eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Peptic Ulcer Disease

Mutaz I Sultan, MBChB, Instructor and Fellow, Department of Pediatrics, Division of Gastroenterology and Nutrition, Medical College of Wisconsin, Children's Hospital
B UK Li, MD, Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Director, Pediatric Fellowships and Gastroenterology Fellowship, Medical Director, Functional Gastrointestinal Disorders and Cyclic Vomiting Program, Medical College of Wisconsin; Attending Gastroenterologist, Children's Hospital of Wisconsin; Ameesh Shah, MD, Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital

Updated: Nov 5, 2009

Introduction

Background

The lesion of peptic ulcer disease (PUD) is a disruption in the mucosal layer of the stomach or duodenum. An ulcer is distinguished from an erosion by its penetration through the muscularis mucosa or the muscular coating of the gastric or duodenal wall. Peptic ulcer disease results from the imbalance between defensive factors that protect the mucosa and offensive factors that disrupt this important barrier. Mucosal protective factors include the water-insoluble mucous gel layer, local production of bicarbonate, regulation of gastric acid secretion, and adequate mucosal blood flow. Aggressive factors include the acid-pepsin environment, infection with Helicobacter pylori, and mucosal ischemia.

Many differences are noted between children and adults with peptic ulcer disease, especially in clinical presentation, in the prevalence rates of different types of ulcer disease, and the prevalence rate of complications.

Peptic ulcer disease has profoundly changed over the last few decades in Western countries in both children and adults. Indeed, the prevalence of H pylori– positive ulcers has declined, and a ‘‘new’’ disease has emerged. H pylori –negative gastric ulcers and duodenal ulcers affect younger patients and have double the recurrence rate.¹

Primary peptic ulcers are still relatively uncommon in children and account for roughly 1 in 2500 pediatric hospital admissions. Primary ulcers are more common in adolescents than in children and tend to recur after initial healing. Although affected children are thought to have high acid secretion, this has not been proven. Many of the primary ulcers seen in teenagers are now thought to be associated with H pylori infection. Secondary ulcers are seen in head trauma, severe burns, and with use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).

Pathophysiology

The 2 most important concepts in understanding the pathophysiology of peptic ulcer disease in children are the host factors that serve to protect the GI mucosa from ulceration and the inflammatory mediators and aggressive factors that contribute to mucosal inflammation and ulceration.

Peptic ulcer disease in children is the result of an imbalance between mucosal defensive and aggressive factors. An overlying physiochemical barrier provides cytoprotection of the gastric mucosa. This barrier comprises water-insoluble gastric mucus, gastrically produced bicarbonate, an unstirred water layer, phospholipids, rapid shedding of cells resulting from epidermal growth factor, normal mucosal blood flow, prostaglandin-stimulated bicarbonate, mucus production, and inhibited acid secretion.

Contributors to mucosal inflammation and ulceration include endogenous factors, such as gastric acidity (approximates adult values by age 3-4 y), acid-dependent pepsin and mucosal ischemia, and exogenous factors, such as drugs (eg, NSAIDs, aspirin, corticosteroids), alcohol, cigarette smoking, corrosive chemicals (eg, lye), and emotional stress. In patients with traumatic injuries, burns, sepsis, respiratory failure, or other critical systemic illnesses, many factors can contribute to erosions and ulcers, including mucosal ischemia, increased gastric acid and pepsin production, higher levels of endogenous catecholamines and steroids, and decreased prostaglandins and mucus production. Important mediators of mucosal inflammation and resultant ulceration include oxygen free radicals, lymphokines, platelets activating factors, tumor necrosis factor, leukotrienes, and monokines.

Peptic ulcer disease can be divided into 2 major categories, primary and secondary, on the basis of underlying etiology. The primary category includes those few disorders known to cause acid hypersecretion, which are usually chronic and are located in the duodenum. Secondary ulceration, which may be gastric or duodenal, occurs in association with severe stress such as systemic illness and are usually acute in nature.

The gram-negative spirochete, H pylori, was first linked to gastritis in 1983. Since then, further study of H pylori has revealed that it is a major part of the triad, which includes acid and pepsin, that contributes to primary peptic ulcer disease. The unique microbiologic characteristics of this organism, such as urease production, allows it alkalinize its microenvironment and survive for years in the hostile acidic environment of the stomach, where it causes mucosal inflammation and, in some individuals, worsens the severity of peptic ulcer disease.

When H pylori colonizes the gastric mucosa, inflammation usually results. The casual association between H pylori gastritis and duodenal ulceration is now well established in the adult and pediatric literature. In patients infected with H pylori, high levels of gastrin and pepsinogen and reduced levels of somatostatin have been measured. In infected patients, exposure of the duodenum to acid is increased. Virulence factors produced by H pylori, including urease, catalase, vacuolating cytotoxin, and lipopolysaccharide, are well described.

