eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Peptic Ulcer Disease

Author: Mutaz I Sultan, MBChB, Instructor and Fellow, Department of Pediatrics, Division of Gastroenterology and Nutrition, Medical College of Wisconsin, Children's Hospital
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; Ameesh Shah, MD, Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital
Contributor Information and Disclosures

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).

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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.

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