Dyspepsia & Peptic Ulcer Disease Flashcards
Peptic Ulcer Disease
defintiion
• Group of ulcerative disorders “ dependent on acid & pepsin
• Primarily refers to gastric (GU) & duodenal ulcer (DU)
• Presentation: Dyspeptic symptoms, (e.g., episodic upper abdominal pain, bloating, abdominal
fullness, nausea, early satiety), Asymptomatic (70%)1, Complicated (hemorrhage, perforation)
• Natural HX: Healing w/o intervention, Upper GI bleeding, Perforation,
Obstruction. (severe)
• Two major causes: H. pylori infection; NSAID use
• Diagnosis: Visualization via endoscopy.
Typically episodic upper abdominal pain
Ulcers
Many pt are asymptomatic, usually heal on its own
Peptic Ulcer Disease
normal defenses
vs aggressive factors
normal:
Mucus
HCO3
Prostaglandins
aggressive:
H. pylori, NSAIDs
Smoking, EtOH
Acid, Pepsin
Dyspepsia
• Definition
– Symptom complex of epigastric pain or discomfort originating in the upper GI (epigastric)
tract (e.g., Nausea, bloating, fullness, early satiety, slow digestion, excessive burping,
heartburn, acid regurgitation)
• Canadian prevalence: 29% 7% of visits to family physicians • Etiology – Organic (40%) • GERD most common (30%) • Peptic Ulcer Disease (20%) • Cancer (<1%) – Functional Dyspepsia (60%) • Non ulcer dyspepsia (NUD) • Non erosive reflux disease (NERD)
Approach to Undiagnosed Dyspepsia
• Research definitions of dyspepsia (Rome Criteria)
attempt to $ inclusion of GERD
– (i.e., exclude pts with heartburn or acid
regurgitation as primary symptom)
• In practice, there is considerable overlap in
symptom presentation & it can be difficult
to distinguish b/w dyspepsia & GERD.
• Clinically relevant definition of dyspepsia:
Predominant epigastric pain lasting at least
1 month.
Approach to Undiagnosed Dyspepsia
flowchart
see slide 7 for more
- check for other causes: cardiac, hepatobiliary, medication
- red flags: >50, vomiting bleeding/anemia, abdominal mass, weight loss, dysphagia –> endoscopy rec
- NSAID and regular ASA use?
- Is dom symptom heartburn regurgitation?
if yes, treat as reflux - do H. pylori test
history - q’s to ask
History
• Exclude non GI sources of pain
• Identify those with predominant reflux like Sx
• Medication History for causes/aggravators of
dyspepsia (e.g., ASA, NSAIDS, antiplatelet,
bisphosphonates, CCB, iron, etc.)
Etiology of PUD
most common
less common
risk factors (4)
• Most common: H. pylori, NSAIDs
• Less common
– Stress ulcers
– Acid hypersecretory states (e.g. Zollinger-Ellison Syndrome)
– Other drugs: clopidogrel, sirolimus, bisphosphonates
– Viral (Herpes simplex, Cytomegalovirus)
– Vascular insufficiency/Crack cocaine
– Chemotherapy/Radiation
– Idiopathic
• Risk Factors
– Smoking, Alcohol, Genetic Factors, Psychological stress,
– Uncertain: Dietary factors
Definitions Peptic Ulcer Gastric ulcer (GU) Duodenal ulcer (DU) Gastritis:
Peptic Ulcer: A mucosal break in the stomach or duodenum ≥5mm.
Gastric ulcer (GU) Most commonly in the antrum & lesser curvature.
Duodenal ulcer (DU) Most commonly in the Duodenal bulb
Gastritis: Inflammation associated with gastric mucosal injury.
