Pediatric dyspepsia

　　First, Etiology

　　The etiology of functional dyspepsia is unknown and is currently considered to be the result of the combined action of multiple factors. These factors include diet and environment, gastric acid secretion, Helicobacter pylori infection, abnormal gastrointestinal motility, psychological factors, and some other gastrointestinal functional disorders, such as gastroesophageal reflux disease (GERD), aerophagia, irritable bowel syndrome, and others.

　　Second, Pathogenesis

　　The pathogenesis is not yet clear and is related to the following mechanisms:

　　The symptoms of functional dyspepsia patients are often related to diet, and many patients often complain that carbonated drinks, coffee, lemon, or other fruits, as well as fried foods, can worsen dyspepsia. Although the significance of food-induced tests by double-blind method has been questioned, many children still feel that their symptoms have improved after avoiding the above foods and balancing their diet.

　　Patients with partial functional dyspepsia due to gastric acid may experience ulcer-like symptoms, such as hunger pain, which gradually subsides after eating, and there is tenderness when pressing on the abdomen. Symptoms can be relieved in the short term by giving acid inhibitors or acid-suppressing drugs. All these suggest that the onset of these patients is related to gastric acid.

　　However, the vast majority of studies have confirmed that there is no increase in the basic gastric acid and maximum gastric acid secretion in patients with functional dyspepsia, and there is no correlation between the secretion of gastric acid and ulcer-like symptoms. Therefore, further research is needed to determine the role of gastric acid in the pathogenesis of functional dyspepsia.

　　Approximately 30% to 50% of patients with chronic gastritis and duodenitis with functional dyspepsia are confirmed to have antral gastritis by histological examination. Many European countries consider chronic gastritis to be a functional dyspepsia, believing that chronic gastritis may affect the motility of the stomach through neural and humoral factors. Some authors also believe that non-ulcerative duodenitis also belongs to functional dyspepsia. It should be pointed out that the severity of the symptoms of functional dyspepsia is not parallel to the inflammatory changes of the gastric mucosa.

　　4. Helicobacter pylori (helicobacterpylori, Hp) infection Hp is a gram-negative bacterium that generally colonizes the surface of the mucus layer of the stomach. The infection rate of Hp in asymptomatic adults is more than 35%, and more than 90% of patients with duodenal ulcer have Hp. Bismuth salts plus antibiotics can eradicate Hp, cause the regression of histological gastritis, and can reduce the recurrence rate of ulcers from more than 80% per year to less than 10% per year. Therefore, Hp is an important cause of duodenal ulcer and chronic antral gastritis, which has been basically clarified.

　　However, the research results on the relationship between chronic Hp infection and functional dyspepsia are very different. Acute Hp infection can cause transient symptoms such as nausea, abdominal pain, and vomiting, but there is no conclusive evidence to show that this bacterium can cause chronic functional dyspepsia. The positive detection rate of Hp in adult patients with functional dyspepsia is 40% to 70%, which is similar to the epidemiological results of the population. Strict control studies have not confirmed that the infection rate of Hp in patients with functional dyspepsia is higher than that in normal healthy people. There is no significant difference in gastrointestinal motility and gastric emptying function between Hp-positive and Hp-negative individuals. Moreover, after the eradication of Hp treatment, the symptoms of dyspepsia in Hp-positive patients with functional dyspepsia do not necessarily disappear.

　　A recent study suggests that the eradication of Helicobacter pylori may be beneficial for symptom relief in the long term, but it cannot take effect immediately. Further research has also confirmed that there is no correlation between Hp-specific antigens and functional dyspepsia. Hp, even its specific serum type CagA, has no relation to any dyspeptic symptoms or any primary functional upper abdominal discomfort symptoms. However, studies in children have found that the infection rate of Helicobacter pylori in children with functional dyspepsia is significantly higher than that in healthy children (P

