Gastrointestinal

Peptic ulcer disease: H. pylori testing and treatment

Clinical Overview and When to Suspect Peptic Ulcer Disease (PUD)

PUD refers to mucosal defects in the stomach or duodenum that extend through the muscularis mucosae, most commonly caused by Helicobacter pylori infection or NSAID use.

— Gnawing/burning epigastric pain, often nocturnal

— Pain improved (duodenal) or worsened (gastric) by eating

— History of NSAID/aspirin use, smoking, or prior H. pylori infection

— Nausea, early satiety, bloating

Board pearl: All patients with documented PUD must be tested for H. pylori — eradication heals ulcers and dramatically reduces recurrence from ~80% to <5%.

Classic patient: middle-aged adult with recurrent epigastric pain, often related to meals

Suspect PUD when:

Duodenal ulcers (DU): ~95% H. pylori-associated; 4× more common than gastric ulcers

Gastric ulcers (GU): ~70% H. pylori; NSAID use is a major contributor

Presentation Patterns and Key History Findings

Duodenal ulcer pattern:

Gastric ulcer pattern:

Critical history elements:

Next best step: Ask about alarm features (see chunk 4) in every patient with dyspepsia — they determine whether to proceed directly to endoscopy vs noninvasive H. pylori testing.

Epigastric pain 2–5 hours after meals and at night ("hunger pain")

Pain relieved by food or antacids

Rarely malignant

Epigastric pain worsened by or occurring with meals

Associated weight loss, nausea, early satiety

Must rule out malignancy (biopsy required at endoscopy)

NSAID/aspirin/corticosteroid use (especially combined)

Anticoagulant/antiplatelet agents → ↑ bleeding risk

Smoking → delays ulcer healing, ↑ recurrence

Alcohol use → mucosal irritation

Prior PUD episodes or H. pylori treatment

Family history of gastric cancer

Physical Exam and Signs of Complications

Uncomplicated PUD:

Signs suggesting complications:

Board pearl: Succussion splash (sloshing sound with gentle rocking) suggests retained gastric contents → think GOO from chronic PUD or malignancy.

Exam is often unremarkable

Mild epigastric tenderness without peritoneal signs

GI bleeding: hematemesis, melena, coffee-ground emesis, tachycardia, orthostatic hypotension, pallor

Perforation: sudden severe epigastric pain → diffuse peritonitis, rigid "board-like" abdomen, absent bowel sounds, Mackenzie sign (referred shoulder pain from diaphragmatic irritation)

Gastric outlet obstruction (GOO): projectile nonbilious vomiting, succussion splash, visible gastric peristalsis, hypochloremic hypokalemic metabolic alkalosis

Penetration (posterior DU → pancreas): pain radiating to back, ↑ lipase

Diagnostic Workup — Indications for EGD vs Noninvasive Testing

Alarm features mandating esophagogastroduodenoscopy (EGD):

Approach without alarm features (age <60):

If EGD performed:

Key distinction: Duodenal ulcers rarely need follow-up EGD; gastric ulcers always need repeat EGD to confirm healing and exclude cancer.

Age ≥60 with new-onset dyspepsia

Unintentional weight loss

Progressive dysphagia/odynophagia

GI bleeding (overt or occult)/iron-deficiency anemia

Persistent vomiting

Palpable abdominal mass

Family history of upper GI malignancy

"Test-and-treat" strategy for H. pylori is first-line

Noninvasive testing → treat if positive → reassess

DU: biopsy not routinely needed (rarely malignant); biopsy for H. pylori

GU: always biopsy ulcer edges (rule out malignancy) + biopsy for H. pylori

Repeat EGD in 8–12 weeks for GU to document healing

H. pylori Testing — Noninvasive and Invasive Methods

Noninvasive tests:

Invasive tests (during EGD):

Critical pre-test requirements:

Board pearl: Serology is the only test unaffected by PPI/antibiotic use but cannot be used for test-of-cure because IgG remains positive long after eradication.