Most patients with duodenal ulcers have impaired duodenal bicarbonate secretion, which has also proven to be caused by H pylori because its eradication reverses the defect.² The combination of increased gastric acid secretion and reduced duodenal bicarbonate secretion lowers the pH in the duodenum, which promotes the development of gastric metaplasia (ie, the presence of gastric epithelium in the first portion of the duodenum). H pylori infection in areas of gastric metaplasia induces duodenitis and enhances the susceptibility to acid injury, thereby predisposing to duodenal ulcers. One study that followed 181 patients with endoscopy-negative, nonulcer dyspepsia found that duodenal colonization by H pylori was a highly significant predictor of subsequent development of duodenal ulcers.³

Frequency

United States

Peptic ulcer disease is an uncommon disease of childhood, with an estimated frequency of 1 case in 2500 hospital admissions. The estimated prevalence of childhood peptic ulcer disease in large general pediatric practices is 1.7%. In a retrospective analysis of 622 endoscopic procedures in the United States, peptic ulcer disease was identified in 11 children (1.8%). In large pediatric medical centers with busy gastroenterology practices, only 5 primary ulcers may be diagnosed per year. The annual incidence of primary duodenal ulcers is estimated to be 5 cases per 100,000 children. The prevalence of H pylori infection is substantially higher than this, an estimated 10% in industrialized countries.

The true incidence of secondary ulcers is unknown and depends on the frequency of systemic illness, traumatic injury, and use of injurious agents. Studies of risk factors for stress ulceration are being conducted in critically ill children, especially those in intensive care units.

International

Peptic ulcer disease has changed profoundly over the last few decades in Western countries in both children and adults. The proportion of H pylori –positive ulcers has declined, and the prevalence of H pylori –negative gastric ulcers and duodenal ulcers has grown. In a recent retrospective study from China, 6.9% of children undergoing esophagogastroduodenoscopy had an ulcer; almost half of these cases (46.5%) had no associated H pylori infection.¹ These data are different from that of other studies, in which only 20-27% of childhood peptic ulcers were not associated with either NSAID use or H pylori infection.

The prevalence of H pylori infection in developing countries is as high as 50-100%. The prevalence of peptic ulcer disease is increasing in developing countries. In a retrospective review of 112 Taiwanese children undergoing upper GI endoscopy for upper GI bleeding, gastric ulcer was confirmed in 10% and duodenal ulcer was confirmed in 15%.

Mortality/Morbidity

The highest mortality rates are found in young infants with secondary stress ulcers, who may present acutely with life-threatening GI hemorrhage or intestinal perforation. Mortality rates from perforated peptic ulcers in adolescent is 3.8%.⁴ In contrast, children with primary gastritis or duodenal ulcer disease have low mortality rates.

GI bleeding is one of the most common presentations of ulcer disease in neonates. GI hemorrhage occurs in both primary and secondary peptic ulcer disease. GI blood loss may be acute and catastrophic, particularly in neonates or in children with a critical medical illness or traumatic injuries, or it may have a slow and chronic course, without posing a serious threat to life.

Perforation of an ulcer is the second main manifestation of peptic ulcer disease in neonates. However, any child who is critically ill or injured is at risk for stress ulceration and perforation. Perforation is often preceded by or associated with GI hemorrhage. Obstruction of the gastric outflow tract because of edema or scarring most often occurs in the setting of duodenal or pyloric channel ulcers.

Since the introduction of H2 receptor antagonist and proton pump inhibitor, and with the recognition and treatment of H pylori, the incidence of bleeding, perforation, and gastric outflow obstruction has dramatically decreased.

Race

In the United States, the prevalence of H pylori infection is higher in blacks and Hispanics than in whites not of Hispanic origin.

Sex

The male-to-female ratio for all childhood peptic ulcer disease is 1.5:1. The incidence of primary peptic ulcer disease is 2-fold to 3-fold higher in boys than in girls; however, no sex difference in the incidence of primary peptic ulcer disease has been noted in infants or young children.

Age

Primary peptic ulcer disease is uncommon in infants and in children younger than 10 years. The prevalence of primary peptic ulcer disease increases during adolescence. Secondary peptic ulcer disease can affect patients of all ages, but its prevalence is increased in patients younger than 6 years.

Clinical

History

• In children in whom peptic ulcer disease (PUD) is suspected, include the following in the history:
  • Review of past illnesses and chronic medical conditions
  • Family history of ulcer disease, including known H pylori infection, or conditions affecting the GI tract (eg, Crohn disease)
  • Character, location, frequency, duration, severity, and exacerbating (especially meals in children) and alleviating factors of abdominal pain
  • Vomiting and description of gastric material
  • Bowel habits and description of stool (eg, profuse diarrhea seen in Zollinger-Ellison syndrome [ZES])
  • Prescribed and over-the-counter (OTC) medications, especially nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids
  • Prior diagnostic testing and specific GI therapies
  • Appetite, diet, and weight changes
  • Family and social stressors
  • Alcohol ingestion and smoking habits
• Abdominal pain is the most common symptom of childhood peptic ulcer disease.
  • The pain is usually dull and vague. The pain is most likely to be dull and aching rather than sharp and burning, as adults describe. Food intake often causes the pain to worsen; this is the opposite of the adult pattern.
  • The pain may be poorly localized or localized to the periumbilical or epigastric areas.
  • In preschool-aged children, the pain is typically periumbilical and worsens after eating.
  • Younger children may not localize pain and present with anorexia and irritability.
  • After the age of 6 years, the child's description of pain may be similar to the description by adults. The classic pain of peptic ulcer disease (ie, pain that awakens the child, worsens with food, and is relieved by fasting) is described infrequently, but it helps in distinguishing GI pathology from psychogenic pathology when present.
  • Frequent exacerbations and remissions of pain extend over weeks to months.
• Vomiting in infants and toddlers may be associated with slow growth. Recurrent vomiting is also noted in preschool-aged and school-aged children.
• GI tract bleeding (eg, melena, hematochezia, hematemesis) may be another presentation in children.
  • In infants and particularly neonates, serious underlying illness and stress ulceration most commonly manifest as acute perforation or hemorrhage.
  • GI bleeding may lead to iron-deficiency anemia (IDA), and patients may present with vague complaints of fatigue, headache, dyspnea, or malaise.
  • As many as 25% of children with duodenal ulcer have silent presentation with painless upper GI bleeding or iron deficiency anemia.
• For children with ulcer perforation, the symptoms are consistent with peritonitis and abrupt in onset.

