GERD, Peptic Ulcer & H. pylori
The commonest complaint in clinic and the commonest reason for a PPI that never gets stopped. Three decisions carry the weight: does this patient need endoscopy or a trial of therapy, is H. pylori driving it, and when does the PPI come off. The 2024 ACG guideline retired clarithromycin triple therapy as first-line, so a regimen most residents were taught is now the wrong answer.
🔍 Overview
Overview
GERD is reflux of gastric contents causing troublesome symptoms or mucosal injury, driven by transient lower esophageal sphincter relaxations rather than simple acid overproduction (which is why prokinetics and antacids underperform acid suppression). Peptic ulcer disease is a mucosal break through the muscularis mucosae, and its two dominant causes are H. pylori and NSAIDs -together they account for the large majority, which is why every ulcer earns a hunt for both.
Presentations and What They Point To
- Typical GERD: heartburn and regurgitation, worse lying flat or after meals. Response to a PPI trial supports the diagnosis but does not confirm it (placebo response is substantial).
- Extraesophageal: chronic cough, hoarseness, laryngitis, asthma. Reflux is a possible contributor, rarely the sole cause -treating these with a PPI alone often fails, and the guideline caution exists because years of PPI get prescribed on this indication without benefit.
- Duodenal ulcer: pain classically 2-5 hours after meals and at night, relieved by food. H. pylori is the dominant cause.
- Gastric ulcer: pain worsened by eating, so patients avoid food and lose weight. Higher malignancy risk, which is why gastric ulcers get biopsied and re-scoped.
- Functional dyspepsia: the commonest endpoint after a negative workup -epigastric pain or postprandial fullness with normal endoscopy. It is a positive diagnosis, not a failure of the workup.
Complications That Change the Plan
- Erosive esophagitis and stricture -stricture presents as progressive solid-food dysphagia and needs dilation plus long-term acid suppression.
- Barrett esophagus -intestinal metaplasia replacing squamous epithelium; the precursor to esophageal adenocarcinoma. Surveillance interval depends on dysplasia grade; dysplasia is treated endoscopically (ablation or resection), not just watched.
- Bleeding or perforated ulcer -the acute presentations; see the upper GI bleed topic for resuscitation and endoscopic therapy.
- Gastric outlet obstruction -vomiting undigested food, succussion splash.
The prescribing problem this topic exists to fix: PPIs are started appropriately and then continued indefinitely without an indication being re-examined. Long-term use is associated with hypomagnesemia, B12 deficiency, C. difficile and enteric infections, and rebound hypersecretion on abrupt withdrawal (which is misread as "the disease returning" and locks the patient back in). Every PPI needs an indication, a duration, and a taper plan.
🧪 Workup & Endoscopy
Alarm Features (endoscopy, not a PPI trial)
- Dysphagia or odynophagia -structural disease until proven otherwise (stricture, ring, eosinophilic esophagitis, malignancy).
- Unintentional weight loss, GI bleeding, iron deficiency anemia, persistent vomiting, palpable mass or lymphadenopathy, family history of upper GI cancer.
- New dyspepsia at age ≥ 60 -age threshold exists because malignancy risk rises and the pre-test probability justifies scoping rather than treating empirically.
No Alarm Features: the Test-and-Treat Pathway
- Under 60 with dyspepsia: test for H. pylori non-invasively and treat if positive (urea breath test or stool antigen). This is more effective and cheaper than empiric PPI in populations where prevalence is meaningful, and it removes a curable cause rather than masking it.
- If negative or symptoms persist: empiric PPI trial for 8 weeks, then reassess -not renew indefinitely.
- Typical GERD symptoms without alarm features need no endoscopy up front. Scope if therapy fails, if symptoms relapse promptly after stopping, or to screen for Barrett in patients with chronic symptoms plus multiple risk factors (age ≥ 50, male, white, obesity, smoking, family history).
Testing for H. pylori (and how to get a false negative)
- Urea breath test or stool antigen -both detect active infection and are the right tests for diagnosis and for test-of-cure.
- ⚠ Hold PPIs for 2 weeks and antibiotics/bismuth for 4 weeks before testing. Suppressed bacterial load produces false negatives, and this is the single commonest reason a genuinely infected patient is told they are clear.
- Serology is nearly useless for management -IgG stays positive after eradication, so it cannot distinguish current from past infection or confirm cure.
- Biopsy-based testing (rapid urease test, histology) when endoscopy is being done anyway; same PPI/antibiotic caveat applies.
- Test-of-cure is mandatory, at least 4 weeks after finishing therapy, by breath or stool test -eradication failure is common enough that assuming success is unsafe.
