The spiral-shaped, gram-negative bacterium Helicobacter pylori is found in gastric mucosa or adher- ent to the lining of the stomach. Acute infection is most commonly asymptomatic but may be associated with epigastric burning, abdominal distention or bloating, belching, nausea, flatulence, and halitosis. H. pylori infection can lead to ulceration of the gastric mucosa and duodenum and is associated with malignancies of the stomach. The prevalence of H. pylori infection is as high as 52 percent.
I. Pathophysiology
A. Helicobacter pylori (HP), a spiral-shaped, flagel-
lated organism, is the most frequent cause of peptic ulcer disease (PUD). Nonsteroidal anti- inflammatory drugs (NSAIDs) and pathologically high acid-secreting states (Zollinger-Ellison syn- drome) are less common causes. More than 90% of ulcers are associated with H. pylori. Eradication of the organism cures and prevents relapses of gastroduodenal ulcers.
B. Complications of peptic ulcer disease include
bleeding, duodenal or gastric perforation, and gastric outlet obstruction (due to inflammation or strictures).
II. Clinical evaluation
A. Symptoms of PUD include recurrent upper ab-
dominal pain and discomfort. The pain of duodenal ulceration is often relieved by food and antacids and worsened when the stomach is empty (eg, at nighttime). In gastric ulceration, the pain may be exacerbated by eating.
B. Nausea and vomiting are common in PUD.
Hematemesis (“coffee ground” emesis) or melena (black tarry stools) are indicative of bleeding.
C. Physical examination. Tenderness to deep
palpation is often present in the epigastrium, and the stool is often guaiac-positive.
Presentation of Uncomplicated Peptic Ulcer Disease
Epigastric pain (burning, vague abdominal discomfort, nau- sea)
Often nocturnal
Occurs with hunger or hours after meals Usually temporarily relieved by meals or antacids Persistence or recurrence over months to years History of self-medication and intermittent relief
D. NSAID-related gastrointestinal complications.
NSAID use and H pylori infection are independent risk factors for peptic ulcer disease. The risk is 5 to 20 times higher in persons who use NSAIDs than in the general population. Misoprostol (Cytotec) has been shown to prevent both NSAID ulcers and related complications. The minimum effective dosage is 200 micrograms twice daily; total daily doses of 600 micrograms or 800 micrograms are significantly more effective.
III. When to test and treat
A. In the absence of alarm symptoms for cancer or
complicated ulcer disease, the approach to testing in patients with dyspepsiacan be divided into four clinical scenarios: (1) known peptic ulcer disease, currently or previously documented; (2) known nonulcer dyspepsia; (3) undifferentiated dyspep- sia, and (4) gastroesophageal reflux disease (GERD).
B. Peptic ulcer disease. Treatment of H. pylori
infection in patients with ulcers almost always cures the disease and reduces the risk for perfora- tion or bleeding.
C. Nonulcer disease. There is no convincing evi-
dence that empiric eradication of H. pylori in patients with nonulcer dyspepsia improves symp- toms.
D. Undifferentiated dyspepsia. A test-and-treat
strategy is recommended in which patients with dyspepsia are tested for the presence of H. pylori with serology and treated with eradication therapy if the results are positive. Endoscopy is reserved for use in patients with alarm signs or those with persistent symptoms despite empiric therapy.
Alarm Signs for Risk of Gastric Cancer of Com- plicated Ulcer Disease
Older Than 45 years Rectal bleeding or melena Weight los of >10 percent of body weight Anemia Dysphagia
Abdominal mass Jaundice
Family history of gastric cancer
Previous history of peptic ulcer
Anorexia/early satiety
Evaluation for Helicobacter pylori-Related Dis- ease
Clinical scenario Recommended test
Dyspepsia in patient with alarm symptoms for cancer or complicated ulcer (eg, bleeding, perforation)
Promptly refer to a gastroenterologist for en- doscopy.
Known PUD, uncompli-
cated Serology antibody test;treat if result is positive. Dyspepsia in patient with
previous history of PUD not previously treated with eradication therapy
Serology antibody test; treat if result is positive.
Dyspepsia in patient with PUD previously treated for H. pylori
Stool antigen or urea breath test; if positive, treat with regimen different from the one previously used; retest to confirm eradica- tion. Consider endoscopy. Undifferentiated dyspepsia
(without endoscopy) Serology antibody test;treat if result is positive. Documented nonulcer dys-
pepsia (after endoscopy) Unnecessary
GERD Unnecessary Asymptomatic with history
of documented PUD not previously treated with eradication therapy
Serology antibody test; treat if result is positive.
Asymptomatic Screening unnecessary
E. Gastroesophageal Reflux Disease. H. pylori
infection does not increase the risk of GERD. Eradication therapy does not eliminate GERD symptoms (sensation of burning and regurgitation.
IV.Helicobacter pylori Tests
A. Once testing and eradication are chosen, several
diagnostic tests are available. Unless endoscopy is planned, a practical approach is to use serology to identify initial infection, and use the stool antigen test or urea breath test to determine cure, if indi- cated.
Noninvasive Testing Options for Detecting Helicobacter pylori Test What does it mea- sure? Sens itivit y Tes t of cur e? Com-ments Serol- ogy: labora- tory-bas ed ELISA IgG 90 to 93 No Accurate;convenient for initial in- fection; titers may remain positive after one year Whole blood: of- fice-bas ed ELISA IgG 50 to 85 No Less accu- rate but fast, convenient
Stool:
HpSA H. pylorianti- gens
95 to
98 Yes Relativelyconvenient and available Urea breath test Urease activity 95 to 100 Yes Sensitivity reduced by acid sup- pression
B. Endoscopy and Biopsy. Alarm symptoms for
cancer or ulcer complication warrant prompt endoscopic evaluation. A gastric antral biopsy specimens is considered the gold standard for
detecting the presence of H. pylori.Cultures of biopsy specimens obtained during endoscopy can be tested for antimicrobial resistance in cases of treatment failure.
C. Serology/ELISA. When endoscopy is not per-
formed, the most commonly used diagnostic approach is the laboratory-based serologic anti- body test. This enzyme-linked immunosorbent assay (ELISA) detects IgG antibodies to H. pylori, indicating current or past infection. A positive serologic test suggests active infection in patients who have not undergone eradication therapy. The serologic test results may not revert to negative once the organism is eradicated; therefore, the test is not used to identify persistent infection.
D. Stool testing with enzyme-linked immunoassay
for H. pylori antigen in stool specimens is highly sensitive and specific, the stool antigen test reverts to negative from five days to a few months after eradication of the organism, with 90 percent speci- ficity. This test is useful in confirming eradication, and, because it is office-based, is less costly and more convenient than the urea breath test. False-positive results may occur even four weeks following eradication therapy.
E. Urea Breath Test. The urea breath test is a
reliable test for cure and can detect the presence or absence of active H. pylori infection with greater accuracy than the serologic test. It is usually administered in the hospital outpatient setting because it requires time and special equipment.
V. Principles of treatment
A. Antimicrobial resistance and incomplete treatment
are major reasons for treatment failure. Continued therapy for 14 days is the most reliable and effec- tive regimen.
Triple Therapy Regimens for Helicobacter
pylori Infection Treatment (10 to 14 days of therapy recommended) Conve- nience factor Tolera bility 1. Omeprazole (Prilosec), 20 mg
two times daily or
Lansoprazole (Prevacid), 30 mg two times daily
plus
Metronidazole (Flagyl), 500 mg two times daily
or
Amoxicillin, 1 g two times daily plus
Clarithromycin (Biaxin), 500 mg two times daily
Prepackaged triple-ther- apy(Prevpac): taken bid for 14
days; consists of 30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin. Twice-d aily dosing Fewer signifi- cant side effects, but more abnor- mal taste versus other regi- mens
2. Ranitidine bismuth citrate
(Tritec), 400 mg twice daily plus
Clarithromycin, 500 mg twice daily or
Metronidazole, 500 mg twice daily plus
Tetracycline, 500 mg twice daily or
Amoxicillin, 1 g twice daily 92 (RMA) Twice-d aily dosing In- crease d diar- rhea versus other regi- mens
B. Triple and quadruple therapies have eradication
rates approaching 90 percent or more.
C. Post-Treatment Followup
1. Routine laboratory testing for cure is not re-
quired in patients whose symptoms respond to eradication therapy.
2. Routine, noninvasive follow-up testing also can
be considered in patients who have persistent symptoms following eradication therapy. In these patients, the stool antigen test, performed four weeks following therapy, is a convenient method. Patients with a history of ulcer compli- cations, gastric mucosa-associated lymphoid tissue (MALT), or early gastric cancer should undergo a routine post-treatment urea breath test or endoscopy to ensure successful eradica- tion.
D. Treatment of NSAID-related ulcers
1. When the ulcer is caused by NSAID use, heal-
ing of the ulcer is greatly facilitated by discon- tinuing the NSAID. Acid antisecretory therapy with an H2-blocker or proton pump inhibitor speeds ulcer healing. Proton pump inhibitors
are more effective in inhibiting gastric acid production and are often used to heal ulcers in patients who require continuing NSAID treat- ment.
2. If serologic or endoscopic testing for H pylori is
positive, antibiotic treatment is necessary.
3. Acute H2-blocker therapy
a. Ranitidine (Zantac), 150 mg bid or 300 mg
qhs.
b. Famotidine (Pepcid), 20 mg bid or 40 mg
qhs.
c. Nizatidine (Axid Pulvules), 150 mg bid or
300 mg qhs.
d. Cimetidine (Tagamet), 400 mg bid or 800
mg qhs.
4. Proton pump inhibitors
a. Omeprazole (Prilosec), 20 mg qd. b. Lansoprazole (Prevacid), 15 mg before
breakfast qd.
c. Esomeprazole (Nexium) 20-40 mg qd. d. Pantoprazole (Protonix) 40 mg PO, 20
minuted before the first meal of the day or IV once daily.
e. Rabeprazole (Aciphex) 20 mg/day, 20 to 30
minutes before the first meal of the day.
VI.Surgical treatment of peptic ulcer disease A. Indications for surgery include exsanguinating
hemorrhage, >5 units transfusion in 24 hours, rebleeding during same hospitalization, intractabil- ity, perforation, gastric outlet obstruction, and endoscopic signs of rebleeding.
B. Unstable patients should receive a truncal
vagotomy, oversewing of bleeding ulcer bed, and pyloroplasty.
References, see page 282.