Physical

• Children with peptic ulcer disease leading to complications (eg, severe blood loss in the GI tract, perforation, obstruction) can appear acutely ill and have evidence of hemodynamic instability or signs of an acute abdomen. Children with long-standing peptic ulcer disease from H pylori may become profoundly anemic from undetected chronic bleeding and have no complaints.
• Include the following in the physical examination:
  • Observation of the general appearance of the child
  • Evaluation of vital signs
  • Assessment of perfusion with attention to mental status, heart rate, pulses, and capillary refill
  • Assessment of hydration status with attention to moisture of the mucous membranes and skin turgor
  • Observation of any pallor of the skin and conjunctivae
  • Thorough chest examination
  • Careful inspection, auscultation, and palpation of the abdomen, with notation of any liver or spleen enlargement
  • Rectal examination and stool guaiac testing
  • Pelvic examination in sexually active female patients with pain
  • Examination of the testicles and inguinal area in male patients
• Hemorrhage accompanies peptic ulcer disease in 15-20% of patients.
• Acute abdomen resulting from perforation of the GI tract occurs in 5% of children with peptic ulcer disease.

Causes

• Primary peptic ulcer disease
  • Primary peptic ulcer disease can be divided into the following:
    • H pylori– associated disease
    • H pylori– negative/idiopathic disease
    • Hypersecretory states - ZES, gastrin (G)-cell hyperplasia/hyperfunction systemic mastocytosis, cystic fibrosis, short bowel syndrome, and hyperparathyroidism.
  • Genetic factors may be important, as indicated by the observation that as many as 50% of children with peptic ulcer disease have a first-degree or second-degree relative with peptic ulcer disease. In addition, a concordance rate that is 3 times higher in monozygotic than in dizygotic twins has been described, and children with blood group O have an increased incidence of peptic ulcer disease.
  • Emotional stress has been described as a factor that predisposes children to peptic ulcer disease.
  • Alcohol has been documented to produce inflammation, erosions, and hemorrhage in the gastric mucosa in animal and adult human studies. Caffeine intake also predisposes children to peptic ulcer disease.
  • Compared with people who do not smoke cigarettes, those who do are twice as likely to develop peptic ulcer disease. Smoking may lead to ulceration, slow healing, and an increased risk of recurrent disease.
• Secondary peptic ulcer disease
  • Corticosteroids, NSAIDs, and aspirin use predispose children to ulceration. These drugs disrupt the mucosal permeability barrier, rendering the mucosa vulnerable to injury. As many as 30% of adults taking NSAIDS have GI adverse effects. Although the prevalence of NSAID gastropathy in children is unknown, it seems to be increasing, especially in children with chronic arthritis treated with NSAIDS. Recent case reports have demonstrated gastric ulceration from low-dose ibuprofen in children, even after 1 or 2 doses.⁵
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    Secondary peptic ulcer disease (PUD).

    
    
  • Serious systemic illness, sepsis, hypotension, respiratory failure, and multiple traumatic injuries increase the risk for secondary (stress) ulceration.
    • Ulcers associated with a brain tumor or injury, or Curling ulcers, are characterized as single, deep, and prone to perforation. They are associated with high gastric acid output and are located in the duodenum or stomach.
    • Extensive burns are also associated with ulcers, namely Curling ulcers.
    • Stress ulceration and upper-GI hemorrhage are complications that are increasingly encountered in critically ill children in the intensive care setting. Severe illness and a decreased gastric pH are related to an increased risk of gastric ulceration and hemorrhage. Neutralization of gastric acid inactivates proteolytic pepsin, which is responsible for gastric mucosal injury. Therefore, gastric pH of critically ill children should be maintained at more than 6 to prevent injury.
  • Other causes of secondary ulcers include the following:
    • Allergic gastritis and eosinophilic gastritis
    • Cytomegalovirus
    • Graft versus host disease
    • Uremic gastropathy
    • Henoch-Schönlein gastritis
    • Corrosive gastropathy
    • Celiac disease
    • Hepatic cirrhosis
    • Bile gastropathy
    • Autoimmune disease
    • Exercise
    • Crohn disease
    • Other granulomatous gastritides (eg, sarcoidosis, histiocytosis X, tuberculosis)
    • Phlegmonous gastritis and emphysematous gastritis
    • Other infections, including Helicobacter heilmanni, herpes simplex, influenza, syphilis, Candida albicans , histoplasmosis, mucormycosis, and anisakiasis
    • Radiation gastropathy
  • ZES is a rare disorder that can cause gastric or duodenal ulcers (usually multiple) from excessive acid secretion. Consider ZES if a patient has severe peptic ulceration, kidney stones, watery diarrhea or malabsorption. ZES can also be associated with multiple endocrine neoplasias type I, which occurs earlier than isolated ZES. In addition to the typical pancreatic gastrinomas, ZES has been reported in children with solitary extrapancreatic gastrinomas in the stomach, liver, and kidney. Compared with adult disease, malignant gastrinomas in children are slow growing. Patients with ZES usually have fasting serum gastrin levels of more than 200 pg/mL and basal gastric acid hypersecretion at more than 15 mEq/h. Protein pump inhibitor therapy should be discontinued at least 2 weeks before the gastrin level is measured.