Peptic Ulcer Disease
Epidemiology
• Lifetime prevalence in North America ~ 10%1
• ~2,500 cases/year in Alberta2
• PUD Trends
– Incidence increases with age
– Similar incidence in men & women
– $ Peptic ulcer & GI cancer rates (upper GI malignancy more common
after 55 years of age)3
– # Peptic ulcer hemorrhage & perforation in older individuals
Helicobacter pylori
• Gram negative bacteria: lives b/w mucous layer & surface epithelial cells
• Causally linked to:
– Gastritis, Peptic ulcer disease
– Gastric cancer (2.8 – 6x risk), (MALT) lymphomas
– Lack of causal evidence for GERD
• Mechanism of injury
– Direct mucosal damage
– Alterations in the immune/inflammatory response
– Hypergastrinemia leads to hypersecretion of gastric acid
• Eradication thought to decrease gastric cancer risk, but unproven
• Of patients with H. pylori infection
– 20% get symptomatic PUD
– < 1% develop stomach cancer
H. pylori Epidemiology
risk factors (3)
transmission
• Prevalence in Canada: 35-40%1
– ~30% of Canadians with dyspepsia have active H. pylori infection.4
– $ Prevalence over time
• Risk Factors: – Population density
– Lower socioeconomic status
– Ethnicity (e.g. up to 95% on a reserve)2 & recent immigrants3
- No association with gender & smoking status
- Transmission: Gastro-oral, Fecal-oral, maternal colonization
- Percent of ulcers that are H. pylori positive
H. pylori Diagnosis
Non-invasive Methods (3)
• Urea breath test (UBT)
– Makes use of H. pylori’s urease enzyme
– Collect breath samples before & after oral ingestion of radiolabeled substrate with a test tube or balloon
– If H. pylori is present, radiolabeled urea is hydrolyzed to ammonia & radiolabeled CO2 “ positive test
– 2 different UBT 13C = Helikit
• Stool antigen test (HpSAT)
– First line test for diagnosis in Alberta
– Also useful for evaluating treatment success
• Serology
– IgG antibodies to H. pylori
– Remains positive after successful eradication
– Higher False Positive rate (~20%)
H. pylori Diagnosis
Invasive (i.e. Endoscopic) Methods (3)
- Biopsy rapid urease:
- H. pylori urease generates ammonia
- Culture:
- Gold standard
- Histology:
- Allows direct identification, look under microscope
H. pylori Diagnosis
Rely on amount of bac present
Affected by current PPI therapy or recent antibiotic ues
False Negative Results are Common
Important with tests that depend on bacterial load
– UBT Prep Stool antigen testPrep Culture, rapid urease, & histology,
• Common after use of antibiotics, proton pump
inhibitors, & bismuth
– To minimize false negatives, when checking H. pylori status
patient should be off (if possible)1
• Antibiotics, bismuth: 4 weeks
• PPI: 1-2 weeks
Goals of Therapy
• Overall goals
– Relieve ulcer pain, Heal ulcer, Prevent ulcer recurrence
– Prevent ulcer complications & A/E from drug therapies
• H. pylori positive: Eradicate H. pylori “ Cure the disease
– Want to use regimens that have ITT cure rates of > 80%
– Successful eradication increase ulcer healing & decrease recurrence
“Need to treat 2 patients with Hp eradication instead of placebo to prevent 1 duodenal ulcer relapse.”
H. pylori Eradication
“Standard Triple Therapy Approach”
what is first line and alternate?
from before?
First Line:
• PAC: PPI + Amoxicillin 1000 mg BID + Clarithromycin 500 mg BID x 7 days
• PMC: PPI + Metronidazole 500 mg BID + Clarithromycin 250 mg BID x 7 days
Alternate First Line (Quadruple Regimen):
• PBMT: PPI + Bismuth 30 ml QID + Metronidazole 250 mg QID + Tetracycline 500 mg QID x 10-14 days
H. pylori Eradication
Toronto Consensus Conference 2015
what recommendations changed
Choice of 1st line therapy consider regional Abx resistance patterns & eradication rates (GRADE: Strong, Low)
• In pts with H. pylori Infx we recommend a Tx duration of 14 days
Recommended Bismuth quadruple (PBMT) PPI + bismuth + metronidazole + tetracycline 14 d
Recommended Concomitant non-bismuth
quadruple (PAMC aka CLAMET)
PPI + amoxicillin + metronidazole +
clarithromycin
Restricted PPI Triple (PAC, PMC, PAM) PPI + amoxicillin + clarithromycin PPI + metronidazole + clarithromycin PPI + amoxicillin + metronidazole Restricted to areas with known low clarithromycin resistance (<15%) or proven high eradication rates(>85%)
which therapys not recommended
Levofloxacin triple (PAL) PPI + amoxicillin + levofloxacin
Sequential non bismuth quadruple (PA followed by
PMC)
PPI + amoxicillin followed by PPI +metronidazole + clarithromycin
Why 14 days instead of 7?
