Peptic ulcer refers primarily to chronic ulcers occurring in the stomach and duodenum, classified as gastric ulcers (GU) and duodenal ulcers (DU). It can affect children of all ages, though it is more commonly observed in school-aged children. In infants and young children, ulcers are typically acute and secondary, often associated with an identifiable primary disease, with a similar incidence of GU and DU. In older children, chronic and primary ulcers are more common, with DU being the predominant type. Boys are more frequently affected than girls, and a significant family history can often be identified.
Etiology and Pathogenesis
The etiology of primary peptic ulcers involves multiple factors, and the precise pathogenesis remains incompletely understood. It is currently believed that ulcers result from an imbalance between aggressive factors (acid, pepsin, bile salts, medications, microorganisms, and other harmful substances) that damage the gastric and duodenal mucosa and mucosal defense factors (mucosal barrier, mucus-bicarbonate barrier, mucosal blood flow, cellular regeneration, prostaglandins, etc.). It is generally thought that factors associated with increased acid production are more significant in DU, while weakened tissue defenses play a greater role in GU.
Aggressive Action of Gastric Acid and Pepsin
Gastric acid and pepsin serve as the primary aggressive factors against the gastric and duodenal mucosa. In newborns, gastric acid secretion peaks within 1–2 days after birth, reaching levels similar to those in adults, then declines around 4–5 days, before gradually increasing again. Consequently, newborns may develop primary peptic ulcers as early as 2–3 days after birth. As gastric acid secretion increases with age, the prevalence of peptic ulcers in older children is higher than in infants.
Mucosal Defense Functions of the Stomach and Duodenum
The capacity of the gastric mucosa to resist damage is determined by factors such as mucosal blood flow, epithelial cell regeneration, mucus secretion, and the integrity of the mucosal barrier. Exposure to various aggressive factors may impair mucosal circulation, secretion, regeneration, and barrier function, leading to mucosal ischemia, necrosis, and ulcer formation.
Helicobacter pylori (Hp) Infection
Studies indicate that the majority of primary ulcer patients have H. pylori infection. The recurrence rate of ulcers decreases significantly following the eradication of H. pylori, demonstrating its critical role in the pathogenesis of ulcer disease.
Genetic Factors
Evidence suggests a genetic predisposition to peptic ulcers. Some affected children have a positive family history, with GU and DU occurring 1.8 times and 2.6 times more frequently, respectively, among siblings compared to the general population. Concordance rates of ulcer disease are also higher in monozygotic twins.
Other Factors
Psychological trauma, central nervous system diseases, trauma, postoperative states, improper dietary habits (such as overeating, consumption of excessively cold or fried foods), seasonal factors, and medications that irritate the gastric mucosa (e.g., NSAIDs, corticosteroids) can all reduce mucosal defenses and cause damage to the gastric mucosa.
Secondary ulcers result from localized damage to the gastric and duodenal mucosa caused by systemic diseases. These ulcers are associated with stress responses induced by critical illnesses.
Pathology
DU primarily occurs in the bulb and occasionally in post-bulbar regions (referred to as post-bulbar ulcers). DUs are mostly solitary but may sometimes be multiple. GU typically arises in the antrum and the gastric angle, although a smaller proportion occurs in the gastric body or pyloric canal. The size and depth of ulcers vary. Endoscopic findings reveal ulcers that are round, irregularly shaped, or linear, with grayish-white coatings at the base and surrounding mucosal hyperemia and edema. Shallow ulcers involve the muscularis mucosae, while deeper ulcers can extend into the muscularis propria or even the serosa. Vascular rupture may result in bleeding, while perforation through the serosa can lead to complications. Repeated inflammation in the duodenal bulb may cause mucosal hyperemia, edema, fibrotic hyperplasia, and contraction, leading to bulb deformation and, in some cases, false diverticula. The simultaneous presence of gastric and duodenal ulcers is referred to as compound ulcers.
Clinical Manifestations
The clinical signs and symptoms vary depending on the most common site, ulcer type, and disease course at different ages. The younger the patient, the less typical the symptoms are.
Neonatal Period
Secondary ulcers are more frequently observed, commonly associated with primary conditions such as prematurity, birth asphyxia with hypoxia-ischemia, sepsis, hypoglycemia, respiratory distress syndrome, and central nervous system disorders. Symptoms typically present as acute onset with hematemesis and melena. Primary ulcers may occur as early as 2–3 days after birth.
Infancy
Secondary ulcers are more prevalent, with acute onset often presenting as gastrointestinal bleeding or perforation. Primary ulcers, mainly GU, present with poor appetite, vomiting, postprandial crying, abdominal distension, and growth retardation. Hematemesis and melena may also occur.