Differential Diagnoses

Other Problems to Be Considered

Autoimmune gastritis
Chronic recurrent abdominal pain
Eosinophilic gastritis

Workup

Laboratory Studies

• A minimum of laboratory studies may be indicated in children with mild peptic ulcer disease (PUD) symptoms and normal examination findings. The following laboratory data may be needed in children who are in unstable condition, in those who have severe or chronic or recurrent symptoms, or in those with serious complications of peptic ulcer disease.
  • Hemoglobin and hematocrit tests: These may be indicated to diagnose anemia in the setting of chronic blood loss from the GI tract, to determine the severity of anemia in the setting of acute or massive GI bleeding, and to guide and monitor transfusion or iron therapy.
  • Iron studies (peripheral smears and test of serum iron, total iron-binding capacity [TIBC], ferritin, reticulocyte count): These tests are used to determine the presence of IDA.
  • H pylori serology: This analysis help to detect H pylori infection not previously diagnosed or treated. The evaluation can be used to identify infection in teenagers, but it is not recommended in children because of its false-positive rate and inability to distinguish colonization from inflammation or previous infection. It can be useful in children if results are negative. Stool studies for H pylori appear to be more sensitive and specific than serology testing in children.
  • Measurement of the prothrombin time (PT) and the activated partial thromboplastin time (aPTT): These values are used to identify coagulopathy in patients with sepsis, multiple injuries, or massive GI bleeding. They are also used to identify those at risk for diffuse intravascular coagulation (DIC).
  • Typing and cross-matching of blood: This is done in preparation for transfusion in patients in unstable condition or in critically ill patients.
  • Determination of electrolyte, BUN, and creatinine levels: These levels aid in assessing patients with volume depletion or those who require fluid resuscitation.
  • Arterial blood gas analysis: The values are used to assess the degree of acidosis in a patient with systemic illness, respiratory failure, or severe hypovolemia, or severe burns or trauma.
  • Urinalysis: Urinalysis is performed to assess the patient's hydration status and to screen for infection or stones.
  • WBC count and differential: These are used to detect peripheral eosinophilia in children with eosinophilic gastritis.
  • Measurement of serum gastrin and gastrin-releasing peptide levels: These data are used to exclude Zollinger-Ellison syndrome (ZES) in patients with refractory ulcers.
• Examine and perform guaiac testing on the stool to confirm GI bleeding. Melena is usually the result of an upper-GI bleed, though blood from a duodenal ulcer that quickly transits the intestinal tract may be visible as red or maroon blood in the stool.

Imaging Studies

• Abdominal and/or chest radiography assist in the diagnosis of perforation.
• Upper-GI series
  • An upper-GI series helps in detecting peptic ulcer disease in approximately 70% of children who are examined. A double-contrast study increases the detection rate, but the child should be older and cooperative, and the study increases the radiation exposure. The false-positive rate may be 30%.
  • The sensitivity is higher for duodenal ulcers than for gastric ulcers.
  • Radiologic findings of duodenal ulcers include filling defects or deformities of the duodenal bulb.
  • A fibrinous clot in the ulcer may lead to false-negative findings. Rates of false-positive findings on barium studies are especially high, as high as 30-40%, in pediatric patients.
  • Gastric-outlet obstruction, the result of pyloric lesions, can be detected on upper-GI imaging.
• Angiography may be necessary in patients with a massive GI bleed in whom endoscopy cannot be performed. An ongoing bleeding rate of 0.5 mL/min or more is needed for the angiography to be able to accurately identify the bleeding source. Angiography can depict the source of the bleeding and can help in providing needed therapy in the form of a direct injection of vasoconstrictive agents in adults.

Procedures

• Esophagogastroduodenoscopy
  • Esophagogastroduodenoscopy (EGD) is the procedure of choice for detecting peptic ulcer disease in the pediatric population.
  • EGD allows for direct visualization of the mucosa; for localization of the source of bleeding; and for the diagnosis of H pylori infection by analyzing biopsy specimens, performing cultures or detecting urease activity.
  • Therapeutic endoscopy for acute bleeding (coagulation of a bleeding ulcer with a heater probe or injection with vasoconstricting agents) is another important indication for EGD.
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    the gross appearance of an active ulcer is a round or oval, punched-out lesion with a smooth, white base and surrounding mucosa that is red and edematous.

    
    
  • 
    

    

    Most gastric ulcers are located in the lesser curvature of the stomach.

