Epidemiology

Peptic ulcer disease is one of the most common human ailments, once affecting up to 15% of the population in industrialized countries. Current estimates suggest that 5% to 10% of the world population is affected, and about 350,000 new cases are diagnosed annually in the United States. The incidence of peptic ulceration peaked between 1900 and 1950 and progressively decreased thereafter. The decline in northern Europe and the United States may be the result of decreased cigarette and aspirin consumption, increased use of vegetable cooking oils (a rich source of raw materials for synthesis of prostaglandins, which have cytoprotective properties), and better sanitation leading to fewer H. pylori infections. The disease affects 5% to 7% of northern Europeans and accounts for about 200,000 hospitalizations annually in the United States. Peptic ulcers are rare in Greenlander Eskimos, southwestern Native Americans, Australian aborigines, and Indonesians.

About two thirds of persons with ulcers are men, and the peak prevalence of peptic ulceration occurs in older adults. First-degree relatives have a threefold greater risk of developing the disease. Persons who smoke and are heavy drinkers of alcohol are more prone to development of the disease. An association with blood type O also is recognized. A higher prevalence is seen among patients with hyperparathyroidism and hypersecretory states (e.g., renal dialysis, Zollinger-Ellison syndrome, mastocytosis). Ingestion of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, for longer than 1 month is associated with an annual rate of 2% to 4% for GI bleeding or ulcer complications in these patients.

The disease is rare in children, with only 1 in 2500 pediatric hospital admissions attributable to peptic ulceration. When a peptic ulcer is diagnosed in a child younger than 10 years of age, the condition most often is associated with an underlying systemic illness, such as severe burn injury or other major trauma. Most deaths that result from PUD occur in patients older than 65 years of age. An average dental practice of 2000 adult patients is predicted to serve about 100 patients with PUD.

Etiology

Peptic ulcers result when the balance between aggressive factors that are potentially destructive to the GI mucosa and defensive factors that usually are protective of the mucosa is disrupted ( Fig. 11.2 ). The primary aggressive factor is H. pylori (formerly Campylobacter pylori ). This organism is associated with more than 80% of duodenal and gastric ulcers in the United States and more than 90% in other parts of the world. Use of NSAIDs is the second most common cause of PUD. Other risk factors include advanced age, psychological and physical stress, acid hypersecretion, cigarette smoking, use of certain drugs ( Table 11.1 ), and major comorbid disease. In addition, cystic fibrosis predisposes to ulcers because it reduces bicarbonate secretion, and cytomegalovirus infection is a rare cause of PUD in human immunodeficiency virus (HIV)–infected persons.

Complex interplay of aggressive and defensive factors involved in the formation of peptic ulcer disease. NSAID, Nonsteroidal antiinflammatory drug.

(Modified from Kumar V, Abbas A, Fausto N, editors: Robbins & Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.)

H. pylori is a microaerophilic, gram-negative, spiral-shaped motile bacillus with four to six flagella. H. pylori was first reported to reside in the antral mucosa by Marshall and Warren. The organism is an adherent but noninvasive bacterium that resides at the interface between the surface of the gastric epithelium and the overlying mucous gel. It produces a potent urease that hydrolyzes urea to ammonia and carbon dioxide. This urease may protect bacteria from the immediate acidic environment by increasing local pH while damaging mucosa through generation of its byproduct, ammonia. Upregulation of cyclooxygenase-2 (COX-2), chemotaxis of neutrophils, and the cellular immune response are involved in the local tissue damage that subsequently occurs.

Humans are the only known hosts of H. pylori. This bacterium infects 0.5% of adults annually, a rate that has been declining since the early 1990s. H. pylori is acquired primarily during childhood, possibly as a result of entry from the oral cavity via contaminated food and poor sanitary habits. The organism resides in the oral cavity, from which it probably descends to colonize the gastric mucosa. H. pylori can persist in the stomach indefinitely, and infection with the bacterium remains clinically silent in most affected persons. The rate of H. pylori acquisition is higher in developing than in developed countries. In developing countries, 80% of the population carries the bacterium by the age of 20 years, but in the United States, only 20% of 20-year-old individuals are infected. The prevalence of infection in the United States among African Americans and Hispanics is twice that for whites. Infection is correlated with lower socioeconomic status, contaminated drinking water, and familial overcrowding, especially during childhood. Approximately 20% of infected persons go on to develop PUD, suggesting that other physiologic and psychological (stress) factors are required for presentation of this disease.