When the Diagnosis Will Not Settle
- Ambulatory pH or pH-impedance monitoring -confirms pathologic reflux when endoscopy is normal and PPI response is poor, and is required before anti-reflux surgery. Done off therapy to establish the diagnosis, on therapy to assess breakthrough.
- Esophageal manometry -before surgery, and to exclude achalasia or a major motility disorder masquerading as refractory reflux.
- Think eosinophilic esophagitis in younger patients with dysphagia or food impaction -diagnosis requires esophageal biopsies (≥ 15 eosinophils/hpf), and biopsies must be taken even if the mucosa looks normal.
🚨 GERD Management
Lifestyle (the measures with actual evidence)
- Weight loss -the intervention with the strongest evidence; even modest loss reduces symptoms because intra-abdominal pressure drives reflux.
- Elevate the head of the bed and avoid eating within 3 hours of lying down -for nocturnal symptoms, where gravity and gastric emptying do the work.
- Targeted trigger avoidance rather than blanket elimination diets -cut what reliably provokes symptoms for that patient; global restriction lists have weak evidence and poor adherence.
- Smoking cessation and alcohol moderation -both reduce sphincter tone.
Acid Suppression: dose, timing, duration
- Standard-dose PPI once daily for 8 weeks is the initial course for symptomatic GERD and erosive esophagitis.
- ⚠ Timing is the commonest fixable failure: take the PPI 30-60 minutes BEFORE the first meal of the day. PPIs irreversibly bind actively secreting proton pumps, so the drug must be present when the meal triggers secretion -a patient taking it at bedtime on an empty stomach gets a fraction of the effect and is labeled a treatment failure.
- Inadequate response: confirm timing and adherence first, then consider twice-daily dosing or switching PPI, then reassess the diagnosis (functional heartburn, eosinophilic esophagitis, achalasia).
- H2 blockers -useful for breakthrough nocturnal symptoms and for on-demand mild disease; tachyphylaxis develops with scheduled use.
- Step down after 8 weeks to the lowest effective dose, on-demand therapy, or stop -except where long-term therapy is indicated.
Who Stays on a PPI Long Term (a real indication list)
- Barrett esophagus, severe erosive esophagitis (LA grade C/D), peptic stricture -mucosal disease that recurs without suppression.
- Ulcer prophylaxis in genuinely high-risk NSAID users: prior ulcer or GI bleed, age ≥ 65, concurrent anticoagulant, antiplatelet or steroid, or high-dose/multiple NSAIDs.
- Zollinger-Ellison syndrome and other hypersecretory states.
- Everyone else gets a deprescribing attempt: taper rather than stop abruptly, because rebound hypersecretion produces symptoms that get misread as relapse. Step to alternate-day dosing or an H2 blocker, and warn the patient the first two weeks may be worse.
When Medication Is Not the Answer
- Anti-reflux surgery (fundoplication) or magnetic sphincter augmentation -for objectively confirmed reflux with incomplete PPI response, large hiatal hernia, or patient preference against lifelong therapy. Requires pH study and manometry first, because operating on functional heartburn or unrecognized achalasia makes patients worse.
- Bariatric surgery -in obesity with GERD, Roux-en-Y gastric bypass treats both; sleeve gastrectomy can worsen reflux, which is a decision point rather than a detail.
🦠 H. pylori & PUD
What changed in 2024 (ACG): CHANGED clarithromycin triple therapy and concomitant therapy are no longer recommended first-line when susceptibility is unknown, because clarithromycin resistance in the US has climbed past the threshold where empiric use is defensible. Bismuth quadruple therapy for 14 days is now the preferred empiric first-line regimen. Clarithromycin- and levofloxacin-based regimens should be used only when susceptibility testing supports them. If you were taught "PPI + clarithromycin + amoxicillin" as the default, that is the recommendation that was retired.
Who Gets Tested and Treated
- Active or prior peptic ulcer disease -eradication heals the ulcer and prevents recurrence, converting a chronic relapsing disease into a cured one.
- Gastric MALT lymphoma -eradication alone can induce remission in early-stage disease.
- Uninvestigated dyspepsia under 60 without alarm features (test-and-treat), and functional dyspepsia, where eradication benefits a subset.
- Early gastric cancer after resection, and first-degree relatives of gastric cancer patients.
- Long-term NSAID or aspirin users with ulcer history, and patients with unexplained iron deficiency anemia or ITP.
- The principle: if you test, you must be prepared to treat and to confirm cure -there is no role for finding it and leaving it.