    
    
  • More than 90% of duodenal ulcers are found in the duodenal bulb. An erosion is small (<3 mm) and superficial defect in the mucosa.
• Consider nasogastric (NG) lavage in a child who is ill and in whom upper-GI hemorrhage is suspected because of hematemesis or melena.

Histologic Findings

• Histologic analysis of an active ulcer reveals 4 zones. From superficial to deep, the zone are (1) a thin layer of necrotic fibrinoid material at the base and margins of the ulcer, (2) a region of mostly polymorphonuclear neutrophil (PMN) leukocytes, (3) active granulation tissue with mononuclear leukocytes, and (4) a solid fibrous or collagenous scar. Ulcers extend through the mucosa and penetrate the muscularis mucosa layer into the submucosa or deeper layers.
• Antral mucosal nodularity and lymphocytic inflammation may be found in association with H pylori gastritis. Hematoxylin and eosin staining reveals the degree of inflammation and ulceration. Giemsa, Diff-Quick, or Warthin-Starry silver staining demonstrates the spiral organisms in the mucous layer overlying the gastric mucosa. With long-standing chronic gastritis, dysplastic changes may be found in the epithelial cells with variation in size, shape, and orientation. These changes support the finding of an increased incidence of gastric cancer in patients with chronic H pylori infection.
• Secondary gastritis, or acute inflammation associated with serious underlying illness or injury, results in a predominance of PMN leukocytes. With the mucosal damage caused by corrosive agents, histologic examination reveals edema, submucosal hemorrhage, and a mild inflammatory cell infiltrate. In children with eosinophilic gastritis, eosinophilic infiltration of the gastric mucosa is the prominent histologic feature.

Treatment

Medical Care

In children with peptic ulcer disease (PUD) who appear to be well, in whom examination findings are normal and symptoms are mild, evaluation may be conducted on an outpatient basis.

• The eradication of H pylori relies on a multidrug regimen.⁶ Triple therapy is considered to be the standard treatment for children, including a proton pump inhibitor combined with 2 antibiotics.⁷ This regimen has been shown to be very effective in eradicating H pylori from the stomach. The current recommendation is treatment with amoxicillin, clarithromycin, and a proton pump inhibitor for 2 weeks.
• Non-H pylori peptic ulcer disease is effectively treated with acid suppression; however, prospective studies are lacking. Complete healing and resolution of symptoms requires appropriate therapy for underlying etiology, as in Crohn disease.
• Proton pump inhibitors are increasingly used in the pediatric population, especially in children with gastroesophageal reflux disease (GERD), than before. Proton pump inhibitors provide consistent gastric pH control, and patients do not develop tachyphylaxis with repeated dosing.
• A recent study in hospitalized adult patients revealed no significant difference among various proton pump inhibitors given through different routes (intravenous [IV] vs oral [PO]) on raising intragastric pH levels above 6 for 72 hours after successful endoscopic hemostasis in patients with a bleeding peptic ulcer.⁸ In addition standard-dose proton pump inhibitor infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding.⁹
  • The risk of adverse effects appear to be minimal with long-term administration. The number of gastrin-secreting cells (G cells) increases, as does the ratio of G cells to D cells. The clinical significance of this effect is unknown. Long-term studies have demonstrated hypergastrinemia and enterochromaffinlike cell hyperplasia in children receiving continuous proton pump inhibitor therapy, but this has not affected histologic findings or caused an increase risk for carcinoid formation.¹⁰
  • Small gastric polyps may develop in some patients during proton pump inhibitor maintenance therapy. These polyps usually develop in the gastric corpus and are hyperplastic or benign fundic gland cysts.
  • Rebound acid hypersecretion arises from the trophic effects of the proton pump inhibitor–induced hypergastrinemia; 44% of previously asymptomatic subjects experienced clinically significant heartburn, acid reflux, or dyspepsia after discontinuing a 2-month course of esomeprazole at 40 mg/d compared with 15% after placebo.¹¹
• Sucralfate is an aluminum salt of sulfated sucrose, which, in the presence of acid pH, forms a complex, pastelike substance that adheres to the damaged mucosal area. It forms a protective coating that acts as a barrier between the lining and gastric acid, pepsin, and bile salts.
• Misoprostol is a synthetic prostaglandin E1 analog with gastric antisecretory and cytoprotective properties. It is effective in adults for the prophylaxis and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Studies on the benefits of misoprostol administration in children are limited.
• Optimal management of severe or refractory peptic ulcer disease requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of recurrent H pylori infection can heal ulceration and also prevent recurrence. Severe, intractable, or recurrent peptic ulcer disease with associated complications mandates a careful evaluation to determine potential etiologies like gastrinomas or Crohn disease.¹²

Surgical Care

Surgical intervention is required in a small percentage of infants and in children with complications of peptic ulcer disease that include perforation, obstruction, intractable pain, and bleeding unresponsive to medical or endoscopic therapy.

• A bleeding ulcer can be treated with a simple plication or oversewing of the bleeding source. A more definitive procedure, such as vagotomy and pyloroplasty, may be required.
• In patients with stress ulcers related to brain injury or burns, the procedure of choice may be pyloroplasty and antrectomy.
• Total gastrectomy is rarely performed to treat multiple gastric ulcers in pediatric patients.
• For perforation, repair is performed by using a simple closure or oversewing.
• Gastric-outlet obstruction is surgically relieved with vagotomy and pyloroplasty or gastroenterostomy.