　　5. Many studies now believe that functional dyspepsia is actually a kind of gastrointestinal dysfunction. It has similar pathogenesis to other gastrointestinal dysfunction diseases. In 1990, an international working group composed of clinical researchers formulated a classification standard for gastrointestinal dysfunction in Rome, known as the Rome criteria. In recent years, with the further understanding of gastrointestinal dysfunction in physiology (motor-sensory), basic science (brain-gut interaction), and socio-psychological aspects, and based on the symptoms and anatomical location, the Rome Committee has revised this diagnostic criteria and formulated new standards, namely the Rome II criteria. The Rome II criteria not only include diagnostic criteria but also provide a detailed description of the basic physiology, pathology, neuroregulation, gastrointestinal hormones, and immune system of gastrointestinal dysfunction. At the same time, it also puts forward guiding opinions on treatment. Therefore, the Rome II criteria are currently a consensus document used for the diagnosis and treatment of functional gastrointestinal diseases in many countries around the world.

　　该标准认为：胃肠道运动在消化期与消化间期有不同的形式和特点。消化间期运动的特点则是呈现周期性移行性综合运动。空腹状态下由胃至末端回肠存在一种周期性运动形式，称消化间期移行性综合运动(MMC)。大约在正常餐后4～6h，这种周期性、特征性的运动起于近端胃，并缓慢传导到整个小肠。每个MMC由4个连续时相组成：Ⅰ相为运动不活跃期;Ⅱ相的特征是间断性蠕动收缩;Ⅲ相时胃发生连续性蠕动收缩，每个慢波上伴有快速发生的动作电位(峰电位)，收缩环中心闭合而幽门基础压力却不高，处于开放状态，故能清除胃内残留食物;Ⅳ相是Ⅲ相结束回到Ⅰ相的恢复期。与之相对应，在Ⅲ期还伴有胃酸分泌、胰腺和胆汁分泌。在消化间期，这种特征性运动有规则的重复出现，每一周期约90min左右。空腹状态下，十二指肠最大收缩频率为12次/min，从十二指肠开始MMC向远端移动速度为5～10cm/min，90min后达末端回肠，其作用是清除肠腔内不被消化的颗粒。

　　消化期的运动形式比较复杂。进餐打乱了消化间期的活动，出现一种特殊的运动类型：胃窦-十二指肠协调收缩。胃底出现容受性舒张，远端胃出现不规则时相性收缩，持续数分钟后进入较稳定的运动模式，即3次/min的节律性蠕动性收缩，并与幽门括约肌的开放和十二指肠协调运动，推动食物进入十二指肠。此时小肠出现不规则、随机的收缩运动，并根据食物的大小和性质，使得这种运动模式可维持2.5～8h。此后当食物从小肠排空后，又恢复消化间期模式。

　　In the long-term study of patients with functional dyspepsia, it was found that about 50% of patients with functional dyspepsia have delayed gastric emptying after meals, which can be a liquid and/or solid emptying obstruction. In children with functional dyspepsia, 61.53% have delayed gastric emptying. This may be a comprehensive manifestation of abnormal gastric motility, including reduced proximal gastric tension, weakened antral motility, and gastric electrical disorder, all of which can affect gastric emptying function. Gastric pressure measurement found that 25% of patients with functional dyspepsia have weakened antral motility, especially after meals, which is significantly lower than that of healthy individuals, and even the antrum may not contract. In children, the amplitude of antral contraction in FD patients is significantly lower than that in healthy children. Gastric volume-pressure relationship curve and electronic constant pressure gauge examination found that patients have impaired proximal gastric accommodation and relaxation function, reduced gastric compliance, and decreased tension of the proximal gastric wall.

　　Some patients with functional dyspepsia have small intestinal motility disorders, mainly in the proximal small intestine. Gastric antrum-duodenal manometry found that the movement of the gastric antrum and duodenum is not coordinated, mainly due to duodenal motility disorder, and about 1/3 of FD patients have irritable bowel syndrome.

　　In addition to the stomach and small intestine, patients with functional dyspepsia may also have other kinetic abnormalities. Margio et al. found, through ultrasonic detection, that 30.7% of patients have delayed biliary excretion. Chinese scholars found, through ultrasonic detection of gastric emptying and postprandial gallbladder emptying in FD children, that about 25% of FD children have delayed postprandial gallbladder emptying at the same time as gastric emptying disorders. Anal manometry found that the resting pressure of the anal canal was significantly higher than that of the normal control group, indicating that patients with functional dyspepsia may not be limited to gastric dysfunction, but may have abnormal smooth muscle function throughout the gastrointestinal tract.