Urea breath test (UBT): sensitivity/specificity >95%; best for initial diagnosis and confirming eradication

Stool antigen test (SAT): sensitivity/specificity >95%; equivalent to UBT; preferred if UBT unavailable

Serology (IgG): sensitivity ~85%; does NOT distinguish active vs past infection → cannot confirm eradication; avoid for test-of-cure

Rapid urease test (CLO test): biopsy-based; sensitivity ~90–95%; result in hours

Histology: gold standard; also assesses for intestinal metaplasia/dysplasia

Culture: low sensitivity; used when antibiotic resistance testing needed

Stop PPIs ≥2 weeks before testing

Stop antibiotics and bismuth ≥4 weeks before testing

Reason: these suppress organism load → false-negative results on all tests except serology

First-Line H. pylori Eradication — Bismuth Quadruple and Clarithromycin Triple Therapy

First-line regimen selection depends on local clarithromycin resistance (<15% → triple OK; ≥15% or unknown → quadruple preferred):

Bismuth quadruple therapy (preferred if resistance unknown):

Clarithromycin-based triple therapy (only if local resistance <15% AND no prior macrolide exposure):

Key principles:

Next best step: Before prescribing, ask about penicillin allergy and prior macrolide exposure — these change the regimen.

PPI (standard dose BID) + bismuth subsalicylate + metronidazole + tetracycline × 14 days

Avoids clarithromycin resistance issue

PPI (BID) + clarithromycin + amoxicillin × 14 days

Alternative: PPI + clarithromycin + metronidazole (if penicillin allergy)

14-day courses are superior to 7- or 10-day regimens

Always use PPI BID, not once daily

Smoking cessation improves eradication rates

Alternative and Salvage H. pylori Regimens

Concomitant therapy (increasingly used first-line):

Levofloxacin-based triple therapy (salvage/second-line):

Rifabutin-based triple therapy (third-line/refractory):

General salvage principles:

Board pearl: After first-line failure, switch to a regimen with completely different antibiotics — do not repeat the same class.

PPI (BID) + clarithromycin + amoxicillin + metronidazole × 14 days

Overcomes single-antibiotic resistance by using all three agents simultaneously

PPI (BID) + levofloxacin + amoxicillin × 14 days

Reserve for treatment failure; fluoroquinolone resistance is rising

PPI (BID) + rifabutin + amoxicillin × 14 days

Risk of myelotoxicity; used when ≥2 prior regimens fail

Never re-use clarithromycin or levofloxacin after failure with those agents

Consider culture with susceptibility testing after ≥2 failed regimens

Ensure compliance — nonadherence is a major cause of treatment failure

Treatment Algorithm and Acid Suppression in PUD

PUD management overview:

1. Test for H. pylori → eradicate if positive

2. Discontinue NSAIDs if possible

3. PPI therapy to heal ulcer:

— DU: PPI × 4–8 weeks

— GU: PPI × 8–12 weeks

4. Confirm H. pylori eradication (test-of-cure)

5. GU: repeat EGD at 8–12 weeks to document healing

If H. pylori-negative and NSAID-negative:

PPI dosing for ulcer healing:

Key distinction: NSAID-related ulcers require NSAID cessation as the primary intervention; H. pylori eradication alone does not heal NSAID-induced ulcers if the drug is continued.

Exclude other causes: Zollinger-Ellison syndrome (gastrinoma), Crohn disease, CMV (immunosuppressed)

Check fasting serum gastrin level if refractory/multiple ulcers

Omeprazole 20 mg BID (for eradication), then 20 mg daily (for healing)

H2 blockers are inferior to PPIs for ulcer healing

Special Populations — Pregnancy, Pediatrics, Elderly

Pregnancy:

Pediatric considerations:

Elderly:

Board pearl: In pregnancy, defer H. pylori eradication if possible; bismuth and tetracycline are absolutely contraindicated.

