Excerpt from Peptic Ulcer Disease

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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.

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