Early Childhood
GU and DU occur with equal frequency. Symptoms commonly include vomiting after meals, episodic periumbilical and epigastric pain, and less commonly, a burning sensation. Pain that awakens the child at night or in the early morning may occur, along with hematemesis, melena, or, in severe cases, perforation.
Preschool to Adolescent Age
Primary DU is more common. Symptoms primarily consist of recurrent periumbilical and epigastric distension and burning pain, which are often more prominent during hunger or at night. Severe cases may present with hematemesis, melena, and anemia. Perforation is characterized by intense pain radiating to the back or the left or right upper quadrants of the abdomen. Some children may present only with anemia, while others may exhibit painless melena, syncope, or even shock in rare cases.
Complications
Chronic ulcers often result in iron-deficiency anemia. Perforation of the ulcer into the abdominal cavity or adjacent organs may lead to peritonitis or pancreatitis. Extensive inflammation and edema can result in acute or chronic obstruction.
Auxiliary Examinations
Laboratory Tests Related to Gastrointestinal Bleeding
Laboratory findings may include hypochromic anemia on complete blood count and positive fecal occult blood tests.
Upper Gastrointestinal Endoscopy
Upper gastrointestinal endoscopy is the most accurate diagnostic method for ulcer disease. Endoscopic observation provides direct visualization, enabling accurate diagnosis of ulcers, assessment of lesion size, severity of surrounding inflammation, and presence of exposed blood vessels on the ulcer surface. Additionally, endoscopy permits mucosal biopsy for histopathological and bacteriological analysis and offers therapeutic options for controlling active bleeding. Endoscopic visualization of ulcers typically reveals round or oval lesions with defined borders and grayish-white exudates at the base. Ulcers can be classified by disease stage: active phase (A), healing phase (H), and scar phase (S), with each stage further divided into one or two subcategories.
Gastrointestinal X-Ray with Barium Contrast
This procedure is suitable for patients unable to undergo endoscopy.
Direct Signs
The detection of niche on the gastric or duodenal wall confirms the diagnosis.
Indirect Signs
Gastric ulcer-related spasm notches on the opposite side of the ulcer or duodenal bulb spasms and deformities may provide diagnostic clues. Due to the superficial nature of ulcers in children, barium passage is rapid, which reduces the detection rate compared to adults and increases the likelihood of false positives. Double-contrast barium imaging can improve diagnostic accuracy.
Helicobacter pylori (Hp) Testing
As discussed in the chronic gastritis section, the diagnosis of active Hp infection in children requires meeting at least one of the following criteria:
- Positive Hp culture.
- Positive results from both histopathological examination and rapid urease test.
- If histopathology and rapid urease test results are inconsistent, further non-invasive tests (e.g., 13C-urea breath test or stool Hp antigen test) are required.
- In cases of ulcer bleeding, any single positive result from histopathological examination or rapid urease test is sufficient for diagnosis.
Diagnosis and Differential Diagnosis
The symptoms and signs of peptic ulcer disease in children are less typical compared to adults. Possible suspicion of peptic ulcer arises in the presence of the following clinical features: burning sensation or hunger pain in the epigastric region; recurrent, postprandial upper abdominal pain alleviated by eating, with notable symptoms during the night or early morning; vomiting associated with meals; repeated gastrointestinal discomfort in children with a family history of ulcer disease, especially DU; unexplained hematemesis or melena; and the presence of anemia with a positive fecal occult blood test. Timely endoscopic examination is crucial to confirming the diagnosis. Differential diagnosis should be considered for the following symptoms:
Abdominal Pain
Abdominal pain should be differentiated from conditions such as intestinal spasm, ascariasis, infections of intra-abdominal organs, gallstones, and Henoch-Schönlein purpura.
Hematemesis
In neonates and infants, hematemesis can result from neonatal hemorrhagic disease or esophageal hiatal hernia. In older children, differentiation is necessary from esophageal variceal rupture secondary to liver cirrhosis, as well as systemic bleeding disorders. In some cases, differentiation from hemoptysis may also be required.
Melena
Bleeding from a peptic ulcer typically presents as black, tarry stools, while bright red stool is observed only in cases of massive bleeding. Differential diagnoses include intussusception, Meckel's diverticulum, polyps, Henoch-Schönlein purpura, and hematological disorders causing gastrointestinal bleeding.
Treatment
The goals of treatment include alleviating and eliminating symptoms, promoting ulcer healing, preventing recurrence, and avoiding complications.
