated in case of treatment failure of the first and second lines for individual therapy selection [10, 54, 95, 109].

If it is technically impossible to perform bacteriological examination, PCR (determination of Helicobacter pylori DNA in gastric mucosa biopsy specimens by PCR) or the FISH test (fluorescence in situ hybridization, which is not included in the approved Nomenclature of Medical Services), the choice of treatment regimen should be based on data on the prevalence of resistant H. pylori strains in a specific region

Table 1

Eradication regimens taking into account established H. pylori antibiotic resistance

Symbols and abbreviations:

AMX – amoxicillin**,

CLA – clarithromycin**,

MET – metronidazole**,

PPI – proton pump inhibitors (#omeprazole**, #rabeprazole, #esomeprazole**),

T – #tetracycline,

B** – bismuth subcitrate dicitrate**

Recommended drug doses are presented in Table 2 [95, 109]

Due to technical difficulties in individual selection of systemic antimicrobial drugs for treatment, preference is given to the regimen prescribed when the susceptibility of H. pylori to these drugs is unknown.

• In patients with gastritis and duodenitis infected with H. pylori, if it is impossible to determine the microorganism's susceptibility to systemic antimicrobial drugs as first-line therapy, it is recommended to use empirically validated effective eradication therapy regimens [95, 109].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment:

One of the following regimens should be used:

• PPI + AMX** + CLA** (+B**)

• PPI + CLA** + MET** (+B**)

• PPI + AMX** + MET** (+B**)

• PPI + AMX** or CLA** + Nifuratel

• PPI + AMX** + Josamycin** (sequential administration of antibiotics for 7 days each) (+B**) (for second-line therapy)

• PPI + #T + B** + MET** (from 8 years of age)

Legend: AMX** – amoxicillin**, CLA** – clarithromycin**, MET** – metronidazole**, PPI – proton pump inhibitors (#omeprazole**, #rabeprazole, #esomeprazole**), T – #tetracycline*, B** – bismuth subcitrate dicitrate**

In the absence of data on H. pylori susceptibility to systemic antimicrobial drugs, it is possible to increase the standard dose of amoxicillin** by 1.5 times (in accordance with ESPGHAN guidelines) or use the latest ESPGHAN regimen [109]. Bismuth subcitrate dicitrate** can be added as a component to triple regimens starting from the first line for children aged 4 years and older. Duration of treatment is 14 days. The administration of PPIs (according to the ATX classification: proton pump inhibitors (A02BC): #omeprazole**, #rabeprazole, #esomeprazole**) or bismuth subcitrate dicitrate** is not prolonged beyond 14 days without special indications.

#Tetracycline can be introduced into eradication regimens taking into account age restrictions (from 8 years of age). Domestic and foreign experience with modern #tetracycline drugs demonstrates its efficacy and safety [95, 109].

Although furazolidone is an inexpensive and highly effective drug against H. pylori, to which virtually no primary or secondary resistance occurs, the high frequency of serious adverse effects (nausea, vomiting, etc.) precludes its recommendation in pediatric practice [142, 143]. According to limited studies in adults and children, the efficacy of 3-component regimens including nifuratel in combination with amoxicillin**, PPIs, or other drugs for the treatment of peptic ulcer disease and GERD (A02BX) (bismuth preparations) is 82.9-86.0% [144-146]. However, it should be noted that there is a lack of meta-analyses on this issue.

There is evidence of the possibility of using josamycin** (dispersible tablets, for children weighing >10 kg) as an alternative to clarithromycin** in children in sequential therapy regimens [118]; indications for use in Helicobacter pylori infection in children are included in the drug's package leaflet.

Sequential therapy, which has no advantages over classical regimens with simultaneous drug administration, may be offered to the patient solely to improve adherence in cases where parents or the patient themselves for various reasons are reluctant to follow standard treatment regimens. Nevertheless, a number of authors recommend sequential therapy in first-line regimens [147, 148].

It should be noted that not all proton pump inhibitors are approved for use in children and not all of them have indications for peptic ulcer disease or use in H. pylori eradication regimens.

• In patients with gastritis and duodenitis infected with H. pylori, if eradication of H. pylori is not achieved after the first course of treatment (follow-up should be performed 4–6 weeks after completion of the regimen), re-therapy is not carried out immediately, but at the time of the subsequent exacerbation in order to ensure maximum safety of treatment [109].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: The choice of treatment regimen should, if possible, be based on H. pylori culture data and individual determination of its antibiotic susceptibility (see Section 2). If this is not feasible, quadruple therapy is used: PPI with #tetracycline, metronidazole**, and bismuth, or regimens including nitrofuran derivatives) [95].