Regimens (all 14 days)
| Regimen | Components | When to use / Watch for |
|---|---|---|
| Bismuth quadruple FIRST-LINE | PPI BID + bismuth subsalicylate QID + tetracycline QID + metronidazole TID-QID | Preferred empiric choice when susceptibility is unknown, and the regimen of choice with penicillin allergy or prior macrolide exposure. Warn about black stools and tongue (harmless bismuth effect) and avoid alcohol with metronidazole. Pill burden is the adherence threat -say so out loud. |
| Vonoprazan dual | Vonoprazan BID + high-dose amoxicillin | Potassium-competitive acid blocker gives faster, more sustained acid suppression than a PPI. Non-inferior to bismuth quadruple with fewer adverse events; simpler regimen aids adherence. Not with penicillin allergy. |
| Vonoprazan triple | Vonoprazan + amoxicillin + clarithromycin | An option where clarithromycin susceptibility is known or local resistance is low. |
| Rifabutin triple | Omeprazole + amoxicillin + rifabutin | Empiric alternative without penicillin allergy, and a salvage option; rifabutin resistance remains rare. Watch myelosuppression and the drug interactions rifamycins bring. |
| Clarithromycin triple NOT FIRST-LINE | PPI + amoxicillin + clarithromycin | Retired as empiric first-line in 2024. Use only with documented clarithromycin susceptibility, and never in a patient with prior macrolide exposure. |
Eradication Failure
- Do not repeat an antibiotic the patient has already failed -resistance is the likeliest reason the first course failed, and reusing the drug repeats the failure.
- Choose salvage by what was used first: bismuth quadruple after a failed clarithromycin regimen; rifabutin triple or a vonoprazan-based regimen after failed bismuth quadruple.
- Susceptibility testing (culture or molecular) after two failures, and consider it earlier where available.
- Re-confirm cure after every salvage course, and re-ask about adherence: a 14-day multi-drug regimen with black stools and a metallic taste has a real dropout rate.
Ulcer Care Beyond Eradication
- Stop the NSAID if at all possible; if not, co-prescribe a PPI and consider a COX-2 selective agent, weighing its cardiovascular tradeoff.
- Gastric ulcers get biopsied at diagnosis and re-scoped at 8-12 weeks to document healing -because a malignant ulcer can look benign and can partially heal on acid suppression, which falsely reassures.
- H. pylori-negative, NSAID-negative ulcers deserve a second thought: Zollinger-Ellison (check fasting gastrin off PPI), Crohn disease, malignancy, or occult NSAID use the patient did not report because they consider it "just ibuprofen."
🏥 Rounds
Pimp Questions
❓ Why did the 2024 ACG guideline drop clarithromycin triple therapy as first-line, and what replaced it?
Clarithromycin resistance in the US rose past the threshold where empiric use is defensible, so eradication rates with triple therapy fell below acceptable levels. Bismuth quadruple therapy for 14 days (PPI + bismuth + tetracycline + metronidazole) is now the preferred empiric first-line regimen, with vonoprazan-based and rifabutin-based regimens as alternatives. Clarithromycin and levofloxacin regimens are reserved for cases with documented susceptibility.
❓ A patient on a PPI for 6 weeks has a negative H. pylori breath test. Can you trust it?
No. PPIs suppress bacterial load and produce false negatives on both urea breath and stool antigen testing. Hold the PPI for 2 weeks (and antibiotics or bismuth for 4 weeks) before testing. This is the commonest reason an infected patient is told they are negative. Serology would sidestep the issue but cannot distinguish active from past infection, so it does not solve the problem either.
❓ Why must a PPI be taken 30-60 minutes before a meal?
PPIs irreversibly bind proton pumps that are actively secreting, and pumps are recruited into activity by a meal. Take the drug on an empty stomach at bedtime and most pumps are quiescent, so the drug is cleared before they activate. Dosing before the first meal puts peak drug levels in circulation exactly when the pumps switch on. Wrong timing is the commonest cause of apparent PPI failure, and should be checked before escalating dose or blaming the diagnosis.
❓ Why are gastric ulcers biopsied and re-scoped when duodenal ulcers usually are not?
Gastric ulcers carry meaningful malignancy risk; duodenal ulcers essentially do not. A malignant gastric ulcer can look benign endoscopically and can partially heal on acid suppression, which produces false reassurance. So gastric ulcers are biopsied at diagnosis and re-scoped at 8-12 weeks to document complete healing, with repeat biopsy if healing is incomplete.
❓ A patient stopping long-term PPI has worse heartburn than before. What is happening?
Rebound acid hypersecretion. Chronic acid suppression raises gastrin, which drives parietal cell hyperplasia; withdrawing the drug unmasks that expanded secretory capacity, and symptoms can exceed baseline for weeks. It is physiologic withdrawal, not proof the original disease requires lifelong therapy, though it is routinely misread that way and locks patients back onto the drug. Manage by tapering, bridging with an H2 blocker or on-demand dosing, and warning the patient in advance that the first two weeks are the hardest.
Sample Presentation
Mr. Delgado is a 52-year-old man with 6 months of epigastric burning, worse at night and 3 hours after meals, partially relieved by food and by over-the-counter antacids. He takes ibuprofen most days for knee pain. No dysphagia, no weight loss, no bleeding, hemoglobin normal. He started omeprazole 3 weeks ago, taking it at bedtime, with only partial relief.
Key Points: (1) No alarm features and age under 60, so this is test-and-treat, not endoscopy -but the breath test must wait until he has been off the PPI for 2 weeks or it will be falsely negative. (2) Two correctable things are already visible: he is taking the PPI at the wrong time (move to 30-60 min before breakfast) and he is on daily NSAIDs, which is both a likely cause and a reason for gastroprotection if the ibuprofen cannot stop. (3) If H. pylori is positive, treat with 14-day bismuth quadruple therapy (not clarithromycin triple, retired as first-line in 2024), then confirm eradication with a breath or stool test at least 4 weeks after finishing -and plan the PPI exit rather than leaving him on it indefinitely.
Clinic Checklist
- Alarm features screened? Dysphagia, weight loss, bleeding, anemia, vomiting, age ≥ 60 with new dyspepsia -any one means scope, not treat.
- NSAID and aspirin use asked about explicitly -patients do not volunteer over-the-counter analgesics.
- PPI timing confirmed (before the first meal) before calling any regimen a failure.
- H. pylori test done off PPI (2 weeks) and off antibiotics/bismuth (4 weeks).
- Test-of-cure scheduled at least 4 weeks after therapy -treatment without confirmation is incomplete care.
- PPI has an indication, a duration, and an exit plan documented; if long-term, the reason is one from the real indication list.
- Gastric ulcer: biopsy at diagnosis and repeat endoscopy at 8-12 weeks on the plan.
📋 Summary
Summary
Alarm Features Decide the First Step
Dysphagia, odynophagia, weight loss, bleeding, iron deficiency anemia, persistent vomiting, mass, or new dyspepsia at 60 or older mean endoscopy, not an empiric trial. Without them, a patient under 60 goes down the test-and-treat path for H. pylori, because that removes a curable cause instead of masking symptoms.
Test H. pylori Correctly or Not at All
Urea breath test or stool antigen, off PPI for 2 weeks and off antibiotics or bismuth for 4 weeks, because suppressed bacterial load is the commonest cause of a false negative. Serology cannot confirm cure since IgG persists after eradication. Test-of-cure at 4+ weeks post-treatment is mandatory -eradication failure is common enough that assuming success is unsafe.
2024 Retired the Regimen You Memorized
Clarithromycin triple and concomitant therapy are no longer empiric first-line (ACG 2024) because US clarithromycin resistance crossed the threshold of usefulness. Bismuth quadruple therapy for 14 days is the preferred empiric choice, with vonoprazan dual or triple and rifabutin triple as alternatives. Clarithromycin and levofloxacin now require documented susceptibility.
Never Reuse a Failed Antibiotic
Resistance is the likeliest reason a first course failed, so repeating that drug repeats the failure. Salvage by what came before: bismuth quadruple after failed clarithromycin, rifabutin or vonoprazan-based after failed bismuth quadruple. Susceptibility testing after two failures, and re-ask about adherence, since a 14-day multi-drug regimen has a real dropout rate.
PPI Timing Is the Fix Before Escalation
30-60 minutes before the first meal, because PPIs bind only actively secreting pumps and meals are what activate them. Bedtime dosing on an empty stomach wastes most of the effect and manufactures "refractory" disease. Check timing and adherence before doubling the dose or doubting the diagnosis.
Every PPI Needs an Exit Plan
Long-term therapy is justified for Barrett, LA grade C/D esophagitis, stricture, hypersecretory states, and genuinely high-risk NSAID users -everyone else gets a deprescribing attempt. Taper rather than stop abruptly: rebound hypersecretion from gastrin-driven parietal cell hyperplasia causes worse-than-baseline symptoms that get misread as relapse and re-anchor the prescription.
Ulcers: Find Both Causes, Not One
H. pylori and NSAIDs cause the large majority, and patients often have both -finding one does not excuse you from asking about the other, including over-the-counter analgesics they will not mention unprompted. An ulcer negative for both deserves a second look: Zollinger-Ellison (fasting gastrin off PPI), Crohn disease, or malignancy.
Gastric Ulcers Get Biopsied and Re-Scoped
Malignant gastric ulcers can look benign and can partially heal on acid suppression, which is exactly the false reassurance that delays a cancer diagnosis. Biopsy at diagnosis, repeat endoscopy at 8-12 weeks to document complete healing. Duodenal ulcers carry negligible malignancy risk and do not need the same follow-up.
