A 10-year-old boy is brought in by his mother because of several episodes of vomiting. The most recent episode was small volume and had some brown-colored material in it. The boy tells you that he has had stomach pain off and on in the past few months and feels nauseated. He has not been having difficulty in school but his mother tells you that they will likely need to move soon as his father lost his job recently and has been unable to find work. The patient is the oldest of the 3 boys and shares a room with his brothers. He worries about his dad and hopes that he will be able to stay at his school. You discuss your concerns and recommend that the patient undergo esophagogastroduodenoscopy (EGD). His mother states that the children have health insurance through a state program and agrees to the testing. You start the patient on generic ranitidine. His EGD reveals a small pyloric ulcer and the biopsy specimens test positive for Helicobacter pylori (Figure 55-1). You prescribe 10 days of triple therapy with bismuth salts, amoxicillin, and metronidazole as the child’s insurance does not cover the more expensive alternative medications.

Peptic ulcer disease (PUD) is a disease of the gastrointestinal (GI) tract characterized by a break in the mucosal lining of the stomach or duodenum secondary to pepsin and gastric acid secretion; this damage is greater than 5 mm in size and with a depth reaching the submucosal layer.¹ PUD can be either primary or secondary; the latter most often due to severe systemic illness (e.g., sepsis) or from ulcerogenic drug ingestion (e.g., nonsteroidal antiinflammatory drugs (NSAIDs) or steroids).

• PUD is a common disorder affecting approximately 4.5 million people annually in the US. It encompasses both gastric and duodenal ulcers (Figures 55-1 to 55-4).²

• One-year point prevalence is 1.8 percent, and the lifetime prevalence is 10 percent in the US.²

• Prevalence is similar in both sexes, with increased incidence with age.¹

• PUD is less common in children. In an Israeli study of 751 symptomatic children referred for endoscopy, peptic ulcers were found in 51 patients (6.8%).³ H. pylori was positive in 112 (66.3%) patients and H. pylori-associated ulcers were more common in children older than age 10 years. A similar rate was demonstrated in a Chinese case series where 43 of 619 children (6.9%) undergoing upper endoscopy for investigation of upper gastrointestinal symptoms had primary PUD.⁴ Authors of an Italian study (N = 2234 endoscopies in children) reported a lower rate of 3.4 percent positive endoscopies for PUD, rates similar to those reported in older endoscopy studies performed on symptomatic children (1.8% to 3.6%).⁵ This is in somewhat less than the 8 percent prevalence of PUD in adults with dyspepsia who undergo endoscopy.⁶

• Rates of non-H. pylori-associated ulcers and erosions appear to be increasing among children.⁷

• Utilizing a US inpatient pediatric database (2008), the estimated incidence of peptic ulcer bleeding ranged from 0.5 to 4.4/100,000 individuals, with a total number of cases between 378 and 3250.⁸

• Causes of PUD include:

  • Nonsteroidal antiinflammatory drugs (NSAIDs), chronic H. pylori infection, and acid hypersecretory states such as Zollinger-Ellison syndrome.²

  • Uncommon causes include Cytomegalovirus (especially in transplant recipients), systemic mastocytosis, Crohn disease (Figures 55-3 and 55-4), lymphoma, and medications other than NSAIDs (e.g., alendronate).²

  • Children with chronic renal failure (CRF) have been shown to have high basal levels of gastrin; in one study of children with CRF on continuous ambulatory peritoneal dialysis (N = 19), almost three quarters had abnormal upper gastrointestinal endoscopic findings including hemorrhagic gastritis or gastroduodenitis, gastric nodular gastritis, and polyps.⁹

• In a 5-year Canadian retrospective study of children admitted to a tertiary care center with PUD (N = 36, aged 3 months to 17 years), about half the cases were secondary; most of these resulting from severe underlying illness (11/17).¹⁰ All children under age 10 years had secondary PUD.

• Infection with H. pylori, a short, spiral-shaped, microaerophilic Gram-negative bacillus, occurs in about half of the world’s population and is the leading cause of PUD in adults. H. pylori infection is associated with up to 70 to 80 percent of duodenal ulcers in adults.² In patients who do not use NSAIDS, infection rates are lower at about 60 percent of those with ulcers.¹¹

• H. Pylori infection is also associated with iron-deficiency anemia, gastric ulcer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and distal gastric cancer.¹² In one study of school-aged Andean children, chronic H. Pylori infection was associated with slowed growth (0.022 cm/month [95% confidence interval 0.008 to 0.035] slower than H. pylori-negative children).¹³

• The role of H. Pylori infection in childhood PUD is unclear as infection less frequently causes clinical disease in this population. It is estimated that, at adolescence, approximately 65 percent of children in developing countries (range 7% to 87%) are infected with H. pylori.¹² Vertical transmission appears to occur, although maternal H. pylori IgG transfer may be protective.¹⁴

• In an older retrospective study of 40 children endoscopically diagnosed with gastritis, gastric ulcer, or duodenal ulcer, H. pylori was found in about half (48%) and was more commonly detected among those with primary gastritis (88%) than either primary (22%) or secondary (50%) duodenal ulcers.¹⁵ This is similar to the rate of 53.5 percent H. pylori-positive PUD found in the Chinese study⁴ but lower than rates reported in older studies where 73 to 80 percent of childhood peptic ulcers were associated with either NSAIDs or H pylori.^16,17

• In a more recent European study of 518 children aged 1 to 14 years with H. pylori infection, 454 children (87.6%) had endoscopically proven gastritis and only 64 had an ulcer (12.3%).⁵ Ulcer disease, however, was more common among Russian children in this sample than the remainder of European children (35% versus 6.7%, respectively).

• H. pylori colonize the deep layers of the gel that coats the mucosa and disrupt its protective properties causing release of certain enzymes and toxins. These make the underlying tissues more vulnerable to damage by digestive juices and thus cause injury to the stomach (Figures 55-1 and 55-2) and duodenum cells (Figures 55-3 and 55-4).¹ One theory is that children’s developing immune system mounts a lesser inflammatory response reducing the risk of disruption to the gastric mucosa.¹² In the Chinese case series, all children with H. pylori disease had evidence of chronic active gastritis on the biopsy specimens.⁴

• NSAIDs are the second most common cause of PUD in adults and account for many H. pylori-negative cases. NSAIDs and aspirin inhibit mucosal cyclooxygenase activity reducing the level of mucosal prostaglandin causing defects in the protective mucous layer.

• There is a 10 to 20 percent prevalence of gastric ulcers and a 2 to 5 percent prevalence of duodenal ulcers in long-term NSAID users.² The annual risk of a life-threatening ulcer-related complication is 1 percent to 4 percent in long-term NSAID users, with older patients having the highest risk.¹⁸

• Polymorphisms of IL-1 gene cluster are associated with histological changes and IL-1β expression in the gastric mucosa in adults and children. In one study of Chinese children with peptic symptoms (N = 128), 60.7 percent of children with moderate or severe gastritis or gastric ulcer had the IL-1B-511TT/-31CC genotype.¹⁹

• Severe physiologic stress—Burns, central nervous system trauma, surgery, and severe medical illness increase the risk for secondary (stress) ulceration.¹¹

• Childhood physical abuse—In a Canadian population study, childhood physical abuse, reported by 1020 individuals (7.3%), was associated with diagnosed peptic ulcers (6.6% of those reporting abuse versus 2.7% of those not reporting abuse [OR 1.68; 95% CI 1.22-2.32]).²⁰

• Smoking—Evidence that tobacco use is a risk factor for duodenal ulcers in not conclusive, with several studies producing contradictory findings. However, smoking in the setting of H. pylori infection may increase the risk of relapse of PUD.²¹ A recent US population study reported an odds ratio (OR) of 1.99 for current and 1.55 for former tobacco use.²²

• Alcohol use—Ethanol is known to cause gastric mucosal irritation and nonspecific gastritis. Evidence that consumption of alcohol is a risk factor for duodenal ulcer is inconclusive.²¹ The preceding population study reported an OR of 1.29 for former alcohol use.²²

• Medications—Corticosteroids alone do not increase the risk for PUD; however, they can potentiate ulcer risk in patients who use NSAIDs concurrently.¹¹

• Other risk factors for gastrointestinal ulcers include, African-American race (OR 1.20), obesity (OR 1.18), chronic renal insufficiency (OR 2.29), and three or more doctor visits in a year (OR 1.49).²² There appears to be an association between duodenal ulceration and celiac disease.²³

• Risk factors for H. pylori infection include socioeconomic factors such as lower family income, household crowding, number of children sharing the same room, parents’ education, and sharing a bed with children.¹²