Recommended treatment regimens (provided they have not been used previously):

• B** + PPI + AMO** + CLA**

• B** + PPI + AMO** or CLA** + nifuratel

• PPI + #T + B** + MET**

Duration of treatment is 14 days.

Designations: AMO** – amoxicillin**, CLA** – clarithromycin**, MET** – metronidazole**, PPI – proton pump inhibitors, T – #tetracycline, B** – bismuth dicitrate tripotassium**

• For patients with gastritis and duodenitis who are H. pylori-positive and have indications for eradication therapy, it is recommended to ensure adherence to the prescribed treatment (compliance), including through a discussion with parents/legal representatives in order to achieve maximum efficacy of pathogen eradication [95, 107, 109, 118, 149, 150].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: Compliance should be considered a key factor in the success of H. pylori eradication therapy. A controlled study showed that when taking more than 60% of the prescribed medications, infection eradication was 96%, while taking less than 60% (low compliance) resulted in 69% [149]. In a large-scale randomized controlled trial, the eradication rate decreased with low compliance (taking less than 80% of prescribed medications) by 34%, and H. pylori persistence was observed in 59% of non-compliant patients [150]. Time should be taken to counsel the patient and/or their relatives, explain how to take complex drug therapy, and evaluate potential side effects of antibiotic therapy. The necessity of completing the treatment and taking the prescribed total dose of medications, as well as the need for a follow-up examination to assess eradication efficacy, should be specifically emphasized.

• When an H. pylori infection is detected in a pediatric patient and there are indications for eradication to prevent reinfection, it is recommended to have a discussion regarding the necessity of screening all family members for H. pylori and selectively prescribing eradication therapy to H. pylori-positive children if indications are present (see above); adult H. pylori-positive individuals should be referred for consultation with an appropriate specialist [151].

GCR CLoE 3Grade of Recommendation C (Level of Evidence – 3)

Comment: H. pylori reinfection is more common in children than in adults, and it is widely recognized that the family plays an important role in primary pediatric infection. In a study of fifty families, each with an index case of H. pylori infection in children (mean age 9.48 years) during long-term follow-up (mean 62.2 months), the reinfection rate was 2.4% per patient-year in the observation group and 0.7% per patient-year in the group where all infected adults underwent eradication (p = 0.31) [151].

3.1.3 Drug therapy

• In patients with gastritis and duodenitis not associated with H. pylori, it is recommended to prescribe medications depending on the existing complaints in order to relieve them [74, 124, 152, 153].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: All medications for symptomatic treatment are prescribed taking age restrictions into account.

For epigastric pain in patients with gastritis and duodenitis, agents with antisecretory effect can be used: aluminum phosphate (A02AB03) in children older than 6 months up to 6 years – 1/2 sachet or 2 teaspoons after each of 4 feedings; in children older than 6 years – 1–2 sachets 2–3 times a day) or magaldrate (A02AX Antacids in combination with other drugs) in children aged 10 to 15 years – 5 ml 3–4 times a day or 10 ml 1–2 times, or 1 sachet 1–2 times a day; from 15 years orally 15 ml, 1–2 hours after meals and at bedtime or as needed (no more than 6 tablespoons per day), proton pump inhibitors (dosages and restrictions are the same as in eradication therapy) – preference is given to the group of "proton pump inhibitors" compared to H2-receptor blockers due to the higher efficacy of the former in eliminating clinical symptoms.

For feelings of heaviness in the epigastric region and early satiety, gastrointestinal motility stimulators may be used (domperidone (A03FA03) in children over 12 years with chronic dyspeptic symptoms 10 mg 3 times a day, including at bedtime if necessary; trimebutine (A03AA05) in children over 12 years 100–200 mg 3 times a day, in children aged 5–12 years: 50 mg 3 times a day, in children aged 3–5 years 25 mg 3 times a day) [74, 124, 152, 153].

In the complex therapy of gastritis and duodenitis in routine practice for the symptomatic treatment of spasmodic abdominal pain, the following symptomatic treatment is most often prescribed:

drotaverine** (40 mg tablets in children from 6 years of age: from 6 to 12 years: 40 mg per single dose 1–2 times a day. Maximum daily dose is 80 mg (two 40 mg tablets); over 12 years: 40 mg per single dose 1–4 times a day or 80 mg per single dose 1–2 times a day. Maximum daily dose is 160 mg (four 40 mg tablets)), etc.

Treatment of special forms of gastritis is carried out individually using mainly symptomatic therapy, as well as with the mandatory involvement of pediatric surgeons to address the issue of surgical intervention.

In a stable course of the disease, in the absence of clinical and laboratory manifestations, patients do not need treatment.