Consultations

• Gastroenterologist
• Radiologist
• Surgeon

Diet

• Recommend abstinence from all caffeine and alcohol.
• In hospitalized children, milk feedings raise gastric pH and prevent GI bleeding.
• Normal intake of milk is not a known risk factor for peptic ulcer disease. Several peptides and hormones found in bovine and human milk may be responsible for the reduction in gastric acidity.

Activity

• Allow common sense to dictate appropriate activity restrictions in children with chronic symptoms.
• Cessation of smoking should be recommended.

Medication

Medications used in patients with peptic ulcer disease (PUD) reduce gastric acidity and serve to eradicate H pylori infection. Proton pump inhibitors, which work at the final common pathway for gastric acid secretion, are the most potent acid inhibitors.

Histamine H2-receptor antagonists

Receptors for histamine are located on the acid-producing parietal cells. Blocking histamine action suppresses gastric acid secretion.

Ranitidine (Zantac)

H2 antagonist studied most often in children. H2 antagonists competitively inhibit histamine at H2 receptors of gastric parietal cells, lowering gastric acid secretion. Course of therapy tried for 8 wks, by which time most ulcers heal. Because H2 antagonists have no antibacterial effect, symptoms caused by H pylori infection may persist or recur. Pediatric preparations are syr 15 mg/mL; tab 75, 150, or 300 mg; and effervescent granules 150 mg.

Dosing

Adult

150 mg/dose PO bid or 300 mg/dose PO qhs
Alternative: 50 mg/dose IV/IM q6-8h

Pediatric

Neonates: 2-4 mg/kg/d PO divided q8-12h or 2 mg/kg/d IV divided q6-8h
Infants and children: 6-9 mg/kg/d PO divided q8-12h or 2-4 mg/kg/d IV divided q6-8h
Continuous infusion: Administer daily IV dose over 24 h

Interactions

May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; avoid in liver disease; may cause malaise, headache, insomnia, sedation, and arthralgias

Proton pump inhibitors

Proton pump inhibitors are more potent acid inhibitors than H2-receptor antagonists. This class of drugs blocks gastric acid secretion at the proton pump (ie, hydrogen/potassium adenosine triphosphatase [H⁺/K+ ATPase] of the gastric parietal cell), which is the final common pathway of secretion. Proton pump inhibitors are recommended as a part of the drug regimen for symptomatic H pylori infection. Proton pump inhibitor therapy alone does not eradicate H pylori infection, but it does have bacteriostatic activity against H pylori.

Omeprazole (Prilosec, Zegerid)

Used in PUD, alone or in combination with antimicrobials to eradicate H pylori. Inhibits gastric acid secretion. Ulcers may heal more rapidly than with H2 antagonists. Best administered just before first meal of day. Enteric-coated granules in caps ensure appropriate bioavailability. In children unable to swallow intact caps, open and mix granules in acidic substance (eg, apple sauce, apple juice). Granules preferred to less bioavailable susp. Preparations include SR caps 10 or 20 mg or oral susp 20 or 40-mg unit-dose powder packets for immediate dispersal in water.

Dosing

Adult

20 mg/d PO for 4-8 wk

Pediatric

0.6-0.7 mg/kg/d PO initially, may increase to 0.6-0.7 mg/kg/dose PO bid; reported effective dose range 0.7-3.3 mg/kg/d

Interactions

Increases half-life of diazepam, phenytoin, and warfarin (because of its metabolism); may decrease absorption of itraconazole, ketoconazole, iron salts, and ampicillin esters; clarithromycin may increase bioavailability

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause headaches, nausea, diarrhea, and vomiting

Antacids

These agents neutralize gastric acid and may be of benefit in children with peptic ulcer disease. Medication compliance may be a problem because of the requirement for frequent dosing.

Aluminum and magnesium hydroxide (Mylanta, Maalox)

Neutralizes gastric acids, raises stomach pH, and helps to provide pain relief. Antacids may be used in multidrug regimens to eradicate H pylori.
Mylanta: Each 5 mL contains 200 mg AlOH, 200 mg MgOH, and 20 mg simethicone
Maalox: Each 5 mL contains 225 mg AlOH and 200 mg MgOH
Mylanta or Maalox chewable tabs: 200 mg AlOH and MgOH

Dosing

Adult

15-45 mL PO q3-6h or q1-3h pc and hs

Pediatric

5-15 mL PO q3-6h or q1-3h pc and hs
Alternative: 1-2 chewable tab PO q1-3h pc and hs

Interactions

Reduces efficacy of fluoroquinolones, corticosteroids, benzodiazepines, and phenothiazines; aluminum and magnesium potentiate effects of valproic acid, sulfonylureas, quinidine, and levodopa

Contraindications

Documented hypersensitivity; hyperphosphatemia, hypokalemia, or renal failure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use aluminum-containing antacids with caution in recent massive upper-GI hemorrhage

Antibiotics

Multidrug regimens have been studied in the eradication of H pylori infection. All regimens contain 1-2 antimicrobials and agents that neutralize acid or inhibit acid secretion.