10-14 days of triple therapy vs. 7 days leads to 10% higher eradication rates (1 SR & MA of n=45 RCTs; 81.9% vs. 72.9%; NNT = 11)
H. pylori & Antibiotic Resistance
Lack of up to date data on H. pylori resistance patterns in Canada and locally in Alberta – Metronidazole resistance: 20% – Clarithromycin resistance: 2 – 8% – Amoxicillin resistance: <1% – Tetracycline: <3%
H. pylori Eradication
“The Bottom Line”
First Line Concomitant Therapy
– PAMC (PPI BID + Amoxicillin 1 g BID + Metronidazole 500 mg BID + Clarithromycin 500 mg BID for 14 days)
– PBMT (PPI BID + Bismuth subsalicylate 2 tabs QID + Metronidazole 500mg QID + Tetracycline 500 mg QID for 14 days)
• Standard Triple therapy “PPI + clarithromycin + amoxicillin x 14 days” is no longer recommended as first line therapy
• Sequential Therapy no longer recommended
– PPI BID 1-14 days; Amoxicillin 1g BID days 1-7 THEN Clarithromycin 500 mg and Metronidazole 500 mg BID days 7-14.
Efficacy & Tolerability of H. pylori
Eradication Regimens Main Adverse Effects
- Metronidazole: Disulfiram reaction (EtoH), Metallic taste
- Clarithromycin: Altered taste, CYP 3A4 DI, QT prolongation
- Tetracycline: Photosensitivity skin reactions
- Amoxicillin: Diarrhea
- Bismuth: Darkening of stool, diarrhea
Is Confirmation of H. pylori Eradication Required?
Whenever H. pylori is identified & treated, testing to prove eradication should be performed using a UBT, Fecal antigen test, or Biopsy at least 4 weeks after Abx therapy and after PPI stopped for 1-2 wks.
review pt >30 days after treatment, does pt still have sx?
No: no further testing required
Yes or if symptoms recur: retest using UBT, if negative reconsider diagnosis
if pos, eradication failure, alternative eradication protocol
How to Manage 1st Line Treatment Failure?
what are 3rd and 4th line
Use a different first line therapy that than used initially…
3rd Line: PAL: (GRADE: Conditional, Low)1
PPI BID + Amoxicillin 1 g BID + Levofloxacin 500 mg daily 14 days
4th line: PAR: 14 days
PPI BID + Amoxicillin 1 g BID + Rifabutin 150 mg BID
“Restrict rifabutin regimens to cases where >=3
recommended options have failed.”1 (GRADE: Strong, Low)
H. Pylori Eradication – 1st & 2nd Line Rx
when to use PAC or PMC?
known local patterns? low clarithromycin resistance or high PPI triple tx success rate: use PAC or PMC
Penicillin Allergy (ACG 2017): • After failure of 1st line therapy, patients with penicillin allergy should be considered for referral for allergy testing.
Is Maintenance Acid Suppression
Required after Successful H. pylori Eradication?
• Uncomplicated duodenal ulcers
– No need for a curative course of acid suppression after therapy for eradication.
• Continued PPI or H2RA therapy may be indicated for: – Uncomplicated gastric ulcers – Patients with frequent ulcer recurrences – History of ulcer related bleeding – Heavy smokers – NSAID users • Dose: standard doses • Duration: 8 weeks PPI (12 weeks H2RA)
PUD in Pregnancy
– If H. pylori testing was done during pregnancy/breastfeeding , postpone
treatment until after pregnancy/breastfeeding.
– No need to test the infant
– 13C UBT is acceptable in pregnancy
Management of Non-Ulcer (i.e., Functional ) Dyspepsia
• Aka “Dyspepsia with a normal endoscopy”
• Non-Drug Management
– Reassurance
– Avoidance of triggers
– Psychological therapy for mood disorder/anxiety
• GRADE: Conditional recommendation, very low quality evidence1
• Drug Therapy
– Empiric PPI x 4-8 weeks; little evidence for long term PPI treatment
– Tricyclic Antidepressants
• GRADE: Conditional recommendation, moderate quality evidence1
– Prokinetic agents (Metoclopramide, Domperidone)
• GRADE: Conditional recommendation, very low quality evidence1