• To accelerate the regression of inflammation and healing of erosions of the gastric and duodenal mucosa, it is recommended that patients with gastritis and duodenitis use bismuth dicitrate tripotassium** [10, 154, 155].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• In the treatment of biliary reflux gastritis, the use of ursodeoxycholic acid** preparations is effective at an average dosage based on 250 mg capsule (for body weight up to 47 kg) or 1 measuring cup (5 ml – 250 mg) (for children from 4 weeks) – or 0.5 tabl. (250 mg) (for children from 3 years -) daily in the evening at bedtime (capsules should not be chewed), washed down with a small amount of water. Course of treatment – from 10–14 days to 6 months, if necessary – up to 2 years [156, 157].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• In the treatment of autoimmune gastritis, it is recommended to treat the underlying disease that triggers the immunopathological process in the gastric mucosa, prevent iron and/or vitamin B12 deficiency, and assess the risk of malignancy [19, 190].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Etiological and pathogenetic treatment of autoimmune gastritis in children has not yet been developed. Treatment is carried out according to relevant guidelines. If Helicobacter pylori infection is detected, a course of eradication therapy is performed using a three- or four-drug regimen [19].

• In patients with gastritis and duodenitis, it is recommended to selectively prescribe medications from the "Antidiarrheal microorganisms" group in order to reduce the risk of side effects and increase the efficacy of anti-Helicobacter therapy (if administered), primarily intestinal dysbiosis associated with antibiotic use, and to prevent antibiotic-associated diarrhea, enhance immunity, reduce epithelial barrier permeability, and correct and prevent gastrointestinal microbiota disorders [132, 158, 159, 164–170].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: The importance of correcting and preventing gastrointestinal microbiota disorders primarily applies to individuals with unstable intestinal microbiota, which includes children.

The efficacy of antidiarrheal microorganisms (probiotics) in increasing the efficacy and safety of H. pylori eradication, including for the prevention of antibiotic-associated diarrhea, has been proven in conducted RCTs and confirmed by subsequent meta-analyses in adults [132, 158, 159].

Currently, the most effective approach is considered to be the use of Lactobacillus rhamnosus GG and Saccharomyces boulardii CNCM I-745 (250 mg twice daily for children aged 1 to 3 years, 500 mg twice daily for children over 3 years). These strains are currently included in the current ESPGHAN-2024 and WGO (2023) guidelines on antidiarrheal microorganisms (probiotics) (registered medicinal product Saccharomyces boulardii). The local methodological guidelines of the ISSMA and RSG on probiotics (2024) also include the probiotic strain Lactobacillus acidophilus (NK1, NK2, NK5, NK12) + kefiran (product: Acidophilus lactobacilli + Kefir grains) for the prevention of antibiotic-associated diarrhea and the improvement of H. pylori eradication outcomes [70, 71, 72, 73, 74, 132].

The action of antidiarrheal microorganisms (probiotics) as immunomodulators is associated with their ability to exhibit direct antimicrobial activity against pathogens by producing antimicrobial substances (bacteriocins), as well as their ability to modulate the immune response via epithelial cells, modulate and activate immune responses using macrophages and dendritic cells, activate CD8+ T-lymphocytes and CD4+ T-lymphocytes, modulate IgA production, stimulate toll-like receptors, and modify the cytokine expression profile [164-168].

The positive effect of antidiarrheal microorganisms (probiotics) in restoring the mucosal barrier is related both to their immunological effects and to their ability to induce mucosal regeneration and improve mucin production, which inhibits pathogen adhesion to epithelial cells and reduces epithelial barrier permeability [164, 169, 170].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• For patients with gastritis and duodenitis, for the purpose of a faster and more complete recovery and relapse prevention, it is recommended selectively to provide spa and resort treatment as indicated after the acute phase of the disease has subsided and eradication therapy has been performed in case of H. pylori infection, as a rule, 3–6 months after the start of treatment [171-173].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: currently, there is no convincing evidence that spa and resort treatment, as well as therapeutic exercise, improves prognosis or affects the outcomes of gastritis and duodenitis. High-quality, large-scale studies are needed to draw a definitive conclusion regarding the necessity of this treatment. The duration of spa and resort treatment is 14–21 days. In the early rehabilitation period, preference should be given to local sanatoriums. Referral to sanatorium-based treatment at locations remote from the patient's residence is possible once persistent clinical remission is established. Consideration should be given to therapeutic exercise (therapeutic exercise for diseases of the esophagus, stomach, and duodenum), medical massage to improve blood and lymph circulation in the abdominal cavity; normalize gastric and duodenal motility, secretory and neurohumoral regulation of digestive processes; create favorable conditions for reparative processes in the gastric and duodenal mucosa in the absence of contraindications [171-173], as well as psychotherapeutic and physiotherapeutic treatment. In the 3rd year of follow-up, children may receive health improvement during sanatorium shifts in summer health camps. Patients with contraindications to this type of treatment, as well as to any balneological procedures (e.g., patients with Ménétrier's disease, gastric polyposis, and gastric neoplasms), are not referred for spa and resort treatment.