　　6. Abnormal visceral sensation Many patients with functional dyspepsia have an abnormal or overly sensitive response to physiological or slight harmful stimuli. Some patients have increased sensitivity to the infusion of acid and saline; some patients will still experience pain after intravenous injection of pentagastrin even when acid secretion is blocked by H2 receptor antagonists. Some studies report that when the balloon is inflated in the proximal stomach, the pain of patients with functional dyspepsia often worsens, and the balloon inflation level during pain episodes is significantly lower than that of the control group.

　　Therefore, abnormal visceral sensation may play a certain role in functional dyspepsia. However, the basis of this abnormal sensation is still unclear. Preliminary research has confirmed that patients with functional dyspepsia have two types of visceral afferent dysfunction: one is an unperceived reflex afferent signal, and the other is a sensory signal. Both abnormalities can exist independently or simultaneously in the same patient. After the gastrointestinal mechanical receptors sense the expansion stimulation, the subjects will produce perception, discomfort, and pain as the expansion capacity gradually increases, thus obtaining different states of expansion capacity. The perception threshold of functional dyspepsia patients is significantly lower than that of normal people, indicating that the patients are hypersensitive.

　　7. There has been controversy over whether psychological and social factors, as well as psychological factors, are related to the onset of functional dyspepsia. Some Chinese scholars have investigated the age, gender, lifestyle, and educational level of 186 patients with FD, and made evaluations of anxiety and depression levels. The results show that older females are more common among FD patients, and its occurrence is obviously related to anxiety and depression. However, there is currently no conclusive evidence to indicate that the symptoms of functional dyspepsia are related to mental abnormalities or chronic stress. The number of major life stress events in patients with functional dyspepsia is not necessarily higher than that of other populations, but it is likely that these patients have a higher sensitivity to stress. Therefore, as doctors, it is necessary to understand the personality characteristics and lifestyle of patients to understand their diseases, which may be very important for treatment.

　　8. Other gastrointestinal functional disorders

　　(1) Gastroesophageal Reflux Disease (GERD): Heartburn and regurgitation are specific symptoms of gastroesophageal reflux, but many GERD patients do not have these obvious symptoms. Some patients complain of both heartburn and dyspepsia. Currently, many scholars have accepted the following view: a few GERD patients do not have esophagitis, and many GERD patients have complex histories of dyspepsia, not just simple heartburn and acid regurgitation symptoms. Research using esophageal 24-hour pH monitoring has found that about 20% of patients with functional dyspepsia and reflux disease are related. Recently, Sandlu et al. reported that in 20 cases of anorexia in children, 12 cases (60%) had gastroesophageal reflux. Therefore, there is sufficient reason to believe that gastroesophageal reflux disease is related to some cases of functional dyspepsia.

　　(2) Aerophagia: Many patients often unconsciously swallow an excessive amount of air, leading to bloating, fullness, and belching. This condition is also often secondary to stress or anxiety. For such patients, appropriate behavioral adjustment during treatment is often very effective.

　　(3) Irritable Bowel Syndrome (IBS): There are often many overlaps between functional dyspepsia and other gastrointestinal disorders. About 1/3 of IBS patients have dyspepsia symptoms; the proportion of IBS symptoms in patients with functional dyspepsia is also approximately the same.

　　It often causes emaciation and malnutrition, leading to decreased body resistance and susceptibility to frequent infectious diseases. Frequent diarrhea can also lead to dehydration. Dehydration refers to a symptom caused by the body's inability to replenish a large amount of water due to illness, resulting in metabolic disorders. In severe cases, it can cause fainting, even life-threatening conditions, and requires fluid replacement through intravenous infusion. A group of clinical symptoms caused by a decrease in extracellular fluid can be divided into hyponatremic dehydration, which is a decrease in extracellular fluid combined with low blood sodium, hypertonic dehydration, which is a decrease in extracellular fluid combined with high blood sodium, and isotonic dehydration, which is a decrease in extracellular fluid with normal blood sodium levels.

　　1. Dysmotility-like dyspepsia: The main symptoms of this type of patient are bloating, early satiety, and belching. Symptoms often worsen after eating. Abdominal pain, nausea, and even vomiting may occur when overfull. Dynamic examination shows that about 50% to 60% of patients have disorders of contraction and relaxation in the proximal and distal parts of the stomach.

　　2. Reflux-like dyspepsia is characterized by pain behind the sternum, heartburn, and regurgitation. Endoscopic examination does not show esophagitis, but 24-hour pH monitoring can detect acid reflux from the stomach to the esophagus in some patients. For those without acid reflux who have such symptoms, it is believed to be related to increased sensitivity of the esophagus to acid.

　　3. Ulcer-like dyspepsia mainly presents with symptoms similar to those of duodenal ulcers, such as pain at night and on an empty stomach, which can be relieved by eating or taking antacid drugs. It may be accompanied by acid regurgitation, and a few patients may have heartburn. The symptoms are chronic and cyclic. Endoscopic examination does not show ulcers or erosive inflammation.

　　4. Non-specific dyspepsia: Dyspepsia symptoms that cannot be classified into the above types often accompany irritable bowel syndrome.

　　However, except for reflux-like dyspepsia, the other classifications have no significant clinical significance. Many patients do not belong to only one subtype; and this classification is unrelated to pathophysiological disorders and clinical efficacy. For example, the incidence of gastroparesis in dyspepsia patients with dysmotility subtype is not higher than that in other subtypes; the efficacy of prokinetic drugs is not necessarily better than that in other subtypes of patients. However, the incidence of gastroesophageal reflux in dyspepsia patients with reflux subtype is indeed higher than that in other subtypes of patients, and the efficacy of anti-reflux treatment is better.

　　5. Diagnosis: For the diagnosis of functional dyspepsia, it is first necessary to exclude organic dyspepsia. In addition to carefully inquiring about the medical history and conducting a comprehensive physical examination, appropriate auxiliary examinations and laboratory tests should be performed. Most cases can be basically diagnosed with functional dyspepsia based on the first-line examination. In addition, many patients with abdominal pain, nausea, and vomiting of unknown etiology often find the cause through gastrointestinal pressure tests, and these tests are also gradually beginning to be applied to pediatric patients.

　　6. General diagnostic criteria for functional dyspepsia

　　(1) Clinical manifestations: Chronic upper abdominal pain, bloating, early satiety, belching, acid regurgitation, heartburn, nausea, vomiting, feeding difficulties, and other upper gastrointestinal symptoms, lasting at least 4 weeks.

　　(2) Auxiliary examinations: Endoscopy did not find gastric or duodenal ulcers, erosions, tumors, and other organic lesions, and no esophagitis was found, nor was there a history of the above diseases. Ultrasound and X-ray examinations excluded liver, gallbladder, and pancreas diseases.

　　(3) Laboratory tests, excluding liver, gallbladder, and pancreas diseases.

　　(4) No history of diabetes, connective tissue disease, kidney disease, and mental illness.

　　(5) No history of abdominal surgery.

　　7. Rome II diagnostic criteria: The Rome II diagnostic criteria for pediatric functional dyspepsia adopt the adult criteria, specifically as follows:

　　The following symptoms appear at least 12 weeks in 12 months, but do not need to be continuous:

　　(1) Persistent or recurrent pain or discomfort in the upper abdomen.

　　(2) There is no evidence of organic disease.

　　(3) The symptoms do not subside after defecation, and there is no change in the frequency and shape of the stool.

　　Not all children with functional dyspepsia need to receive medication. Some children, after diagnosis by the doctor and finding that there is no disease and the examination results are normal, can prevent the disease by changing their lifestyle and adjusting their diet. For example, establishing good living habits, avoiding psychological stress factors and irritant foods, avoiding the use of non-steroidal anti-inflammatory drugs, and for those who cannot stop taking medication, simultaneous use of gastric mucosal protective agents or H2 receptor antagonists should be considered.

　　1. Routine blood tests, liver and kidney function tests, blood sugar, thyroid function tests, fecal occult blood test, and 24-hour pH monitoring of the esophagus and stomach should be performed. Routine examinations often do not reveal any abnormalities, and some may have mild anemia. Diseases such as diabetes, connective tissue disease, thyroid dysfunction, and liver, kidney, and pancreas diseases should be excluded.

　　2. Upper gastrointestinal endoscopy, liver and gallbladder ultrasound, chest X-ray should be performed. Various gastrointestinal motility examination methods such as ultrasound or radioactive isotope gastric emptying examination, gastrointestinal pressure measurement play a very important role in the diagnosis and differential diagnosis of FD.

　　2. Endoscopic examination is mainly used to exclude esophageal, gastric, duodenal inflammation, ulcers, erosions, tumors, and other organic lesions. Ultrasound examination is used to exclude liver, gallbladder, pancreas, kidney, and other lesions.

　　1. Maintain a balanced diet

　　Maintain a balanced diet rich in fiber, such as fresh fruits and vegetables and whole grains. Chew slowly, do not eat quickly.

　　2. Foods to avoid

　　Avoid refined sugars, bread, cakes, pasta, dairy products, caffeine, citrus fruits, tomatoes, green peppers, carbonated drinks, potato chips, junk food, fried food, spicy food, red meat, beans, cola. Reduce salt intake. Processed foods, junk food, and all dairy products can stimulate excessive mucus secretion, leading to malabsorption of protein. Limit the intake of peanuts, lentils, and soybeans. They contain an enzyme inhibitor.

　　3. Pay attention to food pairing

　　Protein and starch, vegetables and fruits are not a good combination, milk is best not to be used with meals, and the combination of sugar with protein or starch is also not conducive to digestion.

　　I. Treatment

　　1. General treatment

　　Generally speaking, the most important thing in treatment is to establish a solid therapeutic relationship between the doctor and the patient. The doctor should gain the patient's trust by asking detailed medical history and conducting a comprehensive and detailed physical examination. After the preliminary examination, the doctor should discuss differential diagnosis with the patient, including the possibility of functional dyspepsia. Reasonable diagnostic and examination steps should be recommended to the patient, and their concerns should be explained. After the diagnostic examination, the patient should be informed of the diagnosis of functional dyspepsia, and they should be educated, doubts should be eliminated, the tendency of 'over-examination' should be suppressed, and the focus should shift from finding the cause of symptoms to helping patients overcome these symptoms.

　　Doctors should explore the patient's life stress situation, including things related to the patient's family, school, interpersonal relationships, and living environment. It is not possible to change their living environment, so patients should be guided on measures to reduce stress responses, such as physical exercise and good eating and sleeping habits.

　　It is also necessary to understand the patient's recent changes in diet or medication. Carefully understand the foods and drugs that may worsen the patient's symptoms, and stop using them.

　　2. Drug treatment

　　The efficacy of drug treatment for functional dyspepsia is not very satisfactory. So far, there is no specific drug that can completely alleviate symptoms. Moreover, the improvement of symptoms may also be related to the ups and downs of symptoms in the natural course of the disease, or the effect of placebos. Therefore, the focus of treatment should be placed on changing lifestyle habits and adopting active coping strategies, rather than solely relying on medication. When symptoms worsen, drug treatment may be helpful, but the dosage should be minimized, and long-term use should only be considered when there is clear benefit.

　　Two, the following introduces the commonly used drugs for the treatment of functional dyspepsia:

　　1. Antacids and Antisecretory drugs:

　　(1) Antacids: Antacids are the most widely used drugs in the treatment of dyspepsia. In Western countries, it is an over-the-counter drug. Some patients have relief of symptoms after taking antacids, but there are also reports that antacids are similar in efficacy to placebos in the treatment of functional dyspepsia.

　　Antacids (sodium bicarbonate, aluminum hydroxide, magnesium oxide, magnesium trisilicate) commonly used in China include Lorne, compound aluminum hydroxide (Gastroplex), Gastrodol (Lekdol), magnesium aluminum hydroxide (Gastadex), and compound bismuth subsalicylate. These drugs have a significant effect on alleviating symptoms such as hunger pain, acid regurgitation, and heartburn. However, the drug has a short duration of action, requires multiple doses, and long-term use may cause adverse reactions.

　　(2) Antisecretory drugs: Antisecretory drugs mainly refer to H2 receptor antagonists and proton pump inhibitors.

　　There are many reports on the use of H2 receptor antagonists in the treatment of functional dyspepsia, and the efficacy of the drugs is statistically significantly better than that of placebos. The main drugs include cimetidine, 20-30mg/(kg·d), taken twice daily; ranitidine, 5-7mg/(kg·d), taken twice daily; famotidine, 0.6-1mg/(kg·d), taken twice daily, etc.

　　The proton pump inhibitor omeprazole, 0.6-0.8mg/(kg·d), once daily, orally, can inhibit the H+-K+-ATPase of parietal cells, has a strong inhibitory effect on acid secretion, with a long duration, and is suitable for patients who have not responded to H2 receptor antagonists.

　   2. Prokinetic drugs:

　　Based on clinical trials with control groups, it is now certain that metoclopramide (Gastroplex), domperidone (Metoclopramide), and cimetidine are effective in eliminating various symptoms of functional dyspepsia. Domperidone (Metoclopramide) is more commonly used in pediatrics.

　　(1) Metoclopramide (Gastroplex): It has both central and peripheral dopamine antagonistic effects, and simultaneously excites 5-HT4 receptors, promotes the release of endogenous acetylcholine, increases the coordination of antrum-duodenal movement, and promotes gastric emptying. The pediatric dose is 0.2mg/kg per dose, taken 3-4 days, 15-20 minutes before meals. Due to the many adverse reactions, its clinical application is gradually decreasing.

　　(2) Domperidone (Metoclopramide): An antiparkinsonian drug that inhibits peripheral dopamine receptors, promotes the emptying of solid and liquid in the stomach, inhibits stomach accommodation and relaxation, coordinates the antrum-duodenal movement, relaxes the pylorus, and thus relieves dyspeptic symptoms. The pediatric dose is 0.3mg/kg per dose, taken 3-4 days, 15-30 minutes before meals. Children under 1 year of age should not take it due to the incomplete development of the blood-brain barrier function.

　　(3) Cisapride: By promoting the release of acetylcholine at the postsynaptic endings of the parasympathetic ganglion fibers of the gastrointestinal muscularis mucosae, it enhances the tone of the lower esophageal sphincter, strengthens the propulsive movements of the esophagus, stomach, small intestine, and colon. The main effects on the stomach are to increase the contraction of the antrum and improve the coordination movement between the antrum and duodenum. Reducing the frequency of the pyloric phase-specific contraction, making the gastric electrical activity tend to normal, thereby accelerating gastric emptying. The pediatric dose is 0.2mg/kg, taken 15-30 minutes before meals for 3-4 days. Clinical studies have found that this drug can significantly improve dyspepsia symptoms, but due to adverse reactions to the heart, its application is limited.

　　(4) Erythromycin: Although it is an antibiotic, it is also a motilin agonist, which can increase the contraction activity of the proximal and distal parts of the stomach, promote propulsive peristalsis of the stomach, accelerate gastric emptying before and after meals, and can be used for FD children.

　　3. Gastric mucosal protective agents:

　   These drugs mainly include colloidal bismuth, sucralfate, misoprostol, enprostil, bismuth subgallate (Smeard), and so on. The clinical application of these drugs is mainly due to the possibility that the onset of functional dyspepsia may be related to chronic gastritis, and the patient may have weakened gastric mucosal barrier function.

　   4. 5-HT3 receptor antagonists and opiate receptor agonists:

　   Both of these drugs have a weak effect on promoting gastric emptying, and their principle of treating functional dyspepsia patients is to regulate the visceral sensory threshold. However, there is no medication experience in pediatrics for these drugs.

　　5. Antianxiety drugs:

　   Some people in China use a combination of low-dose domperidone and metoclopramide combined with psychological counseling to treat patients with functional dyspepsia, and found that it has a significant relieving effect on symptoms such as upper abdominal pain and belching, which is significantly improved compared to patients who do not use domperidone. Therefore, there is certain clinical significance in using drugs to treat psychological disorders in the treatment of FD.

　　3. Prognosis

　　Mostly, symptoms are relieved after carefully finding the cause, gaining the patient's trust and cooperation, and adjusting the treatment.