PPIs (omeprazole, pantoprazole) are generally safe (FDA category B/C)

Avoid bismuth (category D), metronidazole (avoid first trimester), tetracycline (contraindicated)

Amoxicillin + clarithromycin + PPI can be considered if eradication is necessary

Often defer eradication until postpartum unless clinically urgent

H. pylori testing recommended only for symptomatic children (not routine screening)

EGD-based diagnosis preferred over noninvasive testing in children

Treatment: PPI + amoxicillin + clarithromycin (or metronidazole) × 14 days

↑ Risk of PUD complications (bleeding, perforation) due to NSAID polypharmacy, anticoagulants

Lower threshold for EGD (alarm features threshold: age ≥60)

Monitor renal function — adjust medications accordingly

Long-term PPI use concerns: ↑ risk of C. difficile, osteoporotic fractures, hypomagnesemia, B12 deficiency

NSAID-Related PUD and Gastroprotection Strategies

Risk factors for NSAID-induced PUD:

Gastroprotection strategies:

Aspirin users:

Key distinction: H. pylori and NSAIDs are independent, synergistic risk factors. Eradicating H. pylori reduces but does not eliminate NSAID ulcer risk — PPI co-therapy is still needed in high-risk patients on chronic NSAIDs.

Next best step: Before starting long-term NSAID therapy in a patient with PUD history → test for H. pylori, eradicate if positive, AND add PPI.

Age >65, prior PUD/GI bleed, concurrent anticoagulant/antiplatelet/corticosteroid use

High-dose or multiple NSAIDs, H. pylori co-infection

If NSAID is essential and patient has risk factors → co-prescribe PPI

Substitute COX-2 selective inhibitor (celecoxib) + PPI for highest-risk patients

Test and treat H. pylori before chronic NSAID use

Low-dose aspirin + prior GI bleed → add PPI indefinitely

Dual antiplatelet therapy (DAPT) → PPI co-therapy recommended

Complications — Upper GI Bleeding From PUD

PUD is the most common cause of upper GI bleeding (UGIB).

Initial management:

EGD timing:

Forrest classification (endoscopic findings guiding rebleeding risk):

Board pearl: IV PPI infusion is started empirically before EGD in suspected bleeding PUD — it stabilizes clots and reduces the need for endoscopic intervention.

ABCs, two large-bore IV lines, fluid resuscitation

Type and crossmatch; transfuse pRBCs if Hgb <7 g/dL (threshold ↑ to <8 in active CAD)

IV PPI bolus (80 mg) then continuous infusion (8 mg/hr) before EGD

Prokinetic (IV erythromycin 250 mg) 30–60 min pre-EGD to clear gastric blood → improves visualization

Within 24 hours for most UGIB

Emergent (<12 hours) if hemodynamically unstable despite resuscitation

Active spurting (Ia) or oozing (Ib) → endoscopic therapy

Visible vessel (IIa) → endoscopic therapy

Adherent clot (IIb) → attempt removal → treat underlying lesion

Flat pigmented spot (IIc) or clean base (III) → low rebleeding risk → no endoscopic therapy needed

Complications — Perforation and Gastric Outlet Obstruction

Perforation:

Gastric outlet obstruction (GOO):

Board pearl: Anterior DU → perforation; posterior DU → hemorrhage (gastroduodenal artery erosion).

Most common with anterior duodenal ulcers

Sudden onset severe epigastric pain → diffuse peritonitis

Upright chest X-ray/abdominal X-ray: free air under diaphragm (pneumoperitoneum) — sensitivity ~80%

If X-ray negative but high suspicion → CT abdomen/pelvis with oral contrast (sensitivity >95%)

Next best step: NPO, IV fluids, IV antibiotics, emergent surgical consultation → typically Graham patch (omental patch repair)

Posterior DU perforation can erode into gastroduodenal artery → massive hemorrhage

Chronic scarring from recurrent ulcers → pyloric stenosis

Presents with early satiety, nonbilious vomiting, weight loss

Metabolic derangement: hypochloremic, hypokalemic metabolic alkalosis (loss of HCl)

Diagnosis: EGD (preferred — also therapeutic) or barium swallow showing narrowing

Treatment: endoscopic balloon dilation; surgery if refractory

Key Differentials — Dyspepsia and Epigastric Pain

Functional dyspepsia:

Gastric cancer:

Zollinger-Ellison syndrome (ZES):

Key distinction: Isolated gastric ulcer that fails to heal after 12 weeks of PPI + H. pylori eradication → biopsy to exclude malignancy or consider ZES.

Chronic epigastric pain/burning without ulcer on EGD

Rome IV criteria: ≥3 months, onset ≥6 months prior

Management: test-and-treat H. pylori → PPI trial → tricyclic antidepressant

Alarm features: weight loss, early satiety, dysphagia, anemia, palpable mass

EGD with biopsy of all gastric ulcers is mandatory

Risk factors: H. pylori (especially intestinal-type), smoking, salt-preserved foods, family history

Multiple/refractory ulcers, ulcers in unusual locations (distal duodenum/jejunum)

Profuse diarrhea (acid hypersecretion)

Fasting gastrin >1000 pg/mL with gastric pH <2 → diagnostic

Secretin stimulation test if gastrin equivocal

Associated with MEN1 (pituitary, parathyroid, pancreas)

Distinguishing H. pylori-Related vs NSAID-Related PUD

H. pylori-related PUD:

NSAID-related PUD:

Both present:

Board pearl: NSAID ulcers are commonly asymptomatic until complications occur — this is why gastroprophylaxis with PPI is recommended in high-risk patients on chronic NSAIDs.

Multiple or recurrent ulcers

Duodenal > gastric ulcers

Chronic active gastritis on biopsy

Eradication cures disease; ulcer recurrence rate drops from ~80% → <5%

Associated with gastric MALT lymphoma and gastric adenocarcinoma

Gastric > duodenal ulcers

Often painless — may present with bleeding as first symptom (especially elderly)

Mucosal damage via COX-1 inhibition → ↓ prostaglandins → ↓ mucosal protection

Removal of offending agent is critical to healing

H. pylori testing still needed — dual etiology possible

Synergistic risk; eradicate H. pylori AND stop NSAIDs if possible

Test-of-Cure and Post-Treatment Follow-Up

Confirming H. pylori eradication:

Follow-up EGD:

If eradication fails:

Next best step: After completing H. pylori therapy, wait ≥4 weeks off antibiotics and ≥2 weeks off PPIs before performing UBT or stool antigen for test-of-cure.

Test-of-cure is recommended for ALL patients treated for H. pylori

Use UBT or stool antigen test (NOT serology — remains positive)

Timing: ≥4 weeks after completing antibiotics AND ≥2 weeks after stopping PPI

Rationale: ensures eradication, prevents ulcer recurrence, reduces cancer risk

Gastric ulcers: repeat EGD at 8–12 weeks to confirm healing and rebiopsy if not healed

Duodenal ulcers: no routine repeat EGD unless symptoms persist

Use a different regimen (see chunk 7)

Confirm medication compliance

After ≥2 failures → culture with antibiotic susceptibility testing

Screening, Prevention, and Long-Term Monitoring

H. pylori screening indications (even without active PUD):

Long-term PPI monitoring (if ongoing PPI needed):

Prevention of PUD recurrence:

Board pearl: H. pylori eradication in gastric MALT lymphoma achieves complete remission in ~75–80% of localized (stage I) cases — chemotherapy may not be needed.

Active or history of PUD

Gastric MALT lymphoma

Early gastric cancer (after endoscopic resection)

First-degree relative with gastric cancer

Unexplained iron deficiency anemia (after other causes excluded)

Chronic idiopathic thrombocytopenic purpura (ITP)

Before long-term NSAID or aspirin therapy

Ca²⁺ and vitamin D supplementation for osteoporosis risk

Monitor Mg²⁺ levels (hypomagnesemia with chronic use)

B12 levels in elderly on long-term therapy

Reassess PPI necessity annually — step down to lowest effective dose or H2 blocker

Eradicate H. pylori

Avoid NSAIDs; use COX-2 inhibitors + PPI if unavoidable

Smoking cessation

Limit alcohol

Ethical, Legal, and Patient Safety Considerations

Informed consent and shared decision-making:

Antibiotic stewardship:

Medication safety:

Patient adherence:

Board pearl: Nonadherence is the most common cause of H. pylori treatment failure — address it before changing antibiotics.

Discuss risks/benefits of EGD, including sedation risks, perforation (~1:10,000), and bleeding

Patients declining EGD → document informed refusal; pursue noninvasive H. pylori testing

Avoid unnecessary clarithromycin use in areas of high resistance

Use susceptibility-guided therapy when available (especially after treatment failures)

Complete 14-day courses to minimize resistance development

Clarithromycin: QT prolongation risk; check for drug interactions (statins, colchicine, warfarin)

Metronidazole: disulfiram-like reaction with alcohol; peripheral neuropathy with prolonged use

Tetracycline: photosensitivity, contraindicated in pregnancy/children <8

PPIs: educate patients on appropriate duration — avoid indefinite use without indication

Quadruple therapy regimens are complex (4 drugs, multiple doses) → pill burden is high

Counsel on importance of completing full course

Side effects (metallic taste, nausea, diarrhea) are common → preemptive counseling improves adherence

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: H. pylori ↑ risk of both gastric adenocarcinoma and MALT lymphoma but is inversely associated with esophageal adenocarcinoma and GERD.

H. pylori → chronic active gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → gastric adenocarcinoma (Correa cascade)

H. pylori is a WHO Class I carcinogen

Duodenal ulcer: anterior → perforation; posterior → bleeding (gastroduodenal artery)

Gastric MALT lymphoma: eradicate H. pylori first → most regress

ZES: fasting gastrin >1000 + pH <2 = diagnostic; secretin stimulation test if equivocal

Serology = only H. pylori test NOT affected by PPI/antibiotics

UBT and stool antigen = best for test-of-cure

NSAID ulcers are more often painless → present with bleeding

Currant jelly sputum = Klebsiella (don't confuse — PUD context: currant jelly not relevant)

Misoprostol (PGE₁ analog) → mucosal protection but limited by diarrhea/uterine contractions; PPI preferred for gastroprotection

Coffee-ground emesis + melena → upper GI source → PUD until proven otherwise

Board Question Stem Patterns

45M, burning epigastric pain relieved by eating, no alarm features, age <60 → Test-and-treat H. pylori (UBT or stool antigen)

62F, new dyspepsia + 10-lb weight loss → EGD with biopsy (alarm features)

EGD shows gastric ulcer, rapid urease test positive → H. pylori eradication (bismuth quadruple × 14 days) + PPI × 8–12 weeks + repeat EGD to confirm healing

Patient completed triple therapy, wants test-of-cure → Wait ≥4 weeks after antibiotics, ≥2 weeks after PPI → UBT or stool antigen (NOT serology)

Duodenal ulcer on chronic NSAIDs, H. pylori positive → Eradicate H. pylori AND stop NSAID AND PPI to heal ulcer

Sudden severe epigastric pain, rigid abdomen, free air on CXR → Perforated ulcer → IV fluids, antibiotics, emergent surgical repair

Multiple refractory ulcers in unusual location + diarrhea → ZES → fasting gastrin level

GI bleed from DU, visible vessel on EGD → Endoscopic hemostasis (epinephrine + thermal/clips) + IV PPI infusion

First-line H. pylori eradication failed → Switch to different regimen (e.g., bismuth quadruple if triple used first; levofloxacin-based if quadruple failed) — never repeat same antibiotics

Stage I gastric MALT lymphoma, H. pylori positive → Eradicate H. pylori → reassess; ~80% achieve remission

One-Line Recap

Peptic ulcer disease is most commonly caused by H. pylori infection or NSAIDs, diagnosed by EGD (required when alarm features present) or noninvasive test-and-treat strategy (UBT/stool antigen for age <60 without alarm features), treated with 14-day H. pylori eradication using bismuth quadruple therapy (preferred) or clarithromycin triple therapy (if low resistance), PPI for 4–12 weeks to heal the ulcer, NSAID cessation when possible, with mandatory test-of-cure via UBT or stool antigen ≥4 weeks post-antibiotics, repeat EGD for all gastric ulcers to exclude malignancy, and gastroprotection (PPI ± COX-2 inhibitor) for patients requiring continued NSAID/aspirin therapy who have risk factors for ulcer complications.

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