5. Prevention and Dispensary Observation

• For patients with gastritis and duodenitis, follow-up (dispensary observation) is recommended to be carried out jointly by a district pediatrician / general practitioner (family physician) and/or a gastroenterologist in an outpatient setting, taking into account the allocation into groups (I–IV) depending on the acute or remission state of the disease for the purpose of anti-relapse and rehabilitation measures that vary across the registration groups [174].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: In case of persistent long-term clinical and laboratory remission after 3 years of follow-up, the question of discharging the patient from dispensary registration may be raised. Options for dispensary examination depending on gastric secretory function are presented in Tables 10–11.

Table 10

Dispensary observation of children with chronic gastritis with increased secretory and acid-forming function

Table 11

Dispensary observation of children with chronic gastritis with decreased secretory and acid-forming function

• Patients with gastritis and duodenitis are recommended to undergo preventive measures to reduce the frequency and recurrence of the disease [175, 176, 177].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: educational programs for children and their parents providing information on risk factors and clinical manifestations of chronic gastritis and chronic duodenitis are used for prevention. Training is conducted to establish principles of daily routine, nutrition, physical education, and hardening, mastering physical therapy exercise routines, and implementing anti-epidemic measures. The main focus of prevention is aimed at reducing the spread of H. pylori infection. To this end, personal hygiene within the family, screening close relatives for H. pylori infection, and treating infected relatives are mandatory.

For secondary prevention, courses of preventive treatment can be used, including diet therapy, administration of metabolic enhancers, vitamins, mineral waters, herbal medicine, and physiotherapeutic procedures. The courses are conducted twice a year in spring and autumn (in September–October and March–April). For instance, herbal remedies made from chamomile flowers can be used to reduce the inflammatory process in the gastric and duodenal mucosa, and licorice (glycyrrhiza) to improve regeneration. Consuming cabbage dishes also promotes regeneration [175, 176]. Physiotherapeutic methods can also be selectively prescribed to patients with chronic gastritis and chronic duodenitis. There are publications on their anti-inflammatory and analgesic effects, as well as normalization of gastric function and body reactivity. In children, decimeter-wave microwaves (exposure to decimeter-wave electromagnetic radiation (DMW)) with localization of exposure to the thyroid gland, collar, epigastric regions, and pyloroduodenal zone are predominantly used; centimeter-wave microwaves (exposure to centimeter-wave electromagnetic radiation (CMW therapy)); ultrasound (ultrasound exposure for diseases of the esophagus, stomach, and duodenum); variable magnetic field (exposure to a variable magnetic field (VMF)); for local exposure, galvanization for diseases of the esophagus, stomach, and duodenum (the service is absent in the current Nomenclature of Medical Services) and drug electrophoresis (drug electrophoresis for diseases of the stomach and duodenum) are used [177].

• In patients with atrophy of the gastroduodenal mucosa, to prevent the progression of gastritis and duodenitis, as well as the prevention of gastric cancer, endoscopic surveillance is recommended depending on the severity of atrophy: endoscopic surveillance is not recommended for mild and moderate mucosal atrophy restricted solely to the antrum [71, 91, 178–187].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Individuals with severe atrophy and intestinal metaplasia of the gastric mucosa continue to require endoscopic surveillance even after successful H. pylori eradication [10, 34, 71, 91, 178]. A population-based study (405,172 individuals, 1979–2011) showed that in adults who underwent endoscopy with biopsy for non-oncological indications, gastric cancer developed within 20 years in 1 out of 256 cases with normal gastric mucosa, 1 in 85 with gastritis, 1 in 50 with atrophic gastritis, 1 in 39 with intestinal metaplasia, and 1 in 19 cases when dysplasia was detected [178]. Based on data from this study, it can be assumed that severe atrophy and intestinal metaplasia detected in adolescence, in the absence of surveillance, may lead to the development of gastric cancer by age 40–45, i.e., at a young working age. According to data obtained from the examination of 1,755 patients with dyspepsia over an average of 55 months, neoplasia was detected exclusively in individuals with baseline OLGA stages III–IV; there was no risk of neoplasia in patients with OLGA stages 0, I, and II, while it was 36.5 per 1,000 person-years for stage III and 63.1 per 1,000 person-years for stage IV [184]. Even mildly pronounced intestinal metaplasia significantly increased the risk of gastric cancer [180, 181]. The presence of intestinal metaplasia (as a marker of severe gastritis) may be of even greater importance than the degree of atrophy without intestinal metaplasia, and incomplete intestinal metaplasia is a prognostically unfavorable factor for the development of gastric cancer compared to complete intestinal metaplasia; it should be considered as an additional condition for determining the timing of surveillance for patients with gastritis [184, 185]. An additional risk factor for gastric cancer is having close relatives suffering from gastric cancer [186, 187].

