AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. PUD results from the imbalance between defensive factors that protect the mucosa and offensive factors that disrupt this important barrier. Some 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.

Primary peptic ulcers are still relatively uncommon in children and account for roughly 1 in 2500 pediatric hospital admissions. Primary ulcers are seen more often 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 in use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).

Pathophysiology

The 2 most important concepts in understanding the pathophysiology of PUD 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.

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, acid-dependent pepsin, and mucosal ischemia, as well as 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, and monokines.

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 PUD. 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 PUD.

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. However, the specific roles of these factors and the secretory disturbances associated with H pylori infection in subsequent duodenal ulceration remains unclear.

Frequency

United States

PUD is an uncommon disease of childhood, with an estimated frequency of 1 case in 2500 hospital admissions. The estimated prevalence of childhood PUD in large general pediatric practices is 1.7%. 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. H pylori infection can be diagnosed on endoscopic biopsy and urea breath testing. However, serology alone is not recommended because it is overly sensitive and does not help in distinguishing bacterial colonization from peptic injury.

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

The prevalence of H pylori infection in developing countries is as high as 50-100%. The prevalence of PUD is increasing in developing countries.

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. 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 PUD. 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 PUD 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.

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 PUD is 1.5:1. The incidence of primary PUD is 2- to 3-fold higher in boys than in girls; however, no sex difference in the incidence of primary PUD has been noted in infants or young children.

Age

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

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 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 PUD.
• • 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.
  • After the age of 6 years, the child's description of pain may be similar to the description by adults. The classic pain of PUD (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- 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.
• For children with ulcer perforation, the symptoms are consistent with peritonitis and abrupt in onset.

Physical

• 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 PUD in 15-20% of patients.
• Acute abdomen resulting from perforation of the GI tract occurs in 5% of children with PUD.

Causes

• Primary PUD
• • Genetic factors may be important, as indicated by the observation that as many as 50% of children with PUD have a first- or second-degree relative with PUD. 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 PUD.
  • Emotional stress has been described as a factor predisposing children to PUD.
  • 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 PUD.
  • Clinical and laboratory data provide strong evidence that H pylori infection causes chronic gastritis and primary duodenal ulcer disease. H pylori gastritis has not been strongly associated with gastric ulceration in children.
  • Compared with people who do not smoke cigarettes, those who do are twice as likely to develop PUD. Smoking may lead to ulceration, slow healing, and an increased risk of recurrent disease.
• Secondary PUD
• • Corticosteroids, NSAIDs, and aspirin use predispose children to stress 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.¹
  • Serious systemic illness, sepsis, hypotension, respiratory failure, and multiple traumatic injuries increase the risk for secondary (stress) ulceration.
  • • The ulcer associated with a brain tumor or injury, or Curling ulcer, is characterized as single, deep, and prone to perforation. It is associated with high gastric acid output, and it is located in the duodenum or stomach.
    • Extensive burns are also associated with ulcers, namely Curling ulcers.
    • Stress ulceration and upper-I hemorrhage are complications being encountered more often than before 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.
  • ZES is a rare disorder that can cause gastric or duodenal ulcers, usually multiple, from excessive acid secretion. ZES should be suspected if the patient has severe peptic ulceration, kidney stones, watery diarrhea or malabsorption. ZES can also be associated with multiple endocrine neoplasias type I, which occurs at an age earlier than does isolated ZES. 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 (PPI) therapy should be discontinued at least 2 weeks before the gastrin level is measured.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Autoimmune gastritis
Chronic recurrent abdominal pain
Eosinophilic gastritis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• A minimum of laboratory studies may be indicated in children with mild 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 (PUD).
• • 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 help in distinguishing colonization from inflammation or previous infection. It can be useful in children if results are negative.  Stool studies for H pylori seem 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 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 PUD 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, up to 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. Angiograms can depict the source of the bleeding, and they can help in providing needed therapy in the form of a direct injection of vasoconstrictive agents.

Procedures

• Esophagogastroduodenoscopy
• • Esophagogastroduodenoscopy (EGD) is the procedure of choice for detecting PUD 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.
  • On EGD, 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.
• 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

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

In children 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 that consists of 1-2 antibiotics with an antacid, an H2 blocker, or a proton-pump inhibitor.

• PPIs are being used more frequently in the pediatric population, especially in children with gastroesophageal reflux disease (GERD), than before. PPIs provide consistent gastric pH control, and patients do not develop tachyphylaxis with repeated dosing.
• • 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 PPI therapy, but this has not affected histologic findings or caused an increase risk for carcinoid formation.²
  • Small gastric polyps may develop in some patients during PPI maintenance therapy. These polyps usually develop in the gastric corpus and are hyperplastic or benign fundic gland cysts.
• 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 NSAID-induced gastropathy. Studies on the benefits of misoprostol administration in children are limited.

Surgical Care

Surgical intervention is required in a small percentage of infants and in children with complications of peptic ulcer disease (PUD) 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 PUD. 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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Drug Category: Histamine H2-receptor antagonists

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

Drug Category: PPI

PPIs 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. PPIs are recommended as a part of the drug regimen for symptomatic H pylori infection. PPI therapy alone does not eradicate H pylori infection, but it does have bacteriostatic activity against H pylori.

Drug Category: Antacids

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

Drug Category: Antibiotics, macrolide

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.

Drug Category: GI agents

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

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients 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.

In/Out Patient Meds

• Medications include blockers of gastric acid secretion, acid neutralizers, and antibiotics.
• Avoid all irritative medications, including NSAIDs, aspirin, and corticosteroid preparations.
• Patients with 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

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal 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 PUD is warranted in any patient with GI complaints.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. 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].
2. Tolia V, Boyer K. Long-Term Proton Pump Inhibitor Use in Children: A Retrospective Review of Safety. Dig Dis Sci. Aug 4 2007;[Medline].
3. Blecker U, Gold BD. Gastritis and peptic ulcer disease in childhood. Eur J Pediatr. Jul 1999;158(7):541-6. [Medline].
4. 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].
5. 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].
6. 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].
7. 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].
8. 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].
9. 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].
10. Logan RP, Gummett PA, Schaufelberger HD, et al. Eradication of Helicobacter pylori with clarithromycin and omeprazole. Gut. Mar 1994;35(3):323-6. [Medline].
11. 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].
12. Mezoff AG, Balistreri WF. Peptic ulcer disease in children. Pediatr Rev. Jul 1995;16(7):257-65. [Medline].
13. 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].
14. O'Neill JA, Rowe MI, Grosfeld JL. Peptic Ulcer and Other Conditions of the Stomach. Vol 2. 5^th ed. St Louis, MO: Mosby-Year Book; 1998:1119-25.
15. 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].

Article Last Updated: Sep 10, 2007