General Management
Establishing healthy lifestyle habits is essential, with regular and moderate eating, avoidance of excessive fatigue and psychological stress, and elimination of harmful factors (e.g., avoiding irritant foods and medications). In the event of bleeding, close monitoring and medical intervention are necessary to prevent hypovolemic shock. Monitoring of vital signs such as blood pressure, heart rate, and peripheral circulation is required. Fasting is implemented alongside adequate fluid volume replenishment. Severe hemorrhage may necessitate blood transfusions. Local hemostatic interventions, such as topical medications, endoscopic sclerotherapy, or electrocoagulation, as well as systemic hemostatic drugs, may be employed when necessary.
Pharmacological Therapy
The therapeutic principles focus on suppressing gastric acid secretion, neutralizing gastric acid, enhancing mucosal defense, and eradicating Helicobacter pylori (Hp).
Acid Suppression Therapy
This is the key to reducing the impact of aggressive factors.
- H2 Receptor Antagonists (H2RAs): Used to directly inhibit histamine action and block acetylcholine-mediated secretion, thereby reducing acid production and promoting ulcer healing.
- Cimetidine: Administered at 10–15 mg/kg per day, divided into 4 doses taken 10–30 minutes before meals or infused intravenously 1–2 times daily; treatment duration is 4–8 weeks.
- Ranitidine: Administered at 3–5 mg/kg per day, taken once every 12 hours, or once every evening, or infused intravenously 2–3 times daily; treatment duration is 4–8 weeks.
- Famotidine: Administered at 0.9 mg/kg once before bedtime or intravenously once daily (or every 12 hours in severe cases); treatment duration is 2–4 weeks.
- Proton Pump Inhibitors (PPIs): These suppress acid secretion by acting specifically on parietal cells in the gastric mucosa, reducing H+-K+-ATPase activity, and preventing the transport of H+ from the cytoplasm to the gastric lumen.
- Omeprazole: Given at 0.6–0.8 mg/kg per day as a single morning dose; treatment duration is 2–4 weeks. Other options include lansoprazole and esomeprazole, which may be selected based on the patient’s age and needs.
- Antacids: Used to neutralize gastric acid, alleviate symptoms, and promote ulcer healing.
Mucosal Protective Agents
Sucralfate
Dosage is 10–25 mg/kg per dose, or according to age: 250 mg per dose for 1 month–1 year, 500 mg per dose for 2–11 years, and 1 g per dose for 12–14 years. Administered 4–6 times daily, one hour before meals or at bedtime. Maximum dosage is 8 g daily, with a treatment duration of 4–8 weeks.
Bismuth Compounds (≥6 years)
Potassium bismuth citrate or colloidal bismuth pectin is dosed based on bismuth content at 6–8 mg/kg per day, divided into 2 doses, with a maximum of 165 mg per dose, administered twice daily for 4–6 weeks. Side effects include potential irreversible neurological damage and acute renal failure with long-term, high-dose use, necessitating careful monitoring of blood bismuth levels.
Anti-H. pylori Therapy
Eradication therapy is necessary for peptic ulcers with Hp infection. Commonly used drugs include:
- Antibiotics:
- Amoxicillin: 50 mg/(kg·day), divided into 2 doses.
- Clarithromycin: 15–20 mg/(kg·day), divided into 2 doses.
- Metronidazole: 20 mg/(kg·day), divided into 2 doses.
- Tinidazole: 20 mg/(kg·day), divided into 2 doses.
- Bismuth Compounds (≥6 years).
- Acid-Suppressive Drugs: Such as omeprazole.
Combination therapies are recommended, with a treatment duration of 14 days. Individualized triple therapy based on antibiotic sensitivity is preferred where possible. For example, in cases with confirmed sensitivity to clarithromycin, therapy with PPI + clarithromycin + amoxicillin is recommended for 14 days, with metronidazole replacing amoxicillin for penicillin-allergic patients. In regions of high clarithromycin resistance or when resistance status is unknown, the first-line option for patients aged ≥6 years is bismuth-based quadruple therapy (PPI + amoxicillin + metronidazole + bismuth compound). For penicillin-allergic patients, amoxicillin can be replaced with clarithromycin. Treatment duration is 14 days. In patients aged <6 years where resistance testing is not available, or where both clarithromycin and metronidazole resistance are identified, indications for eradication therapy should be strictly evaluated.
Surgical Treatment
Surgery is generally not required for peptic ulcer disease but may be considered under the following circumstances:
- Ulcer complicated by perforation.
- Uncontrollable bleeding with significant blood loss, where blood loss exceeds 30% of total blood volume within 48 hours.
- Cicatricial pyloric obstruction that shows no improvement after 72 hours of conservative management, such as gastrointestinal decompression.
- Chronic intractable pain.