Vaccination

Gastritis and duodenitis are not contraindications for vaccination with any type of vaccine (Order of the Russian Ministry of Health No. 1122n dated December 6, 2021, “On Approval of the National Schedule of Preventive Vaccinations and the Schedule of Preventive Vaccinations According to Epidemic Indications”, Methodological Guidelines MU 3.3.1.1095-02. Medical contraindications to preventive vaccinations with preparations of the national vaccination schedule), as well as for vaccination against the novel coronavirus infection (COVID-19), in accordance with the product instructions

6. Organization of Medical Care

Most patients with gastritis and duodenitis are subject to outpatient follow-up and treatment.

Depending on necessity, medical care of any type, under any conditions, and in any form provided for by the legislation of the Russian Federation may be rendered.

Indications for hospitalization in a medical organization:

1. severe abdominal pain syndrome (8–10 points on a 10-point scale)

2. need for eradication therapy under medical supervision in case of a high risk of allergic reactions or antibiotic-associated diarrhea

3. need for endoscopic examination with multiple biopsies under general anesthesia

4. presence of signs of gastrointestinal bleeding in a patient with suspected erosive gastritis and/or duodenitis – an indication for emergency hospitalization

5. social indications (impossibility of performing examination/treatment on an outpatient basis)

The organization of therapeutic dietary nutrition for patients with gastritis and duodenitis during inpatient treatment in medical organizations is carried out in accordance with Order of the Russian Ministry of Health No. 1008n dated September 23, 2020, “On Approval of the Procedure for Providing Patients with Therapeutic Nutrition” (Appendix 3).

Indications for patient discharge from a medical organization:

1. establishment of a clinical diagnosis, relief of pain syndrome, and exclusion of acute surgical pathology

2. completion of the course of H. pylori eradication therapy

3. performance of endoscopic examination

4. cessation of gastrointestinal bleeding

7. Additional Information

With timely treatment and the absence of signs of high-grade atrophy, metaplasia, and dysplasia in the gastric mucosa, the prognosis is favorable. As structural changes in the gastric mucosa worsen, the prognosis regarding the disease course and the risk of gastric cancer deteriorates.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Novikova Valeria Pavlovna – Doctor of Medical Sciences, Professor, Head of the Department of Propaedeutics of Childhood Diseases with a Course of General Care, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; Head of the Laboratory of Medical and Social Problems in Pediatrics, Research Center of St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; member of the Union of Pediatricians of Russia, member of the Russian Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists

2. Baryshnikova Natalia Vladimirovna – Candidate of Medical Sciences, Associate Professor, Senior Researcher at the Laboratory of Medical and Social Problems in Pediatrics, Research Center of St. Petersburg State Pediatric Medical University of the Russian Ministry of Health

3. Khavkin Anatoly Ilyich – Doctor of Medical Sciences, Professor, Head of the A.V. Mazurin Department of Gastroenterology and Dietetics, Head of the Moscow Regional Center for Pediatric Gastroenterology and Hepatology at the Research Clinical Institute of Pediatrics of the Ministry of Health of Moscow Region; Professor at the Department of Pediatrics with a Course of Pediatric Surgical Diseases, Medical Institute of the Belgorod State National Research University; Chairman of the Russian Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, Member of the Union of Pediatricians of Russia.

4. Gurova Margarita Mikhailovna – Doctor of Medical Sciences, Leading Researcher at the Laboratory of Medical and Social Problems in Pediatrics, Research Center of St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; Professor at the Department of Propaedeutics of Childhood Diseases with a Course of General Care, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; member of the Union of Pediatricians of Russia, member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists; Deputy Chief Medical Officer for Medical Affairs, St. Petersburg State Budgetary Healthcare Institution 'Consultative and Diagnostic Center for Children'

5. Kalinina Elena Yuryevna – Candidate of Medical Sciences, Head of the Department of Normal Anatomy, St. Petersburg State Pediatric Medical University

6. Zavyalova Anna Nikitichna – Doctor of Medical Sciences, Professor at the Department of Propaedeutics of Childhood Diseases with a Course of General Care, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; member of the Union of Pediatricians of Russia, member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, Member of the Union of Pediatricians of Russia.

