Gastritis is an inflammatory process associated with gastric mucosal injury. It is usually classified by histologic features (atrophic or non-atrophic, chemical, granulomatous, eosinophilic, lymphocytic, etc.), time course (acute versus chronic), etiology (Helicobacter pylori, bile, non-steroidal anti-inflammatory drugs (NSAIDs), Crohn’s disease, etc.), and proposed pathophysiology. Peptic ulcers are deep mucosal ulcerations that penetrate into the muscularis mucosa of the stomach or duodenum. Peptic erosions are superficial mucosal lesions; they do not involve the muscularis mucosa. Peptic ulcers and erosions are relatively uncommon in children, found in less than 25% of children undergoing upper gastrointestinal endoscopy for abdominal pain.1H. pylori is by far the most common etiology for gastritis and peptic ulcer disease (PUD) in the pediatric age group.

The Role of H. pylori in Peptic Disease

H. pylori is a Gram-negative spiral organism that colonizes the gastric mucosa of humans. The bacteria live in the gastric mucus and cause chronic gastritis, duodenal ulcers, and, to a lesser extent, gastric ulcers. Infection with H. pylori is strongly associated with gastric adenocarcinoma and mucosal-associated lymphomas (MALT) in humans.4

H. pylori is almost always acquired in childhood (usually before 10 years of age), and if untreated, infection is lifelong.2 It is estimated that 50% of the world’s population is infected with this organism. Infection with H. pylori is prevalent in developing countries where about 80% of children are colonized. The highest rates of H. pylori prevalence are in Eastern Europe, Asia, and many developing countries. The organism is also prevalent in selected populations in the United States (e.g., Native Americans, African Americans, and Hispanics). Lifetime risk of developing PUD from H. pylori infection is 10–15%, while gastric cancer develops in less than 1%.3

The route of transmission of H. pylori remains incompletely defined. Infection is thought to result from direct human-to-human contact via fecal–oral, oral–oral, or gastro-oral routes.4 Contaminated water can also be a reservoir. Low socioeconomic status, poverty, crowding, and poor hygiene are considered as major risk factors for this infection. Twenty-one percent of children whose mothers are infected with H. pylori acquire the infection, compared to 3% of children whose mothers are not infected, confirming that H. pylori-infected mothers are a key source of infection.5H. pylori infection is uncommon in children from developed countries (10%) and the number of symptomatic cases seems to be decreasing.

Pathogenesis of H. pylori-Associated Peptic Disease

Adherence of H. pylori to gastric epithelial cells facilitates access to nutrients and delivery of effector molecules that are essential for the development of the disease.6 The main virulence determinant of H. pylori is a 40-kb genomic “pathogenicity island” called cytotoxin-associated gene or cag. Cag-positive strains are closely associated with PUD and gastric cancer7; patients infected with cag-negative strains tend to have less severe disease. Genes in the cag pathogenicity island encode a type IV secretion system through which an effector protein, CagA, is translocated into the epithelial cell cytoplasm. Once inside the epithelial cell, CagA can disrupt signaling pathways, leading to abnormal proliferation, motility, and cytoskeletal changes. These changes may increase the predisposition to gastric cancer.

Other virulence factors also play a role in H. pylori infections. VacA is a protein encoded by the gene, vacA, which is thought to facilitate colonization by H. pylori.8 All strains of H. pylori possess the vacA gene, but only about 50% express the mature protein. VacA possibly helps increase intracellular permeability, which would make nutrients more available to the organism. BabA2 is another important pathogenetic factor. It is an adhesin that recognizes the blood group antigen A and allows H. pylori to adhere to gastric epithelial cells. H. pylori can cause cytotoxicity and stimulate the release of cytokines via its cell wall lipopolysaccharides (LPS). Exposure of the gastric mucosa to H. pylori LPS leads to loss of mucosal integrity, inhibition of mucin synthesis, and stimulation of pepsinogen secretion, all creating an environment favoring mucosal injury. H. pylori is a powerful producer of urease, an enzyme that generates ammonia from urea. Although urease is probably not essential for colonization and virulence, it helps bacteria survive in the stomach by creating a less acidic environment.

Children have much lower gastritis scores and an intact epithelium when compared to adults with a similar bacterial load. This is probably related to increased activity of regulatory T cells (Tregs) that down-regulate the inflammatory response to H. pylori in children.9

Pathogenesis of Non-H. pylori Peptic Disease

Any agent that disrupts the delicate balance between potentially injurious gastric acid and pepsin and the gastric mucosal protective mechanisms (mucus and bicarbonate secretion, and gastric blood flow) can result in gastric ulcers or gastritis. NSAIDs, alcohol, caustic agents, bilious refluxate from the duodenum, pancreatic enzymes, hemodynamic shock, and a variety of ingested irritants can all upset the balance and result in gastritis or ulcer.

Gastritis and peptic ulcers, regardless of etiology, may present with a wide variety of symptoms, or may be completely asymptomatic, until complications (i.e., gastrointestinal bleeding and perforation) occur (Table 13–1). Therefore, the differential diagnosis may be quite broad (Table 13–2). Abdominal pain, poor appetite, nausea, vomiting, nocturnal awakening, and weight loss may be symptoms of severe gastric inflammation and/or PUD.

In the majority of patients, abdominal pain from peptic injury is experienced in the epigastrium, but may occasionally localize to the right or left upper quadrants or even the hypochondrium. Radiation of pain to the back may occur, but primary back pain is unusual. Although the pain is often burning or hunger-like in quality, it may also be vague and non-specific. Onset may be acute or chronic. Anorexia and weight loss may occur. Recurrent and intractable vomiting may be manifestations of gastritis and PUD. Hematemesis and/or melena may be seen if peptic ulcers are present.

Physical exam findings are usually non-specific (Table 13–3). Children may have some tenderness in the epigastrium and/or right and left upper quadrants. Rebound tenderness is present in a rare incident of perforated ulcer. Pallor may be seen if the patient has iron deficiency anemia secondary to chronic gastrointestinal blood loss. In an acutely bleeding child, signs of hemorrhagic shock (tachycardia, hypotension, prolonged capillary refill, etc.) may predominate.

Clinical Features Specific to H. pylori Infection

Acute H. pylori infection is typically associated with a transient mild illness characterized by epigastric pain and nausea. Transient hypochlorhydria and neutrophilic gastritis are usually seen with the acute infection. Over the several months, acid secretion returns to near-baseline levels and severity of gastritis improves. It is not known how often the acute infection occurs with H. pylori and it spontaneously clears.

Chronic H. pylori infection symptoms run the entire spectrum from none at all to severe abdominal pain and bleeding from ulcers. The association between recurrent abdominal pain/non-ulcer dyspepsia (see Chapter 1 for definitions) and H. pylori infection continues to be debated. RAP and NUD are commonly of functional origin in children. Despite this, the Maastricht III Consensus Report recommends testing children with upper gastrointestinal symptoms for H. pylori infection, after exclusion of other causes of the symptoms.10

H. pylori infection may increase predisposition to gastroesophageal reflux disease (GERD), probably by increasing gastric acid secretion. Although some studies support an association between H. pylori and reflux esophagitis,11 some report no difference in the prevalence of esophagitis in H. pylori-positive and negative patients.12

H. pylori infection has been reported in children with iron deficiency anemia, short stature, growth delay, immune thrombocytopenic purpura (ITP), and migraines. A relationship between these manifestations and H. pylori remains controversial. In children with refractory iron deficiency anemia, testing for H. pylori may be indicated.13

The differential diagnosis for gastritis and PUD includes functional gastrointestinal disorders (functional abdominal pain, non-ulcer dyspepsia, and irritable bowel syndrome), gastroesophageal reflux, gallstones, pancreatitis, Crohn’s disease, and celiac disease (Table 13–2). Other etiologies of gastritis and PUD are collagenous gastritis, eosinophilic gastroenteritis (EGE), Crohn’s disease, lymphocytic gastritis (LG), chronic NSAID use, bile-induced gastritis, and Menetrier disease (Table 13–4).

Functional Gut Disorders

Ten to 20% of school age children complain of recurrent abdominal pain that is commonly of functional origin. In general, these children do not have alarm symptoms (vomiting, weight loss, nocturnal awakening, hematemesis, or melena). If in doubt, an upper gastrointestinal endoscopy will help determine the diagnosis.

Gastroesophageal Reflux Disease

GERD usually manifests with effortless regurgitation, heartburn, and sometimes with chest pain and dysphagia. In infants, GER is benign with a high chance of spontaneous remission by 12 months of age, thus rarely needing any treatment. If children have typical GERD symptoms in the absence of alarming symptoms (hematemesis, melena, weight loss, and dysphagia), a trial of a histamine 2 (H2) blocker or a proton pump inhibitor (PPI) is a reasonable approach. Children with alarm symptoms or no response to acid suppression have to be evaluated by a pediatric gastroenterologist.

Acute–Chronic Pancreatitis

Children with acute and chronic pancreatitis can present with upper abdominal/epigastric pain, nausea, and vomiting. Epigastric tenderness is commonly found if the pancreas is inflamed. Serum amylase and lipase measurement will be helpful in distinguishing pancreatitis from peptic disease. Imaging studies (ultrasound or CT scan) can be used when the distinction is in doubt.

Gallstones

Gallstones may be asymptomatic or cause dyspepsia, epigastric pain, or right upper quadrant pain. Pain is usually postprandial. The cardinal symptom of gallstones is biliary colic. Biliary colic is a moderately severe, crescendo-type pain in the right upper quadrant radiating to the back and right shoulder, which may be accompanied by nausea. Pain may be brought on after ingestion of fatty foods. A right quadrant ultrasound will be helpful in making the differential diagnosis.

Celiac Disease

Celiac disease can present with abdominal pain, chronic or recurrent diarrhea, anorexia, weight loss, failure to thrive, vomiting, constipation, and irritability. Serologic tests, including endomysial and tissue transglutaminase antibodies, are highly sensitive and specific and will be helpful in differential diagnosis.

Chemical Gastropathy/NSAIDs

Chemical gastropathy, also known as chemical or reactive gastritis, is characterized by foveolar cell (gastric surface epithelium) hyperplasia, vascular congestion, lamina propria edema, and prominent mucosal smooth muscle fibers in the absence of mucosal inflammation.14 Common presenting symptoms are epigastric pain and vomiting. Duodenogastric bile reflux and NSAIDs are established causes of chemical gastropathy.

NSAIDs may also cause gastritis and PUD in children, much less frequently than adults. NSAIDs are normally used for the short-term relief of pain and fever in children and are well tolerated. Chronic NSAID therapy may be associated with significant gastric injury: more than 75% of children with abdominal pain while taking NSAIDs have gastritis, antral erosions, or ulcers.15,16

Crohn’s Disease