Amoxicillin (Amoxil, Trimox)

Component of drug combination therapy that effectively treats duodenal ulcer or gastric ulcer associated with H pylori infection. Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Dosing

Adult

250-500 mg/dose PO tid; not to exceed 2-3 g/d

Pediatric

50 mg/kg/d PO divided bid; not to exceed 2-3 g/d

Interactions

Reduces the efficacy of PO contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; may enhance chance of candidiasis

Clarithromycin (Biaxin)

Macrolide antibiotic with antimicrobial spectrum similar to that of erythromycin but more stable in acid environment and has fewer adverse GI effects. Prescribed in 1- and 2-wk regimens for H pylori infection.

Dosing

Adult

500 mg PO tid for 2 wk (with omeprazole) or 500 mg PO bid for 2 wk (with omeprazole and metronidazole or with ranitidine and tetracycline)

Pediatric

7.5 mg/kg PO bid for 2 wk (with omeprazole and metronidazole or with omeprazole only) or for 10 d (with amoxicillin and omeprazole)

Interactions

CYP450 3A4 inhibitor; toxicity increases with coadministration of fluconazole and pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG-CoA–reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both

Contraindications

Documented hypersensitivity; coadministration of pimozide

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Coadministration with ranitidine or bismuth citrate not recommended if CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

GI agents

These agents protect the GI lining. They are effective in treating peptic ulcers and preventing relapse.

Sucralfate (Carafate)

Forms viscous adhesive substance that protects GI lining against pepsin, peptic acid, and bile salts. For short-term management of ulcers. Available as tabs or oral susp 1 g/10 mL.

Dosing

Adult

1 g PO qid

Pediatric

Not established; 40-80 mg/kg/d PO divided q6h have been used

Interactions

May decrease effects (by decreasing bioavailability) of H2 antagonists (eg, ranitidine), ketoconazole, ciprofloxacin, tetracycline, phenytoin, warfarin, quinidine, theophylline, and norfloxacin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure and conditions that impair excretion of absorbed aluminum

Follow-up

Further Inpatient Care

• Admit patients with peptic ulcer disease (PUD) to the hospital for stabilization, supportive care, and diagnostic testing.

Further Outpatient Care

• Carefully monitor medication doses, adverse effects of medications, and relief or persistence of symptoms.

Inpatient & Outpatient Medications

• Medications include blockers of gastric acid secretion, acid neutralizers, and antibiotics.
• Avoid all irritative medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and corticosteroid preparations.
• Patients with iron-deficiency anemia (IDA) may require iron-replacement therapy.

Transfer

• Transfer to a tertiary care children's hospital may be necessary for children who are seriously ill and require critical care or for patients who need emergent subspecialty diagnostic and therapeutic intervention.

Complications

• Pain
• Anemia
• Bleeding
• Perforation
• Obstruction
• Death

Prognosis

• Mortality rates are low in older children with primary ulceration and H pylori infection.
• Mortality rates remain highest in neonates, as well as infants and children with systemic illness or injury, who present with acute bleeding or perforation.
• Children with duodenal ulceration associated with H pylori infection are not expected to die.

Patient Education

• Familiarize patients and families with the predisposing factors for peptic ulcer disease that can be modified, including diet, medication use, alcohol ingestion, emotional stressors, and use of tobacco products.
• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article, Peptic Ulcers.

Miscellaneous

Medicolegal Pitfalls

• In children with severe symptoms, acute GI hemorrhage, instability, or critical illness, failure to appropriately stabilize the patient's condition and transfer him or her to a facility that provides definitive subspecialty care
• In a child with serious illness or traumatic injury, failure to optimize critical care and take the necessary steps to prevent secondary ulceration
• Failure to appropriately examine and perform a workup in children with abdominal pain or any evidence of GI bleeding
• Failure to recognize and treat associated H pylori infection

Special Concerns

• Although a notable percentage of children with abdominal pain may have functional disease, self-limited viral illnesses, or constipation, thorough history taking, physical examination, and consideration of the possibility of peptic ulcer disease (PUD) is warranted in any patient with GI complaints.

Multimedia

Media file 1: the gross appearance of an active ulcer is a round or oval, punched-out lesion with a smooth, white base and surrounding mucosa that is red and edematous.

Media file 2: Secondary peptic ulcer disease (PUD).

Media file 3: Most gastric ulcers are located in the lesser curvature of the stomach.

References

1. Tam YH, Lee KH, To KF, Chan KW, Cheung ST. Helicobacter pylori-positive versus Helicobacter pylori-negative idiopathic peptic ulcers in children with their long-term outcomes. J Pediatr Gastroenterol Nutr. Mar 2009;48(3):299-305. [Medline].

2. Wyatt JI, Rathbone BJ, Dixon MF, Heatley RV. Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis. J Clin Pathol. Aug 1987;40(8):841-8. [Medline].

3. Pietroiusti A, Luzzi I, Gomez MJ, et al. Helicobacter pylori duodenal colonization is a strong risk factor for the development of duodenal ulcer. Aliment Pharmacol Ther. Apr 1 2005;21(7):909-15. [Medline].

4. Hua MC, Kong MS, Lai MW, Luo CC. Perforated peptic ulcer in children: a 20-year experience. J Pediatr Gastroenterol Nutr. Jul 2007;45(1):71-4. [Medline].

5. Berezin SH, Bostwick HE, Halata MS, et al. Gastrointestinal bleeding in children following ingestion of low-dose ibuprofen. J Pediatr Gastroenterol Nutr. Apr 2007;44(4):506-8. [Medline].

6. [Guideline] University of Michigan Health System. Peptic ulcer disease. Ann Arbor (MI): University of Michigan Health System; 2005 May. [Full Text].

7. Day AS, Jones NL, Lynett JT, Jennings HA, Fallone CA, Beech R. cagE is a virulence factor associated with Helicobacter pylori-induced duodenal ulceration in children. J Infect Dis. Apr 2000;181(4):1370-5. [Medline].

8. Javid G, Zargar SA, U-Saif R, Khan BA, Yatoo GN, Shah AH. Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer. J Gastroenterol Hepatol. Jul 2009;24(7):1236-43. [Medline].

9. Andriulli A, Loperfido S, Focareta R, et al. High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study. Am J Gastroenterol. Dec 2008;103(12):3011-8. [Medline].

10. Tolia V, Boyer K. Long-Term Proton Pump Inhibitor Use in Children: A Retrospective Review of Safety. Dig Dis Sci. Aug 4 2007;[Medline].

11. Reimer C, Sondergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. Jul 2009;137(1):80-7, 87.e1. [Medline].

12. Napolitano L. Refractory peptic ulcer disease. Gastroenterol Clin North Am. Jun 2009;38(2):267-88. [Medline].

13. Blecker U, Gold BD. Gastritis and peptic ulcer disease in childhood. Eur J Pediatr. Jul 1999;158(7):541-6. [Medline].

14. Drumm B, Rhoads JM, Stringer DA, et al. Peptic ulcer disease in children: etiology, clinical findings, and clinical course. Pediatrics. Sep 1988;82(3 Pt 2):410-4. [Medline].

15. Ernst PB, Gold BD. Helicobacter pylori in childhood: new insights into the immunopathogenesis of gastric disease and implications for managing infection in children. J Pediatr Gastroenterol Nutr. May 1999;28(5):462-73. [Medline].

16. Gazarian M, Berkovitch M, Koren G, et al. Experience with misoprostol therapy for NSAID gastropathy in children. Ann Rheum Dis. Apr 1995;54(4):277-80. [Medline].

17. Graham DY, Rakel RE, Fendrick AM, et al. Practical advice on eradicating Helicobacter pylori infection. Postgrad Med. Mar 1999;105(3):137-40, 145-8. [Medline].

18. Haizlip JA, Lugo RA, Cash JJ, Vernon DD. Failure of nasogastric omeprazole suspension in pediatric intensive care patients. Pediatr Crit Care Med. Mar 2005;6(2):182-7. [Medline].

19. Israel DM, Hassall E. Omerprazole and other proton pump inhibitors: pharmacology, efficacy, and safety, with special reference to use in children. J Pediatr Gastroenterol Nutr. Nov 1998;27(5):568-79. [Medline].

20. Logan RP, Gummett PA, Schaufelberger HD, et al. Eradication of Helicobacter pylori with clarithromycin and omeprazole. Gut. Mar 1994;35(3):323-6. [Medline].

21. Messer J, Reitman D, Sacks HS, et al. Association of adrenocorticosteroid therapy and peptic-ulcer disease. N Engl J Med. Jul 7 1983;309(1):21-4. [Medline].

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23. Moshkowitz M, Reif S, Brill S, et al. One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for Helicobacter pylori infection in children and adolescents. Pediatrics. Jul 1998;102(1):e14. [Medline]. [Full Text].

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25. Pashankar DS, Israel DM, Jevon GP, Buchan AM. Effect of long-term omeprazole treatment on antral G and D cells in children. J Pediatr Gastroenterol Nutr. Nov 2001;33(5):537-42. [Medline].

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Keywords

peptic ulcer disease, PUD, primary ulcer, secondary ulcer, stress ulcer, peptic ulcer, gastric disease, stomach ulcer, intestinal ulcer, ulceration, infection, mucosal ischemia, treatment, diagnosis

Contributor Information and Disclosures

Author

Mutaz I Sultan, MBChB, Instructor and Fellow, Department of Pediatrics, Division of Gastroenterology and Nutrition, Medical College of Wisconsin, Children's Hospital
Mutaz I Sultan, MBChB is a member of the following medical societies: American Gastroenterological Association and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Disclosure: Nothing to disclose.

Coauthor(s)

B UK Li, MD, Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Director, Pediatric Fellowships and Gastroenterology Fellowship, Medical Director, Functional Gastrointestinal Disorders and Cyclic Vomiting Program, Medical College of Wisconsin; Attending Gastroenterologist, Children's Hospital of Wisconsin
B UK Li, MD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Ameesh Shah, MD, Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital
Ameesh Shah, MD is a member of the following medical societies: North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Medical Editor

Chris A Liacouras, MD, Director of Pediatric Endoscopy, Department of Pediatrics, Division of Gastroenterology and Nutrition, Associate Professor, Children's Hospital of Philadelphia and University of Pennsylvania
Chris A Liacouras, MD is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

B UK Li, MD, Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Director, Pediatric Fellowships and Gastroenterology Fellowship, Medical Director, Functional Gastrointestinal Disorders and Cyclic Vomiting Program, Medical College of Wisconsin; Attending Gastroenterologist, Children's Hospital of Wisconsin
B UK Li, MD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

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