7. Kornienko Elena Alexandrovna – Doctor of Medical Sciences, Professor at the Professor I.M. Vorontsov Department of Childhood Diseases, Faculty of Postgraduate and Additional Professional Education, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health. Chief Freelance Pediatric Gastroenterologist of the Healthcare Committee of the Government of St. Petersburg. Member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, Member of the Union of Pediatricians of Russia.

8. Volynets Galina Vasilyevna – Doctor of Medical Sciences, Professor at the Department of Innovative Pediatrics and Pediatric Surgery, Faculty of Additional Professional Education; Associate Professor at the Department of Pediatrics with Infectious Diseases in Children, Faculty of Additional Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health. Head of the Department of Gastroenterology, Veltischev Research and Clinical Institute of Pediatrics. Member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, member of the Union of Pediatricians of Russia

9. Listopadova Anastasia Pavlovna – Candidate of Medical Sciences, Assistant Professor at the Department of Propaedeutics of Childhood Diseases with a Course of General Child Care, St. Petersburg State Pediatric Medical University; Senior Researcher at the Laboratory of Medical and Social Problems in Pediatrics, Research Center of St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, member of the Union of Pediatricians of Russia

10. Melnikova Irina Yuryevna – Professor, Doctor of Medical Sciences, Head of the Department of Pediatrics and Pediatric Cardiology, North-Western State Medical University named after I.I. Mechnikov; member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, member of the Union of Pediatricians of Russia

11. Belmer Sergey Viktorovich – Professor, Doctor of Medical Sciences, Professor at the Department of Hospital Pediatrics No. 2, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health; Co-Chairman of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, member of the Union of Pediatricians of Russia

12. Bogdanova Natalia Mikhailovna – Candidate of Medical Sciences, Associate Professor at the Department of Propaedeutics of Childhood Diseases with a Course of General Child Care, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists, member of the Union of Pediatricians of Russia

13. Baranov A.A. – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Honorary President of the Union of Pediatricians of Russia, Advisor to the Head of the Research Institute of Pediatrics and Children's Health of the Central Clinical Hospital of the Russian Academy of Sciences, Chief Freelance Pediatrician of the Russian Ministry of Health, Professor at the Department of Pediatrics and Pediatric Rheumatology, N.F. Filatov Clinical Institute of Children's Health, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University)

14. Namazova-Baranova L.S. – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, President of the Union of Pediatricians of Russia; Past President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Children's Health of the Central Clinical Hospital of the Russian Academy of Sciences, Head of the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health; Chief Freelance Pediatric Specialist in Preventive Medicine of the Russian Ministry of Health

15. Gundobina O.S. – Candidate of Medical Sciences, Leading Researcher, Gastroenterologist at the Research Institute of Pediatrics and Children's Health of the Central Clinical Hospital of the Russian Academy of Sciences, member of the Union of Pediatricians of Russia

16. Kaitukova E.V. – Candidate of Medical Sciences, Chief Medical Officer of the Research Institute of Pediatrics and Children's Health of the Central Clinical Hospital of the Russian Academy of Sciences, Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, member of the Union of Pediatricians of Russia

17. Komarova E.V. – Doctor of Medical Sciences, Deputy Head of the Research Institute of Pediatrics and Children's Health of the Central Clinical Hospital of the Russian Academy of Sciences, Gastroenterologist, member of the Union of Pediatricians of Russia

18. Potapov A.S. – Doctor of Medical Sciences, Professor, member of the Union of Pediatricians of Russia

19. Revunenkov G.V. – Candidate of Medical Sciences, Leading Researcher, Head of the Department of Innovative Diagnostic Research Methods, Ultrasound Diagnostics Physician at the Research Institute of Pediatrics and Children's Health of the Central Clinical Hospital of the Russian Academy of Sciences, member of the Union of Pediatricians of Russia.

20. Surkov A.N. – Doctor of Medical Sciences, Head of the Gastroenterology Department with a Hepatology Group, Chief Researcher at the Laboratory of Scientific Foundations of Pediatric Gastroenterology and Hepatology, Speransky Research Institute of Pediatrics; Professor at the Department of Pediatrics and Public Health, Institute of Medical Personnel Training, National Medical Research Center for Children's Health of the Russian Ministry of Health, member of the Union of Pediatricians of Russia

Conflict of interest:

The authors declare no financial support or conflicts of interest that need to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Target audience of these clinical guidelines:

2. Pediatricians

3. General practitioners (family physicians)

4. Gastroenterologists

5. Endoscopists

6. Medical students

7. Residents

Methods used for assessing the quality and strength of evidence:

• electronic database search. Description of methods used to assess the quality and strength of evidence: the evidence base for the recommendations includes publications indexed in the Cochrane Library, EMBASE, MEDLINE, and PubMed databases. Search depth – 10 years.

• expert consensus;

• assessment of significance in accordance with the rating scheme.

