On completion of this lecture participants will be able to:
Recognize the typical clinical presentation and risk factors for peptic ulcer disease
Understand pathophysiology of PUD focusing on H. pylori
Describe an appropriate diagnostic plan based on individual risk factors
Prescribe an appropriate therapeutic regimen
Lifetime Prevalence = 10% of Americans develop PUD
10% of ER patients with abdominal pain diagnosed with PUD
Prevalence decreasing over last 30yrs
Male-to-female ratio of gastritis = 1:1
Male-to-female ratio of PUD = 2:1
Peptic ulcer disease (PUD) = Mucosal defect in the gastrointestinal tract (gastric or duodenal) exposed to acid and pepsin secretion
Gastritis is the precursor to PUD and it is clinically difficult to differentiate the two
Differentiating gastric from peptic ulcer disease
Duodenal ulcers - age 25-75 years.
Gastric ulcer - age 55-65 years
Pain awakening patient from sleep between 12-3 a.m. present in 2/3 duodenal ulcer patients and 1/3 gastric ulcer patients
Mr. Jones is a 45 year old male who
presents to your clinic with epigastric
abdominal pain x 2 weeks.
What is your initial differential diagnosis at this point given the limited information?
Initial Differential Diagnosis
Gastroesophageal reflux disease
Nonulcer dyspepsia/ Gastritis
Biliary colic or cholecystitis
Irritable bowel disease
Stomach/Pancreas/ Hepatobiliary cancers
Atypical manifestion CAD/angina
Posterior Wall AMI
Inflammatory Bowel Dz
Mr. Jones HPI
Mr. Jones is a 45 year old male who presents to your clinic with epigastric abdominal pain x 2 weeks. He describes it as a burning pain which is non-radiating and is worse after he eats. He has frequent belching with bloating sensation but denies nausea, vomiting, diarrhea, constipation, or weight loss. He has tried rolaids which do help a little.
Which symptoms support the possible diagnosis of PUD?
Signs and Symptoms of PUD
Epigastric pain is most common symptom
Pain described as gnawing or burning
May radiate to the back (consider penetration)
Occurs 1-3 hours after meals or at night
Relieved by food, antacids (duodenal), or vomiting (gastric)
Dyspepsia including belching/ bloating
Hematemesis or melena with GI bleeding
NSAID-induced gastritis or ulcers are frequently “silent”
Dyspeptic sx’s are non-specific – approx 20-25% of patients with sx’s will have peptic ulcer on further workup
Mr Jones History
PMH: HTN stable, Osteoarthritis in knees, treated for an ulcer 3 years ago
Meds: Hydrochlorothiazide, ibuprofen prn
Soc HX: Married, employed as bank manager, smokes 1ppd x 20years, drinks 2 beers per day, and 2-4 cups coffee per day
What risk factors can you identify for PUD?
Common Risk Factors for Gastric Mucosal Disruption
NSAIDs/ASA (even at low dose)
Severe physiologic stress (Burns, CNS trauma, Surgery, Severe medical illness)
PUD is a result of acid/pepsin production imbalance with protective mechanisms such as mucous production
Approximately 15% of patients on long-term NSAID develop PUD
NSAIDs/ASA - ↓ prostaglandin (PG) by inhibiting the cyclooxygenase (COX) enzymes
Three isoenzymes COX-1, COX-2, COX-3
COX-1 -> PG production in gastric mucosa
COX-2 specific NSAIDs reduce GI side effects – cardiovascular side effects have limited use
Produces alkaline environment enabling survival in stomach.
Higher prevalence in Low SES
In US more common in Hispanics/Blacks
Estimated 60% of Americans older than 60 H pylori (+)
Almost all duodenal and 2/3 gastric ulcer pt’s infected with HP
Asymptomatic in approx 70% of those who are H pylori (+)
Considered class 1 carcinogen -> gastric cancer
Differentiating between H. pylori and NSAID-induced ulcer
Ulcers associated with H. pylori
more often in duodenum
less severe GI bleeding
Ulcers associated with NSAIDs
more often in stomach
more severe GI bleeding
Other Disease Conditions Associated with PUD
Hypersecretory states: Gastrinoma (Zollinger-Ellison syndrome) or multiple endocrine neoplasia (MEN-I)
Diseases assoc. with increased risk of PUD: cirrhosis, chronic pulmonary disease, renal failure
Mr. Jones Physical Exam
VS: BP 137/82, HR 85, afeb, RR 14
HEENT: conjunctiva pink, OP MMM
Heart: RRR no M/R/G
ABD: Soft, NABS, mild-moderate epigastric TTP, no HSM or masses, no acute abd signs
Skin: no pallor
Rectal: stool brown, heme (-), no masses
What are typical PE findings in PUD?
Physical Exam Findings
In uncomplicated PUD exam findings few and non-specific:
Epigastric tenderness - usually mild.
Bowel sounds - normal.
Rectal exam may show melena/guaiac+ stool from occult blood loss
Signs of peritonitis with perforation
If Mr. Jones Hemoccult is Positive
What PE findings do you want to specifically document if Mr. Jones is Heme (+) indicating a possible active GI bleed?
Look for signs of volume depletion: tachycardia, hypotension, orthostatics, skin turgor, MM appearance
Look for signs of anemia: conjunctiva or skin pallor, new heart murmur
Lab Studies to Evaluate PUD
CBC - evaluate acute/chronic blood loss
- Serologic antibody test for HP – does not determine if active HP infection
- Fecal antigen test tests for active HP
- Urea breath test tests for active HP
Principles in Selecting H. pylori Test
Based on the following:
• Probability of previously eradicated infection
• Probability of current active infection
• Need to document active infection
• Need for rapid result
• Patient preferences
• Cost (both of test and possible unnecessary treatment)
H. Pylori Serology Antibody Test
Office based serology tests faster but less accurate than lab based ELISA tests
Sensitivity and specificity of approx 90%
Not useful for evaluating eradication - antibody levels can persist for a long time, need serial titers to evaluate
When is a Serology Test Useful?
Not useful in
Populations with low disease prevalence
Elderly populations to detect active disease
Patients who never received H. pylori treatment
Symptomatic patients not using NSAIDs- if negative serology – unlikely PUD
H. Pylori Stool Antigen (HpSa) Test
Useful in initial diagnosis + confirmation of eradication
Sensitivity of 91% and a specificity of 92%*
Test requires collection of stool sample- size of an acorn
Performed in lab or newer POCT available
Requires little preparation, however patients may not be compliant with collecting sample
*Gisbert JP, Pajares JM. Stool antigen test for the diagnosis of Helicobacter
pylori infection: a systematic review. Helicobacter 2004;9(4):347-68
Urea Breath Test
Useful for initial diagnosis + confirmation of eradication
Sensitivity and specificity over 90%*
Urease activity is present in the stomach in those infected with H pylori
Ingest urea labeled with radioactive carbon
Hydrolysis of urea -> labeled carbon dioxide (CO2)
Rapidly absorbed into bloodstream and within a few minutes, appears in breath
*Gatta L, Vakil N, Ricci C, et al. A rapid, low-dose, 13C-urea tablet for the detection of Helicobacter pylori infection before and after treatment. Aliment Pharmacol Ther 2003;17(6):793-8
Breath Test Compared to HpSa
Requires more patient preparation
Number of drugs can adversely affect accuracy
Antibiotics and bismuth -> stop for 4 weeks
Proton pump inhibitors -> stop for 7 days
Patients need to fast for at least 6 hours.
Breath test cannot be used in pregnant women
Chest x-ray if perforation is suspected to detect free abdominal air
Upper gastrointestinal series
Performed by experienced radiologist is close to diagnostic accuracy of endoscopy
Not as sensitive as endoscopy in diagnosis of small ulcers (<0.5 cm)
Unable to obtain biopsy to rule out malignancy
Endoscopy indicated in following high risk patients:
>50 years old with new-onset dyspepsia
Dyspepsia with dysphasia and/or weight loss
Evidence of GI bleeding
Failed appropriate trial of empiric therapy
Using NSAIDs or other high risk meds
Signs of UGI tract obstruction (early satiety, vomiting)
Ethnic background assoc. with increased risk UGI malignancies
Excerpts from Guidelines prepared by The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy
Rapid Urease Test and Histopathology
Gastric mucosal biopsy obtained during endoscopy:
Rapid urease tests (CLOtest, Hpfast, Pyloritek) bacterial urease converts urea substrate in kit to ammonia -> changes pH producing color change.
Histopathology often considered gold standard for diagnosis
Mr. Jones Prior Ulcer History
On further questioning Mr. Jones states he had similar abdominal pain three years ago and was told by his physician at that time that it was most likely due to an ulcer. He took “the purple pill” for a month and his symptoms resolved. He had no definitive diagnostic tests done at that time.
What would you do at this time?
H. pylori serology - many patients with history of “ulcer” have not undergone eradication therapy
Test for H. pylori antibody and treat if (+)
Endoscopy if serology negative or if fails to improve with treatment
Moving on to Treatment Options……….
Over The Counter Remedies
Aluminum and magnesium hydroxide salt (Maalox ® , Mylanta ® ) Neutralizes gastric acidity.
Aluminum side effect = constipation
Magnesium side effect = diarrhea
Magnesium and aluminum mixtures used to avoid side effects
Over the Counter Remedies cont’d
Calcium Carbonate (Tums ®, Rolaids®) – calcium salt neutralizes acid
Bismuth subsalicylate (Peptobismol ®) – binds to ulcer base forming a protective coat, has anti-inflammatory and bacteriocidal properties
Selectively block H2-receptors on parietal cells reducing acid secretion
Used primarily in ulcer disease not associated with H pylori
Treatment duration is 6-8 wk.
Side Effects of Cimetidine/Tagamet ®
Elderly patients – confusion
Young males - impotence +/- gynecomastia
May alter levels of other drug - warfarin, TCA’s, triamterene, phenytoin, propranolol, metronidazole, antiarrythmics
May alter renal function requiring lower doses
Proton Pump Inhibitors
Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump
Relieve pain and heal peptic ulcers more rapidly than H2 blockers
Drugs in this class are equally effective
Four weeks to treat active PUD
Eight weeks to treat erosive esophagitis
Other Pharmacotherapy Agents
Sucralfate (Carafate ® ) Binds proteins in exudates and forms a viscous adhesive that protects GI lining
Misoprostol (Cytotec ® ) Prostaglandin analog- protects lining of GI tract by replacing depleted prostaglandin E1. Prevents peptic ulcers in patients taking NSAIDs
H. Pylori Triple Therapy Treatment
Triple therapy for 14 days is treatment of choice
Two forms of triple therapy: PPI–based and bismuth-based
PPI based = PPI + 2 antibiotics for 2 wk, cont PPI for additional 2 weeks.
Bismuth-based = bismuth subsalicylate and 2 antibiotics, for 2 weeks with addition of H2- blocker to optimize ulcer healing.
H Pylori Treatment http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540-21,00.html Cure Rate Side Effect Rating 81-92% low-medium Prevpak 80-85% medium-high Helidac + H2 blocker Combination Products 80-90% medium Amoxicillin + Metronidazole + PPI 80-90% medium-low Amoxicillin + Clarithromycin + PPI 80-90% medium Clarithromycin + Metronidazole + PPI Three Drug Regimens
H. Pylori Therapy cont’d
Successful eradication of H. pylori reduces PUD recurrence rates from 90% to less than 10% per year.
Patients no longer require ongoing chronic acid suppression.
If symptoms return after treatment of PUD, then testing for recurrence should be pursued
Hemorrhagic shock/peritonitis from a perforated ulcer
Symptomatic relief with PPI may mask symptoms of gastric malignancy
Gastritis may present as bleeding, more likely in elderly
Symptoms of anemia (fatigue, dyspnea)
Initial Treatment Plan in the Absence of High Risk Symptoms
Based on current evidence, no single strategy has been demonstrated to be more medically effective than any other.
Empiric therapy with acid suppression
Empiric H pylori testing and treating strategy
Excerpts from Guidelines prepared by The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy
Alarm symptoms = endoscopy.
No alarm symptoms = medical management favored approach
Studies still in progress to evaluate if medical management versus vs endoscopy is both medically and cost effective in long-term
Lack of response or the recurrence of symptoms warrants endoscopy
Medical Legal Pitfalls
Failure to consider non-GI cause of epigastric pain (AMI/AAA)
Failure to consider GI bleed in absence of abdominal pain (especially in elderly)
Lack of follow-up care resulting in failure to diagnose gastric cancer
Failure to recommend endoscopy early in high risk patients
Failure to obtain a history regarding NSAID use
Alternate Scenarios of Mr. Jones Case
Mr Jones is a 63 yo male presenting with previously noted epigastric symptoms and PMH. On physical exam he is noted to have heme (+) stool.
What evaluation would you do next?
Alternate Scenarios to Mr. Jones Case
Mr Jones is a 63 yo male presenting with previously noted epigastric symptoms and PMH. On review of his prior ulcer history he was tested and had a positive H. pylori serology test. He was treated with triple therapy (PPI and 2 antibiotics) and symptoms resolved.
What would you do next? Would you recheck H. pylori serology? Repeat triple therapy?
H. pylori is the most common cause of PUD and is a risk factor for gastric cancer
H Pylori eradication reduces risk of disease recurrence
Test-and-Treat strategy is recommended for patients with undifferentiated dyspepsia
Intial evaluation with endoscopy is recommended for those with alarm symptoms or those failing treatment
Optimum treatment regimens are 14d multidrug with antibiotics and acid suppressants