Use of NSAIDs is an etiologic factor in about 15% of cases of peptic ulcer. These drugs directly damage mucosa, reduce mucosal prostaglandin production, and inhibit mucus secretion. Ulcers caused by NSAIDs are located more often in the stomach than in the duodenum. Risk with NSAID use increases with age older than 60 years; high-dosage long-term therapy; use of NSAIDs with long plasma half-lives (e.g., piroxicam) rather than those with short half-lives (i.e., ibuprofen); and concomitant use of alcohol, corticosteroids, anticoagulants, or aspirin. Use of orally administered nitrogen-containing bisphosphonate drugs (alendronate, risedronate) for the treatment of osteoporosis and immunosuppressive medications such as mycophenolate is associated with development of esophageal and gastric ulcers.

H. pylori –negative, non-NSAID ulcer disease accounts for about 10% of cases and occurs more often in older adults.

Pathophysiology and Complications

Ulcer formation is the result of a complex interplay of aggressive and defensive factors (see Fig. 11.2 ). Resistance to acidic breakdown normally is provided by the mucosa, mucus and prostaglandin production, blood flow, bicarbonate secretion, and ion carrier exchange. Additional resistance is gained from the actions of antibacterial proteins such as lysozyme, lactoferrin, interferon, and α-defensin, or cryptdin.

Under normal circumstances, food stimulates gastrin release, gastrin stimulates histamine release by enterochromaffin-like cells in the stomach, and parietal cells secrete hydrogen ions and chloride ions (hydrochloric acid). Vagal nerve stimulation, caffeine, and histamine also are stimulants of parietal cell secretion of hydrochloric acid. Aggressive factors include vagal overactivity and agents and events that enhance the release of pepsin, gastrin, and histamine. Physical and emotional stress; obsessive-compulsive behavior; parasitic infections; and drugs such as caffeine, high-dose corticosteroids, and phenylbutazone enhance hypersecretion of stomach acid. Alcohol and NSAIDs are directly injurious to gastric mucosa. Alcohol alters cell permeability and can cause cell death. NSAIDs including aspirin disrupt mucosal resistance by impairing prostaglandin production and denaturing mucous glycoproteins. Hyperparathyroidism enhances gastrin secretion, and renal dialysis does not adequately remove circulating gastrin. Smoking tobacco and family history are risk factors independent of gastric acid secretion for PUD. Tobacco smoke, similar to other aggressive factors, can affect gastric mucosa by reducing levels of nitric oxide, which is important for stimulating mucus secretion and maintaining mucosal blood flow.

H. pylori is strongly associated with PUD ; however, the mechanism whereby infection with H. pylori results in PUD is not completely understood. Current evidence suggests that H. pylori causes inflammation of the gastric mucosa by producing proteases and increasing gastrin release by G cells, which leads to increased gastric acid production, acute gastritis, and eventually ulcer formation.

Complications associated with PUD vary with the degree of destruction of the GI epithelium and supporting tissues. Superficial ulcers are characterized by the presence of necrotic debris, fibrin and subjacent inflammatory infiltrate, granulation tissue, and fibrosis. Ulcers that penetrate through the fibrotic tissue into the muscularis layer (muscularis mucosae) can perforate into the peritoneal cavity (peritonitis) or into the head of the pancreas. Arteries or veins in the muscularis layer may be eroded by ulcers (bleeding ulcer), giving rise to acute hemorrhage, anemia, and potential shock. Untreated ulcers often heal by fibrosis, which can lead to pyloric stenosis, gastric outlet obstruction, dehydration, and alkalosis. Complications are more common in older adults and those with comorbid liver, kidney, and malignant disease. Approximately 5% of those with duodenal ulcers die annually as a result of such complications.

H. pylori is associated with the development of a low-grade gastric mucosa–associated lymphoid tissue (MALT) lymphoma. Accordingly, H. pylori has been classified by the World Health Organization as a definite (class I) human carcinogen.

Peptic ulcers rarely undergo carcinomatous transformation. Ulcers of the greater curvature of the stomach have a greater propensity for malignant degeneration than do those of the duodenum. Eradication of H. pylori helps to halt the progression of atrophic gastritis and thus reduces the risk of malignant transformation.

Clinical Presentation

Signs and Symptoms

Although many patients with active peptic ulcer report no ulcer symptoms, most experience epigastric pain that is long-standing (several hours), sharply localized, and recurrent. The pain is described as “burning” or “gnawing” but may be “ill-defined” or “aching.” The discomfort of a duodenal ulcer manifests most commonly on an empty stomach and frequently awakens the patient in the middle of the night. Ingestion of food, milk, or antacids provides rapid relief in most cases. In contrast, patients with gastric ulcers are unpredictable in their response to food; in fact, eating may precipitate abdominal pain. Epigastric tenderness often accompanies the condition.

Changes in the character of pain may indicate the development of complications. For example, increased discomfort, loss of antacid relief, or pain radiating to the back may signal deeper penetration or perforation of the ulcer. Protracted vomiting a few hours after a meal is a sign of gastric outlet (pyloric) obstruction. Melena (bloody stools) or black tarry stools indicate blood loss due to GI hemorrhage.

Laboratory and Diagnostic Findings

A peptic ulcer is diagnosed primarily by fiberoptic endoscopic biopsy and laboratory testing for H. pylori. During endoscopy, a biopsy of the marginal mucosa adjacent to the ulcer is performed to confirm the diagnosis and rule out malignancy. A rapid urease test is then performed to detect the bacterial product urease in the mucosal biopsy specimen. Microscopic analysis of biopsied tissue prepared with Giemsa, acridine orange, and Warthin-Starry stains is effective in the microscopic detection of H. pylori ( Fig. 11.3 ). Culture of the organism is reserved for cases in which antimicrobial resistance is suspected because the technique is tedious, difficult, and no more sensitive than routine histologic analysis.

Helicobacter pylori organisms (dark rods) evident in the lumen of the intestine. (Warthin-Starry stain.)

(Courtesy of Eun Lee, Lexington, KY.)

Nonendoscopic laboratory tests include urea breath tests (UBTs) and, less commonly, H . pylori fecal antigen tests. A UBT is a highly sensitive, noninvasive test that involves the ingestion of urea labeled with carbon-13 ( ¹³ C) or carbon-14 ( ¹⁴ C). Degradation of urea by the bacillus releases ¹³ C or ¹⁴ C in expired carbon dioxide. These tests are advantageous because they indirectly measure the presence of H. pylori before treatment and its eradication after treatment. Upper GI imaging is infrequently performed because it lacks the sensitivity of biopsy. A low red blood count may occur in persons with a GI bleed.

Medical Management

Most patients with PUD suffer for several weeks before going to a doctor for treatment. If the peptic ulcer is confined and uncomplicated and H. pylori is not present, an antisecretory drug, such as a proton pump inhibitor (PPI), is administered for 10 to 14 days ( Table 11.2 ); treatment is for 4 or more weeks if complications occur. If the patient is infected with H. pylori, inhibitors of gastric acid secretion and at least two antimicrobial agents are recommended. Various treatment regimens are used, which vary by country and prevalence of H. pylori antibiotic resistance ( Box 11.1 ). The conventional regimen is “triple” therapy because antisecretory drugs, such as PPIs, provide rapid relief of pain and accelerate healing, and their use in combination with at least two antibiotics is effective in eradicating H. pylori in more than 90% of treated patients. Therapy is typically given for 10 to 14 days, and eradication of infection should be confirmed afterward because of growing antibiotic resistance. Quadruple therapy is used in areas where high prevalence of antimicrobial resistance occurs.

Before 2000, more than 50% of patients with PUD experienced recurrences after treatment. Such recurrence was likely because regimens consisting solely of antisecretory drugs were the treatment of choice; however, these drugs alone do not eradicate H. pylori infection and are noncurative of PUD. Eradication of H. pylori with antibiotic treatment reduces the rate of recurrence of peptic ulceration by 85% to 100%. Reemergence of an ulcer usually is traced to the persistence of H. pylori after treatment because of inappropriate drug choice, discontinuance of drug therapy, lack of behavior modification, or bacterial resistance.

In all patients who undergo peptic ulcer therapy, ulcerogenic factors (e.g., use of alcohol, aspirin or other NSAIDs, and corticosteroids; consumption of foods that aggravate symptoms and stimulate gastric acid secretion; persistent stress) should be eliminated to accelerate healing and limit relapses. Patients benefit from smoking cessation, that is perforation rates are higher in smokers, and continued smoking results in a higher relapse rate after treatment and lower rates of eradication of H. pylori. When H. pylori is successfully eradicated, cigarette smoking does not appear to increase the risk of recurrence.

Elective surgical intervention (e.g., dissection of the vagus nerves from the gastric fundus) largely has been abandoned in the management of PUD. Today, surgery is reserved primarily for complications of PUD such as significant bleeding (when unresponsive to coagulant endoscopic procedures), perforation, and gastric outlet obstruction. On occasions when PUD is associated with hyperparathyroidism and parathyroid adenoma, surgical removal of the affected gland is the treatment of choice. Resolution of GI disease occurs after abnormal endocrine function is terminated. Vaccines against H. pylori continue to be investigated.

Dental Management

Identification.

The dental provider must identify intestinal symptoms through a careful history that is taken before dental treatment is initiated because many GI diseases, although they are chronic and recurrent, remain undetected for long periods. This history includes a careful review of medications (e.g., aspirin and other NSAIDs, oral anticoagulants) and level of alcohol consumption that may result in GI bleeding. If GI symptoms are suggestive of active disease, a medical referral is needed. When the patient returns from the physician and the condition is under control, the dentist should update current medications in the dental record, including the type and dosage, and should follow physician guidelines. Furthermore, periodic physician visits should be encouraged to afford early diagnosis and cancer screenings for at-risk patients.

Risk Assessment.

The dentist is responsible for establishing the severity and stability of a patient with a known history of PUD. Severe disease or poor control is evident by ongoing pain, blood in the stool, anemia, or recent physician visits or hospitalization in which medical treatment has not remedied the condition.

Recommendations

Antibiotics: Infection Risk.

Antibiotics used during PUD therapy would likely keep most dental infections in check. However, the selection of antibiotics for dental issues may need to be altered based on the antibiotics used recently in the treatment of PUD.

Bleeding.

Bleeding from oral tissues is not an issue with PUD. In contrast, GI bleeding associated with PUD can be of major concern and lead to significant complications that can delay dental treatment.

Capacity to Tolerate Care.

Routine dental treatment may be provided during medical therapy for peptic ulceration; however, the decision should be based on patient comfort, convenience, and severity of disease. A patient with ongoing signs and symptoms of active PUD is not a candidate for routine dental care.

Drug Considerations.

Of primary importance are the impact and interactions of certain drugs prescribed to patients with PUD ( Box 11.2 ). In general, the dentist should avoid prescribing aspirin, aspirin-containing compounds, and other NSAIDs to patients with a history of PUD because of the irritative effects of these drugs on the GI epithelium. Acetaminophen and compounded acetaminophen products are recommended instead. If NSAIDs are used, a COX-2–selective inhibitor (e.g., celecoxib (Celebrex]) given in combination with a PPI or misoprostol (Cytotec), 200 µg four times per day—a prostaglandin E ₁ analogue—is advised for short-term use to reduce the risk of GI bleeding. Analgesic selection should be based on patient risk factors (previous GI bleeding; advanced age, use of alcohol, anticoagulants, or steroids) and the lowest dose for the shortest period to achieve the desired effect. Histamine H ₂ receptor antagonists and sucralfate are not beneficial selections because they do not appear to protect patients from NSAID-induced complications.

P

Patient Evaluation and Risk Assessment (see Table 1.1 )

• •

  Evaluate and determine whether GI signs or symptoms (disease) or comorbid conditions exist.

• •

  Obtain medical consultation if patient’s disease is poorly controlled, if signs or symptoms appear suggesting an undiagnosed condition, or if the diagnosis is uncertain.

Potential Issues and Factors of Concern

CBC, Complete blood count; GI, gastrointestinal; IBD, inflammatory bowel disease; MALT, gastric mucosa–associated lymphoid tissue; NSAID, nonsteroidal antiinflammatory drug; PPI, proton pump inhibitor; PUD, peptic ulcer disease; TCA, tricyclic antidepressant.