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Scale for grading levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading the levels of evidence (LE) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. State Register of Medicinal Products: https://grls.rosminzdrav.ru

2. Order of the Ministry of Health of the Russian Federation No. 1183n dated December 20, 2012 "On approval of the nomenclature of positions of medical and pharmaceutical workers".

3. Order of the Ministry of Health of the Russian Federation No. 541n dated July 23, 2010. "Unified Qualification Handbook of Positions of Managers, Specialists, and Employees, Section: Qualification Characteristics of Positions of Healthcare Workers."

4. Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Basics of Protecting the Health of Citizens in the Russian Federation' regarding Clinical Guidelines."

5. Order of the Russian Ministry of Health No. 103n dated February 28, 2019, "On approval of the procedure and timelines for the development of clinical guidelines, their revision, the standard template of clinical guidelines, and requirements for their structure, composition, and scientific validity of the information included in the clinical guidelines."

6. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017 "On approval of the nomenclature of medical services".

7. Order of the Ministry of Health of the Russian Federation No. 4n dated January 14, 2019, "On Approval of the Procedure for Prescribing Medicinal Products, Prescription Forms for Medicinal Products, the Procedure for Issuing Said Forms, Their Accounting, and Storage"

8. Order of the Ministry of Health and Social Development of the Russian Federation No. 366n dated April 16, 2012 «On Approval of the Procedure for the Provision of Pediatric Care»

9. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017 "On approval of criteria for assessing the quality of medical care"

10. Order of the Ministry of Health of Russia No. 1008n dated September 23, 2020, 'On Approval of the Procedure for Providing Patients with Medical Nutrition.'

Appendix A3.1 Endoscopic presentation of gastritis in children

a) Patient, 10 years old. Nodular gastritis with a single erosion

b) Patient, 15 years old. Hemorrhagic gastritis.

Endoscopic appearance of duodenitis in children

Appendix A3.2 Pathoanatomical (histological) presentation of gastritis in children

a) Patient, 10 years old. Inflammation of the gastric body mucosa in a patient with chronic gastritis. Hematoxylin and eosin staining. Magnification ×160.

b) Patient, 8 years old. Inflammation of the gastric antrum mucosa in patients with chronic gastritis. Hematoxylin and eosin staining. Magnification ×120.

c) Patient, 14 years old. Close arrangement of H. pylori on the surface of epithelial cells of the gastric antrum. Alcian blue staining. Magnification ×160.

d) Patient, 12 years old. Biopsy specimen of the gastric antrum mucosa. A large lymphoid follicle with a light center is visible. Hematoxylin and eosin staining. Magnification ×120.

e) Patient, 15 years old. Stromal fibrosis in the gastric mucosa in a patient with chronic gastritis. Van Gieson's picrofuchsin staining. Magnification ×120.

f) Patient, 7 years old. Glandular atrophy in the gastric mucosa in a patient with chronic gastritis. Hematoxylin and eosin staining. Magnification ×120.

g) Patient, 14 years old. Incomplete intestinal metaplasia. Hematoxylin and eosin, and alcian blue staining. Magnification ×120 and ×160.

h) Patient, 10 years old. Chronic autoimmune gastritis with incipient glandular destruction. Magnification ×400. Hematoxylin and eosin staining.

Appendix A3.3 Pathoanatomical (histological) presentation of duodenitis in children

Duodenal mucosa with preserved cytoarchitecture and mild lymphoplasmacytic infiltration. Chronic active duodenitis, grade I according to R. Whitehead (1990). Hematoxylin and eosin staining, mag. ×100	Duodenal mucosa with shortened villi, deepened crypts, and increased inflammatory infiltration. Chronic active duodenitis, grade II according to R. Whitehead (1990). Hematoxylin and eosin staining, mag. ×100
Duodenal mucosa with pronounced shortening of villi, deepened crypts, and marked inflammatory infiltration. Chronic active subatrophic duodenitis, grade II according to R. Whitehead (1990). Hematoxylin and eosin staining, mag. ×100	Chronic active atrophic duodenitis, grade III according to R. Whitehead (1990) in celiac disease, 'bald' mucosa. Lymphoplasmacytic infiltration of both the lamina propria and the submucosa. Hematoxylin and eosin staining, mag. ×100
Chronic active atrophic duodenitis in celiac disease. Intraepithelial infiltration of the surface epithelium (more than 40 per 100 epithelial cells). Hematoxylin and eosin staining, mag. ×400	Chronic active subatrophic duodenitis in celiac disease. CD8 expression. IHC, magn. 100
Chronic active atrophic-hyperplastic duodenitis with extensive erosion in celiac disease. Hematoxylin and eosin stain, magn. 100	Chronic atrophic duodenitis in celiac disease. Marked epithelial proliferative activity in preserved elongated crypts. KI-67 expression. IHC, magn. 40
Chronic inactive atrophic-hyperplastic duodenitis in celiac disease. Irregular numbers of neuroendocrine cells producing serotonin (Fig. A) and chromogranin A (Fig. B). Serotonin and chromogranin A expression. IHC, counterstained with hematoxylin, magn. 400
Chronic active Helicobacter pylori duodenitis: marked architectural distortion due to pronounced diffuse and nodular lymphoplasmacytic infiltration, decreased goblet cell count. Hematoxylin and eosin stain, magn. 100	Same biopsy specimen. Decreased goblet cell count, accumulation of Helicobacter pylori on the surface of the biopsy specimen. May-Grunwald-Giemsa stain, magn. 1000, immersion.
Chronic active duodenitis associated with viral infection. Marked increase in mast cells in the stroma. May-Grunwald-Giemsa stain, magn. 400	Chronic active Helicobacter pylori duodenitis, widespread gastric metaplasia of the epithelium. Mucin 5 expression. IHC, magn. 100
Chronic active duodenitis in rheumatoid arthritis. Against the background of pronounced diffuse lymphoplasmacytic infiltration, IgE expression is noted in the lamina propria. IHC, magn. 400	Chronic atrophic-hyperplastic active duodenitis in cystic fibrosis. Irregular goblet cell count, mucus hyperproduction with crypt dilation and formation of mucous bays. Hematoxylin and eosin, Alcian blue stain, magn. 200
Chronic active duodenitis in tropical sprue: combination of atrophic and hyperplastic changes, lymphonodular hyperplasia, and diffuse polymorphonuclear infiltration of the lamina propria. Hematoxylin and eosin stain, magn. 40	Chronic active duodenitis associated with long-term nonsteroidal anti-inflammatory drug use: diffuse lymphoplasmacytic infiltration and fibrosis of the lamina propria, marked thickening and approximation of villi with a sticking effect, hyperplasia of the surface epithelium with pseudopapillary structure formation. Hematoxylin and eosin, Alcian blue stain, magn. 40.
Chronic active atrophic eosinophilic duodenitis: sharply increased number of eosinophilic granulocytes in the inflammatory infiltrate. Hematoxylin and eosin, Alcian blue stain, magn. 200 (Fig. A) and 400 (Fig. B)
Chronic inactive atrophic duodenitis (collagenous sprue): marked architectural distortion due to diffuse fibrosis of the lamina propria against the background of minimal cellular infiltration of the stroma, atrophy and depletion of the cellular composition of the surface epithelium. Hematoxylin and eosin stain (Fig. A) and Van Gieson's picrofuchsin stain (Fig. B), magn. 200

Appendix B. Physician Action Algorithms

Diagnostic and treatment algorithms for gastritis and duodenitis

Option 1

Option 2

Option 3

Option 4

Diagram

Algorithm for selecting a treatment program based on diagnostic capabilities, including H. pylori verification

Appendix C. Patient Information

Gastritis and duodenitis are multicausal diseases whose development is based on an imbalance between aggressive and protective factors of the gastric and duodenal mucosa. Virtually every case of gastritis is accompanied by concomitant duodenitis, whereas isolated duodenitis is extremely rare. Currently, a microorganism known as Helicobacter pylori is recognized as a major factor causing gastritis. Every patient in whom gastritis is detected during upper gastrointestinal endoscopy should be tested for this infection. If confirmed, indicated treatment aimed at eradicating this microorganism should be performed, followed by efficacy evaluation after 4–6 weeks. If treatment fails, a repeat course of therapy with a different drug regimen should be administered. It is important to maintain treatment adherence and strictly monitor medication intake to increase treatment efficacy, strictly following the doctor's recommendations. Therapy leading to the eradication of Helicobacter pylori is now considered the primary measure aimed at restoring the gastric mucosa and preventing gastric cancer. A family history of gastric cancer in close relatives (parents, grandparents) serves as an additional indication for anti-Helicobacter pylori treatment. In the absence of Helicobacter pylori, treatment is carried out in accordance with the identified complaints and current recommendations.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Visual analogue scale for pathomorphological (histological) evaluation of gastric and duodenal biopsy specimens

Title in Russian: Visual analogue scale for pathomorphological (histological) evaluation of gastric and duodenal biopsy specimens

Original title (if any):

Source (official website of the developers, validation publication):

Type (underline):

- rating scale

- index

- questionnaire

- other (specify):_____________________________________________________

Purpose: pathomorphological (histological) evaluation of gastric and duodenal biopsy specimens

Content (template), Key (interpretation), and Notes: